KRT10

Summary

KRT10 (keratin 10, HGNC:6413) is a protein-coding gene on chromosome 17q21.2, encoding Keratin, type I cytoskeletal 10 (P13645). Plays a role in the establishment of the epidermal barrier on plantar skin.

This gene encodes a member of the type I (acidic) cytokeratin family, which belongs to the superfamily of intermediate filament (IF) proteins. Keratins are heteropolymeric structural proteins which form the intermediate filament. These filaments, along with actin microfilaments and microtubules, compose the cytoskeleton of epithelial cells. Mutations in this gene are associated with epidermolytic hyperkeratosis. This gene is located within a cluster of keratin family members on chromosome 17q21.

Source: NCBI Gene 3858 — RefSeq curated summary.

At a glance

• Gene–disease (curated): annular epidermolytic ichthyosis (Definitive, GenCC) — +7 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 265 total — 28 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 43
• MANE Select transcript: NM_000421

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6413
Approved symbol	KRT10
Name	keratin 10
Location	17q21.2
Locus type	gene with protein product
Status	Approved
Aliases	K10, CK10
Ensembl gene	ENSG00000186395
Ensembl biotype	protein_coding
OMIM	148080
Entrez	3858

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000269576, ENST00000635956

RefSeq mRNA: 2 — MANE Select: NM_000421 NM_000421, NM_001379366

CCDS: CCDS11377, CCDS92302

Canonical transcript exons

ENST00000269576 — 8 exons

Exon	Start	End
ENSE00000950657	40821035	40821117
ENSE00000950659	40820262	40820423
ENSE00000950660	40820049	40820174
ENSE00000950662	40818787	40819161
ENSE00001058143	40819517	40819734
ENSE00001058146	40821959	40822614
ENSE00001332351	40818117	40818482
ENSE00002363018	40820511	40820667

Expression profiles

Bgee: expression breadth ubiquitous, 299 present calls, max score 99.99.

FANTOM5 (CAGE): breadth broad, TPM avg 33.7273 / max 20176.0252, expressed in 259 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165840	32.6891	254
165835	0.1943	16
165831	0.1461	24
165836	0.1375	15
165838	0.1353	18
165839	0.1353	17
165837	0.1033	21
208177	0.0598	12
165834	0.0512	13
165833	0.0374	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper leg skin	UBERON:0004262	99.99	gold quality
penis	UBERON:0000989	99.98	gold quality
mammalian vulva	UBERON:0000997	99.98	gold quality
nipple	UBERON:0002030	99.98	gold quality
upper arm skin	UBERON:0004263	99.98	gold quality
skin of hip	UBERON:0001554	99.97	gold quality
skin of abdomen	UBERON:0001416	99.88	gold quality
skin of leg	UBERON:0001511	99.88	gold quality
zone of skin	UBERON:0000014	99.86	gold quality
cervix squamous epithelium	UBERON:0006922	99.37	gold quality
gingiva	UBERON:0001828	99.14	gold quality
gingival epithelium	UBERON:0001949	99.11	gold quality
sperm	CL:0000019	98.57	gold quality
cervix epithelium	UBERON:0004801	98.55	gold quality
parotid gland	UBERON:0001831	98.14	gold quality
epithelium of nasopharynx	UBERON:0001951	97.85	gold quality
palpebral conjunctiva	UBERON:0001812	97.56	gold quality
vagina	UBERON:0000996	97.47	gold quality
amniotic fluid	UBERON:0000173	97.41	gold quality
male germ cell	CL:0000015	97.40	gold quality
right atrium auricular region	UBERON:0006631	97.33	gold quality
squamous epithelium	UBERON:0006914	97.28	gold quality
periodontal ligament	UBERON:0008266	97.20	gold quality
adenohypophysis	UBERON:0002196	97.06	gold quality
skin epidermis	UBERON:0001003	96.76	gold quality
hair follicle	UBERON:0002073	96.76	gold quality
pituitary gland	UBERON:0000007	96.72	gold quality
body of tongue	UBERON:0011876	96.71	gold quality
lower esophagus mucosa	UBERON:0035834	96.69	gold quality
tongue	UBERON:0001723	96.66	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	6064.17
E-HCAD-5	yes	33.82
E-MTAB-10042	yes	10.42
E-MTAB-10596	no	1383.13
E-MTAB-8559	no	1090.02
E-GEOD-106540	no	370.94
E-ENAD-17	no	40.07
E-GEOD-83139	no	3.13
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA, CEBPB, E2F1, HOXA7, MED1, PAX6, POU2F3, TFAP2A, TP53

miRNA regulators (miRDB)

