PEPD

peptidase D, the group of M24 metallopeptidase family

Basic information

Region (hg38): 19:33386950-33521823

Links

ENSG00000124299 ∙ NCBI:5184 ∙ OMIM:613230 ∙ HGNC:8840 ∙ Uniprot:P12955 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• prolidase deficiency (Definitive), mode of inheritance: AR
• prolidase deficiency (Supportive), mode of inheritance: AR
• prolidase deficiency (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Prolidase deficiency	AR	Allergy/Immunology/Infectious	Individuals may have a number of manifestations, including frequent and severe respiratory and other infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	Allergy/Immunology/Infectious; Biochemical; Craniofacial; Dermatologic; Musculoskeletal; Neurologic	4828441; 874681; 908977; 7095220; 6727550; 1972707; 8198124; 8900231; 12384772; 16470701; 18340504; 19308961; 19937054

ClinVar

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

• not provided (26 variants)
• Prolidase deficiency (9 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PEPD 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			1	172	5	178
missense	1	5	190	8	4	208
nonsense	11					11
start loss	1		2			3
frameshift	13	1				14
inframe indel		1	3			4
splice donor/acceptor (+/-2bp)	3	19	1			23
splice region			10	33		43
non coding			14	143	42	199
Total	29	26	211	323	51

Highest pathogenic variant AF is 0.0000526

Variants in PEPD

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

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

Position	Type	Phenotype	Significance	ClinVar
19-33387004-C-CAGAA		Prolidase deficiency	Uncertain significance (Jun 14, 2016)
19-33387006-G-GAAAGT		Prolidase deficiency	Benign (Jun 14, 2016)
19-33387069-G-C		Prolidase deficiency	Uncertain significance (Jan 13, 2018)
19-33387119-A-T		Prolidase deficiency	Uncertain significance (Jan 12, 2018)
19-33387133-A-G		Prolidase deficiency	Benign (Nov 12, 2018)
19-33387165-G-GTAAT		Prolidase deficiency	Benign (May 15, 2021)
19-33387189-C-T		Prolidase deficiency	Uncertain significance (Jan 12, 2018)
19-33387217-A-G		Prolidase deficiency	Uncertain significance (Jan 13, 2018)
19-33387248-C-T		Prolidase deficiency	Uncertain significance (Jan 12, 2018)
19-33387291-G-A		Prolidase deficiency	Benign (Jan 13, 2018)
19-33387292-A-G		Prolidase deficiency • not specified	Benign (Nov 12, 2023)
19-33387304-A-T		Prolidase deficiency	Uncertain significance (Jan 13, 2018)
19-33387342-C-A		PEPD-related disorder	Likely benign (May 31, 2019)
19-33387356-A-G		Prolidase deficiency • PEPD-related disorder	Benign/Likely benign (Jan 22, 2024)
19-33387363-G-C		Inborn genetic diseases	Uncertain significance (Jul 25, 2022)
19-33387365-G-A			Likely benign (Nov 24, 2023)
19-33387365-G-C			Likely benign (Dec 12, 2023)
19-33387366-G-A			Uncertain significance (Jun 05, 2021)
19-33387371-G-A			Likely benign (Sep 01, 2023)
19-33387372-G-T		Inborn genetic diseases	Uncertain significance (Aug 19, 2022)
19-33387375-T-G			Uncertain significance (Mar 27, 2022)
19-33387384-C-A			Likely benign (Jan 29, 2024)
19-33387391-T-C			Uncertain significance (Feb 23, 2022)
19-33387393-C-T			Uncertain significance (Jun 09, 2023)
19-33387395-T-C			Likely benign (Nov 28, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PEPD	protein_coding	protein_coding	ENST00000244137	15	134845

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.46e-14	0.0483	124762	0	44	124806	0.000176

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.180	342	333	1.03	0.0000250	3198
Missense in Polyphen		116	116.56	0.9952		1055
Synonymous	0.262	133	137	0.971	0.0000116	963
Loss of Function	0.527	23	25.9	0.888	0.00000132	297

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000427	0.000403
Ashkenazi Jewish	0.00	0.00
East Asian	0.000178	0.000167
Finnish	0.00	0.00
European (Non-Finnish)	0.000149	0.000141
Middle Eastern	0.000178	0.000167
South Asian	0.000526	0.000523
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Splits dipeptides with a prolyl or hydroxyprolyl residue in the C-terminal position. Plays an important role in collagen metabolism because the high level of iminoacids in collagen.
• Disease: DISEASE: Prolidase deficiency (PD) [MIM:170100]: A multisystem disorder associated with massive iminodipeptiduria and lack of or reduced prolidase activity in erythrocytes, leukocytes, or cultured fibroblasts. Clinical features include skin ulcers, developmental delay, recurrent infections, and a characteristic facies. {ECO:0000269|PubMed:12384772, ECO:0000269|PubMed:2365824, ECO:0000269|PubMed:8198124, ECO:0000269|PubMed:8900231}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.498

Intolerance Scores

• loftool: 0.298
• rvis_EVS: -0.15
• rvis_percentile_EVS: 42.28

Haploinsufficiency Scores

• pHI: 0.166
• hipred: N
• hipred_score: 0.426
• ghis: 0.490

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.472

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pepd
• Phenotype: immune system phenotype; renal/urinary system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; pigmentation phenotype; embryo phenotype; homeostasis/metabolism phenotype; muscle phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; endocrine/exocrine gland phenotype

Zebrafish Information Network

• Gene name: pepd
• Affected structure: pancreatic B cell
• Phenotype tag: abnormal
• Phenotype quality: decreased area

Gene ontology

• Biological process: proteolysis;cellular amino acid metabolic process;collagen catabolic process
• Cellular component: nucleus;nucleoplasm;extracellular exosome
• Molecular function: aminopeptidase activity;metallocarboxypeptidase activity;protein binding;manganese ion binding;proline dipeptidase activity