STRAP

Chr 12

serine/threonine kinase receptor associated protein

Also known as: MAWD, PT-WD, UNRIP

NCBI Gene: 11171 ENSG00000023734 UniProt: Q9Y3F4 OMIM: 605986

The STRAP protein is a component of the SMN complex that catalyzes the assembly of small nuclear ribonucleoproteins (snRNPs), which are essential building blocks of the spliceosome responsible for pre-mRNA splicing. This gene is highly constrained against loss-of-function variants (pLI=0.90, LOEUF=0.375), suggesting that mutations would likely cause severe developmental consequences, though no specific Mendelian disease has been definitively associated with STRAP mutations to date. Given its critical role in RNA splicing machinery and high constraint scores, pathogenic variants would be expected to follow an autosomal dominant inheritance pattern.

OMIM ResearchSummary from RefSeq, UniProt

Enables RNA binding activity. Involved in maintenance of gastrointestinal epithelium and spliceosomal snRNP assembly. Acts upstream of with a positive effect on negative regulation of transforming growth factor beta receptor signaling pathway. Located in cytosol. Part of SMN complex. Implicated in adenocarcinoma; colorectal carcinoma; large cell carcinoma; lung carcinoma; and squamous cell neoplasm. [provided by Alliance of Genome Resources, Jul 2025]

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

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Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.38

LOEUF

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.38LOEUF

pLI 0.901

Z-score 3.60

OE 0.14 (0.07–0.38)

Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.08Z-score

OE missense 0.57 (0.49–0.67)

106 obs / 185.5 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.14 (0.07–0.38)

0≤0.351.4

Missense OE?0.57 (0.49–0.67)

0≤0.61.4

Synonymous OE?0.83

0≤1.21.6

LoF obs/exp: 3 / 20.7Missense obs/exp: 106 / 185.5Syn Z: 1.05

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 220

344 rare PASS variants

Rare truncating (LoF)

1 in 4,200

46 rare PASS variants

Rare synonymous (reference)

1 in 480

147 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for STRAP. 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 230	1 in 4,500
South Asian	~43k	1 in 230	1 in 4,300
Remaining (unassigned)	~30k	1 in 140	1 in 2,700
European (Finnish)	~27k	1 in 340	≈ 1 in 12,000
Admixed American	~22k	1 in 200	1 in 1,300
African / African American	~21k	1 in 190	≈ 1 in 6,200
East Asian	~20k	1 in 300	≈ 1 in 4,700
Ashkenazi Jewish	~13k	1 in 1,200	none seen
Middle Eastern	~2,884	1 in 250	≈ 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): 8 of 10 coding exons well covered in gnomAD exomes; exons 9, 10 marginal. Genomes: 9 of 10 (exon 10 below).? see exons ↓