PERP

Summary

PERP (p53 apoptosis effector related to PMP22, HGNC:17637) is a protein-coding gene on chromosome 6q23.3, encoding p53 apoptosis effector related to PMP-22 (Q96FX8). Component of intercellular desmosome junctions.

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.

Source: NCBI Gene 64065 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Olmsted syndrome 2 (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 32 total — 6 pathogenic
• Phenotypes (HPO): 37
• MANE Select transcript: NM_022121

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17637
Approved symbol	PERP
Name	p53 apoptosis effector related to PMP22
Location	6q23.3
Locus type	gene with protein product
Status	Approved
Aliases	PIGPC1, dJ496H19.1, KCP1, THW, KRTCAP1
Ensembl gene	ENSG00000112378
Ensembl biotype	protein_coding
OMIM	609301
Entrez	64065

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000421351

RefSeq mRNA: 1 — MANE Select: NM_022121 NM_022121

CCDS: CCDS5188

Canonical transcript exons

ENST00000421351 — 3 exons

Exon	Start	End
ENSE00000764553	138096354	138096494
ENSE00000798930	138107127	138107419
ENSE00001815595	138088505	138092268

Expression profiles

Bgee: expression breadth ubiquitous, 277 present calls, max score 99.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 167.9796 / max 9535.4168, expressed in 1651 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
75898	99.8683	1511
75899	63.6794	1608
75900	3.1578	1261
75897	0.4293	221
75896	0.3197	162
75901	0.2200	100
75902	0.1377	57
75903	0.0952	30
75895	0.0499	16
75904	0.0224	4

Top tissues by expression

288 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
penis	UBERON:0000989	99.96	gold quality
upper leg skin	UBERON:0004262	99.95	gold quality
pharyngeal mucosa	UBERON:0000355	99.94	gold quality
esophagus squamous epithelium	UBERON:0006920	99.94	gold quality
skin of hip	UBERON:0001554	99.92	gold quality
nipple	UBERON:0002030	99.92	gold quality
mammalian vulva	UBERON:0000997	99.90	gold quality
oral cavity	UBERON:0000167	99.87	gold quality
gingival epithelium	UBERON:0001949	99.87	gold quality
gingiva	UBERON:0001828	99.86	gold quality
body of tongue	UBERON:0011876	99.86	gold quality
epithelium of nasopharynx	UBERON:0001951	99.85	gold quality
tongue	UBERON:0001723	99.82	gold quality
amniotic fluid	UBERON:0000173	99.81	gold quality
upper arm skin	UBERON:0004263	99.80	gold quality
superior surface of tongue	UBERON:0007371	99.77	gold quality
bronchial epithelial cell	CL:0002328	99.74	gold quality
epithelium of esophagus	UBERON:0001976	99.74	gold quality
squamous epithelium	UBERON:0006914	99.71	gold quality
parotid gland	UBERON:0001831	99.70	gold quality
urethra	UBERON:0000057	99.66	gold quality
skin of abdomen	UBERON:0001416	99.64	gold quality
zone of skin	UBERON:0000014	99.57	gold quality
trachea	UBERON:0003126	99.54	gold quality
tongue squamous epithelium	UBERON:0006919	99.53	gold quality
skin of leg	UBERON:0001511	99.52	gold quality
esophagus mucosa	UBERON:0002469	99.49	gold quality
lower esophagus mucosa	UBERON:0035834	99.49	gold quality
palpebral conjunctiva	UBERON:0001812	99.35	gold quality
nasal cavity mucosa	UBERON:0001826	99.34	gold quality

Single-cell (SCXA)

Detected in 31 experiment(s), a significant marker in 25.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	5819.38
E-MTAB-10855	yes	4560.22
E-HCAD-1	yes	3363.63
E-MTAB-8221	yes	1995.74
E-MTAB-6308	yes	1912.27
E-MTAB-7008	yes	1345.60
E-HCAD-15	yes	1010.05
E-MTAB-7407	yes	790.07
E-MTAB-9154	yes	618.02
E-ANND-5	yes	603.45
E-HCAD-56	yes	356.45
E-MTAB-10662	yes	276.78
E-MTAB-6701	yes	131.94
E-MTAB-8410	yes	54.05
E-MTAB-10287	yes	47.66

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ETS1, SATB2, TP53, TP63

miRNA regulators (miRDB)

157 targeting PERP, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-218-5P	99.93	72.22	2103

Literature-anchored findings (GeneRIF, showing 20)

• A paper describing the identification of Perp (p53 Apoptosis Effector Related to PMP22). Perp was found as a novel target gene of the p53 tumor suppressor, which is selectively induced during apoptosis compared to cell cycle arrest. (PMID:10733530)
• findings underline the apoptotic pathway mediated by PERP as a critical mechanism employed by uveal melanoma tumours to modulate susceptibility to apoptosis (PMID:19040420)
• pemphigus vulgaris autoantibodies disrupt Perp expression at the membrane and trigger its internalization along with DSG3 into the endosomal pathway, where it is ultimately targeted to the lysosome for degradation (PMID:19158843)
• We demonstrate here that PERP induction is in fact compromised with some, but not all, Ankyloblepharon Ectodermal Dysplasia and Cleft Lip/Palate, AEC-patient derived TP63 mutants. (PMID:19353588)
• Data suggest a temporal sequence whereby PERP loss occurs before E-cadherin loss in the progression of human SCC. (PMID:20975948)
• Our comprehensive mutation scanning did not identify any Arrhythmogenic right ventricular cardiomyopathy (ARVC) causing mutations. (PMID:21254927)
• PERP expression stabilizes active p53 via modulation of p53-MDM2 interaction in uveal melanoma cells. (PMID:21451571)
• Perp expression is reduced in human breast cancer cell lines (PMID:22515648)
• Decreased PERP expression on peripheral blood mononuclear cells from patient with rheumatoid arthritis negatively correlates with disease activity. (PMID:24066004)
• The authors identified the tetraspanning membrane protein, p53 effector related to PMP-22 (PERP), as a Salmonella typhimurium SipA binding partner. (PMID:25486861)
• Salmonella Typhimurium type III secreted effector SipC significantly contributes to PERP redistribution to the apical membrane surface. (PMID:27078059)
• Expression of p63-tGFP induces apoptosis with marked increase in PERP expression and associated p53 accumulation. Lack of p63 contributes to reduced PERP levels and impaired p53-mediated apoptosis in UM. (PMID:27584665)
• Downregulation of desmosomal formation transcripts including PERP may contribute to the aggressive phenotype seen in sparsely granulated GH pituitary tumors and their behavior in response to surgery and medical therapy. (PMID:28323918)
• Study shows that mutations in PERP, encoding a crucial component of desmosomes, cause both dominant and recessive human keratoderma. Heterozygosity for a C-terminal truncation, which produces a protein that appears to be unstably incorporated into desmosomes, causes Olmsted syndrome with severe periorificial and palmoplantar keratoderma in multiple unrelated kindreds. (PMID:30321533)
• MiR-629 regulates hypoxic pulmonary vascular remodelling by targeting FOXO3 and PERP. (PMID:31240850)
• Confirming the recessive inheritance of PERP-related erythrokeratoderma. (PMID:31898316)
• increased level of IL 17 and decreased level of PERP may constitute two major factors in the pathogenesis and activity of rheumatoid arthritis (PMID:31926492)
• Upregulation of METTL14 mediates the elevation of PERP mRNA N(6) adenosine methylation promoting the growth and metastasis of pancreatic cancer. (PMID:32843065)
• Pilot study of loss of the p53/p63 target gene PERP at the surgical margin as a potential predictor of local relapse in head and neck squamous cell carcinoma. (PMID:33034918)
• Ichthyosis, psoriasiform dermatitis, and recurrent fungal infections in patients with biallelic mutations in PERP. (PMID:34863005)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	perp	ENSDARG00000063572
mus_musculus	Perp	ENSMUSG00000019851
rattus_norvegicus	Perp	ENSRNOG00000011994
drosophila_melanogaster	CG45049	FBGN0266409
caenorhabditis_elegans		WBGENE00006875

Paralogs (1): TMEM47 (ENSG00000147027)

Protein

Protein identifiers

p53 apoptosis effector related to PMP-22 — Q96FX8 (reviewed: Q96FX8)

Alternative names: Keratinocyte-associated protein 1, P53-induced protein PIGPC1, Transmembrane protein THW

All UniProt accessions (1): Q96FX8

UniProt curated annotations — full annotation on UniProt →

Function. Component of intercellular desmosome junctions. Plays a role in stratified epithelial integrity and cell-cell adhesion by promoting desmosome assembly. Thereby plays a role in barrier function of the skin against infection. Plays a role in mammary epithelial tissue homeostasis and remodeling during and after pregnancy, potentially via its involvement in desmosome cell-cell junctions. Required for tooth enamel development via facilitating desmosome-mediated ameloblast adhesion to the stratum intermedium during the transitional stage of amelogenesis. May also play a role in downstream transcriptional regulation of other genes involved in amelogenesis such as AMBN, ENAM, MMP20 and KLK4. Plays a role as an effector in the TP53-dependent apoptotic pathway. Positively regulates apoptosis in T-helper 17 (Th17) cell populations via caspase-dependent signaling. Promotes neutrophil transepithelial migration in response to chemoattractants such as hepoxilin A3 (HXA3), N-Formylmethionyl-leucyl-phenylalanine (fMLP) and CXCL8/IL-8. Required for neutrophil transepithelial migration in response to S.typhimurium infection. May act as a positive regulator of endothelial cell apoptosis in response to blood flow-derived shear stress.

Subunit / interactions. (Microbial infection) Interacts with S.typhimurium sipA and sctB1/sipC.

Subcellular location. Cell junction. Desmosome. Cell membrane. Cytoplasm.

Tissue specificity. Expressed in skin, heart, placental, liver, pancreas, keratinocytes and dermal fibroblasts. May translocate to the intestinal apical epithelial cell surface via sipA and sctB1/sipC-promoted exocytic translocation following infection by S. Typhimurium.

Disease relevance. Erythrokeratodermia variabilis et progressiva 7 (EKVP7) [MIM:619209] A form of erythrokeratodermia variabilis et progressiva, a genodermatosis characterized by the coexistence of two independent skin lesions: transient erythema and hyperkeratosis that is usually localized but occasionally occurs in its generalized form. Clinical presentation varies significantly within a family and from one family to another. Palmoplantar keratoderma is present in around 50% of cases. EKVP7 is an autosomal recessive form characterized by palmoplantar keratoderma that extends to the dorsal surface of the hands and feet, as well as erythematous annular skin lesions. Pruritus, woolly hair, and dystrophic nails may also be present. The disease is caused by variants affecting the gene represented in this entry. Olmsted syndrome 2 (OLMS2) [MIM:619208] A form of Olmsted syndrome, a rare congenital disorder characterized by bilateral mutilating palmoplantar keratoderma and periorificial keratotic plaques with severe itching at all lesions. Diffuse alopecia, constriction of digits, and onychodystrophy have also been reported. Infections and squamous cell carcinomas can arise on the keratotic areas. The digital constriction may progress to autoamputation of fingers and toes. OLMS2 is an autosomal dominant form with onset in the first months of life or in early childhood. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the TMEM47 family.

RefSeq proteins (1): NP_071404* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004031	PMP22/EMP/MP20/Claudin	Family
IPR015664	P53_induced	Family

Pfam: PF00822

UniProt features (13 total): sequence variant 5, transmembrane region 4, sequence conflict 3, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96FX8-F1	82.59	0.41

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-6803205	TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain
R-HSA-6809371	Formation of the cornified envelope

MSigDB gene sets: 383 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, BEGUM_TARGETS_OF_PAX3_FOXO1_FUSION_UP, GOBP_POSITIVE_REGULATION_OF_LYMPHOCYTE_APOPTOTIC_PROCESS, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_MAMMARY_GLAND_MORPHOGENESIS, GOBP_GLAND_MORPHOGENESIS, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, GOBP_POSITIVE_REGULATION_OF_LEUKOCYTE_APOPTOTIC_PROCESS, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, GOBP_REGULATION_OF_LEUKOCYTE_APOPTOTIC_PROCESS, JAEGER_METASTASIS_DN, GOBP_MAMMARY_GLAND_EPITHELIUM_DEVELOPMENT, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP

GO Biological Process (13): tissue homeostasis (GO:0001894), desmosome organization (GO:0002934), Notch signaling pathway (GO:0007219), heterotypic cell-cell adhesion (GO:0034113), positive regulation of proteolysis (GO:0045862), mammary gland duct morphogenesis (GO:0060603), positive regulation of T cell apoptotic process (GO:0070234), intrinsic apoptotic signaling pathway by p53 class mediator (GO:0072332), positive regulation of neutrophil chemotaxis (GO:0090023), amelogenesis (GO:0097186), cell-cell adhesion (GO:0098609), apoptotic process (GO:0006915), cell adhesion (GO:0007155)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (8): mitochondrion (GO:0005739), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), cell-cell junction (GO:0005911), desmosome (GO:0030057), cytoplasm (GO:0005737), membrane (GO:0016020), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
TP53 Regulates Transcription of Cell Death Genes	1
Keratinization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	2
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
multicellular organismal-level homeostasis	1
anatomical structure homeostasis	1
cell-cell junction organization	1
cell surface receptor signaling pathway	1
cell-cell adhesion	1
proteolysis	1
regulation of proteolysis	1
positive regulation of protein metabolic process	1
mammary gland morphogenesis	1
epithelial tube morphogenesis	1
mammary gland epithelium development	1
positive regulation of lymphocyte apoptotic process	1
T cell apoptotic process	1
regulation of T cell apoptotic process	1
signal transduction by p53 class mediator	1
intrinsic apoptotic signaling pathway	1
neutrophil chemotaxis	1
positive regulation of granulocyte chemotaxis	1
regulation of neutrophil chemotaxis	1
positive regulation of neutrophil migration	1
odontogenesis of dentin-containing tooth	1
anatomical structure formation involved in morphogenesis	1
cell adhesion	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cellular process	1
binding	1
endomembrane system	1
membrane	1
cell periphery	1
anchoring junction	1
cell-cell junction	1
intracellular anatomical structure	1
cell junction	1

Protein interactions and networks

STRING

1196 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PERP	TP63	Q9H3D4	716
PERP	TP53	P04637	710
PERP	PMAIP1	Q13794	601
PERP	DSC3	Q14574	598
PERP	PKP1	Q13835	574
PERP	TNFRSF10B	O14763	552
PERP	DSG1	Q02413	533
PERP	PKP3	Q9Y446	526
PERP	ZMAT3	Q9HA38	482
PERP	DSP	P15924	465
PERP	MDM2	Q00987	454
PERP	PIDD1	Q9HB75	449
PERP	SHISA5	Q8N114	433
PERP	GJA1	P17302	432
PERP	CCNG1	P51959	432

IntAct

25 interactions, top by confidence:

A	B	Type	Score
ABHD16A	PERP	psi-mi:“MI:0915”(physical association)	0.560
MAL	PERP	psi-mi:“MI:0915”(physical association)	0.560
PERP	GFAP	psi-mi:“MI:0915”(physical association)	0.560
GRN	PERP	psi-mi:“MI:0915”(physical association)	0.560
PERP	HSPB1	psi-mi:“MI:0915”(physical association)	0.560
PERP	WFS1	psi-mi:“MI:0915”(physical association)	0.560
PERP	KIF1B	psi-mi:“MI:0915”(physical association)	0.560
PERP	JPH3	psi-mi:“MI:0915”(physical association)	0.560
PERP	ABHD16A	psi-mi:“MI:0915”(physical association)	0.000
MAL	PERP	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (7): PERP (Affinity Capture-RNA), MAL (Two-hybrid), ABHD16A (Two-hybrid), PERP (Affinity Capture-Western), PERP (Affinity Capture-Western), DDB1 (Affinity Capture-Western), PERP (Affinity Capture-RNA)

ESM2 similar proteins: A0A1D5NY17, A4IF75, B2RVY9, B3SHH9, F6V1J6, O42281, O70578, P19518, P97707, Q06432, Q08CE6, Q08DE1, Q0D289, Q0V9E0, Q14714, Q2MJQ7, Q4R4Z3, Q4V922, Q5CZV0, Q5PRC1, Q5RDV7, Q5XGU1, Q62147, Q66IV3, Q68FV0, Q6AZD1, Q6P0C6, Q6R5J2, Q6ZP80, Q6ZUX7, Q7ZZL8, Q86WI0, Q8BGA2, Q8NBL3, Q8VHW3, Q8VHW4, Q8VHW7, Q8VHW8, Q91Y55, Q925N4

Diamond homologs: E9QHT9, Q1JPA3, Q6IP19, Q6PBE5, Q6PFT6, Q96FX8, Q9BQJ4, Q9JJG6, Q9JK95, Q9XSV3

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
TP63	“up-regulates quantity by expression”	PERP	“transcriptional regulation”
PERP	“down-regulates quantity”	NFKB1	ubiquitination
TP53	“up-regulates quantity by expression”	PERP	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

32 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	0
Uncertain significance	20
Likely benign	1
Benign	4

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
997848	NM_022121.5(PERP):c.453G>A (p.Trp151Ter)	Pathogenic
997849	NM_022121.5(PERP):c.452G>A (p.Trp151Ter)	Pathogenic
997850	NM_022121.5(PERP):c.459C>G (p.Tyr153Ter)	Pathogenic
997851	NM_022121.5(PERP):c.112del (p.Ser38fs)	Pathogenic
997852	NM_022121.5(PERP):c.459C>A (p.Tyr153Ter)	Pathogenic
997853	NM_022121.5(PERP):c.466G>A (p.Gly156Arg)	Pathogenic

SpliceAI

362 predictions. Top by Δscore:

Variant	Effect	Δscore
6:138092264:CACAG:C	acceptor_gain	1.0000
6:138092266:CAG:C	acceptor_gain	1.0000
6:138092267:AG:A	acceptor_gain	1.0000
6:138092269:C:CC	acceptor_gain	1.0000
6:138096373:T:TA	donor_gain	1.0000
6:138096490:CCACG:C	acceptor_gain	1.0000
6:138096491:CACG:C	acceptor_gain	1.0000
6:138096491:CACGC:C	acceptor_gain	1.0000
6:138096492:ACG:A	acceptor_gain	1.0000
6:138096493:CG:C	acceptor_gain	1.0000
6:138096493:CGC:C	acceptor_gain	1.0000
6:138096493:CGCTG:C	acceptor_loss	1.0000
6:138096494:GCTG:G	acceptor_loss	1.0000
6:138096495:C:CC	acceptor_gain	1.0000
6:138096495:CTGCA:C	acceptor_loss	1.0000
6:138096496:T:C	acceptor_loss	1.0000
6:138107126:CCGTA:C	donor_gain	1.0000
6:138092265:ACAG:A	acceptor_gain	0.9900
6:138092265:ACAGC:A	acceptor_gain	0.9900
6:138092266:CAGC:C	acceptor_gain	0.9900
6:138092266:CAGCT:C	acceptor_gain	0.9900
6:138092267:AGC:A	acceptor_gain	0.9900
6:138092268:GCTAA:G	acceptor_gain	0.9900
6:138092269:CTAAA:C	acceptor_gain	0.9900
6:138092270:T:G	acceptor_gain	0.9900
6:138096352:A:AC	donor_gain	0.9900
6:138096352:ACCAG:A	donor_gain	0.9900
6:138096353:C:CC	donor_gain	0.9900
6:138096353:CCAG:C	donor_gain	0.9900
6:138096353:CCAGC:C	donor_gain	0.9900

AlphaMissense

1255 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:138092155:A:G	W157R	1.000
6:138092155:A:T	W157R	1.000
6:138092171:C:A	W151C	1.000
6:138092171:C:G	W151C	1.000
6:138092173:A:G	W151R	1.000
6:138092173:A:T	W151R	1.000
6:138096374:C:T	G112E	1.000
6:138096492:A:G	W73R	1.000
6:138096492:A:T	W73R	1.000
6:138092106:A:T	L173H	0.999
6:138092110:A:G	C172R	0.999
6:138092126:A:C	C166W	0.999
6:138092127:C:T	C166Y	0.999
6:138092128:A:G	C166R	0.999
6:138092130:C:T	G165D	0.999
6:138092131:C:G	G165R	0.999
6:138092153:C:A	W157C	0.999
6:138092153:C:G	W157C	0.999
6:138092157:C:T	G156E	0.999
6:138092158:C:A	G156W	0.999
6:138092158:C:G	G156R	0.999
6:138092158:C:T	G156R	0.999
6:138092159:A:C	F155L	0.999
6:138092159:A:T	F155L	0.999
6:138092161:A:G	F155L	0.999
6:138092163:C:T	G154D	0.999
6:138092164:C:G	G154R	0.999
6:138092167:A:G	Y153H	0.999
6:138092235:G:T	P130H	0.999
6:138092247:A:G	L126P	0.999

dbSNP variants (sampled 300 via entrez): RS1000333480 (6:138101614 T>C), RS1000363738 (6:138105729 C>T), RS1000703631 (6:138107126 C>CG), RS1000708843 (6:138106755 C>A,G), RS1000890478 (6:138095696 A>C), RS1000904808 (6:138100442 A>G), RS1000941173 (6:138093816 A>G), RS1000970636 (6:138093464 C>T), RS1001162625 (6:138100876 A>T), RS1001456207 (6:138090301 C>T), RS1001570600 (6:138090673 A>C), RS1001820562 (6:138106530 A>G), RS1002001606 (6:138100995 A>G), RS1002276466 (6:138102972 G>A,C,T), RS1002366121 (6:138089049 A>G)

Disease associations

OMIM: gene MIM:609301 | disease phenotypes: MIM:619208, MIM:619209

GenCC curated gene-disease

Disease	Classification	Inheritance
Olmsted syndrome 2	Strong	Autosomal dominant
erythrokeratodermia variabilis et progressiva 7	Strong	Autosomal recessive
mutilating palmoplantar keratoderma with periorificial keratotic plaques	Supportive	Autosomal dominant

Mondo (3): Olmsted syndrome 2 (MONDO:0030961), erythrokeratodermia variabilis et progressiva 7 (MONDO:0030941), (MONDO:0019014)

Orphanet (0):

HPO phenotypes

37 total (30 of 37 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000157	Abnormality of the tongue
HP:0000164	Abnormality of the dentition
HP:0000168	Abnormality of the gingiva
HP:0000407	Sensorineural hearing impairment
HP:0000668	Hypodontia
HP:0000670	Carious teeth
HP:0000962	Hyperkeratosis
HP:0000970	Anhidrosis
HP:0000972	Palmoplantar hyperkeratosis
HP:0000982	Palmoplantar keratoderma
HP:0000989	Pruritus
HP:0001036	Parakeratosis
HP:0001072	Thickened skin
HP:0001231	Abnormal fingernail morphology
HP:0001250	Seizure
HP:0001596	Alopecia
HP:0001810	Dystrophic toenail
HP:0002224	Woolly hair
HP:0002289	Alopecia universalis
HP:0002797	Osteolysis
HP:0002861	Melanoma
HP:0003593	Infantile onset
HP:0007410	Palmoplantar hyperhidrosis
HP:0008069	Neoplasm of the skin
HP:0008070	Sparse hair
HP:0010783	Erythema
HP:0011830	Abnormal oral mucosa morphology
HP:0025092	Epidermal acanthosis

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001958_1	Bulimia nervosa	2.000000e-06
GCST003599_7	Systemic lupus erythematosus	2.000000e-14
GCST004250_14	Alanine aminotransferase (ALT) levels after remission induction therapy in actute lymphoblastic leukemia (ALL)	1.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007965	response to combination chemotherapy

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

4 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs117101815	Toxicity	3	cyclophosphamide;epirubicin;fluorouracil	Breast Neoplasms;Neutropenia
rs78428806	Toxicity	3	cyclophosphamide;epirubicin;fluorouracil	Breast Neoplasms;Neutropenia
rs9389568	Toxicity	3	cyclophosphamide;epirubicin;fluorouracil	Breast Neoplasms;Neutropenia
rs9402944	Toxicity	3	cyclophosphamide;epirubicin;fluorouracil	Breast Neoplasms;Neutropenia

CTD chemical–gene interactions

51 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases methylation	7
trichostatin A	affects cotreatment, increases expression	3
Benzo(a)pyrene	affects cotreatment, increases expression	3
methylmercuric chloride	decreases expression	2
mercuric bromide	increases expression, affects cotreatment	2
Acetaminophen	increases expression	2
Cisplatin	affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Aflatoxin B1	decreases methylation, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
tungsten carbide	affects cotreatment, increases expression	1
benzo(b)fluoranthene	affects cotreatment, increases expression	1
arsenite	affects binding, increases reaction	1
sodium arsenite	decreases expression	1
potassium chromate(VI)	increases expression	1
nickel sulfate	increases expression	1
benz(a)anthracene	affects cotreatment, increases expression	1
chrysene	affects cotreatment, increases expression	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects response to substance	1
CGP 52608	affects binding, increases reaction	1
chloropicrin	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
MRK 003	decreases expression	1
enzalutamide	affects expression	1
jinfukang	affects cotreatment, increases expression	1
Resveratrol	increases expression	1
Temozolomide	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1CK	Abcam A-431 PERP KO	Cancer cell line	Female
CVCL_B2AG	Abcam HeLa PERP KO	Cancer cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.