PGPEP1

protein-coding

pyroglutamyl-peptidase I

Gene summary

The gene encodes a cysteine protease and member of the peptidase C15 family of proteins. The encoded protein cleaves amino terminal pyroglutamate residues from protein substrates including thyrotropin-releasing hormone and other neuropeptides. Expression of this gene may be downregulated in colorectal cancer, while activity of the encoded protein may be negatively correlated with cancer progression in colorectal cancer patients. Activity of the encoded protease may also be altered in other disease states including in liver cirrhosis, which is associated with reduced protease activity, and in necrozoospermia, which is associated with elevated protease activity. [provided by RefSeq, Jul 2016]

MANE transcript

NM_017712.4

Inheritance

—

ClinVar variants

U:35

Top phenotype

Prostate cancer

gnomAD constraint

pLI —, LoF o/e 0.45

Max pathogenic AF

—

Genomic locus

chr19:18,340,598-18,369,950

External References & Databases

Ensembl (ENSG00000130517)

Transcript & Mutation Effects

hg38 • Region Span ~29.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PGPEP1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 31

Prostate cancerTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017712.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense			33 clinvar			33
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	35	0	0	35

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 33 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_017712.4	RefSeq	NP_060182.1	5	MANE Select
ENST00000269919.11	Ensembl	ENSP00000269919.3	5	MANE Select
NM_001300927.2	RefSeq	NP_001287856.1	4	Standard
NM_001308366.2	RefSeq	NP_001295295.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

proteolysis

Molecular Function

cysteine-type peptidase activity
pyroglutamyl-peptidase activity

Cellular Component

cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000269919
Coding exons: 5
Length: 29364
Individuals with no LoFs: 125729
Homozygous LoFs: 0
Heterozygous LoFs: 18
Defined: 125747
p: 0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.354	116	127	0.912	0.00000750	1341
Missense (PolyPhen)		27	37.691	0.71635		388
Synonymous	-0.565	67	61.4	1.09	0.00000466	404
Loss of Function	1.68	5	11.0	0.454	6.20e-7	110

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00017	0.00017	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000053	0.000053	rare
South Asian	0.00020	0.00020	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Removes 5-oxoproline from various penultimate amino acid residues except L-proline. {ECO:0000269|PubMed:12651114}.;

Recessive Scores

pRec: 0.219

Intolerance Scores

LoFtool: 0.574
RVIS EVS: -0.21
RVIS percentile EVS: 38.58

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.508

Gene Damage Prediction

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