PEPD (peptidase D)

Gene

• Entrez ID: 5184
• Gene name: Peptidase D
• Gene symbol: PEPD
• Synonyms (NCBI Gene): PROLIDASE
• Chromosome: 19
• Chromosome location: 19q13.11
• Summary: This gene encodes a member of the peptidase family. The protein forms a homodimer that hydrolyzes dipeptides or tripeptides with C-terminal proline or hydroxyproline residues. The enzyme serves an important role in the recycling of proline, and may be rat

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs121917721	C>G,T	Pathogenic	Coding sequence variant, missense variant
rs121917722	C>T	Pathogenic	Intron variant, coding sequence variant, missense variant
rs121917723	C>T	Pathogenic	Coding sequence variant, missense variant
rs121917724	C>T	Pathogenic	Coding sequence variant, missense variant
rs121917725	G>A,C	Pathogenic	Coding sequence variant, missense variant, stop gained
rs200435937	C>T	Conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant
rs267606943	G>A	Pathogenic	Missense variant, coding sequence variant, intron variant
rs267606944	C>T	Pathogenic	Missense variant, coding sequence variant
rs529315200	C>T	Pathogenic-likely-pathogenic	Stop gained, coding sequence variant
rs542228812	C>A,T	Likely-pathogenic	Splice acceptor variant
rs745834191	TAG>-	Likely-pathogenic, pathogenic	Coding sequence variant, inframe deletion
rs747700126	C>A,G,T	Pathogenic	Coding sequence variant, intron variant, missense variant
rs757386104	CTC>-	Pathogenic	Coding sequence variant, inframe deletion
rs794728008	->TCACGGTGGGCCT	Pathogenic	Inframe insertion, intron variant, coding sequence variant, stop gained
rs797045185	A>C,G	Pathogenic	Missense variant, coding sequence variant
rs1204749077	C>T	Pathogenic	Intron variant, splice acceptor variant
rs1600069637	C>T	Likely-pathogenic	Splice acceptor variant
rs1600147235	G>-	Pathogenic	Frameshift variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT042567	hsa-miR-423-3p	CLASH	23622248
MIRT2065614	hsa-miR-4300	CLIP-seq
MIRT2065615	hsa-miR-548m	CLIP-seq
MIRT2065616	hsa-miR-920	CLIP-seq
MIRT2293430	hsa-miR-105	CLIP-seq
MIRT2293431	hsa-miR-518a-5p	CLIP-seq
MIRT2293432	hsa-miR-527	CLIP-seq
MIRT2687582	hsa-miR-1343	CLIP-seq
MIRT2687583	hsa-miR-3074-5p	CLIP-seq
MIRT2687584	hsa-miR-3124-3p	CLIP-seq
MIRT2687585	hsa-miR-3153	CLIP-seq
MIRT2687586	hsa-miR-361-5p	CLIP-seq
MIRT2687587	hsa-miR-4646-5p	CLIP-seq
MIRT2687588	hsa-miR-4668-5p	CLIP-seq
MIRT2687589	hsa-miR-548l	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004181	Function	Metallocarboxypeptidase activity	TAS	1972707
GO:0005515	Function	Protein binding	IPI	16713569, 21044950, 32814053
GO:0006508	Process	Proteolysis	IBA
GO:0006508	Process	Proteolysis	IDA	17081196
GO:0006508	Process	Proteolysis	IEA
GO:0006508	Process	Proteolysis	TAS	1972707
GO:0006520	Process	Amino acid metabolic process	TAS	1972707
GO:0008233	Function	Peptidase activity	IBA
GO:0008233	Function	Peptidase activity	IEA
GO:0008235	Function	Metalloexopeptidase activity	IEA
GO:0008237	Function	Metallopeptidase activity	IEA
GO:0016787	Function	Hydrolase activity	IEA
GO:0016805	Function	Dipeptidase activity	IEA
GO:0030145	Function	Manganese ion binding	IEA
GO:0030574	Process	Collagen catabolic process	IEA
GO:0043069	Process	Negative regulation of programmed cell death	IDA	35165443
GO:0046872	Function	Metal ion binding	IEA
GO:0070006	Function	Metalloaminopeptidase activity	IEA
GO:0070062	Component	Extracellular exosome	HDA	19056867, 23533145
GO:0102009	Function	Proline dipeptidase activity	IDA	17081196, 35165443
GO:0102009	Function	Proline dipeptidase activity	IEA
GO:0140633	Process	CARD8 inflammasome complex assembly	IDA	33053349

