BRK1

Chr 3

BRICK1 subunit of SCAR/WAVE actin nucleating complex

Also known as: C3orf10, HSPC300, MDS027, hHBrk1

NCBI Gene: 55845ENSG00000254999UniProt: Q8WUW1

Enables identical protein binding activity. Contributes to small GTPase binding activity. Involved in Rac protein signal transduction and positive regulation of cellular component organization. Located in extracellular exosome. Part of SCAR complex. [provided by Alliance of Genome Resources, Jul 2025]

182
ClinVar variants
57
Pathogenic / LP
0.69
pLI score
0
Active trials
Clinical Summary— BRK1
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.69) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
57 Pathogenic / Likely Pathogenic· 27 VUS of 182 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.79LOEUF
pLI 0.687
Z-score 1.81
OE 0.00 (0.00–0.79)
Moderately constrained

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.21Z-score
OE missense 0.48 (0.33–0.69)
20 obs / 42.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.79)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.48 (0.33–0.69)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.32
0≤1.21.6
LoF obs/exp: 0 / 3.8Missense obs/exp: 20 / 42.0Syn Z: -0.95

ClinVar Variant Classifications

182 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic53
Likely Pathogenic4
VUS27
Likely Benign1
Benign97
53
Pathogenic
4
Likely Pathogenic
27
VUS
1
Likely Benign
97
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
53
0
53
Likely Pathogenic
0
0
4
0
4
VUS
0
8
19
0
27
Likely Benign
0
0
1
0
1
Benign
0
0
97
0
97
Total081740182

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

View in ClinVar →

Protein Context — Lollipop Plot

BRK1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Proteogenomic network analysis reveals dysregulated mechanisms and potential mediators in Parkinson's disease.
Doostparast Torshizi A et al.·Nat Commun
2024Functional
Extracellular BRICK1 drives heart repair after myocardial infarction in mice.
Polten F et al.·Sci Transl Med
2026
Free Brick1 is a trimeric precursor in the assembly of a functional wave complex.
Derivery E et al.·PLoS One
2008Functional
Refining housekeeping genes and demonstrating their potential for clinical and experimental applications.
Hwang KW et al.·Comput Biol Med
2025
Pan-cancer analysis of BRK1 as a potential immunotherapeutic target.
Wang X et al.·Biotechnol Genet Eng Rev
2024
Genotype-phenotype correlations and clinical outcomes of patients with von Hippel-Lindau disease with large deletions.
Zhang K et al.·J Med Genet
2023Cohort
Brick1 is an essential regulator of actin cytoskeleton required for embryonic development and cell transformation.
Escobar B et al.·Cancer Res
2010
Persistent iatrogenic atrial septal defect after pulmonary vein isolation by cryoballoon: an under-recognized complication.
Chan NY et al.·Europace
2011
Randomized trial of conventional transseptal needle versus radiofrequency energy needle puncture for left atrial access (the TRAVERSE-LA study).
Hsu JC et al.·J Am Heart Assoc
2013
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools