MMP21

Chr 10

matrix metallopeptidase 21

Also known as: HTX7, MMP-21

NCBI Gene: 118856 ENSG00000154485 UniProt: O75900

This gene encodes a matrix metalloproteinase that functions as a protease and may regulate potassium channel surface expression by retaining them in the endoplasmic reticulum. Mutations cause visceral heterotaxy-7, a developmental disorder affecting the normal left-right asymmetry of internal organs, inherited in an autosomal recessive pattern. The gene shows minimal constraint against loss-of-function variation.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the matrix metalloproteinase family. Proteins in this family are involved in the breakdown of extracellular matrix for both normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, and disease processes, such as asthma and tumor metastasis. The encoded protein may play an important role in embryogenesis, particularly in neuronal cells, as well as in lymphocyte development and survival. [provided by RefSeq, May 2013]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 1.20

Clinical Summary— MMP21

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

24 unique Pathogenic / Likely Pathogenic· 116 VUS of 177 total submissions

Explore recent and relevant literature in Research Assistant →

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?

1.20LOEUF

pLI 0.000

Z-score 0.88

OE 0.79 (0.53–1.20)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.34Z-score

OE missense 0.78 (0.70–0.87)

239 obs / 304.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.79 (0.53–1.20)

0≤0.351.4

Missense OE?0.78 (0.70–0.87)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 16 / 20.2Missense obs/exp: 239 / 304.7Syn Z: 0.79

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveMMP21-related heterotaxyLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6647th %ile

GOF

0.5759th %ile

LOF

0.3746th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

177 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11

Likely Pathogenic13

VUS116

Likely Benign24

Benign7

Conflicting1

Pathogenic

Likely Pathogenic

116

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	5	5	1	0	11
Likely Pathogenic	10	3	0	0	13
VUS	0	115	1	0	116
Likely Benign	0	4	3	17	24
Benign	0	2	0	5	7
Conflicting	—				1
Total	15	129	5	22	172

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

66 pathogenic / likely-pathogenic (of 74) ClinVar copy-number / structural variants overlap MMP21 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →