PERP

protein-coding

p53 apoptosis effector related to PMP22

Gene summary

Involved in positive regulation of neutrophil chemotaxis and positive regulation of proteolysis. Predicted to be located in desmosome and plasma membrane. Predicted to be active in cell-cell junction. Implicated in erythrokeratodermia variabilis and mutilating palmoplantar keratoderma with periorificial keratotic plaques. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_022121.5

Inheritance

AR, AD

ClinVar variants

P:6U:20B:6

Top phenotype

Olmsted syndrome 2; Erythrokeratodermia variabilis et progressiva 7

gnomAD constraint

pLI —, LoF o/e 0.36

Max pathogenic AF

—

Genomic locus

chr6:138,088,505-138,107,419

External References & Databases

Ensembl (ENSG00000112378)

Transcript & Mutation Effects

hg38 • Region Span ~18.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

erythrokeratodermia variabilis et progressiva 7MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0030941

Submitter: G2P

mutilating palmoplantar keratoderma with periorificial keratotic plaquesSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0019014

Submitter: Orphanet

erythrokeratodermia variabilis et progressiva 7STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030941

Submitter: Labcorp Genetics (formerly Invitae)

Olmsted syndrome 2STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0030961

Submitter: G2P

Olmsted syndrome 2MODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0030961

Submitter: Ambry Genetics

erythrokeratodermia variabilis et progressiva 7STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0030941

Submitter: PanelApp Australia

Olmsted syndrome 2STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0030961

Submitter: Labcorp Genetics (formerly Invitae)

erythrokeratodermia variabilis et progressiva 7MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0030941

Submitter: Ambry Genetics

Olmsted syndrome 2STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030961

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Olmsted syndrome 2; Erythrokeratodermia variabilis et progressiva 7AD/AR

Manifestation: Dental; Dermatologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 30321533; 31361044; 31898316

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PERP variants in ClinVar

6 Conditions Cataloged

Inborn genetic diseasesTotal: 20

not providedTotal: 7

Olmsted syndrome 2Total: 4

Erythrokeratodermia variabilis et progressiva 7Total: 2

PERP-related disorderTotal: 1

not specifiedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_022121.5. 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	2 clinvar	3
missense	1 clinvar		20 clinvar	1 clinvar	2 clinvar	24
nonsense	3 clinvar	1 clinvar				4
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)						0
Total	5	1	20	2	4	32

Highest pathogenic variant AF is 0.0000031011252

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 5 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_022121.5	RefSeq	NP_071404.2	3	MANE Select
ENST00000421351.4	Ensembl	ENSP00000397157.2	3	MANE Select
ENST00001101667.1	Ensembl	ENSP00000771473.1	3	Standard
ENST00001114423.1	Ensembl	ENSP00000784228.1	4	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
perp	Danio rerio	Structure: pectoral fin Quality: malformed abnormal

Gene / Model

Organism

Observed Phenotype

perp

Danio rerio

Structure: pectoral fin

Quality: malformed

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

p53 signaling pathway - Homo sapiens (human)
TP53 Regulates Transcription of Cell Death Genes
miRNA regulation of p53 pathway in prostate cancer
Keratinization
Developmental Biology

Biological Process

desmosome organization
Notch signaling pathway
heterotypic cell-cell adhesion
regulation of apoptotic process
positive regulation of proteolysis

Cellular Component

mitochondrion
Golgi apparatus
plasma membrane
integral component of plasma membrane
cell junction

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000421351
Coding exons: 3
Length: 19007
Individuals with no LoFs: 125741
Homozygous LoFs: 0
Heterozygous LoFs: 7
Defined: 125748
p: 0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.463	98	112	0.877	0.00000540	1236
Missense (PolyPhen)		26	34.646	0.75044		412
Synonymous	0.790	42	49.0	0.857	0.00000264	387
Loss of Function	1.72	3	8.36	0.359	3.60e-7	81

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000037	0.000035	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of intercellular desmosome junctions. Plays a role in stratified epithelial integrity and cell-cell adhesion by promoting desmosome assembly. Plays a role as an effector in the TP53-dependent apoptotic pathway (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.151

Intolerance Scores

LoFtool: 0.266
RVIS EVS: 0.57
RVIS percentile EVS: 81.99

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.329

Gene Damage Prediction

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