CPE
protein-codingcarboxypeptidase E, the group of M14 carboxypeptidases|MicroRNA protein coding host genes
Gene summary
This gene encodes a member of the M14 family of metallocarboxypeptidases. The encoded preproprotein is proteolytically processed to generate the mature peptidase. This peripheral membrane protein cleaves C-terminal amino acid residues and is involved in the biosynthesis of peptide hormones and neurotransmitters, including insulin. This protein may also function independently of its peptidase activity, as a neurotrophic factor that promotes neuronal survival, and as a sorting receptor that binds to regulated secretory pathway proteins, including prohormones. Mutations in this gene are implicated in type 2 diabetes. [provided by RefSeq, Nov 2015]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~137.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0859150
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Endocrine; Neurologic
Intervention: Endocrine
Rationale: Among other findings, individuals may manifest with hypothyroidism and hypogonadotropic hypogonadism, and awareness may allow medical treatment of these endocrine diosrders; Related to Hypogonadotropic hypogonadism, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CPE variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001873.4. 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 | 2 | 57 | 2 | 61 | ||
| missense | 127 | 9 | 136 | |||
| nonsense | 4 | 1 | 5 | |||
| start loss | 0 | |||||
| frameshift | 1 | 2 | 1 | 4 | ||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 5 | 3 | 131 | 66 | 2 | 207 |
Highest pathogenic variant AF is 0.0000013807978
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001864.1 | 9 | MANE Select | |
| Ensembl | ENSP00000386104.4 | 9 | MANE Select | |
| Ensembl | ENSP00000416601.1 | 3 | Standard | |
| Ensembl | ENSP00000423699.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Type I diabetes mellitus - Homo sapiens (human)
- Peptide hormone metabolism
- Metabolism of proteins
- Insulin processing
- Arf6 trafficking events
Biological Process
- cardiac left ventricle morphogenesis
- cellular protein modification process
- peptide metabolic process
- neuropeptide signaling pathway
- Wnt signaling pathway
Molecular Function
- carboxypeptidase activity
- metallocarboxypeptidase activity
- zinc ion binding
- neurexin family protein binding
- cell adhesion molecule binding
Cellular Component
- extracellular space
- nucleus
- Golgi apparatus
- plasma membrane
- secretory granule
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000402744
- Coding exons
- 9
- Length
- 137127
- Individuals with no LoFs
- 125736
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 10
- Defined
- 125746
- p
- 0.0000398
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.82 | 180 | 263 | 0.684 | 0.0000138 | 3120 |
| Missense (PolyPhen) | 62 | 101.56 | 0.61047 | 1133 | ||
| Synonymous | 1.18 | 84 | 98.9 | 0.850 | 0.00000532 | 906 |
| Loss of Function | 4.10 | 2 | 23.4 | 0.0856 | 0.00000133 | 254 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.00024 | 0.00023 | rare |
| European (Non-Finnish) | 0.000027 | 0.000026 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Removes residual C-terminal Arg or Lys remaining after initial endoprotease cleavage during prohormone processing. Processes proinsulin.;
Recessive Scores
- pRec
- 0.253
Intolerance Scores
- LoFtool
- 0.392
- RVIS EVS
- -0.05
- RVIS percentile EVS
- 50.22
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.749
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |