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PEPD

peptidase D

The PEPD gene provides instructions for producing the enzyme prolidase, also known as peptidase D, which plays a crucial role in breaking down specific protein building blocks, particularly those found in collagen. The PEPD gene is responsible for the enzyme prolidase, essential for the breakdown of certain dipeptides containing proline or hydroxyproline.

Chromosome 19q13.11 HGNC:8840 Tier C
PEPD 19q13.11 p arm q arm 19

PEPD is located on the long (q) arm of chromosome 19, at band 19q13.11. Arm ratio per GRCh38 - banding schematic.

Explore chromosome 19 in the library →

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Clinical tests that include this

Carrier Screening panel
PEPD is 1 of 1,008 genes on this panel
Expanded carrier screening for recessive and X-linked conditions

Overview

The PEPD gene encodes an enzyme called prolidase, or peptidase D. This enzyme is crucial for the body's ability to break down specific types of small protein fragments, known as dipeptides. By performing this function, prolidase helps ensure that essential amino acids are available for constructing new proteins throughout the body.

Its activity is especially significant in the turnover of collagen, a major protein found in skin, bones, cartilage, and other connective tissues. Understanding the PEPD gene is important for comprehending conditions linked to its dysfunction, such as prolidase deficiency.

What the gene does

The prolidase enzyme, produced from the PEPD gene, functions by cleaving dipeptides that contain the amino acids proline or hydroxyproline. These amino acids are then released and become available for the synthesis of other necessary proteins within the body. This enzymatic action is a critical step in the recycling of protein components.

Furthermore, prolidase is involved in the final stages of breaking down proteins acquired from the diet and those no longer needed by the body. Its particular importance lies in the degradation of collagens, a family of proteins that are highly abundant in proline and hydroxyproline. Collagens are fundamental to the extracellular matrix, which provides structural support and strength to connective tissues like skin, bone, and tendons. The ongoing breakdown of collagen is a natural process in the maintenance and remodelling of this matrix.

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Chromosome location

The PEPD gene is located on chromosome 19, specifically at position 19q13.11. This genomic address specifies its precise place within the human genome.

Protein structure

Domain architecture has not been experimentally characterised in detail for this protein.

Key variants

Variations within the PEPD gene can lead to changes in the structure or function of the prolidase enzyme. These genetic alterations can impact the enzyme's ability to break down dipeptides, potentially leading to a range of health implications. The specific effects of a variant depend on its nature and location within the gene.

The table below shows the top 10 pathogenic or likely-pathogenic variants currently classified in ClinVar for PEPD.
View all on ClinVar →

Sample of pathogenic variants

10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.

Variant (HGVS) Protein change Classification Evidence Associated condition
c.1302_1305del
Microsatellite
 p.Phe434fs Pathogenic/Likely pathogenic ★★☆☆ PEPD-related disorder
c.1A>G
single nucleotide variant
 p.Met1Val Pathogenic/Likely pathogenic ★★☆☆ PEPD-related disorder
c.2T>C
single nucleotide variant
 p.Met1Thr Pathogenic/Likely pathogenic ★★☆☆ Prolidase deficiency
c.2T>G
single nucleotide variant
 p.Met1Arg Pathogenic/Likely pathogenic ★★☆☆ PEPD-related disorder
c.418A>T
single nucleotide variant
 p.Lys140Ter Pathogenic/Likely pathogenic ★★☆☆ PEPD-related disorder
c.442-1G>C
single nucleotide variant
 - Pathogenic/Likely pathogenic ★★☆☆ Prolidase deficiency
c.504-1G>A
single nucleotide variant
 - Pathogenic/Likely pathogenic ★★☆☆ Prolidase deficiency
c.549-1G>A
single nucleotide variant
 - Pathogenic ★★☆☆ Prolidase deficiency
c.550C>T
single nucleotide variant
 p.Arg184Ter Pathogenic ★★☆☆ Prolidase deficiency
c.769G>T
single nucleotide variant
 p.Gly257Ter Pathogenic ★★☆☆ not provided

Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.

Associated conditions

Mutations in the PEPD gene are known to cause prolidase deficiency, a condition characterised by a wide array of signs and symptoms, including issues with skin and intellectual disability. In affected individuals, identified PEPD gene mutations typically result in a complete loss of prolidase enzyme activity. The precise mechanisms through which the absence of this enzyme leads to the diverse symptoms of prolidase deficiency are not yet fully understood.

No disease links recorded for this gene in our reference set.

UK clinical status

The PEPD gene is recognised within several UK NHS National Genomic Test Directory panels, indicating its clinical relevance. It is included in panels for COVID-19 research, Developmental Disorders Gene to Phenotype (DDG2P), Foetal anomalies (R21), Intellectual disability, Likely inborn error of metabolism (R98), Primary immunodeficiency or monogenic inflammatory bowel disease (R15), and Undiagnosed metabolic disorders.

Green-listed
High evidence · clinically actionable in NHS testing
Included in NHS GMS signed-off panels
Fetal anomalies · R21 NHS GMS → Likely inborn error of metabolism · R98 NHS GMS → Primary immunodeficiency or monogenic inflammatory bowel disease · R15 NHS GMS → DDG2P NHS GMS → Intellectual disability NHS GMS →
NHS Genomic Medicine Service Jeen carrier screening

Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory

Frequently asked questions

What is the primary function of the PEPD gene?

The PEPD gene provides instructions for making the prolidase enzyme, which is essential for breaking down specific dipeptides containing proline or hydroxyproline. This process helps recycle amino acids for new protein synthesis, especially important in collagen turnover.

What is prolidase deficiency?

Prolidase deficiency is a genetic condition caused by mutations in the PEPD gene, leading to a lack of functional prolidase enzyme. This can result in various symptoms, including skin problems and intellectual disability.

How does the PEPD gene relate to collagen?

The prolidase enzyme, encoded by the PEPD gene, is particularly important in the breakdown of collagens. Collagens are rich in proline and hydroxyproline, and their proper degradation is vital for maintaining the extracellular matrix of connective tissues.

References

  1. Falik-Zaccai TC, Khayat M, Luder A. A broad spectrum of developmental delay in a large cohort of prolidase deficiency patients demonstrates marked interfamilial and intrafamilial phenotypic variability. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics. 2010. PMID: 19308961
  2. Surazynski A, Donald SP, Cooper SK. Extracellular matrix and HIF-1 signaling: the role of prolidase. International journal of cancer. 2008. PMID: 17999410
  3. Lupi A, Tenni R, Rossi A. Human prolidase and prolidase deficiency: an overview on the characterization of the enzyme involved in proline recycling and on the effects of its mutations. Amino acids. 2008. PMID: 18340504
  4. Mitsubuchi H, Nakamura K, Matsumoto S. Inborn errors of proline metabolism. The Journal of nutrition. 2008. PMID: 18806117
  5. Wang H, Kurien BT, Lundgren D. A nonsense mutation of PEPD in four Amish children with prolidase deficiency. American journal of medical genetics. Part A. 2006. PMID: 16470701
  6. Lupi A, Rossi A, Campari E. Molecular characterisation of six patients with prolidase deficiency: identification of the first small duplication in the prolidase gene and of a mutation generating symptomatic and asymptomatic outcomes within the same family. Journal of medical genetics. 2006. PMID: 17142620
  7. Lupi A, De Riso A, Torre SD. Characterization of a new PEPD allele causing prolidase deficiency in two unrelated patients: natural-occurrent mutations as a tool to investigate structure-function relationship. Journal of human genetics. 2004. PMID: 15309682
  8. Forlino A, Lupi A, Vaghi P. Mutation analysis of five new patients affected by prolidase deficiency: the lack of enzyme activity causes necrosis-like cell death in cultured fibroblasts. Human genetics. 2002. PMID: 12384772
Educational content. This page is not medical or genetic advice, is not individually reviewed by a clinician for each reader, and should not replace a consultation with a qualified healthcare professional or genetic counsellor. If you are considering genetic testing or acting on a test result, book a consultation.
Data sources Last updated 18 October 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .