Investigation Of Ultra-Rare De Novo Attention Deficit Hyperactivity Disorder (ADHD) Single Nucleotide Variants
I investigated the 17 single nucleotide variants that are some of the ultra-rare de novo variants that are found in children with Attention Deficit Hyperactivity Disorder (ADHD) according to July 2024 published 'Rare de novo damaging DNA variants are enriched in attention-deficit/hyperactivity disorder and implicate risk genes'.
https://www.nature.com/articles/s41467-024-50247-7
5 are novel. 9 are Stop Gained aka Nonsense which are high impact variants in exons that can lead to loss function. Eight are Missense that are medium impact variants in exon, but one of them involves a Splice Donor that is a high impact varant in an intron that effects splicing (it is with one of the Missense variants).
I used Varsome to get the In-Silico Predictions and HGVS information. I used Ensembl's Variant Effect Predictor (VEP) to get information about the Combined Annotation Dependent Depletion (CADD) scores. I used the HGVS information at ClinGen Allele Registry to get rsID, ClinVar information and Genome Aggregation Database (gnomAD) information about the variants' allele frequencies and rsID's. I looked up information about the expression of the genes and listed parts of the brain and nervous system that are involved in the genes' expressions.
I looked up human phenotypes of the 17 genes of the variants at Mayaan Lab and Gene Cards. 13 have coordination problems as human phenotypes. 9 have ataxia as a human phenotype.7 have autistic traits as human phenotypes. 10 have seizures as human phenotype. According to Simons Foundation Autism Research Initiative (SFARI), 5 are Autism Candidate Genes.
There is a genetic overlap between various neurological conditions. This is no surprise to me because of the comorbidity. I personally understand this as a neuroatypical person with Ataxia, Dyspraxia, ADHD, and Dyslexia.
Cerebellar dysfunction is evident in several developmental disorders, including autism, attention deficit-hyperactivity disorder (ADHD), and developmental dyslexia, and damage to the cerebellum early in development can have long-term effects on movement, cognition, and affective regulation.
https://pubmed.ncbi.nlm.nih.gov/26298473/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6424539/
Dyslexia and Attention-deficit/hyperactivity disorder (ADHD) are highly comorbid neurodevelopmental disorders (estimates of 25–40% bidirectional comorbidity).
https://jneurodevdisorders.biomedcentral.com/articles/10.1186/s11689-019-9287-8
According to the scientific literature, 50 to 70% of individuals with autism spectrum disorder (ASD) also present with comorbid attention deficit hyperactivity disorder (ADHD).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8918663/
Among children with epilepsy, the prevalence of ADHD is at least 20%, substantially higher than the prevalence in the general pediatric population (Kaufmann et al., 2009). In adults with epilepsy, several studies point to a prevalence of up to 20% with comorbid ADHD (Ashjazadeh et al., 2019; Babcock & Ornstein, 2009; Ettinger et al., 2015).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10676030/
32 (17 females, 15 males; mean age 12 yrs) with non-progressive congenital ataxia were examined for neuropsychiatric problems in a study at Sundsvall Hospital; Umea University Hospital; Karolinska Hospital, Stockholm; and Goteborg University, Sweden. 16 of the 32 (50%) patients with ataxia have symptoms of autistic spectrum disorder. 8 of the 32 (25%) have attention deficit hyperactivity disorder. 31% of the 32 have severe learning disability.
The authors highlight the common association of congenital nonprogressive forms of ataxia with learning disability, ADHD, and autistic spectrum disorder. The causes are heterogeneous, but prenatal factors, including chromosomal malformations, are most common with the simple ataxias. Children with congenital ataxia are at risk for learning disability, ADHD, and autistic disorders.
https://pediatricneurologybriefs.com/articles/10.15844/pedneurbriefs-19-4-5
'
Chr16:24567213 A G
RBBP6(NM_006910.5):c.509A>G
Missense, non coding exon
28.7
1 out of 1,604,406 (6.233e-7)
RBBP6 (RB Binding Protein 6, Ubiquitin Ligase) is a Protein Coding gene. Diseases associated with RBBP6 include Myelodysplastic Syndrome and Myeloproliferative Neoplasm. Among its related pathways are Class I MHC mediated antigen processing and presentation and Signaling by Rho GTPases. Gene Ontology (GO) annotations related to this gene include nucleic acid binding and ligase activity. An important paralog of this gene is ZCCHC24.
https://www.genecards.org/cgi-bin/carddisp.pl?gene=RBBP6&keywords=RBBP6
Mayaan Lab Human Phenotypes: Obsessive-compulsive behavior, Drooling Impulsivity, Poor coordination, Broad-based gait
https://maayanlab.cloud/archs4/gene/RBBP6
mRNA Expression by UniProt/SwissProt: Expressed at lower levels in the brain
Evidence on tissue expression from TISSUES: nervous system (4.7)
bgee Expression Scores: right hemisphere of cerebellum (94.62), Brodmann (1909) area 23 (92.71), middle frontal gyrus (91.96), middle temporal gyrus (91.84), ganglionic emininence (91.62), frontal pole (91.02), cortical plate (90.29), right frontal lobe (89.92), corpus callosum (89.87), caudate nucleus (89.79), C1 segment of cervical spinal cord (89.61), amygala (89.21), lateral globus pallidus (89.16), cerebellar vermis (81.14), putamen (89.09), cingulate cortex (89.08), anterior cingulate cortex (89.07), Brodmann (1909) area 9 (88.94), CA1 field of hippocampus (88.70), Brodmann (1909) area 46 (88.29), hypothalamus (88.07), Brodmann (1909) area 10 (87.97), substantia nigra pars reticulata (87.62), ateral nuclear group of thalamus (87.41), cranial nerve II (87.32), inferior vagus X ganglion (87.11), postcentral gyrus (86.96), superior frontal gyrus (86.31), ventral tegmental area (86.17), orbitofrontal cortex (85.80), substantia nigra pars compacta (85.65), subthalamic nucleus (85.23), trigeminal ganglion (84.90), superior vestibular nucleus (84.80), dorsal root ganglion (84.51), pons (82.77)
https://www.bgee.org/gene/ENSG00000122257
Chr14:75276497 C T
YLPM1(NM_019589.3):c.4936C>T
rs954412463
Stop Gained
37.0
4 out of 1,613,568 (0.0002479%) Condition allele frequency is 2.800e-7
https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA263645784
YLPM1 (YLP Motif Containing 1) is a Protein Coding gene. Diseases associated with YLPM1 include Bartter Syndrome, Type 1, Antenatal and Mixed Endometrial Stromal And Smooth Muscle Tumor. Gene Ontology (GO) annotations related to this gene include RNA binding and 6-phosphofructo-2-kinase activity.
