MEP1B
protein-codingmeprin A subunit beta, the group of Astacins
Gene summary
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]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~35.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to MEP1B variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005925.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 3 | 3 | ||||
| missense | 87 | 1 | 88 | |||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 92 | 1 | 0 | 93 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005916.2 | 15 | MANE Select | |
| Ensembl | ENSP00000269202.6 | 15 | MANE Select | |
| RefSeq | NP_001295100.1 | 15 | Standard | |
| Ensembl | ENSP00000463280.1 | 15 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| mep1b | Danio rerio | Structure: post-vent region Quality: disorganized abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Protein digestion and absorption - Homo sapiens (human)
- Posttranslational regulation of adherens junction stability and dissassembly
Biological Process
- proteolysis
- inflammatory response
- toxin transport
Molecular Function
- metalloendopeptidase activity
- protein binding
- zinc ion binding
- identical protein binding
Cellular Component
- extracellular region
- integral component of plasma membrane
- meprin A complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000269202
- Coding exons
- 15
- Length
- 35336
- Individuals with no LoFs
- 124227
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 412
- Defined
- 124639
- p
- 0.00165
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.717 | 341 | 380 | 0.897 | 0.0000195 | 4627 |
| Missense (PolyPhen) | 129 | 143.48 | 0.89909 | 1786 | ||
| Synonymous | 2.12 | 99 | 130 | 0.763 | 0.00000655 | 1284 |
| Loss of Function | 0.158 | 37 | 38.0 | 0.972 | 0.00000202 | 426 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0047 | 0.0047 | notable |
| Latino/Admixed American | 0.00076 | 0.00075 | rare |
| Ashkenazi Jewish | 0.015 | 0.015 | notable |
| East Asian | 0.00062 | 0.00061 | rare |
| Finnish | 0.000093 | 0.000093 | rare |
| European (Non-Finnish) | 0.0010 | 0.00098 | notable |
| South Asian | 0.00093 | 0.00092 | rare |
| Other | 0.0020 | 0.0020 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Membrane metallopeptidase that sheds many membrane-bound proteins. Exhibits a strong preference for acidic amino acids at the P1' position. Known substrates include: FGF19, VGFA, IL1B, IL18, procollagen I and III, E-cadherin, KLK7, gastrin, ADAM10, tenascin-C. The presence of several pro-inflammatory cytokine among substrates implicate MEP1B in inflammation. It is also involved in tissue remodeling due to its capability to degrade extracellular matrix components. {ECO:0000269|PubMed:21693781}.;
Recessive Scores
- pRec
- 0.135
Intolerance Scores
- LoFtool
- 0.854
- RVIS EVS
- 0.76
- RVIS percentile EVS
- 86.82
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.613
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |