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3 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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PM20D2
peptidase M20 domain containing 2
Chromosome 6 · 6q15
NCBI Gene: 135293Ensembl: ENSG00000146281.7HGNC: HGNC:21408UniProt: Q8IYS1
28PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Protease
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
nucleoplasmdipeptidase activityidentical protein bindingproteolysisAbnormality of the gastrointestinal tractplacenta praeviasystemic inflammatory response syndromeocular hypotension
✦AI Summary

PM20D2 is a cytosolic metallopeptidase that catalyzes peptide bond hydrolysis in dipeptides containing basic amino acids (lysine, ornithine, or arginine) at the C-terminus 1. The enzyme preferentially hydrolyzes β-alanyl-lysine, β-alanyl-ornithine, and γ-aminobutyryl-lysine, with lower activity on classic dipeptides like α-alanyl-lysine 1. PM20D2 functions as a metabolite repair enzyme that eliminates aberrant dipeptide byproducts generated during carnosine and homocarnosine synthesis, preventing accumulation of unwanted metabolites while favoring synthesis of physiologically important dipeptides 1. This housekeeping role ensures fidelity in amino acid metabolism pathways operating in skeletal muscle and brain. Clinically, PM20D2 shows dysregulation in disease contexts. The enzyme was identified as an upregulated protein in FASN-silenced osteosarcoma cells, suggesting involvement in tumor-associated metabolic reprogramming 2. Recent meta-analytic evidence indicates sex-specific differential expression of PM20D2 in subcutaneous adipose tissue of females with type 2 diabetes, linking it to metabolic disease pathophysiology and highlighting potential sex-based differences in metabolic regulation 3. These findings suggest PM20D2 participates in broader metabolic networks beyond carnosine synthesis, with potential implications for understanding metabolic diseases and tumor biology.

Sources cited
1
PM20D2 is a β-alanyl-lysine dipeptidase that hydrolyzes dipeptides with basic amino acids at C-terminus and functions in metabolite repair during carnosine and homocarnosine synthesis
PMID: 24891507
2
PM20D2 is among the top 10 upregulated proteins in FASN-silenced osteosarcoma cells
PMID: 33405298
3
PM20D2 shows sex-specific differential expression in subcutaneous adipose tissue of females with type 2 diabetes
PMID: 40157598
⚠Limited data available — This gene has 3 indexed publications. Summary and analysis may be incomplete.
Disease Associationsⓘ20
Abnormality of the gastrointestinal tractOpen Targets
0.32Weak
placenta praeviaOpen Targets
0.24Weak
systemic inflammatory response syndromeOpen Targets
0.02Suggestive
ocular hypotensionOpen Targets
0.02Suggestive
Benign Thyroid Gland NeoplasmOpen Targets
0.02Suggestive
arthritisOpen Targets
0.02Suggestive
breast carcinomaOpen Targets
0.02Suggestive
acute quadriplegic myopathyOpen Targets
0.01Suggestive
Colon Sessile Serrated Adenoma/PolypOpen Targets
0.01Suggestive
amyotrophic lateral sclerosisOpen Targets
0.01Suggestive
colorectal cancerOpen Targets
0.01Suggestive
Alzheimer diseaseOpen Targets
0.01Suggestive
prostate cancerOpen Targets
0.00Suggestive
Adams-Oliver syndromeOpen Targets
0.00Suggestive
oral squamous cell carcinomaOpen Targets
0.00Suggestive
hepatocellular carcinomaOpen Targets
0.00Suggestive
asthmaOpen Targets
0.00Suggestive
type 1 diabetes mellitusOpen Targets
0.00Suggestive
urinary bladder cancerOpen Targets
0.00Suggestive
Uterine CarcinosarcomaOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CNDP1Shared pathway100%PGA4Shared pathway50%PGA3Shared pathway50%CAPN14Shared pathway50%CTRB2Shared pathway50%CAPN8Shared pathway50%
Tissue Expression6 tissues
Ovary
100%
Brain
66%
Heart
65%
Bone Marrow
57%
Lung
37%
Liver
32%
Gene Interaction Network
Click a node to explore
PM20D2CNDP1PGA4PGA3CAPN14CTRB2CAPN8
PROTEIN STRUCTURE
Preparing viewer…
PDB7YH4 · 2.03 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.20LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.88 [0.65–1.20]
RankingsWhere PM20D2 stands among ~20K protein-coding genes
  • #12,417of 20,598
    Most Researched28
  • #12,642of 17,882
    Most Constrained (LOEUF)1.20
Genes detectedPM20D2
Sources retrieved3 papers
Response time—
📄 Sources
3
1
iTRAQ-based proteomic analysis of the molecular mechanisms and downstream effects of fatty acid synthase in osteosarcoma cells.
PMID: 33405298
J Clin Lab Anal · 2021
1.00
2
Metabolite proofreading in carnosine and homocarnosine synthesis: molecular identification of PM20D2 as β-alanyl-lysine dipeptidase.
PMID: 24891507
J Biol Chem · 2014
0.67
3
Landscape of sex differences in obesity and type 2 diabetes in subcutaneous adipose tissue: a systematic review and meta-analysis of transcriptomics studies.
PMID: 40157598
Metabolism · 2025
0.33