Enables RNA binding activity. Predicted to be involved in regulation of telomere maintenance. Predicted to act upstream of or within negative regulation of transcription by RNA polymerase II. Located in cytosol and nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]
https://www.genecards.org/cgi-bin/carddisp.pl?gene=YLPM1
Mayaan Lab Human Phenotypes: Focal motor seizures, motor seizures, focal seizures, Epileptic encephalopathy, Drooling, febrile seizures, Broad-based gait, Gaze-evoked nystagmus, Obsessive-compulsive behavior, Atonic seizures, Visual hallucinations, Truncal ataxia, Action tremor, Dysdiadochokinesis, Impaired smooth pursuit, Dysmetric saccades, Absence seizures, Abnormality of ocular smooth pursuit, Poor eye contact, Inappropriate behavior, Hyperacusis, Abnormal social behavior, Impaired social interactions, Insomnia, Autism, Attention deficit hyperactivity disorder, Dysmetria, Stereotypic behavior, Impulsivity, Scanning speech
https://maayanlab.cloud/archs4/gene/YLPM1
mRNA Expression by UniProt/SwissProt: expressed in neuronal, neuroblastoma cell lines (at protein level)
Evidence on tissue expression from TISSUES: Nervous system(4.8)
bgee Expression Scores: ganglionic eminence (96.47), cortical plate (96.34), medial globus pallidus (94.76), right hemisphere of cerebellum (94.53), corpus callosum (94.02), right frontal lobe (93.42), middle temporal gyrus (92.51), Brodmann (1909) area 9 (92.49), Brodmann (1909) area 23(92.28), putamen (91.94), substantia nigra pars reticulata (91.80), caudate nucleus (91.66), hypothalamus (91.54), amygdala (91.47), lateral globus pallidus (91.46), primary visual cortex (91.42), subthalamic nucleus (91.37), inferior vagus X ganglion (91.27), C1 segment of cervical spinal cord (91.15), prefrontal cortex (90.71), substantia nigra pars compacta (90.38), superior vestibular nucleus (90.01), cingulate cortex (89.78), ventral tegmental area (89.70), lateral nuclear group of thalamus (89.62), Ammon's Horn (89.52), anterior cingulate cortex (89.46), trigeminal ganglion (88.78), dorsal root ganglion (88.72), Brodmann (1909) area 46 (88.32), orbitofrontal cortex (87.54), pons (86.83), superior frontal gyrus (86.62), parietal lobe (85.99), CA1 field of hippocampus (83.90), cerebellar vermis (77.21)
https://www.bgee.org/gene/ENSG00000119596
Chr11:78282471 G A
NARS2(NM_024678.6):c.160C>T
rs751315158
Stop Gain, 5'UTR, non coding transcript exon
39.0
83 out of 1,611,892 (0.005149%) Condition allele frequency is 0.005386%
Clinvar reported as Pathogenic/Likely pathogenic
NARS2 (Asparaginyl-TRNA Synthetase 2, Mitochondrial) is a Protein Coding gene. Diseases associated with NARS2 include Combined Oxidative Phosphorylation Deficiency 24 and Deafness, Autosomal Recessive 94. Among its related pathways are tRNA Aminoacylation and Metabolism of proteins. Gene Ontology (GO) annotations related to this gene include nucleic acid binding and aminoacyl-tRNA ligase activity. An important paralog of this gene is NARS1.
This gene encodes a putative member of the class II family of aminoacyl-tRNA synthetases. These enzymes play a critical role in protein biosynthesis by charging tRNAs with their cognate amino acids. This protein is encoded by the nuclear genome but is likely to be imported to the mitochondrion where it is thought to catalyze the ligation of asparagine to tRNA molecules. Mutations in this gene have been associated with combined oxidative phosphorylation deficiency 24 (COXPD24). [provided by RefSeq, Mar 2015]
https://www.genecards.org/cgi-bin/carddisp.pl?gene=NARS2
Gene Cards Human Phenotypes: Seizure, Nystagmus, Dysarthria, Neuronal loss in central nervous system, Neurodegeneration, Abnormality of the nervous system, EEG abnormality, Abnormality of eye movement, Neurodevelopmental abnormality, Neurodevelopmental delay, Abnormal nervous system physiology, Abnormal involuntary eye movements, Hearing abnormality, Abnormality of nervous system electrophysiology, Abnormality of central nervous system physiology, Abnormal ear physiology, Abnormal communication, Abnormality of movement, Functional motor deficit, Upper motor neuron dysfunction, Abnormality of mental function, Abnormal central motor function, Functional abnormality of the inner ear, Abnormality of speech or vocalization
Evidence on tissue expression from TISSUES: Nervous system(4.6)
bgee Expression Scores: ganglionic eminence (90.53), cortical plate (89.98), prefrontal cortex (81.42), Brodmann (1909) area 9 (81.10), lateral globus pallidus (80.54), cingulate cortex (80.43), anterior cingulate cortex (80.41), cerebellar cortex (80.31), cerebellar hemisphere (80.28), C1 segment of cervical spinal cord (79.84), hypothalamus (79.79), cerebellar vermis (79.62), corpus callosum (79.32), substantia nigra (79.24), amygala (79.13), right hemisphere of cerebellum (79.00), right frontal lobe (78.20), caudate nucleus (77.58), putamen (77.25), Ammon's Horn (77.60), primary visual cortex (76.80), substantia nigra pars reticulata (76.38), Brodmann (1909) area 23 (76.15), substantia nigra pars compacta (75.92), pons (75.77), lateral nuclear group of thalamus (75.66), middle temporal gyrus (75.37), superior frontal gyrus (74.82), superior vestibular nucleus (74.71), Brodmann (1909) area 46 (73.91), ventral tegmental area (72.78), postcentral gyrus (73.81), inferior vagus X ganglion (72.27), dorsal root ganglion (72.05), trigeminal ganglion (71.97), CA1 field of hippocampus (71.57), orbitofrontal cortex (70.86), cranial nerve II (67.81), medial globus pallidus (65.36)
https://www.bgee.org/gene/ENSG00000137513
Chr2:80808942 C T
CTNNA2(NM_004389.4):c.2005C>T
Missense, Intron
28.7
3 out of 1,581,514 (0.0001897%) Condition allele frequency is 2.900e-7
CTNNA2 (Catenin Alpha 2) is a Protein Coding gene. Diseases associated with CTNNA2 include Cortical Dysplasia, Complex, With Other Brain Malformations 9 and Hereditary Breast Ovarian Cancer Syndrome. Among its related pathways are Blood-Brain Barrier and Immune Cell Transmigration: VCAM-1/CD106 Signaling and Sertoli-Sertoli Cell Junction Dynamics. Gene Ontology (GO) annotations related to this gene include structural molecule activity and structural constituent of cytoskeleton. An important paralog of this gene is CTNNA1.
Enables actin filament binding activity. Involved in negative regulation of Arp2/3 complex-mediated actin nucleation; regulation of neuron migration; and regulation of neuron projection development. Located in cytoplasm. Implicated in complex cortical dysplasia with other brain malformations. [provided by Alliance of Genome Resources, Apr 2022]
https://www.genecards.org/cgi-bin/carddisp.pl?gene=CTNNA2
Autism Candidate Gene - Syndromic
https://gene.sfari.org/database/human-gene/CTNNA2
Gene Card Human Phenotypes: Seizure, Delayed gross motor development, EEG abnormality, Absent speech, Autistic behavior, Delayed early-childhood social milestone development, Atonic seizure, Delayed fine motor development, Ataxia, Myoclonic seizure, Motor delay, Delayed speech and language development, Gait disturbance, Abnormality of the nervous system, Neurodevelopmental abnormality, Neurodevelopmental delay, Atypical behavior, Abnormal social behavior, Abnormality of central nervous system electrophysiology, Abnormal nervous system electrophysiology, Abnormal reflex, Abnormal communication, Abnormality of movement, Interictal EEG abnormality, Morphological central nervous system abnormality, Upper motor neuron dysfunction, Abnormality of coordination, Abnormality of mental function, Abnormal central motor function, Language impairment, Motor seizure, Abnormality of speech or vocalization
Mayaan Lab Human Phenotypes: Focal motor seizures, Focal seizures, Visual hallucinations, Epileptic Encephalopathy,Febrile seizures, Progressive cerebellar ataxia, Atonic seizures, Absence seizures, Action tremor,Generalized tonic-clonic seizures, Broad-based gait, Dialeptic seizures, Depression, Spastic gait, Abnormal eating behavior, Poor eye contact, Drooling, Truncal ataxia, Abnormal social behavior, Impaired social interactions, Progressive inability to walk, Dysdiadochokinesis, Dysmetria, Gaze-evoked nystagmus, Anxiety, Postural instability, Agitation, Insomnia, Stereotypic behavior, Gait imblance, Specific learning disability, Inability to walk, Scanning speech, Intention tremor, Impaired smooth pursuit, Inappropriate behavior, Mutism, Absent speech, Inability to walk, Apathy
https://maayanlab.cloud/archs4/gene/CTNNA2
Evidence on tissue expression from TISSUES: Nervous system (4.6)
bgee Expression Scores: frontal lobe (96.62), Brodmann (1909) area 46 (97.25), superior frontal gyrus (97.16), postcentral gyrus (97.07), lateral nuclear group of thalamus (97.06), Brodmann (1909) area 10 (97.05), dorsolateral prefrontal cortex (96.95), orbitofrontal cortex (96.95), orbitofrontal cortex (96.70), amygala (96.55), anterior cingulate cortex (96.45), cranial nerve II (96.42), middle frontal gyrus (96.41), Brodmann (1909) area 9 (96.08), primary visual cortex (95.97), right frontal lobe (95.97), caudate nucleus (95.46), cortical plate (95.31), middle temporal gyrus (95.31), Ammon's Horn (95.19), CA1 field of hippocampus (94.21), nucleus accumbens (94.07), Brodmann (1909) area 23 (93.69), putamen (93.53), hypothalamus (92.78), ganglionic eminence (92.57), substantia nigra (89.59), corpus callosum (89.42), brainstem nucleus (88.62), hindbrain nucleus (88.62), superior vestibular nucleus (88.60), pons (88.59), lateral globulus pallidus (88.38), medial globulus pallidus (88.19), ventral tegmental area (85.53), substantia nigra pars compacta (84.96), cerebellar vermis (83.72), subthalamic nucleus (83.59), substantia nigra pars reticulata (83.56), segment of cervical spinal cord (81.47), right hemisphere of cerebellum (81.29), inferior vagus X ganglion (78.15), trigeminal ganglion (74.92), dorsal root ganglion (74.33)
https://www.bgee.org/gene/ENSG00000066032
Chr1:202704703 G A
KDM5B(NM_006618.5):c.3277C>T
Stop Gained, non coding transcript exon, 3'UTR
40.0
7 out of 1,613,376 (0.0004339%) Condition allele frequency is 7.900e-7
KDM5B (Lysine Demethylase 5B) is a Protein Coding gene. Diseases associated with KDM5B include Intellectual Developmental Disorder, Autosomal Recessive 65 and Autism Spectrum Disorder. Among its related pathways are Gene expression (Transcription) and RNA Polymerase I Promoter Opening. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and 2-oxoglutarate-dependent dioxygenase activity. An important paralog of this gene is KDM5A.
This gene encodes a lysine-specific histone demethylase that belongs to the jumonji/ARID domain-containing family of histone demethylases. The encoded protein is capable of demethylating tri-, di- and monomethylated lysine 4 of histone H3. This protein plays a role in the transcriptional repression or certain tumor suppressor genes and is upregulated in certain cancer cells. This protein may also play a role in genome stability and DNA repair. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Nov 2016]
https://www.genecards.org/cgi-bin/carddisp.pl?gene=KDM5B
Autism Candidate Gene - High Confidence, Syndromic, Functional
https://gene.sfari.org/database/human-gene/KDM5B
Gene Card Human Phenotypes: Delayed speech and language development, Aggressive behavior, Delayed ability to walk, Gait ataxia, Unsteady gait, Motor delay, Gait disturbance, Abnormality of the nervous system, Delayed gross motor development, Abnormality of eye movement, Neurodevelopmental abnormality, Neurodevelopmental delay, Atypical behavior, Abnormal nervous system physiology, Recurrent maladaptive behavior, Abnormal communication, Abnormality of movement, Ataxia, Abnormality of coordination, Abnormality of mental function, Abnormal central motor function, Language impairment, Abnormality of speech or vocalization
Mayaan Lab Human Phenotypes: Impulsivity, Drooling, Poor coordination, Pendular nystagmus, Agnosia, Gait imbalance, Obsessive-compulsive behavior
https://maayanlab.cloud/archs4/gene/KDM5B
Protein differential expression in normal tissues from HIPED: Cerebrospinal fluid (14.6)
Evidence on tissue expression from TISSUES: Nervous system (4.6)
bgee Expression Scores: cortical plate (96.71), ganglionic eminence (96.57), cerebellar hemisphere (84.09), cerebellar hemisphere (84.09), primary visual cortex (82.76), corpus callosum (82.42), right frontal lobe (82.03), middle temporal gyrus (81.91), Brodmann (1909) area 46 (81.68), nucleus acumbens (81.59), prefontal cortex (81.56), Brodmann (1909) area 23 (81.53), dorsolateral prefrontal cortex (81.05), Brodmann (1909) area 9 (80.88), caudate nucleus (80.71), cingulate cortex (80.45), anterior cingulate cortex (80.23), putamen (79.55), amygala (78.79), Ammon's Horn (78.49), superior frontal gyrus (78.13), C1 segment of cervical spinal cord (77.78), hypothalamus (77.65), postcentral gyrus (77.22), orbitofrontal cortex (74.23), substantia nigra (73.30), CA1 field of hippocampus (72.64), dorsal root ganglion (72.49), trigeminal ganglion (72.13), cerebellar vermis (72.02), substantia nigra pars compacta (68.72), inferior vagus X ganglion (67.67), cranial nerve II (67.31), medulla oblongata (67.29), brainstem nucleus (67.20), hindbrain nucleus (67.20), globus pallidus (64.92), pons (64.90), superior vestibular nucleus (67.18), medial globus pallidus (64.16)
https://www.bgee.org/gene/ENSG00000117139
Chr3:136068009 G A
STAG1(NM_005862.3):c.3262C>T
rs1936343493
Stop Gained
36.0
2 out of 28,258 (0.007%) - 14KJPN
1 out 16,760 (0.006%) - 8.3KJPN
https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA354642018
STAG1 (STAG1 Cohesin Complex Component) is a Protein Coding gene. Diseases associated with STAG1 include Intellectual Developmental Disorder, Autosomal Dominant 47 and Cortical Dysplasia, Complex, With Other Brain Malformations 13. Among its related pathways are Separation of Sister Chromatids and Cell Cycle, Mitotic. Gene Ontology (GO) annotations related to this gene include chromatin binding and binding. An important paralog of this gene is STAG2.
This gene is a member of the SCC3 family and is expressed in the nucleus. It encodes a component of cohesin, a multisubunit protein complex that provides sister chromatid cohesion along the length of a chromosome from DNA replication through prophase and prometaphase, after which it is dissociated in preparation for segregation during anaphase. [provided by RefSeq, Jul 2008]
https://www.genecards.org/cgi-bin/carddisp.pl?gene=STAG1
Autism Candidate Gene - Syndromic, Functional
https://gene.sfari.org/database/human-gene/KDM5B
Gene Card Human Phenotypes: Delayed speech and language development, Seizure, Autistic behavior, Epileptic encephalopathy, Abnormality of the nervous system, Abnormality of eye movement, Neurodevelopmental abnormality, Neurodevelopmental delay, Atypical behavior, Abnormal eye physiology, Abnormal communication, Atrophy/Degeneration affecting the central nervous system, Abnormality of mental function, Language impairment, Abnormality of speech or vocalization
Mayaan Lab Human Phenotypes: Truncal ataxia, Obsessive-compulsive behavior, high pitched voice, Hyperacusis
https://maayanlab.cloud/archs4/gene/STAG1
mRNA expression in embryonic tissues and stem cells from LifeMap Discovery: Brain (Nervous System) Striatum/Cerebral Cortex, Neural Tube (Nervous System) Telencephalon
Evidence on tissue expression from TISSUES: Nervous system (3.3)
bgee Expression Scores: ganglionic eminence (91.67), cortical plate (87.72), corpus callosum (86.71), trigeminal ganglion (85.23), CA1 field of hippocampus (83.62), dorsal root ganglion (82.99), Brodmann (1909) area 46 (81.77), cranial nerve II (81.58), cerebellar cortex (81.53), cerebellar vermis (81.43), medial globus pallidus (81.21), right hemisphere of cerebellar (81.25), post central gyrus (80.18), inferior vagus X ganglion (80.16), subthalamic nucleus (79.24), ventral tegmental area (79.23), superior vestibular nucleus (78.83), pons (77.87), C1 segment of cervical spinal cord (77.69), superior frontal gyrus (77.31), substantia nigra pars reticulata (77.11), Brodmann (1909) area 23 (76.92), occipital lobe (76,81), primary visual cortex (76.73), lateral globulus pallidus (76.60), hypothalamus (76.10), amygala (76,04), caudate nucleus (75.46), putamen (75.45), laternal nuclear group of thalamus (75.40), nucleus acumbens (74.67), prefrontal cortex (74.61), middle temporal gyrus (74.51), substantia nigra pars compacta (74.48), right frontal lobe (73.82), Brodmann (1909) area 9 (73.70), cingulate cortex (72.97), anterior cingulate cortex (72.66), orbitofrontal lobe cortex (70.80)
https://www.bgee.org/gene/ENSG00000118007
Chr2:55071273 C T
EML6(NM_001039753.4):c.937C>T
rs1379514961
Stop Gained
37.0
2 out of 1,551,500 (0.0001289%)
EML6 (EMAP Like 6) is a Protein Coding gene. Diseases associated with EML6 include Keratoconus and Brill-Zinsser Disease. An important paralog of this gene is EML5.
Predicted to enable microtubule binding activity. Predicted to be located in cytoplasm and microtubule. [provided by Alliance of Genome Resources, Apr 2022]
https://www.genecards.org/cgi-bin/carddisp.pl?gene=EML6
Mayaan Lab Human Phenotypes: Focal motor seizures, Focal seizures, Epileptic encephalopathy, Febrile seizures, Atonic seizures, Progressive cerebellar ataxia, Absense seizures, Dialeptic seizures, Visual hallucinations, Action tremor, Gaze-evoked nystagmus, Generalized tonic-clonic seizures, Broad-based gait, Truncal ataxia, Dysdiadochokinesis, Dysmetria, Drooling, Impaired smooth pursuit, Inability to walk, Postural instability, Gait imbalance, Depression, Clumsiness, Spastic gait, Anxiety, Intention tremor, Dysmetric saccades, Abnormal eating behavior, Poor eye contact, Scanning speech, Stereotypic behavior, Impaired social interactions, Abnormal social behavior, Inappropriate behavior, Abnormality of saccadic eye movements, Specific learning disability, Agitation, Abnormal drinking behavior, Mutism, Absent speech, Progressive inability to walk
https://maayanlab.cloud/archs4/gene/EML6
mRNA expression in embryonic tissues and stem cells from LifeMap Discovery: Neural Tube (Nervous System) Telencephalon/Diencephalon/Spinal Ventral Columns
mRNA differential expression in normal tissues according to GTEx: overexpressed in Brain - Cerebellum (x4.4)
Protein differential expression in normal tissues from HIPED: overexpressed in Frontal cortex (8.6)
Evidence on tissue expression from TISSUES: Nervous system(3.3)
bgee Expression Scores: middle temporal gyrus (88.99), right hemisphere of cerebellum (87.83), Brodmann (1909) area 23 (87.76), ganglionic eminence (87.53), primary visual cortex (86.74), right frontal lobe (85.55), Brodmann (1909) area 9 (84.05), postcentral gyrus (81.96), cingulate cortex (81.42), anterior cingulate cortex (81.40), superior frontal cortex (81.39), caudate nucleus (79.37), prefrontal cortex (79.15), cortical plate (78.79), putamen (77.81), hypothalamus (77.12), Ammon's Horn (76.85), nucleus acumbens (76.58), corpus callosum (76.21), amygala (75.84), medial globulus pallidus (75.01), Brodmann (1909) area 46 (74.85), substantia nigra (73.29), cerebellar vermis (72.67), C1 segment of cervical spinal cord (69.72), substantia nigra pars compacta (69.13), substantia nigra pars reticulata (67.56), dorsal plus ventral thalamus (67.11), ventral tegmental area (67.10), medulla oblongata (66.94), superior vestibular nucleus (66.85), pons (66.53), trigeminal ganglion (66.26), dorsal root ganglion (66.20)
https://www.bgee.org/gene/ENSG00000214595
Chr11:65623472 T C
CFL1(NM_005507.3):c.245A>G
Novel
Missense
26.1
CFL1 (Cofilin 1) is a Protein Coding gene. Diseases associated with CFL1 include Smith-Lemli-Opitz Syndrome and Endometrial Type Cervical Adenomyoma. Among its related pathways are Response to elevated platelet cytosolic Ca2+ and Semaphorin interactions. Gene Ontology (GO) annotations related to this gene include actin binding. An important paralog of this gene is CFL2.
