SINHCAF

Chr 12

SIN3-HDAC complex associated factor

Also known as: C12orf14, FAM60A, L4, TERA

NCBI Gene: 58516ENSG00000139146UniProt: Q9NP50

SINHCAF encodes a subunit of the Sin3 deacetylase complex that represses TGF-beta signaling pathway genes and is essential for maintaining embryonic stem cell proliferation and preventing premature cell differentiation. The gene is highly constrained against loss-of-function variants (pLI 0.96, LOEUF 0.29), but no specific disease associations have been established in the provided data. Clinical phenotypes and inheritance patterns associated with SINHCAF mutations have not been characterized.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
1
Pubs (1 yr)
32
P/LP submissions
0%
P/LP missense
0.29
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical Summary— SINHCAF
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.96). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
32 unique Pathogenic / Likely Pathogenic· 21 VUS of 60 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.29LOEUF
pLI 0.965
Z-score 2.99
OE 0.00 (0.00–0.29)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.08Z-score
OE missense 0.45 (0.36–0.57)
52 obs / 114.6 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.00 (0.00–0.29)
0≤0.351.4
Missense OE0.45 (0.36–0.57)
0≤0.61.4
Synonymous OE1.06
0≤1.21.6
LoF obs/exp: 0 / 10.4Missense obs/exp: 52 / 114.6Syn Z: -0.29
DN
0.3693th %ile
GOF
0.2298th %ile
LOF
0.77top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.29

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

60 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic29
Likely Pathogenic3
VUS21
Likely Benign2
29
Pathogenic
3
Likely Pathogenic
21
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
29
0
29
Likely Pathogenic
0
0
3
0
3
VUS
0
19
2
0
21
Likely Benign
0
0
0
2
2
Benign
0
0
0
0
0
Total01934255

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

View in ClinVar →

Protein Context — Lollipop Plot

SINHCAF · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 3 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients