SRCAP

Chr 16

Snf2 related CREBBP activator protein

Also known as: DEHMBA, DOMO1, FLHS, SWR1

NCBI Gene: 10847ENSG00000080603UniProt: Q6ZRS2

This gene encodes the core catalytic component of the multiprotein chromatin-remodeling SRCAP complex. The encoded protein is an ATPase that is necessary for the incorporation of the histone variant H2A.Z into nucleosomes. It can function as a transcriptional activator in Notch-mediated, CREB-mediated and steroid receptor-mediated transcription. Mutations in this gene cause Floating-Harbor syndrome, a rare disorder characterized by short stature, language deficits and dysmorphic facial features. [provided by RefSeq, Feb 2012]

Primary Disease Associations & Inheritance

UniProtFloating-Harbor syndrome
UniProtDevelopmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities
2450
ClinVar variants
16
Pathogenic / LP
1.00
pLI score· haploinsufficient
1
Active trials
Clinical Summary— SRCAP
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
16 Pathogenic / Likely Pathogenic· 310 VUS of 2450 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.10LOEUF
pLI 1.000
Z-score 9.81
OE 0.05 (0.03–0.10)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.13Z-score
OE missense 0.86 (0.83–0.90)
1634 obs / 1894.5 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.05 (0.03–0.10)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.86 (0.83–0.90)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.15
0≤1.21.6
LoF obs/exp: 6 / 123.8Missense obs/exp: 1634 / 1894.5Syn Z: -3.11

ClinVar Variant Classifications

2450 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4
Likely Pathogenic12
VUS310
Likely Benign224
Benign7
Conflicting2
4
Pathogenic
12
Likely Pathogenic
310
VUS
224
Likely Benign
7
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
2
0
4
Likely Pathogenic
9
1
2
0
12
VUS
0
298
12
0
310
Likely Benign
0
22
52
150
224
Benign
0
1
5
1
7
Conflicting
—2
Total1132273151559

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SRCAP · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

SRCAP-related neurodevelopmental disorder

strong
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

SRCAP-related Floating-Harbor syndrome

definitive
ADDominant NegativeAltered Gene Product Structure
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Truncating SRCAP variants outside the Floating-Harbor syndrome locus cause a distinct neurodevelopmental disorder with a specific DNA methylation signature.
Rots D et al.·Am J Hum Genet
2021
De novo variants underlying monogenic syndromes with intellectual disability in a neurodevelopmental cohort from India.
Pande S et al.·Eur J Hum Genet
2024Cohort
SRCAP complex promotes lung cancer progression by reprograming the oncogenic transcription of Hippo-YAP/TAZ signaling pathway.
Zhang H et al.·Cancer Lett
2024
Deficient H2A.Z deposition is associated with genesis of uterine leiomyoma.
Berta DG et al.·Nature
2021
Missense variant in SRCAP with distinct DNA methylation signature associated with non-FLHS SRCAP-related neurodevelopmental disorder.
White-Brown A et al.·Am J Med Genet A
2023Case report
Inherited mutations affecting the SRCAP complex are central in moderate-penetrance predisposition to uterine leiomyomas.
Välimäki N et al.·Am J Hum Genet
2023
The Genetic Landscape of Children Born Small for Gestational Age with Persistent Short Stature.
Toni L et al.·Horm Res Paediatr
2024
De novo SRCAP variants cause developmental and epileptic encephalopathy and the phenotypic spectrum.
Liang XY et al.·Epilepsia
2026
Artificial intelligence-driven genotype-epigenotype-phenotype approaches to resolve challenges in syndrome diagnostics.
Mak CCY et al.·EBioMedicine
2025
Purification and assay of the human INO80 and SRCAP chromatin remodeling complexes.
Cai Y et al.·Methods
2006Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
16P11.2 Deletion Syndrome16p11.2 Duplications1Q21.1 Deletion

Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight

RECRUITING
NCT01238250Simons SearchlightStarted 2010-10

External Resources

Links to major genomics databases and tools