CPA1

protein-coding

carboxypeptidase A1, the group of M14 carboxypeptidases

Gene summary

This gene encodes a member of the carboxypeptidase A family of zinc metalloproteases. This enzyme is produced in the pancreas and preferentially cleaves C-terminal branched-chain and aromatic amino acids from dietary proteins. This gene and several family members are present in a gene cluster on chromosome 7. Mutations in this gene may be linked to chronic pancreatitis, while elevated protein levels may be associated with pancreatic cancer. [provided by RefSeq, Jan 2015]

Previous symbols:

MANE transcript

NM_001868.4

Inheritance

ClinVar variants

P:4U:640B:390

Top phenotype

hereditary chronic pancreatitis

gnomAD constraint

pLI —, LoF o/e 0.86

Max pathogenic AF

—

Genomic locus

chr7:130,380,339-130,388,114

External References & Databases

Ensembl (ENSG00000091704)

Transcript & Mutation Effects

hg38 • Region Span ~7.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hereditary chronic pancreatitisSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0008185

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CPA1 variants in ClinVar

5 Conditions Cataloged

Hereditary pancreatitisTotal: 1003

not providedTotal: 391

CPA1-related disorderTotal: 17

not specifiedTotal: 16

Early-onset chronic pancreatitisTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001868.4. 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			3 clinvar	317 clinvar	1 clinvar	321
missense	1 clinvar	3 clinvar	619 clinvar	49 clinvar		672
nonsense			3 clinvar	6 clinvar		9
start loss			1 clinvar	3 clinvar		4
frameshift			5 clinvar	10 clinvar		15
splice donor/acceptor (+/-2bp)			9 clinvar	4 clinvar		13
Total	1	3	640	389	1	1034

Highest pathogenic variant AF is 0.00001303268

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 7 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001868.4	RefSeq	NP_001859.1	10	MANE Select
ENST00000011292.8	Ensembl	ENSP00000011292.3	10	MANE Select
ENST00000476062.5	Ensembl	ENSP00000419408.1	7	Standard
ENST00000481342.5	Ensembl	ENSP00000420218.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Protein digestion and absorption - Homo sapiens (human)
Pancreatic secretion - Homo sapiens (human)

Biological Process

proteolysis

Molecular Function

metallocarboxypeptidase activity
protein binding
zinc ion binding

Cellular Component

extracellular space

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000011292
Coding exons: 10
Length: 7776
Individuals with no LoFs: 125571
Homozygous LoFs: 0
Heterozygous LoFs: 177
Defined: 125748
p: 0.000704

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.04	209	256	0.818	0.0000159	2745
Missense (PolyPhen)		86	109.33	0.78657		1141
Synonymous	1.08	96	110	0.869	0.00000756	821
Loss of Function	0.601	18	21.0	0.858	0.00000107	226

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00043	0.00031	rare
Latino/Admixed American	0.00020	0.00020	rare
Ashkenazi Jewish	0.0044	0.0044	notable
East Asian	0.00043	0.00044	rare
Finnish	0.00033	0.00032	rare
European (Non-Finnish)	0.00068	0.00068	rare
South Asian	0.00072	0.00072	rare
Other	0.0011	0.0011	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Carboxypeptidase that catalyzes the release of a C- terminal amino acid, but has little or no action with -Asp, -Glu, -Arg, -Lys or -Pro. {ECO:0000269|PubMed:8806703}.;

Recessive Scores

pRec: 0.371

Intolerance Scores

LoFtool: 0.825
RVIS EVS: 0.15
RVIS percentile EVS: 64.74

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.225

Gene Damage Prediction

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