ADAM12

Chr 10

ADAM metallopeptidase domain 12

Also known as: ADAM12-OT1, CAR10, MCMP, MCMPMltna, MLTN, MLTNA

The protein functions in skeletal muscle regeneration at the onset of cell fusion and is involved in macrophage-derived giant cell and osteoclast formation. This gene is highly tolerant to loss-of-function variants based on constraint metrics, and no established Mendelian disease associations have been reported in the provided data.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.59
Clinical SummaryADAM12
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.59LOEUF
pLI 0.000
Z-score 3.78
OE 0.41 (0.280.59)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.27Z-score
OE missense 0.84 (0.780.91)
438 obs / 519.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.41 (0.280.59)
00.351.4
Missense OE0.84 (0.780.91)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 19 / 46.9Missense obs/exp: 438 / 519.3Syn Z: 0.10
DN
0.75top 25%
GOF
0.6541th %ile
LOF
0.3067th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ADAM12 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →