SIN3A |
- 3
Haplo
Score - 0
Triplo
Score
Gene Facts External Data Attribution
- HGNC Symbol
- SIN3A (HGNC:19353) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
- HGNC Name
- SIN3 transcription regulator family member A
- Gene type
- protein-coding gene
- Locus type
- gene with protein product
- Previous symbols
- No previous names found
- Alias symbols
- KIAA0700, DKFZP434K2235
- %HI
- 7.32(Read more about the DECIPHER Haploinsufficiency Index)
- pLI
- 1(Read more about gnomAD pLI score)
- LOEUF
- 0.14(Read more about gnomAD LOEUF score)
- Cytoband
- 15q24.2
- Genomic Coordinates
-
GRCh37/hg19: chr15:75661720-75748156 NCBI Ensembl UCSC GRCh38/hg38: chr15:75369379-75455815 NCBI Ensembl UCSC - MANE Select Transcript
- NM_001145358.2 ENST00000394947.8 (Read more about MANE Select)
- Function
- Acts as a transcriptional repressor. Corepressor for REST. Interacts with MXI1 to repress MYC responsive genes and antagonize MYC oncogenic activities. Also interacts with MXD1-MAX heterodimers to repress transcription by tethering SIN3A to DNA. Acts cooperatively with OGT to repress transcription in parallel with histone deacetylation. Involved in the control of the circadian rhythms. Required for the transcriptional repression of circadian target genes, such as PER1, mediated by the large PER ... (Source: Uniprot)
Dosage Sensitivity Summary (Gene)
Dosage ID:
ISCA-10595
ClinGen Curation ID:
CCID:007851
Curation Status:
Complete
Issue Type:
Dosage Curation -
Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency
(3)
Triplosensitivity:
No Evidence for Triplosensitivity
(0)
Related Links:
Last Evaluated:
01/13/2020
Haploinsufficiency (HI) Score Details
HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency
(Disclaimer)
HI Disease:
- chromosome 15q24 deletion syndrome Monarch
HI Evidence:
-
PUBMED:
27399968
Witteveen et al. (2016), report nine patients (from five families) with loss-of-function type variants (frameshift and nonsense) in SIN3A. The clinical features reported in these individuals included intellectual disability, developmental delay (speech and motor), structural brain anomalies, autism spectrum disorder, seizures, microcephaly, short stature, dysmorphic craniofacial features, hearing loss, digital anomalies, hypermobile joints, and additional clinical findings. The craniofacial findings included broad forehead, downslanting palpebral fissures, bilateral telecanthic/epicanthic folds, ear anomalies, small mouth, and a pointed chin. Parental testing identified that three of the five reported mutations were de novo. The two mutations that were inherited were identified in parents (one mother and one father) who were also clinically affected. The authors of this study also report four additional individuals with non-focal SIN3A whole gene deletions. These individuals presented with a similar clinical presentation to the patients with SIN3A loss-of-function type variants.
-
PUBMED:
30267900
Narumi-Kishimoto et al. (2018), report a single individual with a frameshift variant (p.His283fs) in the in the SIN3A gene. The clinical features reported in this patient included intellectual disability, developmental delay (speech and motor), autism spectrum disorder, a long face, depressed nasal bridge, downslanting palpebral fissures, small hands, short 5th finger clinodactyly, hypermobile joints, and additional clinical findings. The identified frameshift mutation was not harbored by either parent, consistent with it representing a de novo event.
HI Evidence Comments:
At this time there is sufficient evidence to support a haploinsufficiency score of 3 for this gene. There have been at least six patients with loss-of-function type variants in SIN3A reported in the literature. These individuals presented with an overlapping clinical presentation that includes intellectual disability, developmental delay, structural brain anomalies, microcephaly, short stature, digital abnormalities, and dysmorphic craniofacial findings. The majority of the reported variants (4/6) represent de novo events, with the other variants (2/6) being inherited from affected parents.
Triplosensitivity (TS) Score Details
TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
At this time there are no focal SIN3A duplications (involving just SIN3A) reported in the literature. Therefore, the triplosensitivity score for this gene is a 0.
Genomic View
Select assembly:
(NC_000015.9)
(NC_000015.10)