MMEL1

Chr 1

membrane metalloendopeptidase like 1

Also known as: MMEL2, NEP2, NEPII, NL1, NL2, SEP

This gene encodes a membrane metalloprotease that degrades small peptides and is involved in sperm function and early embryonic development. Mutations cause autosomal recessive male infertility due to multiple morphological abnormalities of the flagella (MMAF), resulting in asthenozoospermia and reduced fertility. The gene shows no intolerance to loss-of-function variants in the general population, consistent with its reproductive-specific phenotype.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
6
Pubs (1 yr)
0
P/LP submissions
P/LP missense
1.00
LOEUF
GOF
Mechanism· predicted
Clinical SummaryMMEL1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.00LOEUF
pLI 0.000
Z-score 1.57
OE 0.77 (0.601.00)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.13Z-score
OE missense 0.98 (0.911.06)
480 obs / 487.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.77 (0.601.00)
00.351.4
Missense OE0.98 (0.911.06)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 41 / 53.4Missense obs/exp: 480 / 487.8Syn Z: 0.10
DN
0.6164th %ile
GOF
0.74top 25%
LOF
0.2679th %ile

The highest-scoring mechanism for this gene is gain-of-function.

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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

MMEL1 · 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.

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Clinical Literature
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