SYN1 |
- 3
Haplo
Score - 0
Triplo
Score
Gene Facts External Data Attribution
- HGNC Symbol
- SYN1 (HGNC:11494) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
- HGNC Name
- synapsin I
- Gene type
- protein-coding gene
- Locus type
- gene with protein product
- Previous symbols
- MRX50
- Alias symbols
- No aliases found
- %HI
- 9.89(Read more about the DECIPHER Haploinsufficiency Index)
- pLI
- 0.99(Read more about gnomAD pLI score)
- LOEUF
- 0.25(Read more about gnomAD LOEUF score)
- Cytoband
- Xp11.3-p11.23
- Genomic Coordinates
-
GRCh37/hg19: chrX:47431300-47479256 NCBI Ensembl UCSC GRCh38/hg38: chrX:47571901-47619857 NCBI Ensembl UCSC - MANE Select Transcript
- NM_006950.3 ENST00000295987.13 (Read more about MANE Select)
- Function
- Neuronal phosphoprotein that coats synaptic vesicles, and binds to the cytoskeleton. Acts as a regulator of synaptic vesicles trafficking, involved in the control of neurotransmitter release at the pre-synaptic terminal (PubMed:21441247, PubMed:23406870). Also involved in the regulation of axon outgrowth and synaptogenesis (By similarity). The complex formed with NOS1 and CAPON proteins is necessary for specific nitric-oxid functions at a presynaptic level (By similarity). {ECO:0000250|UniProtKB... (Source: Uniprot)
Dosage Sensitivity Summary (Gene)
Haploinsufficiency (HI) Score Details
- X-linked complex neurodevelopmental disorder Monarch
-
PUBMED:
14985377
Garcia et al. (2004) reported a four generation family with multiple males. Some males had epilepsy and normal intelligence and others have various combinations of epilepsy, learning difficulties, macrocephaly, and aggressive behavior. One patient had a diagnosis of autism. All affected males and female carriers were found to have a nonsense variant; however, it was not present in 287 control chromosomes.
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PUBMED:
21441247
Fassio et al. (2011) described a nonsense variant in all affected individuals from a large four generation French-Canadian family segregating partial epilepsy with variable learning disabilities and behavioral disorders. Two patients also had autism. Additionally, three missense variants were found in 1.0 and 3.5% of French-Canadian individuals with autism and epilepsy, respectively. Three out of four variants were clustered in the SynI D-domain which is target of multiple molecular interactions and signal transduction pathways, and were associated with functional defects in nerve terminal function. The nonsense variant was found to impair binding and phosphorylation capacity and disrupt normal trafficking of synaptic vesicles in neurons. The missense variants did not result in impaired binding or phosphorylation but did cause impaired synaptic vesicle trafficking. The authors showed that Syn KO mice exhibited various impairments in cognitive and social behavior compatible with an autism spectrum phenotype in human.
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PUBMED:
34243774
Xiong et al. 2021 reported 2 probands, one with missense and the other with a nonsense variant in the SYN1 gene that was identified by Trio-WES. The first proband was a 6-year-old male patient presenting with a profound global developmental delay, two febrile convulsions and bilateral esotropia. He had no history of behavioural abnormalities. The variant was detected in the patient in a hemizygous state and in his mother, grandmother and great grandmother in a heterozygous state but was absent from his unaffected brother. The second proband was an 8.5-year-old boy presenting with intellectual disability, epilepsy, abnormal social behaviour and ametropia. The variant was identified in his mother in a heterozygous state and absent from his father.
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PUBMED:
34078716
Accogli et al. 2021 reported 12 patients from 10 unrelated families with different nonsense (6 variants) and missense variants (4 variants) in the SYN1 gene. They presented with bathing epilepsy, varying degrees of intellectual disability (2 had normal intelligence), ASD and ADHD. Two of the affected patients were females and the rest were males and this was attributed to the skewed X-inactivation. The affected females also had intellectual disabilities and unprovoked seizures. The mothers were carriers in all 10 families.
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PUBMED:
30390306
Peron el al. 2018 (PMID: 30390306) reported a splice site variant in a male patient with a reflex seizure induced by contact with water and normal but below-average intelligence (IQ 80) and learning disability. A maternal uncle with the same variant had the same type of seizure and mild intellectual disability. The mother and the grandmother were carriers.
The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.
Triplosensitivity (TS) Score Details
The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.