CPN1

carboxypeptidase N subunit 1, the group of M14 carboxypeptidases

Basic information

Region (hg38): 10:100042192-100081869

Links

ENSG00000120054 ∙ NCBI:1369 ∙ OMIM:603103 ∙ HGNC:2312 ∙ Uniprot:P15169 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• carboxypeptidase N deficiency (Limited), mode of inheritance: AR
• carboxypeptidase N deficiency (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Carboxypeptidase N deficiency	AR	General	The consequences of the condition are unclear, though genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Allergy/Immunology/Infectious	7437116; 12560874; 18068674
Heterozygotes may demonstrate milder manifestations

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CPN1 gene.

• Inborn genetic diseases (19 variants)
• Hereditary angioedema with normal C1Inh (1 variants)
• not specified (1 variants)
• Anaphylotoxin inactivator deficiency (1 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CPN1 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					1	1
missense			17	2	1	20
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	17	2	2

Variants in CPN1

This is a list of pathogenic ClinVar variants found in the CPN1 region.

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

Position	Type	Phenotype	Significance	ClinVar
10-100048762-G-A		not specified	Uncertain significance (Aug 10, 2023)
10-100048769-C-T		Hereditary angioedema with normal C1Inh	not provided (Feb 01, 2020)
10-100048838-T-C		not specified	Uncertain significance (Mar 06, 2023)
10-100048855-C-T		not specified	Uncertain significance (Mar 16, 2022)
10-100048871-G-A		not specified	Uncertain significance (Dec 27, 2023)
10-100057042-G-A		not specified	Uncertain significance (Dec 06, 2021)
10-100057048-C-T		not specified	Uncertain significance (Dec 05, 2023)
10-100065197-G-A		CPN1-related disorder	Benign (Dec 05, 2019)
10-100065200-C-T			Benign (Mar 05, 2018)
10-100065249-C-G		not specified	Uncertain significance (Jun 07, 2023)
10-100065279-T-C		not specified	Uncertain significance (Jul 13, 2021)
10-100065306-T-C		not specified	Uncertain significance (Jun 28, 2022)
10-100065346-T-G		not specified	Uncertain significance (Aug 16, 2021)
10-100065364-G-A		not specified	Uncertain significance (Jul 31, 2023)
10-100069730-T-C		not specified	Uncertain significance (Jun 16, 2023)
10-100069757-C-T		Anaphylotoxin inactivator deficiency • not specified	Benign (May 28, 2019)
10-100075922-C-A		not specified	Uncertain significance (Sep 20, 2023)
10-100075964-T-C		not specified	Uncertain significance (Jun 29, 2023)
10-100075988-C-T		not specified	Uncertain significance (Aug 08, 2022)
10-100076007-C-G		CPN1-related disorder	Benign (Jan 28, 2020)
10-100076009-G-A		not specified	Uncertain significance (Nov 10, 2021)
10-100076032-G-A		not specified	Uncertain significance (Apr 07, 2022)
10-100076062-G-A		not specified	Likely benign (Nov 18, 2022)
10-100076093-T-C		not specified	Uncertain significance (Jul 12, 2022)
10-100081405-G-A		not specified	Likely benign (Apr 25, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CPN1	protein_coding	protein_coding	ENST00000370418	9	39685

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.70e-8	0.750	125677	0	71	125748	0.000282

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.342	263	279	0.942	0.0000186	3016
Missense in Polyphen		114	124.81	0.91336		1312
Synonymous	-1.40	133	114	1.17	0.00000837	881
Loss of Function	1.34	14	20.6	0.680	9.51e-7	231

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000389	0.000387
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.000185	0.000185
European (Non-Finnish)	0.000212	0.000211
Middle Eastern	0.000109	0.000109
South Asian	0.000915	0.000915
Other	0.000489	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Protects the body from potent vasoactive and inflammatory peptides containing C-terminal Arg or Lys (such as kinins or anaphylatoxins) which are released into the circulation.
• Pathway: Androgen Receptor Network in Prostate Cancer;Human Complement System;Steroid Biosynthesis;Innate Immune System;Immune System;Regulation of Complement cascade;Complement cascade (Consensus)

Recessive Scores

• pRec: 0.273

Intolerance Scores

• loftool: 0.716
• rvis_EVS: -0.56
• rvis_percentile_EVS: 19.73

Haploinsufficiency Scores

• pHI: 0.112
• hipred: N
• hipred_score: 0.379
• ghis: 0.418

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.872

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cpn1
• Phenotype: immune system phenotype

Gene ontology

• Biological process: peptide metabolic process;bradykinin catabolic process;protein processing;regulation of complement activation;response to glucocorticoid
• Cellular component: extracellular region;extracellular space
• Molecular function: metallocarboxypeptidase activity;zinc ion binding