ADAMTS7

Chr 15

ADAM metallopeptidase with thrombospondin type 1 motif 7

Also known as: ADAM-TS 7, ADAM-TS7, ADAMTS-7

NCBI Gene: 11173 ENSG00000136378 UniProt: Q9UKP4 OMIM: 605009

The protein encoded by this gene is a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) 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 encoded preproprotein is proteolytically processed to generate the mature enzyme. This enzyme contains two C-terminal TS motifs and may regulate vascular smooth muscle cell (VSMC) migration. Mutations in this gene may be associated with susceptibility to coronary artery disease. [provided by RefSeq, Feb 2016]

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.65

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.65LOEUF

pLI 0.000

Z-score 4.03

OE 0.49 (0.37–0.65)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.71Z-score

OE missense 0.94 (0.89–0.99)

960 obs / 1024.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.49 (0.37–0.65)

0≤0.351.4

Missense OE?0.94 (0.89–0.99)

0≤0.61.4

Synonymous OE?1.07

0≤1.21.6

LoF obs/exp: 35 / 71.9Missense obs/exp: 960 / 1024.1Syn Z: -1.09

Background carrier burden — how many people carry a rare variant somewhere in ADAMTS7?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 15

2,124 rare PASS variants

Rare truncating (LoF)

1 in 760

195 rare PASS variants

Rare synonymous (reference)

1 in 15

972 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ADAMTS7. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 23	1 in 1,000
South Asian	~43k	1 in 12	1 in 570
Remaining (unassigned)	~30k	1 in 13	1 in 520
European (Finnish)	~27k	1 in 45	1 in 1,300
Admixed American	~22k	1 in 15	1 in 590
African / African American	~21k	1 in 15	1 in 640
East Asian	~20k	1 in 17	1 in 430
Ashkenazi Jewish	~13k	1 in 48	1 in 470
Middle Eastern	~2,884	1 in 17	≈ 1 in 1,200

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 21 of 24 coding exons well covered in gnomAD exomes; exons 1, 14, 23 marginal. Genomes: 23 of 24 (exon 14 below).? see exons ↓