DCSTAMP

Chr 8

dendrocyte expressed seven transmembrane protein

Also known as: FIND, TM7SF4, hDC-STAMP

NCBI Gene: 81501 ENSG00000164935 UniProt: Q9H295 OMIM: 605933

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.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a seven-pass transmembrane protein that is primarily expressed in dendritic cells. The encoded protein is involved in a range of immunological functions carried out by dendritic cells. This protein plays a role in osteoclastogenesis and myeloid differentiation. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2012]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.16

Clinical Summary— DCSTAMP

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

55 VUS of 66 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?

1.16LOEUF

pLI 0.000

Z-score 1.11

OE 0.70 (0.44–1.16)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.36Z-score

OE missense 0.94 (0.84–1.04)

234 obs / 249.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.70 (0.44–1.16)

0≤0.351.4

Missense OE?0.94 (0.84–1.04)

0≤0.61.4

Synonymous OE?1.16

0≤1.21.6

LoF obs/exp: 11 / 15.8Missense obs/exp: 234 / 249.9Syn Z: -1.28

This gene — mechanism propensity

0.7131th %ile

GOF

0.73top 25%

LOF

0.2387th %ile

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.

GOFprediction above median

DNprediction 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

66 submitted variants in ClinVar

ClinVar

Classification Summary

VUS55

Likely Benign7

Benign1

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	55	55
Likely Benign	7	7
Benign	1	1
Total	63	63

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

View in ClinVar →

38 pathogenic / likely-pathogenic (of 44) ClinVar copy-number / structural variants overlap DCSTAMP — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →