MMP23B

Chr 1

matrix metallopeptidase 23B

ENSG00000189409 UniProt: O75900 OMIM: 603321

The protein is a matrix metalloproteinase that degrades extracellular matrix components and may regulate potassium channel surface expression by retaining them in the endoplasmic reticulum. Based on the provided information, there are no established diseases associated with MMP23B mutations. The gene shows low constraint to loss-of-function variation (pLI = 0.12, LOEUF = 1.83), suggesting it may tolerate inactivating variants.

OMIM ResearchSummary from RefSeq, UniProt

Protease. May regulate the surface expression of some potassium channels by retaining them in the endoplasmic reticulum (By similarity)

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.83

Clinical Summary— MMP23B

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Population Constraint (gnomAD)

Low constraint (pLI 0.12) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

28 VUS of 31 total submissions

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Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.83LOEUF

pLI 0.117

Z-score 0.38

OE 0.66 (0.21–1.83)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.54Z-score

OE missense 0.77 (0.59–1.03)

35 obs / 45.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.66 (0.21–1.83)

0≤0.351.4

Missense OE?0.77 (0.59–1.03)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 1 / 1.5Missense obs/exp: 35 / 45.2Syn Z: -0.38

This gene — mechanism propensity

0.6841th %ile

GOF

0.7127th %ile

LOF

0.3647th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

31 submitted variants in ClinVar

ClinVar

Classification Summary

VUS28

Likely Benign3

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	28	0	28
Likely Benign	2	1	3
Benign	0	0	0
Total	30	1	31

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

View in ClinVar →

135 pathogenic / likely-pathogenic (of 156) ClinVar copy-number / structural variants overlap MMP23B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →