DCSTAMP
Chr 8dendrocyte expressed seven transmembrane protein
Also known as: FIND, TM7SF4, hDC-STAMP
The protein is a seven-pass transmembrane receptor that regulates cellular fusion and differentiation in immune cells, playing essential roles in osteoclast formation and bone resorption, myeloid cell differentiation, and dendritic cell antigen presentation. Mutations cause autosomal recessive osteopetrosis, a severe bone disease characterized by dense but brittle bones due to defective osteoclast function. The gene is highly intolerant to loss-of-function variants (pLI nearly 1.0), indicating that complete loss of protein function is likely incompatible with normal development.
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
110 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 | 38 | 0 | 38 |
Likely Pathogenic | 0 | 0 | 0 | 0 | 0 |
VUS | 0 | 55 | 6 | 0 | 61 |
Likely Benign | 0 | 7 | 0 | 0 | 7 |
Benign | 0 | 1 | 0 | 0 | 1 |
| Total | 0 | 63 | 44 | 0 | 107 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
DCSTAMP · 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