MMEL1

Chr 1

membrane metalloendopeptidase like 1

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

NCBI Gene: 79258ENSG00000142606UniProt: Q495T6OMIM: 618104

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.

OMIMResearchSummary from RefSeq, UniProt
GOFmechanismLOEUF 1.00
Clinical Summary— MMEL1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
117 unique Pathogenic / Likely Pathogenic· 160 VUS of 316 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.00LOEUF
pLI 0.000
Z-score 1.57
OE 0.77 (0.60–1.00)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.13Z-score
OE missense 0.98 (0.91–1.06)
480 obs / 487.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.77 (0.60–1.00)
0≤0.351.4
Missense OE0.98 (0.91–1.06)
0≤0.61.4
Synonymous OE0.99
0≤1.21.6
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

316 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic115
Likely Pathogenic2
VUS160
Likely Benign14
Benign13
115
Pathogenic
2
Likely Pathogenic
160
VUS
14
Likely Benign
13
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
115
0
115
Likely Pathogenic
0
0
2
0
2
VUS
0
142
18
0
160
Likely Benign
0
7
1
6
14
Benign
0
3
4
6
13
Total015214012304

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

View 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
A Phenome-Wide Mendelian Randomization and Colocalization Study Reveals Genetic Association Between PBC and Other Autoimmune Disorders
Shi S et al.·Can J Gastroenterol Hepatol
2025
The Drosophila Neprilysin 4 gene is essential for sperm function following sperm transfer to females.
Ohsako T et al.·Genes Genet Syst
2021
Distinct by Design: Unraveling the Unique Clinical and Transcriptomic Identity of Juvenile Scleromyositis Overlap Compared to Juvenile Systemic Sclerosis and Juvenile Dermatomyositis: Implications for Care and Pathogenesis.
Robinson AD et al.·ACR Open Rheumatol
2026
Genetic architecture of primary sclerosing cholangitis: shared pathways with inflammatory bowel disease and gut-liver axis mediation
Chen Y et al.·Int J Surg
2025
In silico prioritisation of microRNA-associated common variants in multiple sclerosis
Fashina IA et al.·Hum Genomics
2023
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Identification of MMEL1 as a novel therapeutic target for primary sclerosing cholangitis: Integrating Mendelian randomization and transcriptome landscapes.
Li CL et al.·Medicine (Baltimore)
2025
Investigating the association of polymorphisms of ANKRD55 and MMEL1 with susceptibility to multiple sclerosis in Iranian population.
Yazdanpanah M et al.·Int J Neurosci
2022
Interaction analysis between BLK rs13277113 polymorphism and BANK1 rs3733197 polymorphism, MMEL1/TNFRSF14 rs3890745 polymorphism in determining susceptibility to rheumatoid arthritis.
Huang H et al.·Autoimmunity
2017
Replication of GWAS Coding SNPs Implicates MMEL1 as a Potential Susceptibility Locus among Saudi Arabian Celiac Disease Patients.
Saadah OI et al.·Dis Markers
2015Open AccessCohort
Association of variants in MMEL1 and CTLA4 with rheumatoid arthritis in the Han Chinese population.
Danoy P et al.·Ann Rheum Dis
2011
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients