PERP

p53 apoptosis effector related to PMP22

Basic information

Region (hg38): 6:138088505-138107419

Links

ENSG00000112378 ∙ NCBI:64065 ∙ OMIM:609301 ∙ HGNC:17637 ∙ Uniprot:Q96FX8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mutilating palmoplantar keratoderma with periorificial keratotic plaques (Supportive), mode of inheritance: AD
• Olmsted syndrome 2 (Strong), mode of inheritance: AD
• erythrokeratodermia variabilis et progressiva 7 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Olmsted syndrome 2; Erythrokeratodermia variabilis et progressiva 7	AD/AR	General	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	Dental; Dermatologic	30321533; 31361044; 31898316

ClinVar

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

• not provided (1 variants)
• Erythrokeratodermia variabilis et progressiva 7 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PERP 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					2	2
missense			8	1	2	11
nonsense						0
start loss						0
frameshift	1					1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	1	0	8	1	4

Highest pathogenic variant AF is 0.0000131

Variants in PERP

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

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

Position	Type	Phenotype	Significance	ClinVar
6-138092091-T-C		Inborn genetic diseases	Uncertain significance (Mar 30, 2024)
6-138092158-C-T		Erythrokeratodermia variabilis et progressiva 7	Pathogenic (Feb 25, 2021)
6-138092165-G-C		Olmsted syndrome 2	Pathogenic (Feb 25, 2021)
6-138092165-G-T		Olmsted syndrome 2	Pathogenic (Feb 25, 2021)
6-138092171-C-T		Olmsted syndrome 2	Pathogenic (Feb 25, 2021)
6-138092172-C-T		Olmsted syndrome 2	Pathogenic (Feb 25, 2021)
6-138092232-A-G		Inborn genetic diseases	Uncertain significance (Jun 10, 2022)
6-138092233-C-T		Inborn genetic diseases	Uncertain significance (Apr 17, 2023)
6-138092236-G-A		Inborn genetic diseases	Uncertain significance (Sep 16, 2021)
6-138096400-C-A		Inborn genetic diseases	Uncertain significance (Dec 21, 2022)
6-138096415-G-A			Benign (May 21, 2018)
6-138096471-T-C		Inborn genetic diseases	Uncertain significance (Oct 10, 2023)
6-138096479-G-A		Inborn genetic diseases	Uncertain significance (Feb 13, 2024)
6-138107131-C-G		Inborn genetic diseases	Uncertain significance (Apr 17, 2023)
6-138107166-C-T		PERP-related disorder	Likely benign (Mar 01, 2023)
6-138107216-C-A			Benign (Jul 18, 2018)
6-138107228-GA-G		Erythrokeratodermia variabilis et progressiva 7	Pathogenic (Nov 22, 2022)
6-138107241-C-T		Inborn genetic diseases	Uncertain significance (Aug 20, 2023)
6-138107242-G-A			Benign (Aug 15, 2018)
6-138107271-C-A			Benign (May 21, 2018)
6-138107289-G-T		Inborn genetic diseases	Uncertain significance (Jun 17, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PERP	protein_coding	protein_coding	ENST00000421351	3	19007

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0795	0.877	125741	0	7	125748	0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.463	98	112	0.877	0.00000540	1236
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000582	0.0000582
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000372	0.0000352
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

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}.
• Pathway: p53 signaling pathway - Homo sapiens (human);TP53 Regulates Transcription of Cell Death Genes;miRNA regulation of p53 pathway in prostate cancer;Keratinization;Developmental Biology;Gene expression (Transcription);Generic Transcription Pathway;TP53 Regulates Transcription of Cell Death Genes;RNA Polymerase II Transcription;TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain;Validated transcriptional targets of TAp63 isoforms;Transcriptional Regulation by TP53;Direct p53 effectors;Validated transcriptional targets of deltaNp63 isoforms;Formation of the cornified envelope (Consensus)

Recessive Scores

• pRec: 0.151

Intolerance Scores

• loftool: 0.266
• rvis_EVS: 0.57
• rvis_percentile_EVS: 81.99

Haploinsufficiency Scores

• pHI: 0.220
• hipred: Y
• hipred_score: 0.706
• ghis: 0.447

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.329

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Perp
• Phenotype: immune 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); hematopoietic system phenotype; 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); neoplasm; cellular 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); endocrine/exocrine gland phenotype

Zebrafish Information Network

• Gene name: perp
• Affected structure: pectoral fin
• Phenotype tag: abnormal
• Phenotype quality: malformed

Gene ontology

• Biological process: desmosome organization;Notch signaling pathway;heterotypic cell-cell adhesion;regulation of apoptotic process;positive regulation of proteolysis;cornification;intrinsic apoptotic signaling pathway by p53 class mediator;amelogenesis;activation of cysteine-type endopeptidase activity
• Cellular component: mitochondrion;Golgi apparatus;plasma membrane;integral component of plasma membrane;cell junction;desmosome