PRCP

protein-coding

prolylcarboxypeptidase, the group of M14 carboxypeptidases|Minor histocompatibility antigens

Gene summary

This gene encodes a member of the peptidase S28 family of serine exopeptidases. The encoded preproprotein is proteolytically processed to generate the mature lysosomal prolylcarboxypeptidase. This enzyme cleaves C-terminal amino acids linked to proline in peptides such as angiotension II, III and des-Arg9-bradykinin. The cleavage occurs at acidic pH, but the enzyme activity is retained with some substrates at neutral pH. This enzyme has been shown to be an activator of the cell matrix-associated prekallikrein. The importance of angiotension II, one of the substrates of this enzyme, in regulating blood pressure and electrolyte balance suggests that this gene may be related to essential hypertension. A pseudogene of this gene has been identified on chromosome 2. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Jan 2016]

MANE transcript

NM_005040.4

Inheritance

—

ClinVar variants

U:80B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.79

Max pathogenic AF

—

Genomic locus

chr11:82,822,936-82,970,584

External References & Databases

Ensembl (ENSG00000137509)

Transcript & Mutation Effects

hg38 • Region Span ~147.6 kb

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GenCC 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 PRCP variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 73

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005040.4. 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						0
missense			74 clinvar	1 clinvar	2 clinvar	77
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	80	1	2	83

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 56 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005040.4	RefSeq	NP_005031.1	9	MANE Select
ENST00000313010.8	Ensembl	ENSP00000317362.3	9	MANE Select
NM_001319214.2	RefSeq	NP_001306143.1	7	Standard
NM_199418.4	RefSeq	NP_955450.2	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Renin-angiotensin system - Homo sapiens (human)
Protein digestion and absorption - Homo sapiens (human)
Neutrophil degranulation
Innate Immune System
Immune System

Biological Process

regulation of thyroid hormone mediated signaling pathway
plasma kallikrein-kinin cascade
negative regulation of systemic arterial blood pressure
proteolysis
blood coagulation, intrinsic pathway

Molecular Function

serine-type carboxypeptidase activity
protein binding
dipeptidyl-peptidase activity

Cellular Component

plasma membrane
azurophil granule membrane
basal part of cell
extracellular exosome
ficolin-1-rich granule membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000393399
Coding exons: 10
Length: 147083
Individuals with no LoFs: 125701
Homozygous LoFs: 0
Heterozygous LoFs: 44
Defined: 125745
p: 0.000175

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0402	270	268	1.01	0.0000126	3369
Missense (PolyPhen)		95	98.973	0.95986		1221
Synonymous	-0.657	106	97.7	1.08	0.00000461	984
Loss of Function	0.965	20	25.2	0.793	0.00000114	301

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00034	0.00031	rare
Latino/Admixed American	0.00011	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00023	0.00022	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00022	0.00022	rare
South Asian	0.00013	0.00013	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Cleaves C-terminal amino acids linked to proline in peptides such as angiotensin II, III and des-Arg9-bradykinin. This cleavage occurs at acidic pH, but enzymatic activity is retained with some substrates at neutral pH.;

Recessive Scores

pRec: 0.210

Intolerance Scores

LoFtool: 0.466
RVIS EVS: 0.2
RVIS percentile EVS: 67.3

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0137

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium