SART1

Chr 11

spliceosome associated factor 1, recruiter of U4/U6.U5 tri-snRNP

Also known as: Ara1, HAF, HOMS1, SART1259, SNRNP110, Snu66

NCBI Gene: 9092 ENSG00000175467 UniProt: O43290 OMIM: 605941

The SART1 protein functions as a component of the U4/U6-U5 tri-snRNP complex essential for mRNA splicing and may also bind to DNA. Mutations cause neurodevelopmental disorders with intellectual disability and developmental delay, inherited in an autosomal dominant pattern. This gene is highly constrained against loss-of-function variants (pLI 0.88, LOEUF 0.34), reflecting its essential cellular role.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes two proteins, the SART1(800) protein expressed in the nucleus of the majority of proliferating cells, and the SART1(259) protein expressed in the cytosol of epithelial cancers. The SART1(259) protein is translated by the mechanism of -1 frameshifting during posttranscriptional regulation; its full-length sequence is not published yet. The two encoded proteins are thought to be involved in the regulation of proliferation. Both proteins have tumor-rejection antigens. The SART1(259) protein possesses tumor epitopes capable of inducing HLA-A2402-restricted cytotoxic T lymphocytes in cancer patients. This SART1(259) antigen may be useful in specific immunotherapy for cancer patients and may serve as a paradigmatic tool for the diagnosis and treatment of patients with atopy. The SART1(259) protein is found to be essential for the recruitment of the tri-snRNP to the pre-spliceosome in the spliceosome assembly pathway. [provided by RefSeq, Jul 2008]

OMIM 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

0.34

LOEUF· LoF intol.

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.34LOEUF

pLI 0.882

Z-score 5.10

OE 0.19 (0.12–0.34)

Highly constrained

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

Missense Constraint?

2.30Z-score

OE missense 0.71 (0.65–0.77)

349 obs / 492.8 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.19 (0.12–0.34)

0≤0.351.4

Missense OE?0.71 (0.65–0.77)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 9 / 46.6Missense obs/exp: 349 / 492.8Syn Z: -0.53

Background carrier burden — how many people carry a rare variant somewhere in SART1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 53

959 rare PASS variants

Rare truncating (LoF)

1 in 2,700

56 rare PASS variants

Rare synonymous (reference)

1 in 64

495 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SART1. 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 88	1 in 3,000
South Asian	~43k	1 in 52	1 in 6,700
Remaining (unassigned)	~30k	1 in 58	≈ 1 in 8,900
European (Finnish)	~27k	1 in 190	none seen
Admixed American	~22k	1 in 68	1 in 1,500
African / African American	~21k	1 in 46	1 in 1,100
East Asian	~20k	1 in 84	≈ 1 in 18,000
Ashkenazi Jewish	~13k	1 in 230	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 64	none seen

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): 19 of 20 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 20.? see exons ↓