SAP18

Chr 13

Sin3A associated protein 18

Also known as: 2HOR0202, SAP18P

NCBI Gene: 10284 ENSG00000150459 UniProt: O00422

The encoded protein is a component of the SIN3 histone deacetylase complex that mediates transcriptional repression and also functions in the exon junction complex to regulate mRNA splicing, particularly inhibiting formation of proapoptotic splice variants. Mutations cause autosomal recessive neurodevelopmental disorder with seizures, microcephaly, and developmental delay. The gene shows moderate tolerance to loss-of-function variants (pLI 0.08, LOEUF 0.92), consistent with recessive inheritance.

ResearchSummary from RefSeq, UniProt

Histone acetylation plays a key role in the regulation of eukaryotic gene expression. Histone acetylation and deacetylation are catalyzed by multisubunit complexes. The protein encoded by this gene is a component of the histone deacetylase complex, which includes SIN3, SAP30, HDAC1, HDAC2, RbAp46, RbAp48, and other polypeptides. This protein directly interacts with SIN3 and enhances SIN3-mediated transcriptional repression when tethered to the promoter. A pseudogene has been identified on chromosome 2. [provided by RefSeq, Dec 2008]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.92

LOEUF

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.92LOEUF

pLI 0.083

Z-score 1.74

OE 0.35 (0.16–0.92)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.77Z-score

OE missense 0.79 (0.66–0.95)

80 obs / 101.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.35 (0.16–0.92)

0≤0.351.4

Missense OE?0.79 (0.66–0.95)

0≤0.61.4

Synonymous OE?1.39

0≤1.21.6

LoF obs/exp: 3 / 8.5Missense obs/exp: 80 / 101.8Syn Z: -1.90

Background carrier burden — how many people carry a rare variant somewhere in SAP18?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 340

227 rare PASS variants

Rare truncating (LoF)

1 in 2,800

29 rare PASS variants

Rare synonymous (reference)

1 in 410

134 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SAP18. 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 530	1 in 3,400
South Asian	~43k	1 in 160	1 in 600
Remaining (unassigned)	~30k	1 in 320	1 in 6,000
European (Finnish)	~27k	1 in 590	none seen
Admixed American	~22k	1 in 280	≈ 1 in 5,200
African / African American	~21k	1 in 520	1 in 2,400
East Asian	~20k	1 in 510	≈ 1 in 6,600
Ashkenazi Jewish	~13k	1 in 460	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 290	≈ 1 in 2,900

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 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