SRCAP |
- 1
Haplo
Score - 0
Triplo
Score
Gene Facts External Data Attribution
- HGNC Symbol
- SRCAP (HGNC:16974) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
- HGNC Name
- Snf2 related CREBBP activator protein
- Gene type
- protein-coding gene
- Locus type
- gene with protein product
- Previous symbols
- No previous names found
- Alias symbols
- KIAA0309, SWR1, DOMO1
- %HI
- 34.43(Read more about the DECIPHER Haploinsufficiency Index)
- pLI
- 1(Read more about gnomAD pLI score)
- LOEUF
- 0.1(Read more about gnomAD LOEUF score)
- Cytoband
- 16p11.2
- Genomic Coordinates
-
GRCh37/hg19: chr16:30710492-30752730 NCBI Ensembl UCSC GRCh38/hg38: chr16:30699171-30741409 NCBI Ensembl UCSC - MANE Select Transcript
- NM_006662.3 ENST00000262518.9 (Read more about MANE Select)
- Function
- Catalytic component of the SRCAP complex which mediates the ATP-dependent exchange of histone H2AZ/H2B dimers for nucleosomal H2A/H2B, leading to transcriptional regulation of selected genes by chromatin remodeling. Acts as a coactivator for CREB-mediated transcription, steroid receptor-mediated transcription, and Notch- mediated transcription. {ECO:0000269|PubMed:10347196, ECO:0000269|PubMed:11522779, ECO:0000269|PubMed:14500758, ECO:0000269|PubMed:16024792, ECO:0000269|PubMed:16634648, ECO:000... (Source: Uniprot)
Dosage Sensitivity Summary (Gene)
Dosage ID:
ISCA-20217
Curation Status:
Complete
Issue Type:
Dosage Curation -
Gene
Haploinsufficiency:
Little Evidence for Haploinsufficiency
(1)
Triplosensitivity:
No Evidence for Triplosensitivity
(0)
Last Evaluated:
05/31/2018
Haploinsufficiency (HI) Score Details
HI Score:
1
HI Evidence Strength:
Little Evidence for Haploinsufficiency
(Disclaimer)
HI Evidence:
-
PUBMED:
28263302
Yuen et al - MSSNG project, WGS, autism study, 2,066 families, one de novo LOF in SRCAP exon 27
-
PUBMED:
25363768
Iossifov et al - Simons Simplex Collection, WES, autism study, 2,517 families, one de novo LOF in SRCAP exon 29
HI Evidence Comments:
SRCAP has a well established association with Floating-Habor syndrome via a dominant negative mechanism:
Hood et al (2012, PMID:22265015) reported 5 mutations (nonsense or frameshift) in 13 patients with Floating-Harbor syndrome. Parental specimens were available for testing in 6 cases and all were de novo. However, based on a study done by Monroy et al (2001, PMID:1152279), the non-random clustering of the mutations, and two HapMap control individuals with deletions involving SRCAP, Hood et al. conclude that these mutations likely result in a dominant-negative effect. Additionally, Le Goff et al (2013, PMID:22965468) reported the same mutations in 6 of 9 patients with Floating-Harbor syndrome and Reschen et al (2012, PMID:23165645) reported one patient with a recurrent mutation.
See also PMID 25326637: Lee et al - WES, clinical service, 814 cases, one de novo LOF in SRCAP (p.Arg2435*) in patient with develomental delay, speech delay, short stature, microcephaly, dysmorphic features, ptosis, brachydactyly, Coffin-Siris syndrome, Kabuki. This patient is consistent with Floating-Habor as well.
Following re-review of this gene, there are also 2 de novo LOFs in patients with autism (PMID 28263302 & 25363768). Therefore, an updated haploinsufficiency score of 1 has been assigned.
Triplosensitivity (TS) Score Details
TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
Genomic View
Select assembly:
(NC_000016.9)
(NC_000016.10)