PREP

protein-coding

prolyl endopeptidase

Gene summary

The protein encoded by this gene is a cytosolic prolyl endopeptidase that cleaves peptide bonds on the C-terminal side of prolyl residues within peptides that are up to approximately 30 amino acids long. Prolyl endopeptidases have been reported to be involved in the maturation and degradation of peptide hormones and neuropeptides. [provided by RefSeq, Jul 2008]

MANE transcript

NM_002726.5

Inheritance

—

ClinVar variants

P:2U:86B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.26

Max pathogenic AF

—

Genomic locus

chr6:105,273,218-105,454,062

External References & Databases

Ensembl (ENSG00000085377)

Transcript & Mutation Effects

hg38 • Region Span ~180.8 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 PREP variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 81

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002726.5. 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			1 clinvar		1 clinvar	2
missense			81 clinvar	2 clinvar		83
nonsense			2 clinvar			2
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)	1 clinvar		2 clinvar			3
Total	2	0	86	2	1	91

Highest pathogenic variant AF is 0.0000027364385

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 30 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002726.5	RefSeq	NP_002717.3	15	MANE Select
ENST00000652536.2	Ensembl	ENSP00000499089.1	15	MANE Select
ENST00000369110.8	Ensembl	ENSP00000358106.4	13	Standard
ENST00000369110.9	Ensembl	ENSP00000358106.4	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Renin-angiotensin system - Homo sapiens (human)

Biological Process

proteolysis

Molecular Function

endopeptidase activity
serine-type endopeptidase activity
protein binding
serine-type peptidase activity
serine-type exopeptidase activity

Cellular Component

nucleus
cytoplasm
cytosol
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000369110
Coding exons: 15
Length: 125520
Individuals with no LoFs: 125709
Homozygous LoFs: 0
Heterozygous LoFs: 39
Defined: 125748
p: 0.000155

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.27	277	406	0.683	0.0000220	4695
Missense (PolyPhen)		47	123.97	0.37913		1450
Synonymous	-0.392	166	160	1.04	0.00000996	1294
Loss of Function	4.31	10	39.1	0.256	0.00000200	461

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.00029	0.00029	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00022	0.00022	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00016	0.00016	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Cleaves peptide bonds on the C-terminal side of prolyl residues within peptides that are up to approximately 30 amino acids long.;

Recessive Scores

pRec: 0.389

Intolerance Scores

LoFtool: 0.473
RVIS EVS: -1
RVIS percentile EVS: 8.47

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.403

Gene Damage Prediction

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