36 targeting KRT10, 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-6753-3P	99.93	66.57	637
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-664A-3P	99.22	71.08	2696
HSA-MIR-877-3P	99.09	68.10	1637
HSA-MIR-4796-3P	99.08	68.38	1681
HSA-MIR-511-5P	98.97	70.94	2268
HSA-MIR-4711-5P	98.89	68.00	965
HSA-MIR-3124-3P	98.87	68.95	2123
HSA-MIR-4272	98.76	68.74	1810
HSA-MIR-5581-3P	98.55	70.31	1161
HSA-MIR-4490	98.51	68.47	943
HSA-MIR-676-5P	98.49	68.87	1492

Literature-anchored findings (GeneRIF, showing 40)

• Mutations in codon 156 of K10, i.e. R156S, R156P, R156H were found in epidermolytic hyperkeratosis. (PMID:12234709)
• cytokeratin 10 molecules were shown to be exposed on the surface of both desquamated nasal epithelial cells and keratinocytes; Staphylococcus aureus clumping factor B (ClfB) was shown to bind to cytokeratin K10 from the desquamated nasal epithelial cells (PMID:12427098)
• Impaired NF-kappa B activation and increased production of tumor necrosis factor alpha is observed in transgenic mice expressing keratin K10 in the basal layer of the epidermis. (PMID:12566451)
• normal cornified cell envelope is formed during the process of human epidermal keratinization, even if the suprabasal keratin filament network is disrupted as with this particular K10 mutation, M150T in BCIE (PMID:14705805)
• cytokeratin 10 may have a role in progression of head and neck squamous cell carcinoma. (PMID:15254692)
• We demonstrate that a recessive mutation in KRT10 leading to a complete human K10 knockout can cause EHK (PMID:16505000)
• Candidate autoantigen in chronic, antibiotic-resistant Lyme arthritis. (PMID:16888010)
• Squamous cell carcinoma (SCC) in mature cystic teratoma (MCT) expressed CK10 less frequently, but CK18 more frequently. SCC in MCT may be derived from metaplastic squamous epithelium. (PMID:17542994)
• Mild recessive bullous congenital ichthyosiform erythroderma due to a previously unidentified homozygous keratin 10 nonsense mutation. (PMID:18219278)
• siRNA for PRKD1 resulted in reduction of mRNA levels of PKD1, altered cell phenotype and promotion of keratinocyte differentiation, demonstrated by increased expression of involucrin and K10 mRNAs (PMID:18259765)
• CK10 alone, or in combination with CK19, can be a novel predictor for poor prognosis of hepatocellular carcinoma patients after curative resection. (PMID:18559605)
• RT-PCR and western blot analysis revealed a delay in the expression of the differentiation markers K1, K10 and involucrin in HaCaT cells compared with normal human keratinocytes (PMID:18637039)
• EHK is an autosomal dominant disorder of keratinization, caused by mutations in either the KRT1 or KRT10 genes. Our patient presents EHK with palmoplantar involvement and KRT10 mutation. (PMID:19443303)
• premature termination codon of KRT10 maybe involved in recessive epidermolytic hyperkeratosis (PMID:19474805)
• Infection by HPV may alter the differentiation status of the epidermis, leading to delayed or absent expression of cytokeratin 10. (PMID:19515043)
• Expression was altered in oral lichen planus lesions (PMID:19776502)
• Data show that TIMP-1 and cytokeratin-10 were identified as 2 newly synthesized secreted proteins in (PMID:19904223)
• mapping and identifying disease-causing mutations in gene encoding KRT10 in ichthyosis with confetti; high frequency of somatic reversion suggests revertant stem cell clones are under positive selection and/or rate of mitotic recombination is elevated (PMID:20798280)
• mutation analysis in patients with epidermolytic ichthyosis by direct sequencing of KRT1 and KRT10 genes; identified 14 different mutations, of which four have not been published previously (PMID:21271994)
• Pneumococcal ligands K10, laminin receptor and platelet-activating factor receptor are elevated in aged lungs and contribute to the enhanced susceptibility to pneumonia. (PMID:21615674)
• Most of the orthokeratotic dysplasia constituent cells were immunopositive for keratin 10, but not for keratins 13, 17 or 19. (PMID:22734720)
• Molecular mimicry between HSP 65 of Mycobacterium leprae and cytokeratin 10 of the host keratin play the role in pathogenesis of leprosy. (PMID:23121977)
• Among Japanese patients with bullous congenital ichthyosiform erythroderma for which genetic diagnosis was determined, all showed mustations in KRT1 or KRT10. (PMID:23182068)
• Case Report: extensive postzygotic mosaicism for a novel keratin 10 mutation in epidermolytic ichthyosis. (PMID:24096702)
• Data indicate that KRT10 is a downstream molecule of PTEN which improves cisplatin-resistance of ovarian cancer cells. (PMID:24434152)
• The diagnosis of ichthyosis with confetti was confirmed by the identification of 2 previously unreported mutations in intron 6 and exon 7 of KRT10. (PMID:24626314)
• We present the spectrum of clinical variability of ichthyosis with confetti in 6 patients with confirmed mutations in KRT10. (PMID:25210931)
• recombinant adenovirus-mediated overexpression of KRT10 and PTEN may improve the cisplatin resistance of ovarian cancer in vitro and in vivo (PMID:26125866)
• findings provide structural insights into phenotypic variation in epidermolytic ichthyosis due to KRT10 mutations (PMID:26176760)
• Complete structure of an epithelial keratin 1/keratin 10 dimer has been presented. (PMID:26181054)
• We present an autosomal dominant pedigree with epidermolytic ichthyosis resulting from a new heterozygous missense mutation in keratin 10. (PMID:26338057)
• Mutations in the highly conserved helix initiation motif of K10 were associated with mild or severe form of epidermolytic ichthyosis (PMID:26373619)
• Report genetic/clinical spectrum of KRT10 mutations in keratinopathic ichthyosis. (PMID:26581228)
• KRT10 gene mutation was present in all of the affected individuals, but absent in the five unaffected and 100 ethnically-matched healthy controls. (PMID:27212473)
• Results show that missense mutations exert dominant negative effects on the keratins K1/K10 protein structure by altering inter-chain interactions. (PMID:27421141)
• Case Report: post-zygotic mosaicism of KRT/1o mutations in epidermolytic Ichthyosis. (PMID:27722766)
• The molecular diagnostics by the whole exome sequencing showed a novel de novo (c.1374-2A>C) mutation in the KRT10 gene responsible for the development of IWC (KRT10 defect was confirmed by immunofluorescent study). Concurrently, the m.14484T>C mutation in mitochondrial MTND6 gene (characteristic for Leber’s hereditary optic neuropathy or LHON) was detected in patient, his mother and brother (PMID:28944608)
• These findings indicate that alpha112:alpha556 (IV) network, which is the only network that includes the alpha6(IV) chain, is one regulator of KRT10 expression in keratinization of oral mucosal epithelium. (PMID:29422532)
• Results showed identical expression pattern for KRT1 and KRT10, their expression was higher in pediatric cases than in adults, especially in pediatric recurrent samples. (PMID:30021014)
• The Keratin 1-keratin 10-1B knob/pocket mechanism is conserved across keratins and many non-keratin intermediate filaments.Light scattering and circular dichroism measurements demonstrated enhanced aggregation of K1(S233L)/K10-1B in solution without affecting secondary structure. The K1(S233L)/K10-1B octamer structure revealed S233L(K1) causes aberrant hydrophobic interactions between 1B tetramers. (PMID:31036554)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Krt10	ENSMUSG00000019761
rattus_norvegicus	Krt10	ENSRNOG00000030170

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 I cytoskeletal 10 — P13645 (reviewed: P13645)

Alternative names: Cytokeratin-10, Keratin-10

All UniProt accessions (2): A0A1B0GVI3, P13645

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in the establishment of the epidermal barrier on plantar skin. Involved in the maintenance of cell layer development and keratin filament bundles in suprabasal cells of the epithelium. (Microbial infection) Acts as a mediator of S.aureus adherence to desquamated nasal epithelial cells via clfB, and hence may play a role in nasal colonization. (Microbial infection) Binds S.pneumoniae PsrP, mediating adherence of the bacteria to lung cell lines. Reduction of levels of KRT10 keratin decrease adherence, overexpression increases adherence. Neither protein has to be glycosylated for the interaction to occur.

Subunit / interactions. Heterotetramer of two type I and two type II keratins. Heterodimer with KRT1. Two heterodimers of KRT1 and KRT10 form a heterotetramer. The KRT10 subunit in the heterotetramer is probably disulfide-linked. Interacts with PLEC isoform 1C, when in a heterodimer with KRT1. (Microbial infection) Interacts (via C-terminal tail domain) with the S.aureus clumping factor, clfB; this interaction probably mediates S.aureus attachment to the keratinized squamous epithelial cells from the nasal cavity. (Microbial infection) Interacts (via the C-terminal tail domain) with S.pneumoniae serine-rich repeat protein PsrP; this interaction probably mediates S.pneumoniae adherence to lung tissue and subsequent pathogenesis. Neither protein has to be glycosylated for the interaction to occur.

Subcellular location. Secreted. Extracellular space. Cell surface. Cytoplasm.

Tissue specificity. Seen in all suprabasal cell layers including stratum corneum. Expressed on the surface of lung cell lines. Localized on the surface of desquamated nasal epithelial cells (at protein level).

