CNDP2

protein-coding

carnosine dipeptidase 2, the group of M20 metallopeptidases

Gene summary

CNDP2, also known as tissue carnosinase and peptidase A (EC 3.4.13.18), is a nonspecific dipeptidase rather than a selective carnosinase (Teufel et al., 2003 [PubMed 12473676]).[supplied by OMIM, Mar 2008]

Previous symbols:

PEPA

MANE transcript

NM_018235.3

Inheritance

—

ClinVar variants

U:88B:5

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.6

Max pathogenic AF

—

Genomic locus

chr18:74,495,816-74,523,454

External References & Databases

Ensembl (ENSG00000133313)

Transcript & Mutation Effects

hg38 • Region Span ~27.6 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 CNDP2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 80

not providedTotal: 7

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018235.3. 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			2 clinvar	2 clinvar		4
missense			80 clinvar	2 clinvar	1 clinvar	83
nonsense			4 clinvar			4
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	88	4	1	93

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 222 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_018235.3	RefSeq	NP_060705.2	11	MANE Select
ENST00000324262.9	Ensembl	ENSP00000325548.4	11	MANE Select
NM_001168499.2	RefSeq	NP_001161971.1	9	Standard
NM_001370248.1	RefSeq	NP_001357177.1	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Arginine and proline metabolism - Homo sapiens (human)
beta-Alanine metabolism - Homo sapiens (human)
Histidine metabolism - Homo sapiens (human)
Glutathione conjugation
Phase II - Conjugation of compounds

Biological Process

proteolysis
glutathione biosynthetic process

Molecular Function

carboxypeptidase activity
metallopeptidase activity
metal ion binding
cytosolic dipeptidase activity
alanylglutamate dipeptidase activity

Cellular Component

nucleoplasm
cytosol
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000324262
Coding exons: 11
Length: 25316
Individuals with no LoFs: 125695
Homozygous LoFs: 0
Heterozygous LoFs: 53
Defined: 125748
p: 0.000211

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.110	289	294	0.982	0.0000179	3116
Missense (PolyPhen)		67	89.671	0.74718		954
Synonymous	-0.345	142	137	1.04	0.0000104	928
Loss of Function	1.82	15	24.8	0.605	0.00000130	268

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00018	0.00018	rare
Latino/Admixed American	0.00021	0.00020	rare
Ashkenazi Jewish	0.00030	0.00030	rare
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00026	0.00025	rare
South Asian	0.00023	0.00023	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Hydrolyzes a variety of dipeptides including L-carnosine but has a strong preference for Cys-Gly (PubMed:19346245). Acts as a functional tumor suppressor in gastric cancer via activation of the mitogen-activated protein kinase (MAPK) pathway. An elevated level of CNDP2 activates the p38 and JNK MAPK pathways to induce cell apoptosis, and a lower level of CNDP2 activates the ERK MAPK pathway to promote cell proliferation (PubMed:24395568). Isoform 2 may play a role as tumor suppressor in hepatocellular carcinoma (HCC) cells (PubMed:17121880). Catalyzes the production of N- lactoyl-amino acids from lactate and amino acids by reverse proteolysis (PubMed:25964343). {ECO:0000269|PubMed:17121880, ECO:0000269|PubMed:19346245, ECO:0000269|PubMed:24395568, ECO:0000269|PubMed:25964343}.;

Recessive Scores

pRec: 0.418

Intolerance Scores

LoFtool: 0.396
RVIS EVS: -0.75
RVIS percentile EVS: 13.67

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.373

Gene Damage Prediction

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