KRT6B

Summary

KRT6B (keratin 6B, HGNC:6444) is a protein-coding gene on chromosome 12q13.13, encoding Keratin, type II cytoskeletal 6B (P04259).

The protein encoded by this gene is a member of the keratin gene family. The type II cytokeratins consist of basic or neutral proteins which are arranged in pairs of heterotypic keratin chains coexpressed during differentiation of simple and stratified epithelial tissues. As many as six of this type II cytokeratin (KRT6) have been identified; the multiplicity of the genes is attributed to successive gene duplication events. The genes are expressed with family members KRT16 and/or KRT17 in the filiform papillae of the tongue, the stratified epithelial lining of oral mucosa and esophagus, the outer root sheath of hair follicles, and the glandular epithelia. Mutations in these genes have been associated with pachyonychia congenita. The type II cytokeratins are clustered in a region of chromosome 12q12-q13.

Source: NCBI Gene 3854 — RefSeq curated summary.

At a glance

• Gene–disease (curated): pachyonychia congenita 4 (Strong, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 262 total — 3 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 35
• MANE Select transcript: NM_005555

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6444
Approved symbol	KRT6B
Name	keratin 6B
Location	12q13.13
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000185479
Ensembl biotype	protein_coding
OMIM	148042
Entrez	3854

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000252252

RefSeq mRNA: 1 — MANE Select: NM_005555 NM_005555

CCDS: CCDS8828

Canonical transcript exons

ENST00000252252 — 9 exons

Exon	Start	End
ENSE00001212088	52446651	52447425
ENSE00001609907	52449758	52449853
ENSE00001629006	52451539	52452146
ENSE00001630883	52450012	52450072
ENSE00001639616	52447539	52447573
ENSE00001680361	52448842	52448967
ENSE00001682578	52449469	52449633
ENSE00001692709	52447778	52447998
ENSE00001706164	52450406	52450620

Expression profiles

Bgee: expression breadth ubiquitous, 168 present calls, max score 99.95.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 11.5221 / max 3710.1060, expressed in 110 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
131036	11.5221	110

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gingiva	UBERON:0001828	99.95	gold quality
gingival epithelium	UBERON:0001949	99.94	gold quality
cervix squamous epithelium	UBERON:0006922	99.94	gold quality
tongue squamous epithelium	UBERON:0006919	99.91	gold quality
hair follicle	UBERON:0002073	99.86	gold quality
squamous epithelium	UBERON:0006914	99.69	gold quality
upper leg skin	UBERON:0004262	99.50	gold quality
esophagus squamous epithelium	UBERON:0006920	99.50	gold quality
upper arm skin	UBERON:0004263	99.26	gold quality
mammalian vulva	UBERON:0000997	99.25	gold quality
epithelium of esophagus	UBERON:0001976	98.78	gold quality
oral cavity	UBERON:0000167	98.68	gold quality
cervix epithelium	UBERON:0004801	98.61	gold quality
body of tongue	UBERON:0011876	98.60	gold quality
pharyngeal mucosa	UBERON:0000355	98.54	gold quality
esophagus mucosa	UBERON:0002469	98.40	gold quality
lower esophagus mucosa	UBERON:0035834	97.76	gold quality
nipple	UBERON:0002030	97.41	gold quality
skin of hip	UBERON:0001554	97.18	gold quality
amniotic fluid	UBERON:0000173	96.84	gold quality
tongue	UBERON:0001723	95.53	gold quality
skin of abdomen	UBERON:0001416	94.35	gold quality
zone of skin	UBERON:0000014	94.12	gold quality
skin of leg	UBERON:0001511	93.13	gold quality
periodontal ligament	UBERON:0008266	90.87	gold quality
epithelium of mammary gland	UBERON:0003244	90.12	gold quality
superior surface of tongue	UBERON:0007371	90.06	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.84	gold quality
mammary duct	UBERON:0001765	89.77	gold quality
mouth mucosa	UBERON:0003729	88.73	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	3529.21
E-HCAD-1	yes	2392.42
E-ANND-3	yes	35.67
E-MTAB-10596	no	9351.44

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPB

miRNA regulators (miRDB)

31 targeting KRT6B, 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-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-4519	99.48	66.10	859
HSA-MIR-544B	99.18	67.41	1632
HSA-MIR-3199	99.17	65.19	696
HSA-MIR-8052	99.17	65.01	719
HSA-MIR-1253	99.12	67.08	1688
HSA-MIR-421	98.90	67.04	1883
HSA-MIR-4711-5P	98.89	68.00	965
HSA-MIR-5000-3P	98.79	65.63	1251
HSA-MIR-4272	98.76	68.74	1810
HSA-MIR-2276-3P	98.76	67.75	1384
HSA-MIR-4766-3P	98.48	67.94	1347
HSA-MIR-4277	98.34	67.17	1323
HSA-MIR-211-3P	98.14	66.77	1052
HSA-MIR-4436A	98.05	64.83	1140
HSA-MIR-4771	97.43	67.69	596
HSA-MIR-4772-5P	95.60	68.04	617
HSA-MIR-4330	95.44	66.39	993
HSA-MIR-5681B	94.82	69.30	514

Literature-anchored findings (GeneRIF, showing 7)

• Studies show that the intrinsic molecular signature of five markers, ER, PR, HER-2, CK 5/6, and EGFR, demonstrated specificity of 100% and sensitivity of 75%, compared with classification by gene expression profiling. (PMID:19720911)
• We found that the KRT16 mutation carriers developed plantar keratoderma at a similar age to KRT6a carriers wheras KRT6B and KRT17 carriers were significantly more likely to report later onset. (PMID:22264670)
• Data show that calretinin and CK5/6 were positive in 100 and 64% of mesotheliomas, and 92 and 31% of reactive effusions, respectively, and desmin was negative in all malignant cases and positive in 85% of reactive effusions. (PMID:23075894)
• These results suggested that the upregulation of notch1 and KRT6B might be involved in the development, progression and prognosis of human renal cell carcinoma (PMID:26464664)
• Several missense polymorphisms in KRT6A, KRT6B and KRT6C that lead to a higher risk for dental caries. (PMID:29357356)
• Data indicate that cytokeratin 5/6 (CK5/6) is an independent prognostic biomarker in urothelial carcinoma and therefore can be used in the prognostic stratification of the patients with bladder cancer. (PMID:29587848)
• PDE3B regulates KRT6B and increases the sensitivity of bladder cancer cells to copper ionophores. (PMID:38165426)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
mus_musculus	Krt6b	ENSMUSG00000023041
mus_musculus	Krt6a	ENSMUSG00000058354
mus_musculus	Gm5414	ENSMUSG00000064232
rattus_norvegicus	AABR07001416.1	ENSRNOG00000059050
rattus_norvegicus	LOC102553726	ENSRNOG00000067545
rattus_norvegicus	LOC100365213	ENSRNOG00000068586
rattus_norvegicus	LOC120093742	ENSRNOG00000068784
rattus_norvegicus	Krt6c	ENSRNOG00000070470

Paralogs (68): KRT33A (ENSG00000006059), VIM (ENSG00000026025), KRT31 (ENSG00000094796), NEFM (ENSG00000104722), KRT23 (ENSG00000108244), KRT37 (ENSG00000108417), KRT32 (ENSG00000108759), KRT18 (ENSG00000111057), LMNB1 (ENSG00000113368), KRT36 (ENSG00000126337), KRT17 (ENSG00000128422), 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)

Protein

Protein identifiers

Keratin, type II cytoskeletal 6B — P04259 (reviewed: P04259)

Alternative names: Cytokeratin-6B, Keratin-6B, Type-II keratin Kb10

All UniProt accessions (1): P04259

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Heterodimer of a type I and a type II keratin. KRT6 isomers associate with KRT16 and/or KRT17.

Tissue specificity. Constitutively expressed in distinct types of epithelia such as those in oral mucosa, esophagus, papillae of tongue and hair follicle outer root sheath.

Disease relevance. Pachyonychia congenita 4 (PC4) [MIM:615728] An autosomal dominant genodermatosis characterized by hypertrophic nail dystrophy, painful and highly debilitating plantar keratoderma, oral leukokeratosis, and a variety of epidermal cysts. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. There are at least six isoforms of human type II keratin-6 (K6). There are two types of cytoskeletal and microfibrillar keratin, I (acidic) and II (neutral to basic) (40-55 and 56-70 kDa, respectively).

Similarity. Belongs to the intermediate filament family.

RefSeq proteins (1): NP_005546* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003054	Keratin_II	Family
IPR018039	IF_conserved	Conserved_site
IPR032444	Keratin_2_head	Domain
IPR039008	IF_rod_dom	Domain

Pfam: PF00038, PF16208

UniProt features (26 total): region of interest 9, sequence conflict 5, sequence variant 4, compositionally biased region 3, initiator methionine 1, chain 1, site 1, modified residue 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P04259-F1	69.76	0.40

Functional residue map

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

Catalytic / active sites (1): 414 (stutter)

Post-translational modifications (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-6805567	Keratinization
R-HSA-6809371	Formation of the cornified envelope
R-HSA-1266738	Developmental Biology

MSigDB gene sets: 163 (showing top): GOBP_EPITHELIUM_DEVELOPMENT, GOBP_INTERMEDIATE_FILAMENT_BASED_PROCESS, GU_PDEF_TARGETS_DN, GOBP_INTERMEDIATE_FILAMENT_ORGANIZATION, JAEGER_METASTASIS_DN, GOBP_EPIDERMAL_CELL_DIFFERENTIATION, GOBP_ECTODERM_DEVELOPMENT, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, MARTINEZ_RB1_TARGETS_DN, MODULE_298, GOBP_EPIDERMIS_DEVELOPMENT, TURASHVILI_BREAST_DUCTAL_CARCINOMA_VS_DUCTAL_NORMAL_DN, CHARAFE_BREAST_CANCER_LUMINAL_VS_BASAL_DN, MODULE_98, VANTVEER_BREAST_CANCER_ESR1_DN

GO Biological Process (3): ectoderm development (GO:0007398), keratinization (GO:0031424), intermediate filament organization (GO:0045109)

GO Molecular Function (3): structural constituent of cytoskeleton (GO:0005200), structural constituent of skin epidermis (GO:0030280), protein binding (GO:0005515)

GO Cellular Component (4): cytosol (GO:0005829), keratin filament (GO:0045095), extracellular exosome (GO:0070062), intermediate filament (GO:0005882)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Developmental Biology	1
Keratinization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
structural molecule activity	2
tissue development	1
keratinocyte differentiation	1
multicellular organismal process	1
intermediate filament cytoskeleton organization	1
supramolecular fiber organization	1
cytoskeleton	1
cytoskeleton organization	1
binding	1
cytoplasm	1
cellular anatomical structure	1
intermediate filament	1
extracellular vesicle	1
intermediate filament cytoskeleton	1
polymeric cytoskeletal fiber	1

Protein interactions and networks

STRING

1371 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KRT6B	PCSK5	Q92824	723
KRT6B	KRT16	P08779	696
KRT6B	KRT17	Q04695	536
KRT6B	S100A7	P31151	525
KRT6B	KRT9	P35527	514
KRT6B	TP53	P04637	513
KRT6B	PCSK7	Q16549	512
KRT6B	KRT10	P13645	501
KRT6B	SPRR1B	P22528	480
KRT6B	HSPB6	O14558	456
KRT6B	SERPINB4	P48594	456
KRT6B	KRT2	P35908	443
KRT6B	SPRR2A	P35326	439
KRT6B	SPRR3	Q9UBC9	436
KRT6B	DSG3	P32926	435

IntAct

149 interactions, top by confidence:

A	B	Type	Score
KRT6B	KRT15	psi-mi:“MI:0915”(physical association)	0.780
KRT15	KRT6B	psi-mi:“MI:0915”(physical association)	0.780
KRT6B	KRT38	psi-mi:“MI:0915”(physical association)	0.750
KRT38	KRT6B	psi-mi:“MI:0915”(physical association)	0.750
KRT31	KRT6B	psi-mi:“MI:0915”(physical association)	0.720
KRT6B	TRIM54	psi-mi:“MI:0915”(physical association)	0.720
KRT6B	TFIP11	psi-mi:“MI:0915”(physical association)	0.720
KRT6B	KRT31	psi-mi:“MI:0915”(physical association)	0.720
TRIM54	KRT6B	psi-mi:“MI:0915”(physical association)	0.720
KRT6B	KRT19	psi-mi:“MI:0915”(physical association)	0.670
NCBP1	KPNA3	psi-mi:“MI:0914”(association)	0.640
AQP7	PLIN1	psi-mi:“MI:0914”(association)	0.570
KRT13	KRT6B	psi-mi:“MI:0915”(physical association)	0.560
KRT6B	NDC80	psi-mi:“MI:0915”(physical association)	0.560
GOLGA2	KRT6B	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (172): KRT6B (Two-hybrid), KRT6B (Two-hybrid), KRT13 (Two-hybrid), KRT15 (Two-hybrid), KRT31 (Two-hybrid), KRT38 (Two-hybrid), NDC80 (Two-hybrid), TFIP11 (Two-hybrid), TRIM54 (Two-hybrid), KRT15 (Two-hybrid), KRT19 (Two-hybrid), KRT6B (Affinity Capture-MS), KRT6B (Affinity Capture-MS), KRT6B (Affinity Capture-MS), KRT6B (Affinity Capture-MS)

ESM2 similar proteins: A5A6M6, A5A6M8, O95678, P02535, P02537, P02538, P04104, P04259, P04264, P06394, P07744, P08776, P12035, P13645, P13647, P16878, P18520, P19013, P35527, P35908, P48668, P50446, Q01546, Q08D91, Q148H7, Q29426, Q2M2I5, Q3TTY5, Q3UV17, Q4FZU2, Q5XQN5, Q6EIY9, Q6EIZ0, Q6EIZ1, Q6IFW6, Q6IFZ6, Q6IG00, Q6IG01, Q6IG02, Q6IG05

Diamond homologs: A0A8C0N8E3, A5A6M8, A5A6N0, A6QQJ3, B4F721, O62654, O77788, O93532, O95678, P02538, P02540, P02541, P02542, P02543, P02544, P02547, P02548, P03995, P04259, P05786, P05787, P07196, P07197, P08551, P08552, P08553, P08670, P08729, P08776, P09654, P11679, P12035, P12036, P12839, P13647, P14136, P15331, P16053, P16878, P16884

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 98 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	14	18.9×	5e-12
Keratinization	14	12.0×	1e-09

GO biological processes:

GO term	Partners	Fold	FDR
morphogenesis of an epithelium	14	57.3×	7e-19
intermediate filament organization	14	40.1×	9e-17
epithelial cell differentiation	13	27.2×	3e-13

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	1
Uncertain significance	150
Likely benign	49
Benign	40

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
14633	NM_005555.4(KRT6B):c.1414G>A (p.Glu472Lys)	Pathogenic
66600	NM_005555.4(KRT6B):c.510CAA[2] (p.Asn172del)	Pathogenic
816696	NM_005555.4(KRT6B):c.1406T>G (p.Leu469Arg)	Pathogenic
430318	NM_005555.4(KRT6B):c.533T>A (p.Ile178Asn)	Likely pathogenic

SpliceAI

552 predictions. Top by Δscore:

Variant	Effect	Δscore
12:52447537:A:AC	donor_gain	1.0000
12:52447538:C:CT	donor_gain	1.0000
12:52447538:CAG:C	donor_gain	1.0000
12:52447570:CAGC:C	acceptor_gain	1.0000
12:52447572:GCC:G	acceptor_loss	1.0000
12:52447573:CCTG:C	acceptor_loss	1.0000
12:52447574:C:CC	acceptor_gain	1.0000
12:52447575:T:G	acceptor_loss	1.0000
12:52447774:CCA:C	donor_loss	1.0000
12:52447774:CCACC:C	donor_gain	1.0000
12:52447775:CACC:C	donor_loss	1.0000
12:52447776:A:AC	donor_gain	1.0000
12:52447777:C:CC	donor_gain	1.0000
12:52447777:CCT:C	donor_loss	1.0000
12:52447994:GCACA:G	acceptor_gain	1.0000
12:52447995:CACA:C	acceptor_gain	1.0000
12:52447995:CACAC:C	acceptor_gain	1.0000
12:52447996:ACA:A	acceptor_gain	1.0000
12:52447997:CA:C	acceptor_gain	1.0000
12:52447997:CAC:C	acceptor_gain	1.0000
12:52447999:C:CC	acceptor_gain	1.0000
12:52448008:C:CT	acceptor_gain	1.0000
12:52448009:A:T	acceptor_gain	1.0000
12:52448838:ATAC:A	donor_loss	1.0000
12:52448839:TA:T	donor_loss	1.0000
12:52448841:C:CT	donor_loss	1.0000
12:52448841:CCTG:C	donor_gain	1.0000
12:52448964:CGTA:C	acceptor_gain	1.0000
12:52448968:C:CC	acceptor_gain	1.0000
12:52448972:A:T	acceptor_gain	1.0000

AlphaMissense

3691 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:52447799:A:G	L468P	0.999
12:52447829:A:G	L458P	0.999
12:52450015:C:A	K271N	0.999
12:52450015:C:G	K271N	0.999
12:52450589:A:G	L191P	0.999
12:52451555:G:T	A175D	0.999
12:52451557:A:C	F174L	0.999
12:52451557:A:T	F174L	0.999
12:52451558:A:C	F174C	0.999
12:52451558:A:G	F174S	0.999
12:52451559:A:G	F174L	0.999
12:52451566:G:C	N171K	0.999
12:52451566:G:T	N171K	0.999
12:52451567:T:A	N171I	0.999
12:52447820:T:A	E461V	0.998
12:52447850:A:G	L451P	0.998
12:52447968:C:G	A412P	0.998
12:52450579:C:A	K194N	0.998
12:52450579:C:G	K194N	0.998
12:52450601:T:G	Q187P	0.998
12:52450604:T:G	Q186P	0.998
12:52450610:A:G	L184P	0.998
12:52450616:C:G	R182P	0.998
12:52451570:A:G	L170P	0.998
12:52447805:C:G	R466P	0.997
12:52447809:A:G	Y465H	0.997
12:52447837:C:A	K455N	0.997
12:52447837:C:G	K455N	0.997
12:52447935:C:G	A423P	0.997
12:52448924:A:G	L374P	0.997

dbSNP variants (sampled 300 via entrez): RS1000376828 (12:52449245 A>G), RS1000663226 (12:52448525 T>G), RS1000716513 (12:52448212 C>A,T), RS1000898640 (12:52454105 T>A), RS1002044238 (12:52453841 CTT>C,CT,CTTT,CTTTT), RS1002155865 (12:52447643 A>C,G), RS1002263514 (12:52453563 G>A,T), RS1002602158 (12:52452146 C>G,T), RS1002807342 (12:52446533 C>T), RS1003565476 (12:52446838 T>A,C,G), RS1005114603 (12:52451407 C>A,G), RS1005186725 (12:52450054 G>C), RS1005672684 (12:52453548 G>A,T), RS1006009704 (12:52446523 C>G,T), RS1006668918 (12:52449455 C>T)

Disease associations

OMIM: gene MIM:148042 | disease phenotypes: MIM:615728, MIM:167210

GenCC curated gene-disease

Disease	Classification	Inheritance
pachyonychia congenita 4	Strong	Autosomal dominant
pachyonychia congenita	Supportive	Autosomal dominant

Mondo (3): pachyonychia congenita 4 (MONDO:0014325), pachyonychia congenita 2 (MONDO:0008174), pachyonychia congenita (MONDO:0016471)

Orphanet (1): Pachyonychia congenita (Orphanet:2309)

HPO phenotypes

35 total (30 of 35 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000695	Natal tooth
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: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
HP:0030268	Hyperplastic callus formation
HP:0030318	Angular cheilitis

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

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

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	decreases expression, increases expression, affects cotreatment	4
Particulate Matter	affects cotreatment, increases abundance, increases expression	4
sodium arsenite	decreases expression, increases expression	2
Mustard Gas	increases alkylation, increases expression	2
Nickel	increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
pyrogallol 1,3-dimethyl ether	decreases expression, affects cotreatment, affects localization	1
3,4-dichloroaniline	increases expression	1
phenyl isocyanate	affects binding	1
cupric chloride	increases expression	1
isobutyl alcohol	affects cotreatment, increases abundance, increases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	decreases ADP-ribosylation	1
4-((3-bromophenyl)amino)-6,7-dimethoxyquinazoline	affects expression, affects cotreatment	1
CGP 52608	affects binding, increases reaction	1
monomethylarsonous acid	decreases expression	1
abrine	increases expression	1
(+)-JQ1 compound	decreases expression	1
Troglitazone	affects cotreatment, affects expression, increases expression	1
Air Pollutants	increases abundance, increases expression	1
Ethanol	affects cotreatment, increases abundance, increases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Cadmium	affects binding	1
Calcitriol	increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Dinitrochlorobenzene	affects binding	1
Diuron	increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Formaldehyde	decreases expression	1
Furaldehyde	affects cotreatment, affects localization, 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