MMEL1 (Membrane Metallo-Endopeptidase-Like 1)
Genetic Insights into MMEL1: A Key Player in Immune Regulation and Disease Susceptibility
Gene Information Card
| Symbol | MMEL1 |
|---|---|
| Full Name | Membrane Metallo-Endopeptidase-Like 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 1p36.32 |
| NCBI Gene ID | 79258 ncbi.nlm.nih.gov/gene/79258 |
| Ensembl ID | ENSG00000142611 |
| UniProt ID | Q495T6 |
| OMIM ID | 607243 |
| HGNC ID | 14668 |
| Aliases | NEP2, NEPII, NEP-like 1, NEPLP, SEP, NEP2L |
Description
MMEL1 (Membrane Metallo-Endopeptidase-Like 1) encodes a zinc-dependent metalloprotease belonging to the neprilysin (NEP) family. The protein is involved in the cleavage of various bioactive peptides, including neuropeptides and hormones, and is expressed in multiple tissues, notably in immune cells. Genetic variants in MMEL1 have been associated with susceptibility to autoimmune diseases such as rheumatoid arthritis and multiple sclerosis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Rheumatoid Arthritis | Genetic variants in MMEL1 (e.g., rs3890745) are associated with altered immune regulation, potentially affecting peptide processing and antigen presentation. | GWAS studies (PMID: 20453842, 19503088) |
| Multiple Sclerosis | MMEL1 polymorphisms (e.g., rs3748816) contribute to disease risk, possibly through modulation of neuropeptide degradation and neuroinflammation. | GWAS meta-analysis (PMID: 21833088) |
| Type 1 Diabetes | MMEL1 locus variants show nominal association with type 1 diabetes, suggesting a role in autoimmune pathogenesis. | Immunochip study (PMID: 22830473) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 5.2 | Low |
| Lung | 3.8 | Low |
| Spleen | 6.1 | Low |
| Lymph node | 7.4 | Low |
| Testis | 4.5 | Low |
| Kidney | 3.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 2.3 | Low expression |
| K-562 | 1.8 | Low expression |
| Jurkat | 4.0 | Moderate expression |
| THP-1 | 3.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs3890745 | SNP (intronic) | 0.25 (MAF in Europeans) | Associated with reduced risk of rheumatoid arthritis; functional effect unclear |
| rs3748816 | SNP (intronic) | 0.30 (MAF in Europeans) | Associated with multiple sclerosis risk; may alter splicing or regulatory elements |
| rs10876930 | SNP (intergenic) | 0.20 (MAF in Europeans) | Nominally associated with type 1 diabetes |
Mutation functional classification
Loss of Function (LOF)
No confirmed loss-of-function mutations reported in MMEL1 in human disease; experimental knockdown in cell lines reduces peptide cleavage activity.
Gain of Function (GOF)
No gain-of-function mutations described.
Dominant Negative (DN)
Not reported.
View complete mutation data：
Gene Ontology (GO)
| • metalloendopeptidase activity (GO:0004222) | • zinc ion binding (GO:0008270) |
| • proteolysis (GO:0006508) | • integral component of membrane (GO:0016021) |
| • plasma membrane (GO:0005886) |
Pathways
• Neuropeptide processing and degradation (Reactome: R-HSA-6798695)
• Peptide hormone metabolism (Reactome: R-HSA-422356)
Protein Summary
MMEL1 (also known as NEP2 or neprilysin 2) is a type II transmembrane zinc metalloprotease that cleaves a range of small peptides, including substance P, bradykinin, and neurotensin. It is structurally similar to neprilysin (MME) but has distinct substrate specificity and tissue distribution. The protein is expressed in immune cells and the brain, where it modulates peptide signaling. Its role in autoimmune disease susceptibility highlights its importance in immune homeostasis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MMEL1 Knockout HEK293 Cell Line | EDJ-KQ10785 | Human | 79258 | Details Get a Quote |
| MMEL1 Knockout HCT 116 Cell Line | EDJ-KQ38416 | Human | 79258 | Details Get a Quote |
| MMEL1 Knockout HeLa Cell Line | EDJ-KQ57157 | Human | 79258 | Details Get a Quote |
| MMEL1 Knockout A-549 Cell Line | EDJ-KQ65671 | Human | 79258 | Details Get a Quote |
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