The protein encoded by this gene can polymerize and depolymerize F-actin and G-actin in a pH-dependent manner. Increased phosphorylation of this protein by LIM kinase aids in Rho-induced reorganization of the actin cytoskeleton. Cofilin is a widely distributed intracellular actin-modulating protein that binds and depolymerizes filamentous F-actin and inhibits the polymerization of monomeric G-actin in a pH-dependent manner. It is involved in the translocation of actin-cofilin complex from cytoplasm to nucleus.[supplied by OMIM, Apr 2004]
https://www.genecards.org/cgi-bin/carddisp.pl?gene=CFL1
Mayaan Lab Human Phenotypes: Hyperacusis, Insomnia, Agnosia, Personality changes, Poor head control, High pitched voice, Loss of speech, Difficulty climbing stairs, Diminished motivation, Apathy
https://maayanlab.cloud/archs4/gene/CFL1
mRNA expression in embryonic tissues and stem cells from LifeMap Discovery: Brain (Nervous System) Cerebral Cortex
Evidence on tissue expression from TISSUES: Nervous system (5.5)
bgee Expression Scores: pons (99.92), inferior vagus X ganglion (99.91), ventral tegmental area (99.91), Brodmann (1909) area 46 (99.90), subthalamic nucleus (99.89), superior vestibular nucleus (99.89), laternal nuclear group of thalamus (99.89), parietal lobe (99.86), trigeminal ganglion (99.86), prefrontal cortex (99.85), CA1 field of hippocampus (99.85), superior frontal gyrus (99.83), cranial nerve II (99.83), substantia nigra pars compacta (99.82), substantia nigra pars reticulata (99.82), lateral globus pallidus (99.81), dorsal root ganglion (99.79), right frontal lobe (99.78), orbitofrontal cortex (99.78), cortical plate (99.78), dorsolateral prefrontal cortex (99.76), ganglionic eminence (99.73), middle temporal gyrus (99.73), rodmann (1909) area 9 (99.72), occipital lobe (99.71), right hemisphere of cerebellum (99.70), hypothalamus (99.69), cingulate cortex (99.68), anterior cingulate cortex (99.67), spinal cord (99.96), amygala (99.66), Brodmann (1909) area 23 (99.65), putamen (99.65), nucleus acumbens (99.65), caudate nucleus (99.65), C1 segment of cervical spinal cord (99.64), primary visual cortex (99.64), superficial temporary artery (99.60), corpus callosum (99.56), medial globus pallidus (99.28), Brodmann (1909) area 10 (99.28), cerebellar vermis (99.25), frontal pole (98.49), middle frontal gyrus (98.37)
https://www.bgee.org/gene/ENSG00000172757
Chr19:17337532 G T
OCEL1(NM_024578.3):c.100G>T
Stop Gain, 5'UTR, no coding transcript exon
NMD escaping
39.0
Novel, but there is a co-location variant listed under rs2073363552
OCEL1 (Occludin/ELL Domain Containing 1) is a Protein Coding gene. Diseases associated with OCEL1 include Aicardi Syndrome and Vulvar Non-Keratinizing Squamous Cell Carcinoma. An important paralog of this gene is MARVELD2.
Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]
https://www.genecards.org/cgi-bin/carddisp.pl?gene=OCEL1
Mayaan Lab Human Phenotypes: Irritability
https://maayanlab.cloud/archs4/gene/OCEL1
bgee Expression Scores: prefrontal cortex (87.77), right frontal lobe (87.55), cingulate cortex (86.55), anterior cingulate cortex (86.54), right hemisphere of cerebellum (86.39), C1 segment of cervical spinal cord (85.81), Brodmann (1909) area 9 (85.08), amygala (84.66), putamen (83.01), caudate nucleus (82.76), nucleus acumbens (82.03), hypothalamus (81.82), primary visual cortex (80.72), Brodmann (1909) area 10 (80.47), substantia nigra (80.36), Ammon's Horn (78.49), cortical plate (76.32), ganglionic eminence (74.32), dorsal root ganglion (72.99), superior vestibular nucleus (72.85), cranial ganglion (72.84), superior vestibular nucleus (72.85), middle temporal gyrus (72.46), trigeminal ganglion (72.36), globus pallidus (71.72), Brodmann (1909) area 46 (71.69), medial globus pallidus (71.47), frontal pole (71.42), superior frontal gyrus (70.89), Brodmann (1909) area 23 (68.37), parietal lobe (68.21), cranial nerve II (68.05), corpus callosum (67.31), postcentral gyrus (66.98),
https://www.bgee.org/gene/ENSG00000099330
Chr7:138819468 G A
IFT56(NM_024926.4):c.71G>A
aka TTC26
rs1218505907
Splice Donor, Missense, non coding transcript exon
22.4
1 out of 1,614,106 (6.195e-7)
https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA369395065
IFT56 (Intraflagellar Transport 56) is a Protein Coding gene. Diseases associated with IFT56 include Biliary, Renal, Neurologic, And Skeletal Syndrome and Hydrocephalus. Among its related pathways are Organelle biogenesis and maintenance and Bardet-Biedl syndrome.
Predicted to enable intraciliary transport particle B binding activity. Predicted to be involved in cilium organization; protein localization to cilium; and smoothened signaling pathway. Predicted to act upstream of or within manchette assembly. Predicted to be located in cilium. Predicted to be part of intraciliary transport particle B. Predicted to be active in ciliary basal body and ciliary base. [provided by Alliance of Genome Resources, Apr 2022]
https://www.genecards.org/cgi-bin/carddisp.pl?gene=IFT56
Gene Card Human Phenotypes: Seizure, Abnormality of cardiovascular system electrophysiology, Abnormality of the nervous system, Neurodevelopmental abnormality, Neurodevelopmental delay, Abnormal nervous system physiology, Hearing abnormality, Upper motor neuron dysfunction, Abnormality of mental function, Abnormal central motor function
Mayaan Lab Human Phenotypes: Gait imbalance, Pendular nystagmus, Oculomotor apraxia, Abnormal drinking behavior, Poor coordination, Agnosia, Febrile seizures, Spinal rigidity
https://maayanlab.cloud/archs4/gene/TTC26
Evidence on tissue expression from TISSUES: Nervous system(4.4)
bgee Expression Scores: ganglionic eminence (75.23), cortical plate (74.78), prefrontal cortex (67.07), cerebellar cortex (64.32), cerebellar hemisphere (64.31), Brodmann (1909) area 9 (63.70), nucleus accumbens (63.37), right hemisphere (63.33), hypothalamus (63.22), anterior cingulate cortex (62.87), right frontal lobe (62.73), C1 segment of cervical spinal cord (61.63), amygala (60.68), putamen (60.37), cranial nerve II (60.27), Ammon's Horn (58.66), corpus callosum (57.55), primary visual cortex (57.03), substantia nigra (55.93), superior frontal gyrus (55.27)
https://www.bgee.org/gene/ENSG00000105948
Chr2:48035289 G A
FBXO11(NM_001190274.2):c.2752C>T
Novel
Missense
24.6
FBXO11 (F-Box Protein 11) is a Protein Coding gene. Diseases associated with FBXO11 include Intellectual Developmental Disorder With Dysmorphic Facies And Behavioral Abnormalities and Hematologic Cancer. Among its related pathways are Class I MHC mediated antigen processing and presentation and Metabolism of proteins. Gene Ontology (GO) annotations related to this gene include ubiquitin-protein transferase activity and protein-arginine N-methyltransferase activity. An important paralog of this gene is FBXO10.
This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbxs class. It can function as an arginine methyltransferase that symmetrically dimethylates arginine residues, and it acts as an adaptor protein to mediate the neddylation of p53, which leads to the suppression of p53 function. This gene is known to be down-regulated in melanocytes from patients with vitiligo, a skin disorder that results in depigmentation. Polymorphisms in this gene are associated with chronic otitis media with effusion and recurrent otitis media (COME/ROM), a hearing loss disorder, and the knockout of the homologous mouse gene results in the deaf mouse mutant Jeff (Jf), a single gene model of otitis media. Alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jun 2010]
https://www.genecards.org/cgi-bin/carddisp.pl?gene=FBXO11
Autism Candidate Gene - Strong Candidate, Syndromic
https://gene.sfari.org/database/human-gene/FBXO11
Gene Cards Human Phenotypes: Delayed speech and language development, Seizure, Hyperactivity
Mayaan Lab Human Phenotypes: Focal motor seizures, focal seizures, Visual hallucinations, Febrile seizures, Broad-based gait, Atonic seizures, Progressive cerebellar ataxia, Epileptic encephalopathy, Drooling, Inappropriate behavior, Action tremor, Absence seizures, Gaze-evoked nystagmus, Truncal ataxia, Generalized tonic-clonic seizures, Dialeptic seizures, Agitation, Progressive Inability to walk, Dysmetric saccades, Gait imbalance, Absent speech, Impaired smooth pursuit, Depression, Stereotypic behavior, Dysdiadochokinesis, Disinhibition, Poor eye contact, Impaired social interactions, Mutism, Difficulty running, Apathy
https://maayanlab.cloud/archs4/gene/FBXO11
Protein differential expression in normal tissues from HIPED: Fetal Brain (9.3)
Evidence on tissue expression from TISSUES: Nervous system(4.8)
bgee Expression Scores: cortical plate (97.92), ganglionic eminence (97.19), cerebellar hemisphere (96.12), right hemisphere of cerebellum (95.82), superficial temporary artery (95.00), corpus callosum (94.53), primary visual cortex (94.21), prefrontal cortex (93.87), dorsolateral prefrontal cortex (93.81), Brodmann (1909) area 9 (93.40), right frontal lobe (93.27), laternal nuclear group of thalamus (93.07), pons (92.99), anterior cingulate cortex (92.93), dorsal root ganglion (92.44), nucleus accumbens (92.39), superior frontal gyrus (92.28), caudate nucleus (92.26), trigeminal ganglion (92.24), parietal lobe (92.21), medial globus pallidus (91.98), amygala (91.97), Brodmann (1909) area 23 (91.92), postcentral gyrus (91.88), putamen (91.80), hypothalamus (91.78), Ammon's horn (91.63), inferior vagus X ganglion (91.44), substantia nigra reticulata (91.27), ventral tegmental area (91.03), subthalamic nucleus (91.00), orbitofrontal cortex (90.94), CA1 field of hippocampus (90.87), substantia nigra pars compacta (90.60), C1 segment of cervical spinal cord (90.00), lateral globus pallidus (88.89), cerebellar vermis (88.70), cranial nerve II (88.61), Brodmann (1909) area 46 (88.49), middle temporal gyrus (83.22)
https://www.bgee.org/gene/ENSG00000138081
Chr6:30691669 G A
TUBB(NM_178014.4):c.830G>A
rs2127749601
Missense
26.5
Clinvar reported as Uncertain Significance back in 2019
https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA363148769
TUBB (Tubulin Beta Class I) is a Protein Coding gene. Diseases associated with TUBB include Cortical Dysplasia, Complex, With Other Brain Malformations 6 and Skin Creases, Congenital Symmetric Circumferential, 1. Among its related pathways are Loss of proteins required for interphase microtubule organization from the centrosome and Cell Cycle, Mitotic. Gene Ontology (GO) annotations related to this gene include GTP binding and structural molecule activity. An important paralog of this gene is TUBB4B.
This gene encodes a beta tubulin protein. This protein forms a dimer with alpha tubulin and acts as a structural component of microtubules. Mutations in this gene cause cortical dysplasia, complex, with other brain malformations 6. Alternative splicing results in multiple splice variants. There are multiple pseudogenes for this gene on chromosomes 1, 6, 7, 8, 9, and 13. [provided by RefSeq, Jun 2014]
https://www.genecards.org/cgi-bin/carddisp.pl?gene=TUBB
Gene Cards Human Phenotypes: Motor delay, Delayed speech and language development, Ataxia, Neurodevelopmental abnormality, Neurodevelopmental delay, Abnormal nervous system physiology, Abnormal communication, Abnormality of coordination, Abnormality of mental function, Abnormal central motor function, Language impairment, Abnormality of speech or vocalization
Mayaan Lab Human Phenotypes: Hyperacusis, Insomnia, Obsessive-compulsive behavior
https://maayanlab.cloud/archs4/gene/TUBB
mRNA Expression by UniProt/SwissProt: Tissue specificity: Ubiquitously expressed with highest levels in immature brain
Evidence on tissue expression from TISSUES: Nervous system(4.7)
bgee Expression Scores: cortical plate (99.92), ganglionic eminence (99.89), superior frontal gyrus (99.05), hypothalamus (99.04), anterior cingulate cortex (98.76), Brodmann (1909) area 9 (98.75), right frontal lobe (98.70), cerebellum (98.52), cerebellar cortex (98.52), cerebellar hemisphere (98.51), primary visual cortex (98.49), C1 segment of cervical spinal cord (98.48), right hemisphere of cerebellum (98.48), temporal lobe (98.41), amygala (98.40), substantia nigra (98.25), nucleus accumbens (98.06), caudate nucleus (97.93), putamen (97.72), prefrontal cortex (94.23)
https://www.bgee.org/gene/ENSG00000183311
Chr3:121435768 A C
GOLGB1(NM_001366282.2):c.1104T>G
Stop Gained, 3'UTR
24.8
519 out of 1,613,304 (0.03217%) Disease allele frequency is 0.003757%
GOLGB1 (Golgin B1) is a Protein Coding gene. Diseases associated with GOLGB1 include Spinal Muscular Atrophy With Lower Extremity Predominant 1 and Arthritis. Among its related pathways are Transport to the Golgi and subsequent modification and Vesicle-mediated transport. Gene Ontology (GO) annotations related to this gene include RNA binding and sequence-specific DNA binding.
Enables RNA binding activity. Involved in protein localization to pericentriolar material. Located in Golgi apparatus and endoplasmic reticulum-Golgi intermediate compartment. [provided by Alliance of Genome Resources, Apr 2022]
https://www.genecards.org/cgi-bin/carddisp.pl?gene=GOLGB1
Mayaan Lab Human Phenotypes: Symptomatic seizures, Agitation, Resting tremor, Dysmetric saccades, Action tremor, Visual hallucinations
https://maayanlab.cloud/archs4/gene/GOLGB1
Evidence on tissue expression from TISSUES: Nervous system (4.3)
bgee Expression Scores: cranial nerve II (91.26), corpus callosum (90.51), cerebellar hemisphere (88.85), right hemisphere of cerebellum (88.69), right frontal lobe (88.54), C1 segment of cervical spinal cord (87.69), ganglionic eminence (87.44), middle temporal gyrus (86.88), medial globus pallidus (86.56), caudate nucleus (86.55), nucleus accumbens (86.55), amygala (86.28), putamen (86.25), cortical plate (86.22), substantia nigra (86.12), Broadmann (1909) area 9 (85.88), hypothalamus (85.66), cingulate cortex (85.46), prefrontal cortex (85.28), anterior cingulate cortex (85.27), Broadmann (1909) area 46 (82.56), superior frontal gyrus (82.37), dorsal root ganglion (82.28), substantia nigra pars compacta (81.63), substantia nigra pars reticulata (81.63), primary visual cortex (81.59), trigeminal ganglion (81.47), postcentral gyrus (81.16), lateral globus pallidus (80.35), cerebellar vermis (79.80), Brodmann (1909) area 23 (79.35), orbitofrontal cortex (78.71), superior vestibular nucleus (78.61), inferior vagus X ganglion (78.37), dorsal plus ventral thalamus (78.25), ventral tegmental area (78.21), laternal nuclear group of thalamus (78.17), subthalmic nucleus (78.13), pons (77.37), Brodmann (1909) area 10 (76.00), middle frontal gyrus (75.32), frontal pole (75.18), CA1 field of hippocampus (74.61)
https://www.bgee.org/gene/ENSG00000173230
Chr1:62676185 C A
L1TD1(NM_019079.5):c.1739C>A
Novel
Stop Gained
NMD escaping, Predicted to be BP4 Supporting
34.0
L1TD1 (LINE1 Type Transposase Domain Containing 1) is a Protein Coding gene. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and obsolete signal transducer activity.
Predicted to enable single-stranded RNA binding activity. Predicted to be involved in transposition, RNA-mediated. Located in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]
https://www.genecards.org/cgi-bin/carddisp.pl?gene=L1TD1
Mayaan Lab Human Phenotypes: Agnosia, Impulsivity, Symptomatic seizures, Pendular nystagmus
https://maayanlab.cloud/archs4/gene/L1TD1
bgee Expression Scores: corpus callosum (49.38), primary visual cortex (46.26), putamen (41.35), Ammon's Horn (32.54)
https://www.bgee.org/gene/ENSG00000240563
Chr5:180665146 T C
RACK1(NM_006098.5):c.730A>G
Novel
Missense
26.6
RACK1 (Receptor For Activated C Kinase 1) is a Protein Coding gene. Diseases associated with RACK1 include Round Cell Sarcoma With Ewsr1-Patz1 Gene Fusion and Lung Cancer. Among its related pathways are TNF signaling and Regulation of CFTR activity (norm and CF).
Enables several functions, including cyclin binding activity; enzyme binding activity; and protein domain specific binding activity. Involved in several processes, including positive regulation of hydrolase activity; regulation of cellular protein metabolic process; and regulation of signal transduction. Located in several cellular components, including midbody; perinuclear region of cytoplasm; and phagocytic cup. Part of IRE1-RACK1-PP2A complex. [provided by Alliance of Genome Resources, Apr 2022]
https://www.genecards.org/cgi-bin/carddisp.pl?gene=RACK1
Mayaan Lab Human Phenotypes: Agnosia, High pitched voice, Hyperacusis, Impulsivity, Pendular nystagmus
https://maayanlab.cloud/archs4/gene/RACK1
Evidence on tissue expression from TISSUES: Nervous system (5)
bgee Expression Scores: cerebellar vermis (99.95), trigeminal ganglion (99.91), pons (99.86), dorsal root ganglion (99.83), ganglionic eminence (99.93), superficial temporary artery (99.82), cortical plate (99.82), superior vestibular nucleus (99.74), inferior vagus X ganglion (99.69), middle frontal gyrus (99.57), ventral tegmental area (99.57), right hemisphere (99.56), subthalamic nucleus (99.54), C1 segment of cervical spinal cord (99.46), frontal pole (99.42), nucleus accumbens (99.36), lateral globus pallidus (99.36), amygala (99.34), Brodmann (1909) area 10 (99.33), hypothalamus (99.32), caudate nucleus (99.28), putamen (99.26), corpus callosum (99.25), right frontal lobe (99.23), cingulate cortex (99.22), anterior cingulate cortex (99.22), substantia nigra pars reticulata (99.20), substania nigra pars compacta (99.15), dorsolateral prefrontal cortex (99.08), Brodmann (1909) area 9 (99.05), cranial nerve II (99.00), laternal nuclear group of thalamus (98.81), Ammon's horn (98.72), postcentral gyrus (98.47), CA1 field of hippocampus (98.37), orbitofrontal cortex (98.21), medial globus pallidus (98.16), Brodmann (1909) area 46 (98.11), dorsal motor nucleus of vagus nerve (97.81), superior frontal gyrus (97.30), occipital lobe (98.80), primary visual cortex (94.56), middle temporal gyrus (91.90), Brodmann (1909) area 23 (88.93)
https://www.bgee.org/gene/ENSG00000204628
Chr11:77103522 G A
PAK1(NM_001128620.2):c.44C>T
27.3
Missense
4 out of 1,613,654 (0.0002479%) Disease allele frequency is 7.900e-7
PAK1 (P21 (RAC1) Activated Kinase 1) is a Protein Coding gene. Diseases associated with PAK1 include Intellectual Developmental Disorder With Macrocephaly, Seizures, And Speech Delay and Epilepsy. Among its related pathways are EPH-Ephrin signaling and Semaphorin interactions. Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is PAK3.
This gene encodes a family member of serine/threonine p21-activating kinases, known as PAK proteins. These proteins are critical effectors that link RhoGTPases to cytoskeleton reorganization and nuclear signaling, and they serve as targets for the small GTP binding proteins Cdc42 and Rac. This specific family member regulates cell motility and morphology. Mutations in this gene have been associated with macrocephaly, seizures, and speech delay. Overexpression of this gene is also reported in many cancer types, and particularly in breast cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2020]
https://www.genecards.org/cgi-bin/carddisp.pl?gene=PAK1
Autism Candidate Gene - Syndromic
https://gene.sfari.org/database/human-gene/PAK1
Gene Cards Human Phenotypes: Motor delay, Delayed speech and language development, Seizure, Delayed ability to walk, Receptive language delay, Poor speech, Gait ataxia, Unsteady gait, Gait disturbance, Abnormality of the nervous system, Delayed gross motor development, Abnormality of eye movement, Neurodevelopmental abnormality, Neurodevelopmental delay, Abnormal nervous system physiology, Abnormal conjugate eye movement, Abnormal eye physiology, Abnormal communication, Abnormality of movement, Ataxia, Abnormality of coordination, Abnormality of mental function, Abnormal central motor function, Language impairment, Abnormality of speech or vocalization
Mayaan Lab Human Phenotypes: Focal motor seizures, Epileptic Encephalopathy, Focal seizures, Atonic seizures, Visual hallucinations, Febrile seizures, Progressive cerebellar ataxia, Absence seizures, Broad-based gait, Dialeptic seizures, Gaze-evoked nystagmus, Generalized tonic-clonic seizures, Action tremor, Dysmetria, Scanning speech, Poor eye contact, Dysdiadochokinesis, Slow saccadic eye movements, Spastic gait, Abnormal eating behavior, Truncal ataxia, Depression, Drooling, Intention tremor, Impaired social interactions, Abnormal social behavior, Memory impairment, Anxiety, Agnosia, Impaired smooth pursuit, Postural stability, Dysmetric saccades, Progressive inability to walk, Mutism, Absent speech, Apathy, Stereotypic behavior, Inability to walk, Inappropriate behavior, Diminished motivation, Abnormality of ocular smooth pursuit, Rigidity, Gait imbalance, Parkinsonism with favorable response to dopaminergic medication, Specific learning disability, Disinhibition, Gait ataxia, Abnormality of saccadic eye movements, Dementia, Delusions, Psychosis, Postural tremor
https://maayanlab.cloud/archs4/gene/PAK1
mRNA differential expression in normal tissues according to GTEx: overexpressed in Brain - Frontal Cortex (BA9) (x4.9), Brain - Cortex (x4.5)
Protein differential expression in normal tissues from HIPED: overexpressed in Frontal cortex (10.1)
Evidence on tissue expression from TISSUES: Nervous system(4.8)
bgee Expression Scores: middle temporal gyrus (99.29), pons (97.87), cerebellar cortex (97.61), cerebellar hemisphere (97.60), right hemisphere of cerebellum (97.55), right frontal lobe (97.43), laternal nuclear group of thalamus (97.37), prefrontal cortex (97.36), primary visual cortex (96.83), superior frontal gyrus (96.56), cerebellar vermis (96.48), cortical plate (96.14), dorsolateral prefrontal cortex (96.07), parietal lobe (95.71), ganglionic eminence (95.67), frontal pole (95.17), anterior cingulate cortex (94.84), Brodmann (1909) area 9 (94.29), superior vestibular nucleus (92.90), amygala (92.57), nucleus accumbens (91.66), Ammon's horn (90.12), lateral globus pallidus (89.56), caudate nucleus (89.36), ventral tegmental area (89.32), substantia nigra pars compacta (89.27), Brodmann (1909) area 10 (88.75), corpus callosum (88.73), substantia nigra pars reticulata (88.24), dorsal root ganglion (88.02), putamen (87.95), C1 segment of cervical spinal cord (87.06), hypothalamus (85.29), trigeminal ganglion (85.08), inferior vagus X ganglion (84.08), Brodmann (1909) area 46 (81.65), middle frontal gyrus (80.69), superficial temporary (76.97), orbitofrontal cortex (68.90)
https://www.bgee.org/gene/ENSG00000149269W
Chr10:75331247 G A
USP54(NM_152586.4):c.172C>T
rs766013576
Stop Gain, non coding transcript exon
NMD escaping
36.0
5 out of 1,613,480 (0.0003099%) Condition allele frequency is 0.000554%
https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA5556810
USP54 (Ubiquitin Specific Peptidase 54) is a Protein Coding gene. Among its related pathways is Ubiquitin-Proteasome Dependent Proteolysis. Gene Ontology (GO) annotations related to this gene include cysteine-type deubiquitinase activity. An important paralog of this gene is USP53.
Predicted to enable thiol-dependent deubiquitinase. Predicted to be involved in protein deubiquitination. [provided by Alliance of Genome Resources, Apr 2022]
https://www.genecards.org/cgi-bin/carddisp.pl?gene=USP54
Mayaan Lab Human Phenotypes: Focal motor seizures, Intention tremor, Dysmetria, Focal motor seizures, Spastic gait, Action tremor, Scanning speech, Clumsiness, Dysmetric saccades, Dysdiadochokinesis, Slow saccadic eye movements, Progressive cerebellar ataxia, Focal seizures, Postural instability, Epileptic encephalopathy, Broad-based gait, Gaze-evoked nystagmus, Febrile seizures, Truncal ataxia, Generalized tonic-clonic seizures, Frequency falls, Abnormality of saccadic eye movements, Difficulty running, Absense seizures, Atonic seizures,Dialeptic seizures,Depression, Anxiety, Gait imbalance, Drooling, Abnormal social behavior, Impaired social interactions, Poor coordination
https://maayanlab.cloud/archs4/gene/USP54
Protein differential expression in normal tissues from HIPED: overexpressed in Frontal cortex (28.7), and Spinal cord (6.4)
Evidence on tissue expression from TISSUES: Nervous system(4.7)
bgee Expression Scores: corpus callosum (98.88), inferior vagus X ganglion (98.39), C1 segment of cervical spinal cord (97.68), subthalamic nucleus (97.26), medulla oblongata (96.83), lateral globus pallidus (96.54), ventral tegmental area (96.54), superior vestibular nucleus (96.19), substantia nigra (96.09), medial globus pallidus (96.04), substantia nigra pars reticulata (95.62), putamen (94.55), amygala (94.35), pons (94.25), substantia nigra pars compacta (94.07), Ammon's horn (93.58), hypothalamus (93.57), caudate nucleus (93.45), lateral nuclear group of thalamus (92.60), right frontal lobe (91.95), Brodmann (1909) area 9 (91.74), prefrontal cortex (91.67), nucleus accumbens (91.59), occipital lobe (91.23), parietal lobe (90.95), trigeminal ganglion (90.46), cingulate cortex (90.39), anterior cingulate cortex (90.39), primary visual cortex (90.32), Brodmann (1909) area 46 (89.09), superior frontal gyrus (88.36), dorsal root ganglion (88.30), cerebellar vermis (87.88), right hemiphere of cerebellum (87.76), ganglionic eminence (86.23), cortical plate (85.83), Brodmann (1909) area 23 (84.69), middle temporal gyrus (81.89),
https://www.bgee.org/gene/ENSG00000149269
Comments