U2AF1

Chr 21

U2 small nuclear RNA auxiliary factor 1

Also known as: FP793, RN, RNU2AF1, U2AF35, U2AFBP

NCBI Gene: 7307 ENSG00000160201 UniProt: Q01081

The U2AF1 protein is essential for accurate RNA splicing, recruiting U2 snRNP to pre-mRNA branch points and mediating critical protein interactions required for proper 3'-splice site selection. This gene is highly constrained against loss-of-function variants (pLI=0.99), but pathogenic variants have not yet been definitively linked to human disease. Given its fundamental role in splicing and extreme intolerance to variation, variants in this gene may potentially cause developmental disorders, though clinical associations remain to be established.

ResearchSummary from RefSeq, UniProt

This gene belongs to the splicing factor SR family of genes. U2 auxiliary factor, comprising a large and a small subunit, is a non-snRNP protein required for the binding of U2 snRNP to the pre-mRNA branch site. This gene encodes the small subunit which plays a critical role in both constitutive and enhancer-dependent RNA splicing by directly mediating interactions between the large subunit and proteins bound to the enhancers. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtMyelodysplastic syndrome

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

109

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.22

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

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.22LOEUF

pLI 0.990

Z-score 3.44

OE 0.00 (0.00–0.22)

Highly constrained

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

Missense Constraint?

3.85Z-score

OE missense 0.19 (0.14–0.25)

34 obs / 178.8 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.22)

0≤0.351.4

Missense OE?0.19 (0.14–0.25)

0≤0.61.4

Synonymous OE?0.89

0≤1.21.6

LoF obs/exp: 0 / 13.8Missense obs/exp: 34 / 178.8Syn Z: 0.71

Background carrier burden — how many people carry a rare variant somewhere in U2AF1?

gnomAD v4 · ~383k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 4,100

6 rare PASS variants

Rare truncating (LoF)

1 in 33,000

1 rare PASS variants

Rare synonymous (reference)

1 in 1,900

13 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for U2AF1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 6 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~260k	1 in 3,500	1 in 16,000
European (Finnish)	~21k	≈ 1 in 17,000	none seen
Remaining (unassigned)	~18k	≈ 1 in 6,000	none seen
Admixed American	~13k	≈ 1 in 9,200	none seen
African / African American	~13k	1 in 2,000	none seen
Ashkenazi Jewish	~9,264	≈ 1 in 6,100	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): 0 of 8 coding exons well covered in gnomAD exomes; exons 1, 2, 3, 4, 5 and 3 more poorly covered. Genomes: 0 of 8 (exons 1, 2, 3, 4, 5 and 3 more below).? see exons ↓