SINHCAF

Chr 12

SIN3-HDAC complex associated factor

Also known as: C12orf14, FAM60A, L4, TERA

NCBI Gene: 58516 ENSG00000139146 UniProt: 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.

ResearchSummary from RefSeq, UniProt

Involved in negative regulation of cell migration. Part of Sin3-type complex. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.29

LOEUF· LoF intol.

LOF

Mechanism· predicted

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?

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 OE?0.00 (0.00–0.29)

0≤0.351.4

Missense OE?0.45 (0.36–0.57)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 0 / 10.4Missense obs/exp: 52 / 114.6Syn Z: -0.29

Background carrier burden — how many people carry a rare variant somewhere in SINHCAF?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 270

132 rare PASS variants

Rare truncating (LoF)

1 in 2,300

13 rare PASS variants

Rare synonymous (reference)

1 in 1,000

71 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SINHCAF. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 970	1 in 2,200
South Asian	~43k	1 in 1,600	1 in 1,500
Remaining (unassigned)	~30k	1 in 1,500	1 in 3,300
European (Finnish)	~27k	1 in 3,300	≈ 1 in 13,000
Admixed American	~22k	1 in 350	1 in 680
African / African American	~21k	1 in 820	1 in 1,800
East Asian	~20k	1 in 440	1 in 3,200
Ashkenazi Jewish	~13k	≈ 1 in 6,400	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 560	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