CNDP2

carnosine dipeptidase 2, the group of M20 metallopeptidases

Basic information

Region (hg38): 18:74495815-74523454

Previous symbols: [ "PEPA" ]

Links

ENSG00000133313 ∙ NCBI:55748 ∙ OMIM:169800 ∙ HGNC:24437 ∙ Uniprot:Q96KP4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CNDP2 gene.

• Inborn genetic diseases (23 variants)
• not provided (5 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CNDP2 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				2		2
missense			21	2	1	24
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding				1		1
Total	0	0	21	5	1

Variants in CNDP2

This is a list of pathogenic ClinVar variants found in the CNDP2 region.

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

Position	Type	Phenotype	Significance	ClinVar
18-74499978-C-T		not specified	Uncertain significance (Jul 09, 2021)
18-74500006-A-G		not specified	Uncertain significance (May 11, 2022)
18-74501350-A-G		not specified	Uncertain significance (Jan 27, 2022)
18-74501359-G-A		not specified	Uncertain significance (Dec 09, 2023)
18-74501366-C-T		not specified	Uncertain significance (Sep 27, 2022)
18-74501372-C-T			Benign (Jul 03, 2018)
18-74505871-C-T		not specified	Uncertain significance (Oct 05, 2023)
18-74505895-G-T		not specified	Uncertain significance (Jan 03, 2024)
18-74505924-G-A		not specified	Uncertain significance (Jan 31, 2022)
18-74505930-A-G		not specified	Uncertain significance (Jul 28, 2021)
18-74505979-A-G		not specified	Uncertain significance (Sep 01, 2021)
18-74505987-C-G		not specified	Uncertain significance (Feb 05, 2024)
18-74506020-C-T			Likely benign (Jun 26, 2018)
18-74508879-C-T		not specified	Uncertain significance (May 11, 2022)
18-74508886-C-T			Likely benign (Dec 01, 2017)
18-74508887-G-A		not specified	Uncertain significance (Sep 06, 2022)
18-74508902-C-A		not specified	Uncertain significance (Oct 25, 2023)
18-74508924-G-T		not specified	Uncertain significance (Nov 21, 2022)
18-74510816-A-T		not specified	Uncertain significance (Aug 08, 2023)
18-74510819-C-T		not specified	Uncertain significance (Mar 01, 2024)
18-74510842-C-T			Likely benign (Jul 03, 2018)
18-74510925-A-G		not specified	Uncertain significance (Apr 18, 2023)
18-74510966-C-G		not specified	Uncertain significance (Mar 21, 2023)
18-74510981-G-A		not specified	Uncertain significance (Sep 23, 2023)
18-74512488-G-C		not specified	Uncertain significance (Oct 03, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CNDP2	protein_coding	protein_coding	ENST00000324262	11	25316

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.01e-7	0.930	125695	0	53	125748	0.000211

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.110	289	294	0.982	0.0000179	3116
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000398	0.000398
Ashkenazi Jewish	0.000298	0.000298
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.000257	0.000255
Middle Eastern	0.000109	0.000109
South Asian	0.000229	0.000229
Other	0.000326	0.000326

dbNSFP

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}.
• Pathway: 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 oxidations;Metabolism;γ-glutamyl cycle;Glutathione synthesis and recycling (Consensus)

Recessive Scores

• pRec: 0.418

Intolerance Scores

• loftool: 0.396
• rvis_EVS: -0.75
• rvis_percentile_EVS: 13.67

Haploinsufficiency Scores

• pHI: 0.274
• hipred: N
• hipred_score: 0.426
• ghis: 0.544

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.373

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cndp2

Gene ontology

• Biological process: proteolysis;glutathione biosynthetic process
• Cellular component: nucleoplasm;cytosol;extracellular exosome
• Molecular function: carboxypeptidase activity;metallopeptidase activity;metal ion binding;cytosolic dipeptidase activity;alanylglutamate dipeptidase activity