CPA1

carboxypeptidase A1, the group of M14 carboxypeptidases

Basic information

Region (hg38): 7:130380338-130388114

Previous symbols: [ "CPA" ]

Links

ENSG00000091704 ∙ NCBI:1357 ∙ OMIM:114850 ∙ HGNC:2296 ∙ Uniprot:P15085 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hereditary chronic pancreatitis (Strong), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CPA1 gene.

• Hereditary pancreatitis (594 variants)
• not provided (285 variants)
• not specified (4 variants)
• Inborn genetic diseases (4 variants)
• Early-onset chronic pancreatitis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CPA1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	206	4	213
missense		3	371	11		385
nonsense			3	2		5
start loss			1	1		2
frameshift			4	4		8
inframe indel			3			3
splice donor/acceptor (+/-2bp)			6			6
splice region			11	16	1	28
non coding			4	20	16	40
Total	0	3	395	244	20

Highest pathogenic variant AF is 0.00000657

Variants in CPA1

This is a list of pathogenic ClinVar variants found in the CPA1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
7-130380516-G-C		Hereditary pancreatitis	Uncertain significance (Mar 20, 2023)
7-130380520-C-G		Hereditary pancreatitis	Uncertain significance (May 12, 2021)
7-130380522-T-C		Hereditary pancreatitis	Conflicting classifications of pathogenicity (Mar 03, 2023)
7-130380522-TGCGGGG-GCA		Hereditary pancreatitis	Likely benign (Oct 05, 2022)
7-130380523-G-T			Uncertain significance (Dec 03, 2023)
7-130380524-C-T		Hereditary pancreatitis	Uncertain significance (Nov 15, 2023)
7-130380525-G-A		Hereditary pancreatitis • CPA1-related disorder	Benign/Likely benign (Sep 10, 2023)
7-130380524-C-CGG		Hereditary pancreatitis	Conflicting classifications of pathogenicity (Dec 05, 2023)
7-130380528-G-T		Hereditary pancreatitis	Uncertain significance (Aug 07, 2023)
7-130380529-G-A		Hereditary pancreatitis	Likely benign (Oct 21, 2021)
7-130380529-G-T		Hereditary pancreatitis	Likely benign (Nov 28, 2023)
7-130380530-T-A		Hereditary pancreatitis	Uncertain significance (Nov 30, 2023)
7-130380532-G-A			Likely benign (Mar 23, 2023)
7-130380534-T-C		Hereditary pancreatitis	Uncertain significance (Feb 27, 2023)
7-130380535-G-A		Hereditary pancreatitis	Uncertain significance (Oct 11, 2021)
7-130380537-T-C		Hereditary pancreatitis	Uncertain significance (Dec 24, 2022)
7-130380539-T-C		Hereditary pancreatitis	Likely benign (Mar 11, 2021)
7-130380543-G-T		Hereditary pancreatitis	Uncertain significance (Oct 27, 2023)
7-130380550-G-A		Hereditary pancreatitis	Likely benign (May 24, 2021)
7-130380550-G-C		Hereditary pancreatitis	Likely benign (Dec 01, 2021)
7-130380551-T-C		Hereditary pancreatitis	Likely benign (Aug 17, 2023)
7-130380553-G-T		Hereditary pancreatitis	Uncertain significance (Dec 15, 2021)
7-130380556-G-A		Hereditary pancreatitis	Likely benign (Apr 19, 2022)
7-130380557-G-A		Hereditary pancreatitis	Uncertain significance (Nov 17, 2023)
7-130380560-G-C		Hereditary pancreatitis	Uncertain significance (Sep 19, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CPA1	protein_coding	protein_coding	ENST00000011292	10	7776

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.66e-11	0.145	125571	0	177	125748	0.000704

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.04	209	256	0.818	0.0000159	2745
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000635	0.000510
Ashkenazi Jewish	0.00439	0.00437
East Asian	0.000435	0.000435
Finnish	0.000335	0.000323
European (Non-Finnish)	0.000680	0.000677
Middle Eastern	0.000435	0.000435
South Asian	0.000719	0.000719
Other	0.00115	0.00114

dbNSFP

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}.
• Pathway: Protein digestion and absorption - Homo sapiens (human);Pancreatic secretion - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.371

Intolerance Scores

• loftool: 0.825
• rvis_EVS: 0.15
• rvis_percentile_EVS: 64.74

Haploinsufficiency Scores

• pHI: 0.467
• hipred: N
• hipred_score: 0.239
• ghis: 0.395

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.225

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cpa1
• Phenotype: normal phenotype

Gene ontology

• Biological process: proteolysis
• Cellular component: extracellular space
• Molecular function: metallocarboxypeptidase activity;protein binding;zinc ion binding