ADAMTS4

Chr 1

ADAM metallopeptidase with thrombospondin type 1 motif 4

Also known as: ADAMTS-2, ADAMTS-4, ADMP-1

This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. Members of this family share several distinct protein modules, including a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. Individual members of this family differ in the number of C-terminal TS motifs, and some have unique C-terminal domains. The enzyme encoded by this gene lacks a C-terminal TS motif. The encoded preproprotein is proteolytically processed to generate the mature protease. This protease is responsible for the degradation of aggrecan, a major proteoglycan of cartilage, and brevican, a brain-specific extracellular matrix protein. The expression of this gene is upregulated in arthritic disease and this may contribute to disease progression through the degradation of aggrecan. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Feb 2016]

ResearchGenerating clinical summary…
3
Active trials
56
Pubs (1 yr)
P/LP submissions
P/LP missense
0.71
LOEUF
Multiple*
Mechanism· predicted
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.71LOEUF
pLI 0.000
Z-score 2.85
OE 0.46 (0.310.71)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
1.15Z-score
OE missense 0.86 (0.790.93)
454 obs / 528.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.46 (0.310.71)
00.351.4
Missense OE?0.86 (0.790.93)
00.61.4
Synonymous OE?0.95
01.21.6
LoF obs/exp: 15 / 32.5Missense obs/exp: 454 / 528.7Syn Z: 0.59

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ADAMTS4 · protein map & ClinVar variants

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