CORIN
protein-codingcorin, serine peptidase, the group of Scavenger receptor cysteine rich domain containing|Type II transmembrane serine proteases
Gene summary
This gene encodes a member of the type II transmembrane serine protease class of the trypsin superfamily. Members of this family are composed of multiple structurally distinct domains. The encoded protein converts pro-atrial natriuretic peptide to biologically active atrial natriuretic peptide, a cardiac hormone that regulates blood volume and pressure. This protein may also function as a pro-brain-type natriuretic peptide convertase. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2013]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~244.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: Unknown
Disease ID:MONDO:0013817
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Cardiovascular; Obstetric
Intervention: Cardiovascular; Obstetric
Rationale: Individuals with Cardiomyopathy, familial hypertrophic, 30, atrial may manifest with cardiovascular complications, including hypertension, cardiomyopathy, and arrhthymia, and awareness may allow early identification and medical management; Individuals with Preeclampsia/eclampsia may be at high risk for pregnancy complications such as preeclampsia/eclampsia, and thus preconception planning, surveillance during pregnancy (eg, including related to proteinuria, hypertension, liver function, and hematologic parameters), as well as delivery planning may be beneficial in order to decrease associated morbidity and mortality
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CORIN variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006587.4. 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 | 10 | 2 | 12 | |||
| missense | 2 | 181 | 13 | 4 | 200 | |
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | 1 | 3 | ||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 3 | 1 | 183 | 24 | 6 | 217 |
Highest pathogenic variant AF is 0.000019840401
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006578.2 | 22 | MANE Select | |
| Ensembl | ENSP00000273857.4 | 22 | MANE Select | |
| RefSeq | NP_001265514.1 | 20 | Standard | |
| RefSeq | NP_001265515.1 | 14 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Physiological factors
- Myometrial Relaxation and Contraction Pathways
- corticosteroids and cardioprotection
- Cardiac conduction
- Muscle contraction
Biological Process
- regulation of systemic arterial blood pressure by atrial natriuretic peptide
- female pregnancy
- regulation of blood pressure
- peptide hormone processing
- regulation of renal sodium excretion
Molecular Function
- serine-type endopeptidase activity
Cellular Component
- extracellular region
- plasma membrane
- cell surface
- actin cytoskeleton
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000273857
- Coding exons
- 22
- Length
- 244109
- Individuals with no LoFs
- 125145
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 603
- Defined
- 125748
- p
- 0.00240
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.167 | 608 | 597 | 1.02 | 0.0000323 | 6943 |
| Missense (PolyPhen) | 252 | 255.4 | 0.98668 | 2938 | ||
| Synonymous | 0.164 | 224 | 227 | 0.986 | 0.0000135 | 1871 |
| Loss of Function | 0.134 | 53 | 54.1 | 0.980 | 0.00000245 | 667 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0065 | 0.0043 | notable |
| Latino/Admixed American | 0.0017 | 0.0017 | notable |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.021 | 0.021 | notable |
| Finnish | 0.00028 | 0.00028 | rare |
| European (Non-Finnish) | 0.00063 | 0.00061 | rare |
| South Asian | 0.00056 | 0.00056 | rare |
| Other | 0.0016 | 0.0016 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Serine-type endopeptidase involved in atrial natriuretic peptide hormone (NPPA) processing. Converts through proteolytic cleavage the non-functional propeptide NPPA into the active hormone, thereby regulating blood pressure in heart and promoting natriuresis, diuresis and vasodilation. Proteolytic cleavage of pro-NPPA also plays a role in female pregnancy by promoting trophoblast invasion and spiral artery remodeling in uterus. Also acts as a regulator of sodium reabsorption in kidney. May also process pro-NPPB the B-type natriuretic peptide.;
- Disease
- DISEASE: Pre-eclampsia/eclampsia 5 (PEE5) [MIM:614595]: A hypertensive disorder of pregnancy characterized by new hypertension (blood pressure 140/90 or greater) presenting after 20 weeks' gestation with clinically relevant proteinuria. It impacts 2 individuals, the mother and her child, both of whom can be severely affected. Preeclampsia is one of the causes of maternal mortality and morbidity worldwide. {ECO:0000269|PubMed:22437503}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Intolerance Scores
- LoFtool
- 0.201
- RVIS EVS
- -0.15
- RVIS percentile EVS
- 42.34
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0322
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |