KRT17

Summary

KRT17 (keratin 17, HGNC:6427) is a protein-coding gene on chromosome 17q21.2, encoding Keratin, type I cytoskeletal 17 (Q04695). Type I keratin involved in the formation and maintenance of various skin appendages, specifically in determining shape and orientation of hair.

This gene encodes the type I intermediate filament chain keratin 17, expressed in nail bed, hair follicle, sebaceous glands, and other epidermal appendages. Mutations in this gene lead to Jackson-Lawler type pachyonychia congenita and steatocystoma multiplex.

Source: NCBI Gene 3872 — RefSeq curated summary.

At a glance

• Gene–disease (curated): sebocystomatosis (Definitive, GenCC) — +2 more curated relationships
• Clinical variants (ClinVar): 190 total — 14 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 37
• MANE Select transcript: NM_000422

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6427
Approved symbol	KRT17
Name	keratin 17
Location	17q21.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000128422
Ensembl biotype	protein_coding
OMIM	148069
Entrez	3872

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 protein_coding, 4 retained_intron

ENST00000311208, ENST00000463128, ENST00000491673, ENST00000493253, ENST00000577817, ENST00000590038, ENST00000648859, ENST00000649249, ENST00000862596

RefSeq mRNA: 1 — MANE Select: NM_000422 NM_000422

CCDS: CCDS11402

Canonical transcript exons

ENST00000311208 — 8 exons

Exon	Start	End
ENSE00001885108	41624078	41624575
ENSE00001955322	41619442	41619688
ENSE00003725901	41622950	41623032
ENSE00003726525	41622355	41622511
ENSE00003729131	41620536	41620558
ENSE00003734942	41620659	41620879
ENSE00003750262	41621593	41621754
ENSE00003754516	41620966	41621091

Expression profiles

Bgee: expression breadth ubiquitous, 224 present calls, max score 99.86.

FANTOM5 (CAGE): breadth broad, TPM avg 37.3930 / max 2935.1487, expressed in 342 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
166011	35.0222	267
166008	0.6954	89
166002	0.5745	132
166004	0.2211	72
166007	0.1954	77
166003	0.1312	67
165999	0.1097	53
166000	0.0965	42
166001	0.0891	46
166010	0.0891	54

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gingival epithelium	UBERON:0001949	99.86	gold quality
gingiva	UBERON:0001828	99.79	gold quality
lower esophagus mucosa	UBERON:0035834	99.67	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.47	gold quality
amniotic fluid	UBERON:0000173	99.42	gold quality
mammalian vulva	UBERON:0000997	99.42	gold quality
upper leg skin	UBERON:0004262	99.37	gold quality
hair follicle	UBERON:0002073	99.36	gold quality
upper arm skin	UBERON:0004263	99.33	gold quality
skin of abdomen	UBERON:0001416	99.20	gold quality
tongue squamous epithelium	UBERON:0006919	98.97	gold quality
nipple	UBERON:0002030	98.88	gold quality
zone of skin	UBERON:0000014	98.87	gold quality
skin of leg	UBERON:0001511	98.80	gold quality
buccal mucosa cell	CL:0002336	98.44	gold quality
mouth mucosa	UBERON:0003729	98.06	gold quality
body of tongue	UBERON:0011876	98.05	gold quality
minor salivary gland	UBERON:0001830	98.01	gold quality
mammary duct	UBERON:0001765	97.92	gold quality
trachea	UBERON:0003126	97.75	gold quality
epithelium of mammary gland	UBERON:0003244	97.61	gold quality
periodontal ligament	UBERON:0008266	97.55	gold quality
penis	UBERON:0000989	97.52	gold quality
saliva-secreting gland	UBERON:0001044	97.50	gold quality
tongue	UBERON:0001723	96.88	gold quality
cervix epithelium	UBERON:0004801	96.58	gold quality
cervix squamous epithelium	UBERON:0006922	96.58	gold quality
tonsil	UBERON:0002372	96.35	gold quality
mucosa of paranasal sinus	UBERON:0005030	96.32	gold quality
pharyngeal mucosa	UBERON:0000355	96.24	gold quality

Single-cell (SCXA)

Detected in 23 experiment(s), a significant marker in 22.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	18842.34
E-MTAB-10855	yes	18692.76
E-MTAB-10885	yes	13850.78
E-MTAB-9154	yes	12140.56
E-CURD-7	yes	12018.29
E-ENAD-21	yes	11979.69
E-MTAB-9841	yes	10624.76
E-MTAB-6308	yes	9026.82
E-MTAB-6653	yes	8508.36
E-CURD-126	yes	5300.19
E-ANND-2	yes	4187.53
E-HCAD-38	yes	3684.74
E-CURD-79	yes	2978.32
E-HCAD-15	yes	2707.60
E-MTAB-10283	yes	1929.12

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BRCA1, GLI2, IL17A, JUN, PITX2, STAT1, STAT3, STAT5A, STAT5B

miRNA regulators (miRDB)

18 targeting KRT17, 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-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-3199	99.17	65.19	696
HSA-MIR-8052	99.17	65.01	719
HSA-MIR-8077	99.17	66.67	862
HSA-MIR-6809-5P	99.13	68.45	1223
HSA-MIR-485-5P	99.10	64.78	1889
HSA-MIR-6884-5P	99.10	64.50	1987
HSA-MIR-5701	98.97	69.54	1502
HSA-MIR-4742-5P	98.89	68.41	1542
HSA-MIR-6829-3P	97.45	64.31	1137
HSA-MIR-4743-5P	88.08	64.31	91

Literature-anchored findings (GeneRIF, showing 40)

• expression in breast cancer cells was associated with a poor clinical outcome (PMID:12466114)
• CK17 expression is significantly higher in thyroid papillary carcinoma than benign thyroid tissue; and this characteristic can have important diagnostic value. (PMID:14761598)
• Mutation in second half of 1A domain of K17 might delay onset of clinical phenotype. (PMID:15102078)
• Epitopes S1 (118-132), S2 (169-183), S4 (323-337) and S4 (348-362) are immunodominant DR B1-restricted T cell epitopes for psoriasis. S1 (118-132) contains the ALEEAN sequence. Others with different amino acid sequence have not been reported before. (PMID:15795121)
• KRT 17 seemed to be the most accurate marker for the diagnosis of micrometastases of a size >450 mum. (PMID:16638858)
• Four new missense and five known mutations in K6a, one new deletion and three previously identified missense mutations in K16, plus one known mutation in K17 are reported in pachyonychia congenita. (PMID:17719747)
• findings showed that out of all cytokeratins, CK17 was up-regulated strongest in oral squamous cell carcinoma compared to normal samples, and over-expression was most significantly associated with diagnosis (PMID:17786476)
• The mutation p.M88K is in the helix initiation motif (HIM) of KRT17, where 13 of the reported 14 mutations of KRT17 in PC-2 have been mapped, and the residue M88 of the HIM is also a mutation hotspot of other keratin disorders (http://www.interfil.org/). (PMID:18547302)
• human ScFv against keratin 17 can inhibit the proliferation of keratinocytes (PMID:18936942)
• Positive expression of CK5/6 or CK17 in patients with triple-negative breast cancer is correlated with poor prognosis, high grade differentiation and axillary lymph node metastasis. (PMID:19102940)
• An N92S (p.Asn92Ser) germline keratin 17 gene mutation in a pachyonychia congenita type 2 female patient is presented. (PMID:19107515)
• Positive staining for CK5/6 or CK17 was associated with a worse prognosis, high tumor grade and positive axillary lymph nodes. (PMID:19366057)
• two novel missense mutations of K17 in two Chinese families with steatocystoma multiplex (PMID:19470054)
• Increased expression of keratins in endothelial cells, such as keratin 17, may contribute to the angiogenesis induced by HepG2 cells. (PMID:19558792)
• higher expression in the fetal skin than in adult skin (PMID:19701759)
• Overexpression of KRT17 is associated with basal-like phenotype in breast cancer. (PMID:19882246)
• mutation of KRT17 may play a major role in the pathogenesis of this pedigree with pachyonychia congenita type 2. (PMID:21287500)
• AIRE expression in HaCaT epidermal keratinocytes, as well as its interaction with K17, was confirmed. (PMID:21356351)
• KRT17 is upregulated in gastric adenocarcinoma and is associated with tumor progression. (PMID:21443102)
• The data suggested that IL-17A can upregulate keratin-17 expression in keratinocytes in a dose-dependent manner through STAT1- and STAT3-dependent mechanisms. (PMID:21796151)
• Type I keratin 17 protein is phosphorylated on serine 44 by p90 ribosomal protein S6 kinase 1 (RSK1) in a growth- and stress-dependent fashion (PMID:22006917)
• Both moesin and KRT17 demonstrated a tendency of increased expression as pT stage advanced. (PMID:22076435)
• a novel interaction involving K17 and AnxA2 and identify AnxA2 as a potential regulator of keratin filaments. (PMID:22235123)
• We observed a higher likelihood of oral leukokeratosis in individuals harboring KRT6A mutations, and a strong association of natal teeth and cysts in carriers of a KRT17 mutation. (PMID:22264670)
• A report on homozygosity for dominant missense mutations in keratin 17 that modify the pachyonychia congenita phenotype. (PMID:22336949)
• Data indicate that cytokeratin 17 (CK17) expression could be associated with the differentiation and the malignancy of oral squamous cell carcinoma (OSCC). (PMID:22466643)
• We identified a known mutation in the KRT17 gene in a family with steatocystoma (PMID:22639854)
• Keratin-17 expression is correlated with tumor progression in gastric adenocarcinoma and may serve as a biomarker for poor prognosis. (PMID:22695933)
• Keratin 17 is a therapeutic target for the treatment of psoriasis [review] (PMID:22795618)
• IL-22 up-regulates K17 expression in keratinocytes in a dose-dependent manner through STAT3- and ERK1/2-dependent mechanisms. (PMID:22808266)
• a novel mutation in a Chinese pedigree of pachyonychia congenita type 2 with typical clinical presentations and an autosomal dominant inheritance pattern (PMID:23278621)
• Overexpression of keratin 17 is associated with epithelial ovarian cancer. (PMID:23430585)
• novel heterozygous mutation, p.L91P (c.272T>C) in the helix initiation motif, associated with pachyonychia congenita type 2 (PMID:23855588)
• KRT17 is necessary for oncogenic transformation in Ewing sarcoma and accounts for much of the GLI1-mediated transformation function but via a mechanism independent of AKT signaling. (PMID:24043308)
• Report overexpression of keratin 17 in premalignant and malignant squamous lesions of the cervix. (PMID:24051697)
• BerEp4 alone is unreliable for differentiation between BCCm (basal cell carcinoma with squamous metaplasia) and bSCC (basaloid squamous cell carcinoma). The addition of either CK14 or CK17 will augment BCCm versus bSCC differential diagnosis. (PMID:24168496)
• Immunoexpression of CK13 and CK17 in light green-stained superficial cells was associated with more severe morphological atypia in tongue squamous cell carcinoma (PMID:24247036)
• Peripheral or diffuse staining for CK17 is a useful marker of invasion in anal squamous neoplastic lesions. (PMID:24335642)
• keratin14 expression can be used to detect early epithelial dysplasia, and that keratin13 and keratin17 expression are useful for detecting neoplastic changes (PMID:24471966)
• Case Report: polycystic kidney disease with steatocystoma multiplex. PKD1 mutations disrupt keratin 17 polymerization. (PMID:25111597)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Krt17	ENSMUSG00000035557
rattus_norvegicus	Krt17	ENSRNOG00000026371

Paralogs (68): KRT33A (ENSG00000006059), VIM (ENSG00000026025), KRT31 (ENSG00000094796), NEFM (ENSG00000104722), KRT23 (ENSG00000108244), KRT37 (ENSG00000108417), KRT32 (ENSG00000108759), KRT18 (ENSG00000111057), LMNB1 (ENSG00000113368), KRT36 (ENSG00000126337), GFAP (ENSG00000131095), KRT34 (ENSG00000131737), KRT33B (ENSG00000131738), NES (ENSG00000132688), PRPH (ENSG00000135406), KRT85 (ENSG00000135443), KRT7 (ENSG00000135480), KRT71 (ENSG00000139648), INA (ENSG00000148798), LMNTD1 (ENSG00000152936), LMNA (ENSG00000160789), KRT84 (ENSG00000161849), KRT82 (ENSG00000161850), KRT80 (ENSG00000167767), KRT1 (ENSG00000167768), KRT24 (ENSG00000167916), KRT8 (ENSG00000170421), KRT78 (ENSG00000170423), KRT86 (ENSG00000170442), KRT75 (ENSG00000170454), KRT6C (ENSG00000170465), KRT4 (ENSG00000170477), KRT74 (ENSG00000170484), KRT72 (ENSG00000170486), KRT83 (ENSG00000170523), BFSP2 (ENSG00000170819), KRT19 (ENSG00000171345), KRT15 (ENSG00000171346), KRT38 (ENSG00000171360), KRT13 (ENSG00000171401)

Protein

Protein identifiers

Keratin, type I cytoskeletal 17 — Q04695 (reviewed: Q04695)

Alternative names: 39.1, Cytokeratin-17, Keratin-17

All UniProt accessions (4): Q04695, A0A3B3IS58, K7EPJ9, K7ESE1

UniProt curated annotations — full annotation on UniProt →

Function. Type I keratin involved in the formation and maintenance of various skin appendages, specifically in determining shape and orientation of hair. Required for the correct growth of hair follicles, in particular for the persistence of the anagen (growth) state. Modulates the function of TNF in the specific context of hair cycling. Regulates protein synthesis and epithelial cell growth through binding to the adapter protein SFN and by stimulating Akt/mTOR pathway. Involved in tissue repair. May be a marker of basal cell differentiation in complex epithelia and therefore indicative of a certain type of epithelial ‘stem cells’. Acts as a promoter of epithelial proliferation by acting a regulator of immune response in skin: promotes Th1/Th17-dominated immune environment contributing to the development of basaloid skin tumors. May act as an autoantigen in the immunopathogenesis of psoriasis, with certain peptide regions being a major target for autoreactive T-cells and hence causing their proliferation.

Subunit / interactions. Heterodimer of a type I and a type II keratin. KRT17 associates with KRT6 isomers (KRT6A or KRT6B). Interacts with TRADD and SFN.

Subcellular location. Cytoplasm.

Tissue specificity. Expressed in the outer root sheath and medulla region of hair follicle specifically from eyebrow and beard, digital pulp, nail matrix and nail bed epithelium, mucosal stratified squamous epithelia and in basal cells of oral epithelium, palmoplantar epidermis and sweat and mammary glands. Also expressed in myoepithelium of prostate, basal layer of urinary bladder, cambial cells of sebaceous gland and in exocervix (at protein level).

Post-translational modifications. Phosphorylation at Ser-44 occurs in a growth- and stress-dependent fashion in skin keratinocytes, it has no effect on filament organization.

Disease relevance. Pachyonychia congenita 2 (PC2) [MIM:167210] An autosomal dominant ectodermal dysplasia characterized by hypertrophic nail dystrophy resulting in onchyogryposis (thickening and increase in curvature of the nail), palmoplantar keratoderma and hyperhidrosis, follicular hyperkeratosis, multiple epidermal cysts, absent/sparse eyebrow and body hair, and by the presence of natal teeth. The disease is caused by variants affecting the gene represented in this entry. Steatocystoma multiplex (SM) [MIM:184500] Disease characterized by round or oval cystic tumors widely distributed on the back, anterior trunk, arms, scrotum, and thighs. The disease is caused by variants affecting the gene represented in this entry. KRT16 and KRT17 are coexpressed only in pathological situations such as metaplasias and carcinomas of the uterine cervix and in psoriasis vulgaris. Defects in KRT17 may be the cause of a keratinization disorder with associated thrombocytopenia characterized by generalized harlequin ichthyosis that progress into palmoplantar keratoderma.

Induction. Induced in damaged or stressed epidermis. Induced by the cytokines interferon-gamma (IFN-gamma), tumor necrosis factor alpha (TNF) and transforming growth factor-alpha (TGF-alpha), and by the potent NF-kappa B inhibitor compounds Bay 11-7082 and Bay 11-7085. Down-regulated by the drug Imatinib.

Miscellaneous. There are two types of cytoskeletal and microfibrillar keratin: I (acidic; 40-55 kDa) and II (neutral to basic; 56-70 kDa).

Similarity. Belongs to the intermediate filament family.

RefSeq proteins (1): NP_000413* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002957	Keratin_I	Family
IPR018039	IF_conserved	Conserved_site
IPR039008	IF_rod_dom	Domain

Pfam: PF00038

UniProt features (98 total): sequence conflict 35, sequence variant 21, region of interest 11, mutagenesis site 11, modified residue 9, cross-link 9, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q04695-F1	79.28	0.57

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (18): 12, 13, 25, 32, 39, 44, 110, 279, 323, 15, 15, 278, 399, 399, 400, 400, 419, 419

Mutagenesis-validated functional residues (11):

Position	Phenotype
103	down-regulates both proliferation of psoriatic t-cells and ifn-gamma production; suppresses keratinocyte growth when par
106	down-regulates proliferation of psoriatic t-cells and ifn-gamma production when part of the altered peptide epitope s1.
109	no significant effect on t-cell proliferation or ifn-gamma production when part of the altered peptide epitope s1.
154	no significant effect on t-cell proliferation but reduces ifn-gamma production when part of the altered peptide epitope
155	no significant effect on t-cell proliferation but reduces ifn-gamma production when part of the altered peptide epitope
157	down-regulates proliferation of psoriatic t-cells and ifn-gamma production when part of the altered peptide epitope s2.
160	no significant effect on t-cell proliferation but reduces ifn-gamma production when part of the altered peptide epitope
333	no significant effect on t-cell proliferation but reduces ifn-gamma production when part of the altered peptide epitope
334	no significant effect on t-cell proliferation but can induce ifn-gamma production when part of the altered peptide epito
336	no significant effect on t-cell proliferation but reduces ifn-gamma production when part of the altered peptide epitope
339	down-regulates both proliferation of psoriatic t-cells and ifn-gamma production; suppresses keratinocyte growth when par

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-6805567	Keratinization
R-HSA-6809371	Formation of the cornified envelope
R-HSA-9925563	Developmental Lineage of Pancreatic Ductal Cells
R-HSA-1266738	Developmental Biology

MSigDB gene sets: 307 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, RNGTGGGC_UNKNOWN, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_EPIDERMIS_MORPHOGENESIS, GOBP_INTERMEDIATE_FILAMENT_BASED_PROCESS, HNF3ALPHA_Q6, GOBP_INTERMEDIATE_FILAMENT_ORGANIZATION, JAEGER_METASTASIS_DN, SHEPARD_CRASH_AND_BURN_MUTANT_UP, MODULE_418, GOBP_GROWTH, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, PID_REG_GR_PATHWAY, GOBP_REGULATION_OF_HAIR_CYCLE, GGGTGGRR_PAX4_03

GO Biological Process (8): morphogenesis of an epithelium (GO:0002009), positive regulation of cell growth (GO:0030307), epithelial cell differentiation (GO:0030855), hair follicle morphogenesis (GO:0031069), keratinization (GO:0031424), intermediate filament organization (GO:0045109), positive regulation of translation (GO:0045727), positive regulation of hair follicle development (GO:0051798)

GO Molecular Function (3): structural constituent of skin epidermis (GO:0030280), structural molecule activity (GO:0005198), protein binding (GO:0005515)

GO Cellular Component (8): cornified envelope (GO:0001533), cytosol (GO:0005829), cytoskeleton (GO:0005856), keratin filament (GO:0045095), intermediate filament cytoskeleton (GO:0045111), cytoplasm (GO:0005737), intermediate filament (GO:0005882), cell periphery (GO:0071944)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Developmental Biology	1
Keratinization	1
Developmental Cell Lineages of the Exocrine Pancreas	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
epithelium development	2
hair follicle development	2
tissue morphogenesis	1
regulation of cell growth	1
cell growth	1
positive regulation of growth	1
positive regulation of cellular process	1
cell differentiation	1
anatomical structure morphogenesis	1
hair cycle process	1
epidermis morphogenesis	1
keratinocyte differentiation	1
multicellular organismal process	1
intermediate filament cytoskeleton organization	1
supramolecular fiber organization	1
translation	1
regulation of translation	1
positive regulation of gene expression	1
positive regulation of protein metabolic process	1
positive regulation of developmental process	1
positive regulation of multicellular organismal process	1
regulation of hair follicle development	1
structural molecule activity	1
molecular_function	1
binding	1
plasma membrane	1
cytoplasm	1
intracellular membraneless organelle	1
intermediate filament	1
cytoskeleton	1
intracellular anatomical structure	1
intermediate filament cytoskeleton	1
polymeric cytoskeletal fiber	1

Protein interactions and networks

STRING

2162 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KRT17	SFN	P31947	951
KRT17	TXNDC9	O14530	897
KRT17	EGFR	P00533	698
KRT17	CCHCR1	Q8TD31	679
KRT17	LIAT1	Q6ZQX7	581
KRT17	KRT5	P13647	546
KRT17	ERBB2	P04626	544
KRT17	HLA-C	P04222	540
KRT17	KRT6B	P04259	536
KRT17	PGR	P06401	513
KRT17	CDH3	P22223	508
KRT17	GLI1	P08151	495
KRT17	FN1	P02751	490
KRT17	TRADD	Q15628	489
KRT17	CDSN	Q15517	477

IntAct

72 interactions, top by confidence:

A	B	Type	Score
GRB2	EGFR	psi-mi:“MI:0914”(association)	0.980
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	KRT18	psi-mi:“MI:0914”(association)	0.710
YWHAZ	HSPB1	psi-mi:“MI:0914”(association)	0.680
TRIM69	KRT17	psi-mi:“MI:0915”(physical association)	0.560
KRT17	TRIM69	psi-mi:“MI:0915”(physical association)	0.560
YWHAZ	LMNA	psi-mi:“MI:0914”(association)	0.560
KRT17	KRT6A	psi-mi:“MI:0915”(physical association)	0.550
KRT6A	KRT17	psi-mi:“MI:0915”(physical association)	0.550
EGFR	XPOT	psi-mi:“MI:0914”(association)	0.530
KRT17	CCDC85B	psi-mi:“MI:0915”(physical association)	0.510
KRT17	Eef1g	psi-mi:“MI:0915”(physical association)	0.400
KRT17	EEF1G	psi-mi:“MI:0915”(physical association)	0.400
AGAP2	KRT17	psi-mi:“MI:0915”(physical association)	0.400
KRT8	KRT17	psi-mi:“MI:0915”(physical association)	0.400
ARAP2	KRT17	psi-mi:“MI:0915”(physical association)	0.400
KRT17	KRT77	psi-mi:“MI:0915”(physical association)	0.400
KDM1A	KRT17	psi-mi:“MI:0915”(physical association)	0.370
KRT17	ZDHHC17	psi-mi:“MI:0915”(physical association)	0.370
APC	BBX	psi-mi:“MI:0914”(association)	0.350
Cdh1	ARVCF	psi-mi:“MI:0914”(association)	0.350
Flot1	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
NETO2	TIA1	psi-mi:“MI:0914”(association)	0.350
Myh10	LMO7	psi-mi:“MI:0914”(association)	0.350
AXIN1	PUF60	psi-mi:“MI:0914”(association)	0.350
Coro1c	PLEKHG3	psi-mi:“MI:0914”(association)	0.350

BioGRID (289): TRIM69 (Two-hybrid), KRT17 (Two-hybrid), KRT17 (Affinity Capture-MS), KRT17 (Affinity Capture-MS), CCDC85B (Two-hybrid), KRT17 (Two-hybrid), KRT17 (Affinity Capture-MS), CCDC85B (Affinity Capture-Western), KRT17 (Affinity Capture-MS), KRT17 (Proximity Label-MS), KRT17 (Affinity Capture-MS), KRT17 (Affinity Capture-MS), KRT17 (Affinity Capture-MS), KRT17 (Affinity Capture-MS), KRT17 (Affinity Capture-MS)

ESM2 similar proteins: A1KQY9, A1L595, A5A6M0, A6QQQ9, O57607, O57611, O77727, O93256, P02533, P05781, P05783, P05784, P05786, P05787, P08727, P08728, P08730, P08776, P08777, P08778, P08802, P11679, P19001, P19012, P25030, P35900, P51856, Q04695, Q07427, Q10758, Q5BJY9, Q5K2N3, Q5K2N9, Q5K2P6, Q5R8S9, Q61414, Q63279, Q6IFU7, Q6IFU8, Q6IFV1

Diamond homologs: A1KQY9, A1L317, A1L595, A5A6M0, A5A6M5, A5A6N2, A5A6P3, A6BLY7, A6QQQ9, A7YWM2, B0LKP1, B1AQ75, O57607, O57611, O76009, O76013, O77727, O93256, P02533, P02534, P02535, P02537, P05781, P05783, P05784, P06394, P08727, P08728, P08730, P08777, P08778, P08779, P08802, P13645, P13646, P19001, P19012, P25030, P25690, P35527

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
IL17A	“up-regulates quantity by expression”	KRT17	“transcriptional regulation”
STAT1	“up-regulates quantity by expression”	KRT17	“transcriptional regulation”
STAT3	“up-regulates quantity by expression”	KRT17	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 84 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Formation of the cornified envelope	6	9.6×	8e-04
Cargo recognition for clathrin-mediated endocytosis	5	9.5×	2e-03
Keratinization	6	6.1×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	14
Likely pathogenic	2
Uncertain significance	77
Likely benign	46
Benign	34

Top pathogenic / likely-pathogenic (16)

Variant ID	HGVS	Classification
14586	NM_000422.3(KRT17):c.274A>G (p.Asn92Asp)	Pathogenic
14587	NM_000422.3(KRT17):c.275A>G (p.Asn92Ser)	Pathogenic
14588	NM_000422.3(KRT17):c.292T>G (p.Tyr98Asp)	Pathogenic
14589	NM_000422.3(KRT17):c.274A>C (p.Asn92His)	Pathogenic
14591	NM_000422.3(KRT17):c.280C>T (p.Arg94Cys)	Pathogenic
14592	NM_000422.3(KRT17):c.263T>C (p.Met88Thr)	Pathogenic
14593	NM_000422.3(KRT17):c.281_295del (p.Arg94_Tyr98del)	Pathogenic
14594	NM_000422.3(KRT17):c.281G>C (p.Arg94Pro)	Pathogenic
14595	NM_000422.3(KRT17):c.284T>A (p.Leu95Gln)	Pathogenic
14596	NM_000422.3(KRT17):c.284T>C (p.Leu95Pro)	Pathogenic
14598	NM_000422.3(KRT17):c.296T>C (p.Leu99Pro)	Pathogenic
14599	NM_000422.3(KRT17):c.304G>A (p.Val102Met)	Pathogenic
523369	NM_000422.3(KRT17):c.960+5G>A	Pathogenic
66188	NM_000422.3(KRT17):c.325A>G (p.Asn109Asp)	Pathogenic
4709806	NM_000422.3(KRT17):c.281G>T (p.Arg94Leu)	Likely pathogenic
66181	NM_000422.3(KRT17):c.1163T>C (p.Leu388Pro)	Likely pathogenic

SpliceAI

723 predictions. Top by Δscore:

Variant	Effect	Δscore
17:41619686:CCG:C	acceptor_gain	1.0000
17:41619687:CG:C	acceptor_gain	1.0000
17:41619687:CGC:C	acceptor_gain	1.0000
17:41619689:C:CC	acceptor_gain	1.0000
17:41620532:TTA:T	donor_loss	1.0000
17:41620533:TA:T	donor_loss	1.0000
17:41620534:A:AC	donor_gain	1.0000
17:41620534:ACGTT:A	donor_gain	1.0000
17:41620535:C:CG	donor_gain	1.0000
17:41620535:CG:C	donor_gain	1.0000
17:41620535:CGT:C	donor_gain	1.0000
17:41620535:CGTT:C	donor_gain	1.0000
17:41620535:CGTTC:C	donor_gain	1.0000
17:41620554:TCAGG:T	acceptor_gain	1.0000
17:41620555:CAGG:C	acceptor_gain	1.0000
17:41620555:CAGGC:C	acceptor_gain	1.0000
17:41620556:AGG:A	acceptor_gain	1.0000
17:41620557:GG:G	acceptor_gain	1.0000
17:41620559:C:CC	acceptor_gain	1.0000
17:41620653:A:AC	donor_gain	1.0000
17:41620654:C:CC	donor_gain	1.0000
17:41620654:CTCA:C	donor_gain	1.0000
17:41620655:TCACT:T	donor_loss	1.0000
17:41620656:CAC:C	donor_loss	1.0000
17:41620657:A:AC	donor_gain	1.0000
17:41620657:A:T	donor_loss	1.0000
17:41620658:C:CA	donor_gain	1.0000
17:41620658:CT:C	donor_gain	1.0000
17:41620658:CTG:C	donor_gain	1.0000
17:41620658:CTGG:C	donor_gain	1.0000

AlphaMissense

2822 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:41620680:A:G	L387P	0.999
17:41620710:A:G	L377P	0.999
17:41620985:A:G	L314P	0.999
17:41624226:A:T	L95Q	0.999
17:41624238:A:G	L91P	0.999
17:41624238:A:T	L91H	0.999
17:41620686:C:G	R385P	0.998
17:41620690:A:G	Y384H	0.998
17:41620698:A:C	I381S	0.998
17:41621616:C:G	A271P	0.998
17:41622969:C:G	A166P	0.998
17:41622981:C:G	A162P	0.998
17:41624188:C:G	A108P	0.998
17:41624226:A:G	L95P	0.998
17:41624229:C:G	R94P	0.998
17:41620701:T:A	E380V	0.997
17:41620710:A:T	L377Q	0.997
17:41620731:A:G	L370P	0.997
17:41620782:A:G	L353P	0.997
17:41620857:A:G	L328P	0.997
17:41620980:A:G	S316P	0.997
17:41621657:C:G	R257P	0.997
17:41622437:A:G	L197P	0.997
17:41624163:A:G	I116T	0.997
17:41624196:A:G	L105P	0.997
17:41620698:A:T	I381N	0.996
17:41620718:C:A	K374N	0.996
17:41620718:C:G	K374N	0.996
17:41620773:A:G	L356P	0.996
17:41620824:A:G	L339P	0.996

dbSNP variants (sampled 300 via entrez): RS1000283762 (17:41625948 C>T), RS1000335624 (17:41625707 A>G,T), RS1000439334 (17:41621201 C>G,T), RS1000578801 (17:41621586 C>A,G), RS1000887802 (17:41624743 C>T), RS1003839720 (17:41623498 C>A,T), RS1004188346 (17:41623453 G>A,C), RS1004302828 (17:41623703 A>G), RS1004520072 (17:41622216 T>C), RS1006320595 (17:41619187 C>T), RS1007681944 (17:41625277 C>A), RS1007985385 (17:41623127 C>T), RS1008246147 (17:41622882 T>C), RS1008529846 (17:41626353 G>A), RS1009096542 (17:41626533 G>T)

Disease associations

OMIM: gene MIM:148069 | disease phenotypes: MIM:167210, MIM:184500, MIM:206800

GenCC curated gene-disease

Disease	Classification	Inheritance
sebocystomatosis	Definitive	Autosomal dominant
pachyonychia congenita 2	Strong	Autosomal dominant
pachyonychia congenita	Supportive	Autosomal dominant

Mondo (4): pachyonychia congenita 2 (MONDO:0008174), sebocystomatosis (MONDO:0008485), nonsyndromic congenital nail disorder 4 (MONDO:0008798), pachyonychia congenita (MONDO:0016471)

Orphanet (4): Pachyonychia congenita (Orphanet:2309), Sebocystomatosis (Orphanet:841), Isolated congenital anonychia (Orphanet:79143), Anonychia congenita totalis (Orphanet:94150)

HPO phenotypes

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

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000695	Natal tooth
HP:0000787	Nephrolithiasis
HP:0000972	Palmoplantar hyperkeratosis
HP:0000982	Palmoplantar keratoderma
HP:0001508	Failure to thrive
HP:0001596	Alopecia
HP:0001609	Hoarse voice
HP:0001818	Paronychia
HP:0002098	Respiratory distress
HP:0002164	Nail dysplasia
HP:0002209	Sparse scalp hair
HP:0002745	Oral leukoplakia
HP:0006288	Advanced eruption of teeth
HP:0007410	Palmoplantar hyperhidrosis
HP:0007446	Palmoplantar blistering
HP:0007490	Linear arrays of macular hyperkeratoses in flexural areas
HP:0007502	Follicular hyperkeratosis
HP:0008392	Subungual hyperkeratosis
HP:0008401	Onychogryphosis of toenails
HP:0008404	Nail dystrophy
HP:0009720	Adenoma sebaceum
HP:0010765	Palmar hyperkeratosis
HP:0011359	Dry hair
HP:0011968	Feeding difficulties
HP:0012035	Steatocystoma multiplex
HP:0012514	Lower limb pain
HP:0025084	Folliculitis
HP:0025245	Cutaneous cyst
HP:0025248	Eruptive vellus hair cyst

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D053549	Pachyonychia Congenita	C16.131.077.350.856; C16.131.831.350.856; C16.320.850.250.856; C17.800.529.594; C17.800.804.350.856; C17.800.827.250.856
C536377	Anonychia congenita (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression	6
sodium arsenite	affects expression, decreases expression, increases expression	5
Tobacco Smoke Pollution	affects expression, increases expression	5
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression, increases expression	4
Valproic Acid	increases methylation, affects cotreatment, decreases expression, affects expression, increases expression	4
cadmium sulfate	increases expression	3
Estradiol	increases expression, affects cotreatment, decreases expression	3
bisphenol A	decreases expression, increases expression	2
perfluorooctane sulfonic acid	decreases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	2
Cadmium	increases expression, affects binding	2
Cisplatin	affects response to substance, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Smoke	increases abundance, increases expression	2
Isotretinoin	decreases expression	2
Cadmium Chloride	increases expression, decreases expression	2
2,2’,3,4’,5,5’,6-heptachlorobiphenyl	decreases expression	1
Glupearl 19S	increases expression	1
4-oxoretinoic acid	decreases expression	1
apocarotenal	decreases expression	1
propylparaben	decreases expression	1
lead acetate	increases expression	1
pyrogallol 1,3-dimethyl ether	affects localization, decreases expression, affects cotreatment	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	affects expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
o,p’-DDT	decreases expression	1
sulforaphane	decreases expression	1
sulindac sulfide	increases expression	1
ferrous chloride	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04520750	PHASE3	COMPLETED	VALO-2: Study Evaluating the Safety and Efficacy of PTX022 in the Treatment of Adults With Pachyonychia Congenita
NCT05180708	PHASE3	COMPLETED	A Multicenter, Phase 3 Randomized, Double-Blind, Vehicle-Controlled Study Evaluating the Safety and Efficacy of QTORIN 3.9% Rapamycin Anhydrous Gel in the Treatment of Pachyonychia Congenita
NCT05643872	PHASE3	RECRUITING	A Study Evaluating the Safety and Pharmacokinetics of QTORIN Rapamycin 3.9% Anhydrous Gel in the Treatment of Adults With Pachyonychia Congenita
NCT00716014	PHASE1	COMPLETED	Study of TD101, a Small Interfering RNA (siRNA) Designed for Treatment of Pachyonychia Congenita
NCT02152007	PHASE1	COMPLETED	Topical Sirolimus for the Treatment of Pachyonychia Congenita (PC)
NCT02592954	PHASE1	COMPLETED	Effect of Broccoli Sprout Extract on Keratinocyte Differentiation in Normal Skin
NCT05435638	PHASE1	COMPLETED	Study Designed to Evaluate Safety and Efficacy of 1% Topical Formulation of KM-001 on Type 1 Punctate Palmoplantar Keratoderma or Pachyonychia Congenita Diseases
NCT05956314	PHASE1	COMPLETED	Assessment of KM-001 - Safety, Tolerability, and Efficacy in Patients With PPPK1 or PC
NCT03920228	PHASE2/PHASE3	COMPLETED	Phase 2/3 Study Evaluating the Safety and Efficacy of PTX-022 in Treatment of Adults With Pachyonychia Congenita
NCT06545695	PHASE1/PHASE2	NOT_YET_RECRUITING	Epidermal Growth Factor Receptor Inhibition for Keratinopathies
NCT01382511	Not specified	UNKNOWN	Simvastatin Treatment of Pachyonychia Congenita
NCT02321423	Not specified	RECRUITING	International Pachyonychia Congenita Research Registry