Disease relevance. Epidermolytic hyperkeratosis 2A (EHK2A) [MIM:620150] An autosomal dominant form of epidermolytic hyperkeratosis, a skin disorder characterized by widespread blistering and an ichthyotic erythroderma at birth that persist into adulthood. Histologically there is a diffuse epidermolytic degeneration in the lower spinous layer of the epidermis. Within a few weeks from birth, erythroderma and blister formation diminish and hyperkeratoses develop. EHK2 inheritance is autosomal dominant or autosomal recessive. The disease is caused by variants affecting the gene represented in this entry. Epidermolytic hyperkeratosis 2B, autosomal recessive (EHK2B) [MIM:620707] An autosomal recessive form of epidermolytic hyperkeratosis, a skin disorder characterized by widespread blistering and an ichthyotic erythroderma at birth that persist into adulthood. Histologically there is a diffuse epidermolytic degeneration in the lower spinous layer of the epidermis. Within a few weeks from birth, erythroderma and blister formation diminish and hyperkeratoses develop. The disease is caused by variants affecting the gene represented in this entry. Ichthyosis, annular epidermolytic, 1 (AEI1) [MIM:607602] A form of annular epidermolytic ichthyosis, an autosomal dominant skin disorder characterized by polycyclic, migratory erythematous and scaly plaques. AEI1 is characterized by the development of widespread erythematous blistering in the neonatal period or early childhood that subsides over time. The disease is caused by variants affecting the gene represented in this entry. Ichthyosis with confetti (IWC) [MIM:609165] An autosomal dominant, rare skin condition characterized by slowly enlarging islands of normal skin surrounded by erythematous ichthyotic patches in a reticulated pattern. The condition starts in infancy as a lamellar ichthyosis, with small islands of normal skin resembling confetti appearing in late childhood and at puberty. Histopathologic findings include band-like parakeratosis, psoriasiform acanthosis, and vacuolization of keratinocytes with binucleated cells in the upper epidermis, sometimes associated with amyloid deposition in the dermis. Ultrastructural abnormalities include perinuclear shells formed from a network of fine filaments in the upper epidermis. The disease is caused by variants affecting the gene represented in this entry. Ichthyosis histrix, Lambert type (IHL) [MIM:146600] An autosomal dominant form of ichthyosis, a disorder of keratinization with abnormal differentiation and desquamation of the epidermis, resulting in abnormal skin scaling. IHL is characterized by normal skin at birth that develops striking spiny hyperkeratotic lesions within a few months. There is sparing of the face, palms, and soles, and affected individuals do not experience blistering. The disease may be caused by variants affecting the gene represented in this entry.

Induction. Repressed in keratinocytes by all-trans retinoic acid (ATRA), via reduction of mRNA stability.

Polymorphism. A number of alleles are known that mainly differ in the Gly-rich region (positions 490-560).

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 (2): NP_000412, NP_001366295 (=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 (82 total): sequence conflict 33, sequence variant 23, region of interest 9, modified residue 6, compositionally biased region 3, strand 3, helix 2, chain 1, domain 1, disulfide bond 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
6UUI	X-RAY DIFFRACTION	2.07
4F1Z	X-RAY DIFFRACTION	2.3
6E2J	X-RAY DIFFRACTION	2.39
3ASW	X-RAY DIFFRACTION	2.6
6EC0	X-RAY DIFFRACTION	2.98
4ZRY	X-RAY DIFFRACTION	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P13645-F1	68.70	0.44

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 (6): 14, 16, 42, 53, 56, 170

Disulfide bonds (1): 401

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-6805567	Keratinization
R-HSA-6809371	Formation of the cornified envelope
R-HSA-9725554	Differentiation of Keratinocytes in Interfollicular Epidermis in Mammalian Skin
R-HSA-1266738	Developmental Biology
R-HSA-9734767	Developmental Cell Lineages

MSigDB gene sets: 217 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOBP_EPITHELIUM_DEVELOPMENT, MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_INTERMEDIATE_FILAMENT_BASED_PROCESS, FAELT_B_CLL_WITH_VH_REARRANGEMENTS_DN, GOBP_INTERMEDIATE_FILAMENT_ORGANIZATION, GOBP_REGULATION_OF_EPIDERMIS_DEVELOPMENT, JAEGER_METASTASIS_DN, GOCC_CELL_SURFACE, HINATA_NFKB_TARGETS_KERATINOCYTE_UP, GOBP_EPIDERMAL_CELL_DIFFERENTIATION, GOBP_PROTEIN_HETEROTETRAMERIZATION, HOWLIN_PUBERTAL_MAMMARY_GLAND, MURAKAMI_UV_RESPONSE_1HR_UP

GO Biological Process (7): morphogenesis of an epithelium (GO:0002009), keratinocyte differentiation (GO:0030216), intermediate filament organization (GO:0045109), positive regulation of epidermis development (GO:0045684), protein heterotetramerization (GO:0051290), cornification (GO:0070268), peptide cross-linking (GO:0018149)

GO Molecular Function (4): structural constituent of skin epidermis (GO:0030280), protein heterodimerization activity (GO:0046982), structural molecule activity (GO:0005198), protein binding (GO:0005515)

GO Cellular Component (12): cornified envelope (GO:0001533), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), cytoskeleton (GO:0005856), intermediate filament (GO:0005882), cell surface (GO:0009986), membrane (GO:0016020), keratin filament (GO:0045095), extracellular exosome (GO:0070062), extracellular region (GO:0005576)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Developmental Biology	2
Keratinization	1
Developmental Cell Lineages of the Integumentary System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
tissue morphogenesis	1
epithelium development	1
epidermal cell differentiation	1
skin development	1
intermediate filament cytoskeleton organization	1
supramolecular fiber organization	1
epidermis development	1
regulation of epidermis development	1
positive regulation of developmental process	1
protein tetramerization	1
protein heterooligomerization	1
programmed cell death	1
keratinization	1
cornified envelope assembly	1
protein modification process	1
structural molecule activity	1
protein dimerization activity	1
molecular_function	1
binding	1
plasma membrane	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
intracellular membraneless organelle	1
intermediate filament cytoskeleton	1
polymeric cytoskeletal fiber	1
intermediate filament	1
extracellular vesicle	1

Protein interactions and networks

STRING

1966 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KRT10	KRT1	P04264	968
KRT10	LORICRIN	P23490	938
KRT10	IVL	P07476	933
KRT10	FLG	P20930	917
KRT10	FLG2	Q5D862	916
KRT10	TGM1	P22735	720
KRT10	EPHA6	Q9UF33	712
KRT10	CDSN	Q15517	681
KRT10	DSG1	Q02413	645
KRT10	AKT1	P31749	553
KRT10	DSC1	Q08554	518
KRT10	KRTDAP	P60985	513
KRT10	KLK6	Q92876	512
KRT10	JUP	P14923	510
KRT10	S100A7	P31151	507

IntAct

88 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	KRT18	psi-mi:“MI:0914”(association)	0.710
KRT10	KRT1	psi-mi:“MI:0407”(direct interaction)	0.650
KRT10	KRT1	psi-mi:“MI:0915”(physical association)	0.650
CFTR	VIM	psi-mi:“MI:0914”(association)	0.610
TJP1	ACTN4	psi-mi:“MI:0914”(association)	0.600
VCAM1	PSMD11	psi-mi:“MI:0914”(association)	0.530
PPP2R2B	DDX3X	psi-mi:“MI:0914”(association)	0.460
KRT10	SRC	psi-mi:“MI:0915”(physical association)	0.400
ALB	CDC45	psi-mi:“MI:0914”(association)	0.350
IGHA1	PLG	psi-mi:“MI:0914”(association)	0.350
IGHG1	PDPK1	psi-mi:“MI:0914”(association)	0.350
ALB	CNOT1	psi-mi:“MI:0914”(association)	0.350
ALB	SH3BP5	psi-mi:“MI:0914”(association)	0.350
Tnf		psi-mi:“MI:0914”(association)	0.350
RICTOR	WIZ	psi-mi:“MI:0914”(association)	0.350
MME		psi-mi:“MI:0914”(association)	0.350
METTL3	TUBAL3	psi-mi:“MI:0914”(association)	0.350
WTAP	DDX39A	psi-mi:“MI:0914”(association)	0.350
METTL14	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350
CAND1	GTPBP10	psi-mi:“MI:0914”(association)	0.350

BioGRID (250): KRT10 (Reconstituted Complex), KRT10 (Affinity Capture-MS), KRT10 (Affinity Capture-MS), KRT10 (Co-fractionation), KRT10 (Co-fractionation), KRT10 (Co-fractionation), KRT16 (Co-fractionation), KRT77 (Co-fractionation), PRSS1 (Co-fractionation), KRT10 (Affinity Capture-MS), KRT10 (Affinity Capture-MS), KRT10 (Affinity Capture-MS), KRT10 (Affinity Capture-MS), KRT10 (Affinity Capture-MS), KRT10 (Affinity Capture-MS)

ESM2 similar proteins: A2ZJC9, A3C5A7, A3CG83, C0HM81, O18740, O22612, O48848, P02674, P05834, P06649, P09789, P0C5C7, P0DUT6, P10495, P10496, P11898, P12796, P13396, P13645, P17816, P19469, P19470, P22357, P35527, P37703, P37704, P86797, P86798, P86857, Q07202, Q09134, Q1HVF7, Q25055, Q3KSS4, Q3TTY5, Q54M35, Q54T37, Q5AMF7, Q6IG02, Q6RHW0

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

1 interactions.

