STAP1

Chr 4

signal transducing adaptor family member 1

Also known as: BRDG1, STAP-1

NCBI Gene: 26228ENSG00000035720UniProt: Q9ULZ2OMIM: 604298

STAP1 encodes a docking protein that functions in B-cell receptor signaling by interacting with and upregulating the tyrosine kinase TEC through a positive feedback loop. Mutations cause autosomal dominant hypercholesterolemia characterized by elevated LDL cholesterol levels and increased risk of coronary vascular disease. The gene shows very low constraint to loss-of-function variants (pLI 0.00002, LOEUF 1.02), suggesting tolerance to protein-disrupting mutations.

OMIMResearchSummary from RefSeq, UniProt
GOFmechanismLOEUF 1.02
Clinical Summary— STAP1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
12 unique Pathogenic / Likely Pathogenic· 60 VUS of 110 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.02LOEUF
pLI 0.000
Z-score 1.50
OE 0.60 (0.37–1.02)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.03Z-score
OE missense 0.99 (0.87–1.14)
155 obs / 155.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.60 (0.37–1.02)
0≤0.351.4
Missense OE0.99 (0.87–1.14)
0≤0.61.4
Synonymous OE1.20
0≤1.21.6
LoF obs/exp: 10 / 16.6Missense obs/exp: 155 / 155.9Syn Z: -1.16
DN
0.5966th %ile
GOF
0.6736th %ile
LOF
0.2872th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

110 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11
Likely Pathogenic1
VUS60
Likely Benign25
Benign1
11
Pathogenic
1
Likely Pathogenic
60
VUS
25
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
11
0
11
Likely Pathogenic
0
1
0
0
1
VUS
0
57
3
0
60
Likely Benign
0
5
1
19
25
Benign
0
1
0
0
1
Total064151998

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

STAP1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients