ADAM8

Chr 10

ADAM metallopeptidase domain 8

Also known as: CD156, CD156a, MS2

NCBI Gene: 101ENSG00000151651UniProt: P78325

The protein is a membrane-anchored metalloprotease and disintegrin involved in cell-cell and cell-matrix interactions during neurogenesis and neurodegeneration, and may facilitate leukocyte extravasation. No definitive disease associations have been established for ADAM8 mutations based on the available information.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
37
Pubs (1 yr)
97
P/LP submissions
0%
P/LP missense
0.93
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— ADAM8
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
97 unique Pathogenic / Likely Pathogenic· 163 VUS of 324 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
0.93LOEUF
pLI 0.000
Z-score 1.94
OE 0.68 (0.50–0.93)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.38Z-score
OE missense 0.95 (0.88–1.03)
467 obs / 490.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.68 (0.50–0.93)
0≤0.351.4
Missense OE0.95 (0.88–1.03)
0≤0.61.4
Synonymous OE1.11
0≤1.21.6
LoF obs/exp: 28 / 41.5Missense obs/exp: 467 / 490.7Syn Z: -1.26
DN
0.73top 25%
GOF
0.6931th %ile
LOF
0.2679th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction 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

324 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic93
Likely Pathogenic4
VUS163
Likely Benign46
Benign5
Conflicting2
93
Pathogenic
4
Likely Pathogenic
163
VUS
46
Likely Benign
5
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
93
0
93
Likely Pathogenic
0
0
4
0
4
VUS
1
145
17
0
163
Likely Benign
0
40
1
5
46
Benign
0
4
1
0
5
Conflicting
—2
Total11891165313

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

View in ClinVar →

Protein Context — Lollipop Plot

ADAM8 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients