MMP20

Chr 11AR

matrix metallopeptidase 20

Also known as: AI2A2, MMP-20

NCBI Gene: 9313 ENSG00000137674 UniProt: O60882 OMIM: 604629

Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. The protein encoded by this gene degrades amelogenin, the major protein component of dental enamel matrix, and thus thought to play a role in tooth enamel formation. A mutation in this gene, which alters the normal splice pattern and results in premature termination of the encoded protein, has been associated with amelogenesis imperfecta. This gene is part of a cluster of MMP genes located on chromosome 11q22.3. [provided by RefSeq, Aug 2011]

OMIM Research

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Amelogenesis imperfecta, type IIA2MIM #612529

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Amelogenesis imperfecta, type IIA2; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.37

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.37LOEUF

pLI 0.000

Z-score 0.22

OE 0.95 (0.67–1.37)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.57Z-score

OE missense 1.10 (1.00–1.21)

301 obs / 274.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.95 (0.67–1.37)

0≤0.351.4

Missense OE?1.10 (1.00–1.21)

0≤0.61.4

Synonymous OE?1.22

0≤1.21.6

LoF obs/exp: 21 / 22.1Missense obs/exp: 301 / 274.6Syn Z: -1.75

Background carrier burden — how many people carry a rare variant somewhere in MMP20?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 66

705 rare PASS variants

Rare truncating (LoF)

1 in 1,900

97 rare PASS variants

Rare synonymous (reference)

1 in 160

265 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MMP20. 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 110	1 in 2,100
South Asian	~43k	1 in 66	1 in 1,400
Remaining (unassigned)	~30k	1 in 52	1 in 3,000
European (Finnish)	~27k	1 in 190	1 in 1,200
Admixed American	~22k	1 in 75	1 in 900
African / African American	~21k	1 in 67	1 in 990
East Asian	~20k	1 in 87	1 in 450
Ashkenazi Jewish	~13k	1 in 300	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 52	≈ 1 in 2,900

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): 10 of 10 coding exons well covered in gnomAD exomes. Genomes: 9 of 10 (exon 7 below).? see exons ↓