CNDP2

Chr 18

carnosine dipeptidase 2

Also known as: CN2, CPGL, HEL-S-13, HsT2298, PEPA

This gene encodes a nonspecific dipeptidase that hydrolyzes peptide bonds in dipeptides, particularly threonyl dipeptides and cysteinylglycine (an intermediate in glutathione metabolism), and also metabolizes N-lactoyl-amino acids. Mutations cause carnosinase deficiency 2, an autosomal recessive disorder characterized by elevated carnosine levels in cerebrospinal fluid. The gene is not highly constrained against loss-of-function variants.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
21
Pubs (1 yr)
153
P/LP submissions
0%
P/LP missense
0.93
LOEUF
DN
Mechanism· predicted
Clinical SummaryCNDP2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
151 unique Pathogenic / Likely Pathogenic· 98 VUS of 280 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.93LOEUF
pLI 0.000
Z-score 1.82
OE 0.60 (0.400.93)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.11Z-score
OE missense 0.98 (0.891.08)
289 obs / 294.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.60 (0.400.93)
00.351.4
Missense OE0.98 (0.891.08)
00.61.4
Synonymous OE1.04
01.21.6
LoF obs/exp: 15 / 24.8Missense obs/exp: 289 / 294.3Syn Z: -0.34
DN
0.6842th %ile
GOF
0.5759th %ile
LOF
0.2776th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

280 submitted variants in ClinVar

Classification Summary

Pathogenic145
Likely Pathogenic6
VUS98
Likely Benign7
Benign3
145
Pathogenic
6
Likely Pathogenic
98
VUS
7
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
145
0
145
Likely Pathogenic
0
0
6
0
6
VUS
0
76
22
0
98
Likely Benign
0
2
3
2
7
Benign
0
1
2
0
3
Total0791782259

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CNDP2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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