Other IDs

• MIM: 613230
• HGNC: 8840
• e!Ensembl: ENSG00000124299

Protein

• UniProt ID: P12955
• Protein name: Xaa-Pro dipeptidase (X-Pro dipeptidase) (EC 3.4.13.9) (Imidodipeptidase) (Peptidase D) (Proline dipeptidase) (Prolidase)
• Protein function: Dipeptidase that catalyzes the hydrolysis of dipeptides with a prolyl (Xaa-Pro) or hydroxyprolyl residue in the C-terminal position (PubMed:17081196, PubMed:35165443). The preferred dipeptide substrate is Gly-Pro, but other Xaa-Pro dipeptides, s
• PDB: 2IW2, 2OKN, 5M4G, 5M4J, 5M4L, 5M4Q, 5MBY, 5MBZ, 5MC0, 5MC1, 5MC2, 5MC3, 5MC4, 5MC5, 6H2P, 6H2Q, 6QSB, 6QSC, 6SRE, 6SRF, 6SRG
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF05195	AMP_N	23 → 144	Aminopeptidase P, N-terminal domain	Domain
  PF00557	Peptidase_M24	193 → 459	Metallopeptidase family M24	Domain

• Sequence:

  MAAATGPSFWLGNETLKVPLALFALNRQRLCERLRKNPAVQAGSIVVLQGGEETQRYCTD
  TGVLFRQESFFHWAFGVTEPGCYGVIDVDTGKSTLFVPRLPASHATWMGKIHSKEHFKEK
  YAVDDVQYVDEIASVLTSQKPSVLLTLRGVNTDSGSVCREASFDGISKFEVNNTILHPEI
  VECRVFKTDMELEVLRYTNKISSEAHREVMKAVKVGMKEYELESLFEHYCYSRGGMRHSS
  YTCICGSGENSAVLHYGHAGAPNDRTIQNGDMCLFDMGGEYYCFASDITCSFPANGKFTA
  DQKAVYEAVLRSSRAVMGAMKPGVWWPDMHRLADRIHLEELAHMGILSGSVDAMVQAHLG
  AVFMPHGLGHFLGIDVHDVGGYPEGVERIDEPGLRSLRTARHLQPGMVLTVEPGIYFIDH
  LLDEALADPARASFLNREVLQRFRGFGGVRIEEDVVVTDSGIELLTCVPRTVEEIEACMA
  GCDKAFTPFSGPK

• Sequence length: 493

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Megaconial type congenital muscular dystrophy	Likely pathogenic; Pathogenic	rs750548522	RCV004785314	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Melanoma	Likely pathogenic	rs121917722	RCV005887120	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Nonpapillary renal cell carcinoma	Likely pathogenic; Pathogenic	rs542228812	RCV005912185	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
PEPD-related disorder	Likely pathogenic; Pathogenic	rs2513410026, rs745834191	RCV003404248 RCV004754394	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Prolidase deficiency	Pathogenic; Likely pathogenic	rs764650519, rs1204749077, rs1170952773, rs750548522, rs375391662, rs1305209476, rs121917721, rs121917722, rs121917723, rs121917724, rs121917725, rs267606944, rs794728008, rs267606943, rs797045185, rs747700126, rs907881705, rs745834191, rs542228812, rs1600147235	RCV001730007 RCV001730008 RCV001782595 RCV001794936 RCV002497819 RCV005023444 RCV003448442 RCV000000232 RCV000000235 RCV000000236 RCV000000237 RCV000000239 RCV000000240 RCV000000241 RCV000000242 RCV000194259 RCV000195145 RCV005208215 RCV000273249 RCV000991408 RCV000995831 RCV000995832	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Thyroid cancer, nonmedullary, 1	Pathogenic; Likely pathogenic	rs542228812, rs2513508907	RCV005931427 RCV005931655 RCV005912186	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ANDROGENETIC ALOPECIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CATARACT	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHRONIC SKIN ULCER	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEFICIENCY OF PROLIDASE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DIABETES MELLITUS, NON-INSULIN-DEPENDENT	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DIABETES MELLITUS, TYPE 2	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GESTATIONAL DIABETES	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEPATOMEGALY	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPERTENSION	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
METABOLIC SYNDROME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PSORIASIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
RESPIRATORY TRACT DISEASES	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCHIZOPHRENIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SKIN ULCER	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SPLENOMEGALY	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 2 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
VENOUS THROMBOEMBOLISM	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Anemia	Anemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Aortic Aneurysm Abdominal	Aortic aneurysm	Pubtator	21247474	Associate	★☆☆☆☆ Found in Text Mining only
Aortic Aneurysm, Abdominal	Aortic Aneurysm	BEFREE	21247474		★☆☆☆☆ Found in Text Mining only
Arachnodactyly	Arachnodactyly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Arthritis Rheumatoid	Rheumatoid arthritis	Pubtator	32013628	Associate	★☆☆☆☆ Found in Text Mining only
Asthma	Asthma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Atrial Fibrillation	Atrial Fibrillation	LHGDN	18514097		★☆☆☆☆ Found in Text Mining only
Bipolar Disorder	Bipolar disorder	Pubtator	29930383	Associate	★☆☆☆☆ Found in Text Mining only
Blepharoptosis	Ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	16875494, 18443378, 23549681, 32918543	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	26078578	Associate	★☆☆☆☆ Found in Text Mining only
Cardiovascular Diseases	Cardiovascular Diseases	BEFREE	31739742		★☆☆☆☆ Found in Text Mining only
Cardiovascular Diseases	Cardiovascular disease	Pubtator	31739742	Stimulate	★☆☆☆☆ Found in Text Mining only
Chronic lung disease	Lung Diseases	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cognition Disorders	Cognitive disorder	BEFREE	26198764		★☆☆☆☆ Found in Text Mining only
Colitis	Colitis	BEFREE	28323866		★☆☆☆☆ Found in Text Mining only
Connective Tissue Diseases	Connective tissue disease	Pubtator	38088248	Associate	★☆☆☆☆ Found in Text Mining only
Coronary Artery Disease	Coronary artery disease	LHGDN	18607169		★☆☆☆☆ Found in Text Mining only
Crusting erythematous dermatitis	Crusting erythematous dermatitis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Deficiency of prolidase	Deficiency Of Prolidase	CLINVAR_DG	12384772, 15309682, 17142620, 19308961, 23516557, 28062424, 8198124, 8900231		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Deficiency of prolidase	Deficiency Of Prolidase	UNIPROT_DG	12384772, 2365824, 8198124, 8900231		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Deficiency of prolidase	Deficiency Of Prolidase	GENOMICS_ENGLAND_DG	15309682, 16470701, 19308961		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Deficiency of prolidase	Deficiency Of Prolidase	BEFREE	16470701, 16681595, 17142620, 18000661, 2010534, 23287645		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Deficiency of prolidase	Deficiency Of Prolidase	CTD_human_DG	16470701, 1972707		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Deficiency of prolidase	Deficiency Of Prolidase	ORPHANET_DG	18340504		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Diabetes Mellitus	Diabetes mellitus	Pubtator	35320353	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus Type 2	Diabetes mellitus, type 2	Pubtator	19401414, 24086726, 31739742	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	BEFREE	22158537, 26087900, 31145772		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	CTD_human_DG	22158537		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	GWASDB_DG	22158537		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	GWASCAT_DG	22158537, 30718926		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Erectile Dysfunction	Erectile dysfunction	Pubtator	29930383	Associate	★☆☆☆☆ Found in Text Mining only
Exophthalmos	Proptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Familial Mediterranean Fever	Familial mediterranean fever	Pubtator	31846428	Associate	★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	BEFREE	26198764		★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Immune System Diseases	Immune system disease	Pubtator	26159719	Associate	★☆☆☆☆ Found in Text Mining only
Impaired cognition	Impaired Cognition	BEFREE	26198764		★☆☆☆☆ Found in Text Mining only
Inflammatory Bowel Diseases	Inflammatory Bowel Disease	BEFREE	28323866		★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Intellectual developmental disorder	Pubtator	18806117, 8198124	Associate	★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Irritable Bowel Syndrome	Irritable Bowel Syndrome	BEFREE	28323866		★☆☆☆☆ Found in Text Mining only
Keratoderma, Palmoplantar	Palmoplantar keratoderma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Lung Neoplasms	Lung neoplasms	Pubtator	11168680	Associate	★☆☆☆☆ Found in Text Mining only
Lupus Erythematosus, Systemic	Lupus Erythematosus	LHGDN	17570078		★☆☆☆☆ Found in Text Mining only
Lupus Erythematosus, Systemic	Lupus Erythematosus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	17377743		★☆☆☆☆ Found in Text Mining only
Mammary Neoplasms	Mammary Neoplasms	LHGDN	17999410		★☆☆☆☆ Found in Text Mining only
melanoma	Melanoma	LHGDN	17377743		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Micrognathism	Micrognathism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Mitral Valve Stenosis	Mitral Valve Stenosis	LHGDN	18514097		★☆☆☆☆ Found in Text Mining only
Myotonic Dystrophy	Myotonic dystrophy	BEFREE	6881909		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	29233996		★☆☆☆☆ Found in Text Mining only
Osteoarthritis	Osteoarthritis	Pubtator	34477138	Inhibit	★☆☆☆☆ Found in Text Mining only
Osteoarthritis Knee	Osteoarthritis	Pubtator	27777643, 34477138	Associate	★☆☆☆☆ Found in Text Mining only
Osteoarthritis, Knee	Knee osteoarthritis	LHGDN	17096092		★☆☆☆☆ Found in Text Mining only
Osteogenesis Imperfecta	Osteogenesis imperfecta	Pubtator	11277941	Associate	★☆☆☆☆ Found in Text Mining only
Panic Disorder	Panic Disorder	GWASDB_DG	19165232		★☆☆☆☆ Found in Text Mining only
Prolidase Deficiency	Prolidase deficiency	Pubtator	1688567, 30066404	Inhibit	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Prolidase Deficiency	Prolidase deficiency	Pubtator	17142620, 2010534, 37023562, 38088248, 8198124	Associate	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Prolidase deficiency	Prolidase deficiency	Orphanet			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Prostatic Hyperplasia	Prostatic hyperplasia	Pubtator	25551736	Associate	★☆☆☆☆ Found in Text Mining only
Ptosis	Ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Pulmonary Disease Chronic Obstructive	Chronic obstructive pulmonary disease	Pubtator	37447386	Associate	★☆☆☆☆ Found in Text Mining only
Recurrent aphthous ulcer	Aphthous Ulcer	BEFREE	31249217		★☆☆☆☆ Found in Text Mining only
Recurrent cystitis	Cystitis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Respiratory Tract Diseases	Respiratory Tract Diseases	CTD_human_DG	16470701		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Schizophrenia	Schizophrenia	GWASCAT_DG	26198764		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Schizophrenia	Schizophrenia	Pubtator	32065947	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sjogren's Syndrome	Sjogren syndrome	Pubtator	38088248	Associate	★☆☆☆☆ Found in Text Mining only
Skin Ulcer	Skin ulcer	Pubtator	18806117, 8198124	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Varicosity	Vulval varices	BEFREE	29216795		★☆☆☆☆ Found in Text Mining only
Venous Insufficiency	Venous Insufficiency	BEFREE	29216795		★☆☆☆☆ Found in Text Mining only