MEP1B

Chr 18

meprin A subunit beta

Meprins are multidomain zinc metalloproteases that are highly expressed in mammalian kidney and intestinal brush border membranes, and in leukocytes and certain cancer cells. They are involved in the hydrolysis of a variety of peptide and protein substrates, and have been implicated in cancer and intestinal inflammation. Mature meprins are oligomers of evolutionarily related, but separately encoded alpha and/or beta subunits. Homooligomers of alpha subunit are secreted, whereas, oligomers containing the beta subunit are plasma membrane-bound. This gene encodes the beta subunit. Targeted disruption of this gene in mice affects embryonic viability, renal gene expression profiles, and distribution of the membrane-associated alpha subunit in kidney and intestine. [provided by RefSeq, Oct 2011]

0
Active trials
0
Pubs (1 yr)
42
P/LP submissions
0%
P/LP missense
1.28
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryMEP1B
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
40 unique Pathogenic / Likely Pathogenic· 83 VUS of 135 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.28LOEUF
pLI 0.000
Z-score 0.16
OE 0.97 (0.751.28)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.72Z-score
OE missense 0.90 (0.820.98)
341 obs / 380.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.97 (0.751.28)
00.351.4
Missense OE0.90 (0.820.98)
00.61.4
Synonymous OE0.76
01.21.6
LoF obs/exp: 37 / 38.1Missense obs/exp: 341 / 380.4Syn Z: 2.12
DN
0.6551th %ile
GOF
0.6442th %ile
LOF
0.3068th %ile

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

DNprediction above median
GOFprediction 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

135 submitted variants in ClinVar

Classification Summary

Pathogenic39
Likely Pathogenic1
VUS83
Likely Benign4
39
Pathogenic
1
Likely Pathogenic
83
VUS
4
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
39
0
39
Likely Pathogenic
0
0
1
0
1
VUS
0
82
1
0
83
Likely Benign
0
1
3
0
4
Benign
0
0
0
0
0
Total083440127

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

View in ClinVar →

Protein Context — Lollipop Plot

MEP1B · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