PLEKHM1
Chr 17ARADpleckstrin homology and RUN domain containing M1
Also known as: AP162, B2, OPTA3, OPTB6
The protein functions as a multivalent adapter that regulates RAB7-dependent and HOPS complex-dependent fusion events in the endolysosomal system, facilitating late endosomal and lysosomal maturation, autophagosome clearance, and bone resorption in osteoclasts. Mutations cause osteopetrosis through both autosomal recessive (type 6) and autosomal dominant (type 3) inheritance patterns. The pathogenic mechanism involves impaired endolysosomal trafficking and defective osteoclast function, leading to deficient bone resorption.
Primary Disease Associations & Inheritance
Limited evidence — not for standalone diagnostic reporting
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
ClinVar Variant Classifications
8 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 | 1 | 0 | 6 | 0 | 7 |
Likely Pathogenic | 0 | 0 | 0 | 0 | 0 |
VUS | 0 | 1 | 0 | 0 | 1 |
Likely Benign | 0 | 0 | 0 | 0 | 0 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 1 | 1 | 6 | 0 | 8 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
PLEKHM1 · 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