BCAS4
Chr 20breast carcinoma amplified sequence 4
Also known as: CNOL
The BCAS4 protein is predicted to be part of the BLOC-1 complex in the cytoplasm, which is involved in biogenesis of lysosome-related organelles. Mutations in BCAS4 cause Hermansky-Pudlak syndrome type 9, an autosomal recessive disorder characterized by oculocutaneous albinism, bleeding diathesis due to platelet storage pool deficiency, and variable pulmonary fibrosis. The gene shows low constraint to loss-of-function variants, consistent with the recessive inheritance pattern.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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
68 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 10 | 0 | 10 |
Likely Pathogenic | 0 | 0 | 4 | 0 | 4 |
VUS | 0 | 35 | 1 | 0 | 36 |
Likely Benign | 0 | 6 | 1 | 3 | 10 |
Benign | 0 | 1 | 1 | 0 | 2 |
| Total | 0 | 42 | 17 | 3 | 62 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
BCAS4 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools