MMP8

Chr 11

matrix metallopeptidase 8

Also known as: CLG1, HNC, MMP-8, PMNL-CL

NCBI Gene: 4317 ENSG00000118113 UniProt: P22894

This gene encodes a member of the matrix metalloproteinase (MMP) family of proteins. These proteins are involved in the breakdown of extracellular matrix in embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Proteolysis at different sites on this protein results in multiple active forms of the enzyme with distinct N-termini. This protein functions in the degradation of type I, II and III collagens. The gene is part of a cluster of MMP genes which localize to chromosome 11q22.3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

Research

ResearchGenerating clinical summary…

Active trials

126

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.76

LOEUF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.76LOEUF

pLI 0.000

Z-score -1.49

OE 1.33 (1.00–1.76)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.61Z-score

OE missense 1.11 (1.00–1.23)

277 obs / 249.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.33 (1.00–1.76)

0≤0.351.4

Missense OE?1.11 (1.00–1.23)

0≤0.61.4

Synonymous OE?1.23

0≤1.21.6

LoF obs/exp: 32 / 24.1Missense obs/exp: 277 / 249.8Syn Z: -1.70

Background carrier burden — how many people carry a rare variant somewhere in MMP8?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 66

712 rare PASS variants

Rare truncating (LoF)

1 in 330

138 rare PASS variants

Rare synonymous (reference)

1 in 160

231 rare PASS variants

Rare missense and truncating variants are carried at similar rates in MMP8; this gene does not show strong loss-of-function constraint by this measure. 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 100	1 in 520
South Asian	~43k	1 in 92	1 in 420
Remaining (unassigned)	~30k	1 in 71	1 in 230
European (Finnish)	~27k	1 in 210	1 in 4,400
Admixed American	~22k	1 in 71	1 in 390
African / African American	~21k	1 in 96	1 in 740
East Asian	~20k	1 in 89	1 in 250
Ashkenazi Jewish	~13k	1 in 520	1 in 910
Middle Eastern	~2,884	1 in 70	1 in 400

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 8 of 10 coding exons well covered in gnomAD exomes; exons 6, 8 marginal. Genomes: 8 of 10 (exons 6, 8 below).? see exons ↓