A	Effect	B	Mechanism
HOXA7	“down-regulates quantity by repression”	KRT10	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 97 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
VEGFR2 mediated cell proliferation	5	46.0×	1e-05
Signaling by high-kinase activity BRAF mutants	5	25.6×	9e-05
MAP2K and MAPK activation	5	23.0×	1e-04
Signaling by RAF1 mutants	5	22.5×	1e-04
Signaling by moderate kinase activity BRAF mutants	5	20.5×	2e-04
Paradoxical activation of RAF signaling by kinase inactive BRAF	5	20.5×	2e-04
Signaling downstream of RAS mutants	5	20.5×	2e-04
Regulation of RAS by GAPs	6	18.7×	6e-05

GO biological processes:

GO term	Partners	Fold	FDR
intrinsic apoptotic signaling pathway	7	31.4×	1e-06
autophagosome maturation	5	21.9×	7e-04
mitophagy	5	19.9×	8e-04
G1/S transition of mitotic cell cycle	6	15.1×	7e-04
autophagosome assembly	5	14.0×	3e-03
cellular response to starvation	5	12.1×	5e-03
positive regulation of canonical Wnt signaling pathway	5	9.7×	1e-02
DNA damage response	9	6.0×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	28
Likely pathogenic	6
Uncertain significance	101
Likely benign	55
Benign	40

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1236189	NM_000421.5(KRT10):c.1374-1G>C	Pathogenic
1236190	NM_000421.5(KRT10):c.1373+1del	Pathogenic
1236191	NM_000421.5(KRT10):c.1403_1417delinsA (p.Ser468fs)	Pathogenic
1299620	NM_000421.5(KRT10):c.470T>C (p.Leu157Pro)	Pathogenic
14569	NM_000421.5(KRT10):c.482T>C (p.Leu161Ser)	Pathogenic
14572	NM_000421.5(KRT10):c.478T>G (p.Tyr160Asp)	Pathogenic
14575	NM_000421.5(KRT10):c.1325T>A (p.Leu442Gln)	Pathogenic
14576	NM_000421.5(KRT10):c.466C>T (p.Arg156Cys)	Pathogenic
14577	NM_000421.5(KRT10):c.449T>G (p.Met150Arg)	Pathogenic
14578	NM_000421.5(KRT10):c.1315A>G (p.Lys439Glu)	Pathogenic
14579	NM_000421.5(KRT10):c.449T>C (p.Met150Thr)	Pathogenic
14580	NM_000421.5(KRT10):c.1264_1265delinsGA (p.Arg422Glu)	Pathogenic
14581	NM_000421.5(KRT10):c.1374-2A>G	Pathogenic
14582	NM_000421.5(KRT10):c.1373+1G>A	Pathogenic
14583	NM_000421.5(KRT10):c.1449dup (p.Gly484fs)	Pathogenic
14584	NM_000421.5(KRT10):c.1560_1561del (p.Gly521fs)	Pathogenic
29764	NM_000421.5(KRT10):c.1300C>T (p.Gln434Ter)	Pathogenic
29765	NM_000421.5(KRT10):c.1281C>A (p.Cys427Ter)	Pathogenic
3255316	NM_000421.5(KRT10):c.1304T>C (p.Leu435Pro)	Pathogenic
3661484	NM_000421.5(KRT10):c.458T>G (p.Leu153Arg)	Pathogenic
432261	NM_000421.5(KRT10):c.1373+2T>C	Pathogenic
449615	NM_000421.5(KRT10):c.1374-2A>C	Pathogenic
4710372	NM_000421.5(KRT10):c.1370G>T (p.Gly457Val)	Pathogenic
66161	NM_000421.5(KRT10):c.1314_1315insC (p.Lys439fs)	Pathogenic
66163	NM_000421.5(KRT10):c.1337T>C (p.Ile446Thr)	Pathogenic
66172	NM_000421.5(KRT10):c.457C>G (p.Leu153Val)	Pathogenic
66174	NM_000421.5(KRT10):c.466C>A (p.Arg156Ser)	Pathogenic
66177	NM_000421.5(KRT10):c.472G>C (p.Ala158Pro)	Pathogenic
1489919	NM_000421.5(KRT10):c.461A>G (p.Asn154Ser)	Likely pathogenic
2431374	NM_000421.5(KRT10):c.1374-1G>A	Likely pathogenic

SpliceAI

993 predictions. Top by Δscore:

Variant	Effect	Δscore
17:40819519:T:A	donor_gain	1.0000
17:40819520:C:A	donor_gain	1.0000
17:40819525:T:A	donor_gain	1.0000
17:40820173:CT:C	acceptor_gain	1.0000
17:40820175:C:CC	acceptor_gain	1.0000
17:40820256:CTTTA:C	donor_gain	1.0000
17:40820258:TTA:T	donor_loss	1.0000
17:40820260:A:AC	donor_gain	1.0000
17:40820260:AC:A	donor_gain	1.0000
17:40820261:C:CC	donor_gain	1.0000
17:40820261:CC:C	donor_gain	1.0000
17:40820261:CCT:C	donor_gain	1.0000
17:40820419:ATTTC:A	acceptor_gain	1.0000
17:40820420:TTTC:T	acceptor_gain	1.0000
17:40820421:TTC:T	acceptor_gain	1.0000
17:40820422:TC:T	acceptor_gain	1.0000
17:40820423:CC:C	acceptor_gain	1.0000
17:40820424:C:CC	acceptor_gain	1.0000
17:40820424:C:G	acceptor_loss	1.0000
17:40820425:T:G	acceptor_loss	1.0000
17:40820498:A:C	donor_gain	1.0000
17:40820505:TGTCA:T	donor_loss	1.0000
17:40820508:CACC:C	donor_loss	1.0000
17:40820509:ACCT:A	donor_gain	1.0000
17:40820509:ACCTC:A	donor_loss	1.0000
17:40820510:CC:C	donor_loss	1.0000
17:40820510:CCTC:C	donor_gain	1.0000
17:40820512:T:TA	donor_gain	1.0000
17:40820513:C:A	donor_gain	1.0000
17:40820663:CATAC:C	acceptor_gain	1.0000

AlphaMissense

3755 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:40819545:A:G	Y449H	1.000
17:40819553:A:C	I446S	1.000
17:40819553:A:G	I446T	1.000
17:40819565:A:G	L442P	1.000
17:40819586:A:G	L435P	1.000
17:40822086:A:G	L167P	1.000
17:40822116:A:G	L157P	1.000
17:40822128:A:G	L153P	1.000
17:40822128:A:T	L153Q	1.000
17:40819535:A:G	L452P	0.999
17:40819553:A:T	I446N	0.999
17:40819556:T:A	E445V	0.999
17:40819556:T:C	E445G	0.999
17:40819565:A:T	L442Q	0.999
17:40819573:C:A	K439N	0.999
17:40819573:C:G	K439N	0.999
17:40819575:T:C	K439E	0.999
17:40819583:A:G	L436P	0.999
17:40820293:C:G	R333P	0.999
17:40821054:C:G	A231P	0.999
17:40821059:A:G	L229P	0.999
17:40821066:C:G	A227P	0.999
17:40821969:A:G	L206P	0.999
17:40822065:A:G	L174P	0.999
17:40822114:C:G	A158P	0.999
17:40822116:A:T	L157Q	0.999
17:40822119:C:G	R156P	0.999
17:40822120:G:T	R156S	0.999
17:40822124:A:C	N154K	0.999
17:40822124:A:T	N154K	0.999

dbSNP variants (sampled 300 via entrez): RS1000230568 (17:40823416 T>C), RS1000579821 (17:40817702 T>A), RS1001724571 (17:40817666 T>C), RS1002010694 (17:40819275 G>A,T), RS1002631670 (17:40821568 T>G), RS1003685246 (17:40821006 T>C), RS1004508387 (17:40819290 T>A,C), RS1004669521 (17:40820977 G>A,T), RS1005102922 (17:40821488 A>T), RS1006667421 (17:40824361 C>T), RS1006919636 (17:40824016 A>T), RS1007773842 (17:40823961 A>C,G), RS1008135889 (17:40823976 G>A), RS1008249630 (17:40818072 A>G), RS1008746362 (17:40820441 A>C)

Disease associations

OMIM: gene MIM:148080 | disease phenotypes: MIM:113800, MIM:607602, MIM:609165, MIM:620150, MIM:146600, MIM:620707, MIM:131760

GenCC curated gene-disease

Disease	Classification	Inheritance
annular epidermolytic ichthyosis	Definitive	Autosomal dominant
epidermolytic hyperkeratosis 2A, autosomal dominant	Strong	Autosomal dominant
epidermolytic hyperkeratosis 2B, autosomal recessive	Strong	Autosomal recessive
epidermolytic ichthyosis	Strong	Autosomal dominant
congenital reticular ichthyosiform erythroderma	Strong	Autosomal dominant
ichthyosis, annular epidermolytic 1	Strong	Autosomal dominant
ichthyosis	Strong	Autosomal dominant
autosomal recessive epidermolytic ichthyosis	Supportive	Autosomal recessive

Mondo (14): epidermolytic ichthyosis (MONDO:0007239), annular epidermolytic ichthyosis (MONDO:0011870), congenital reticular ichthyosiform erythroderma (MONDO:0012208), epidermolytic hyperkeratosis 2A, autosomal dominant (MONDO:0700248), epidermolytic acanthoma (MONDO:0002962), autosomal dominant epidermolytic ichthyosis (MONDO:0020702), epidermolytic nevus (MONDO:0044656), epidermolytic hyperkeratosis 1 (MONDO:0700249), ichthyosis histrix, Lambert type (MONDO:0007809), ichthyosis, annular epidermolytic 1 (MONDO:0100303), epidermolytic hyperkeratosis 2B, autosomal recessive (MONDO:0700245), epidermolysis bullosa simplex 1A, generalized severe (MONDO:0007550), autosomal recessive epidermolytic ichthyosis (MONDO:0044742), ichthyosis (MONDO:0019269)

Orphanet (6): Annular epidermolytic ichthyosis (Orphanet:281139), Congenital reticular ichthyosiform erythroderma (Orphanet:281190), Autosomal dominant epidermolytic ichthyosis (Orphanet:312), Epidermolytic nevus (Orphanet:497737), Autosomal dominant generalized epidermolysis bullosa simplex, severe form (Orphanet:79396), Ichthyosis hystrix gravior (Orphanet:79504)

HPO phenotypes

43 total (30 of 43 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000486	Strabismus
HP:0000639	Nystagmus
HP:0000656	Ectropion
HP:0000962	Hyperkeratosis
HP:0000972	Palmoplantar hyperkeratosis
HP:0000982	Palmoplantar keratoderma
HP:0000989	Pruritus
HP:0000992	Cutaneous photosensitivity
HP:0000998	Hypertrichosis
HP:0001019	Erythroderma
HP:0001217	Clubbing
HP:0001595	Abnormal hair morphology
HP:0001597	Abnormal nail morphology
HP:0001824	Weight loss
HP:0002557	Hypoplastic nipples
HP:0003577	Congenital onset
HP:0003593	Infantile onset
HP:0003623	Neonatal onset
HP:0004322	Short stature
HP:0004325	Decreased body weight
HP:0004396	Poor appetite
HP:0004906	Hypernatremic dehydration
HP:0005595	Generalized hyperkeratosis
HP:0007453	Flexural lichenification
HP:0007475	Congenital bullous ichthyosiform erythroderma
HP:0007479	Congenital nonbullous ichthyosiform erythroderma
HP:0008064	Ichthyosis
HP:0008066	Abnormal blistering of the skin

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002726_32	Glucose homeostasis traits	4.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004471	insulin sensitivity measurement

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D017488	Hyperkeratosis, Epidermolytic	C16.131.831.512.400.375; C16.320.850.400.375; C16.614.492.400.375; C17.800.428.333.250.375; C17.800.804.512.400.375; C17.800.827.400.375
D007057	Ichthyosis	C16.131.831.512; C16.614.492; C17.800.428.333; C17.800.804.512
C563781	Erythrokeratoderma, Reticular (supp.)
C536087	Ichthyosis hystrix gravior (supp.)
C564367	Ichthyosis, Cyclic, with Epidermolytic Hyperkeratosis (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases reaction, decreases reaction, increases expression (+1 more)	7
Tetrachlorodibenzodioxin	decreases expression, increases expression	4
Tobacco Smoke Pollution	affects expression, decreases expression	4
Particulate Matter	decreases expression, increases abundance	4
sodium arsenate	increases reaction, decreases expression, increases abundance, increases expression	3
arsenite	decreases expression, increases abundance, increases reaction, affects binding, decreases reaction	3
Tretinoin	increases expression, decreases expression	3
U 0126	increases reaction, decreases reaction, increases expression, decreases expression, increases abundance	2
N-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester	decreases reaction, increases expression, decreases expression	2
Antimony Potassium Tartrate	decreases expression, increases abundance, increases reaction, decreases reaction	2
Arsenic	increases expression, decreases expression, increases abundance	2
Benzo(a)pyrene	increases methylation, affects cotreatment, decreases expression	2
Calcitriol	decreases expression, increases expression, affects cotreatment	2
Estradiol	decreases expression, decreases reaction	2
Mustard Gas	increases expression	2
Nickel	affects binding, affects expression, decreases reaction	2
Cyclosporine	increases expression	2
aristolochic acid I	decreases expression	1
4-oxoretinoic acid	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects expression, decreases reaction	1
chlorophyllin	increases expression	1
titanium dioxide	increases expression	1
VX-agent	affects binding	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
trichostatin A	affects expression, decreases reaction	1
perfluorooctanoic acid	increases expression	1
triphenyltin	increases expression	1
4-bromo-A-23187	increases expression	1
diallyl trisulfide	increases expression	1

Cellosaurus cell lines

4 cell lines: 2 cancer cell line, 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SV06	HAP1 KRT10 (-) 1	Cancer cell line	Male
CVCL_SV07	HAP1 KRT10 (-) 2	Cancer cell line	Male
CVCL_ZE31	EH21	Transformed cell line
CVCL_ZE32	EH31	Transformed cell line

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04996485	PHASE4	UNKNOWN	Scientific Substantiation and Assessment of the Effectiveness of Pathogenetic Methods of Therapy for Congenital Ichthyosis in Children
NCT00004690	PHASE3	COMPLETED	Phase III Study of Monolaurin Cream Therapy for Patients With Congenital Ichthyosis
NCT05295732	PHASE3	COMPLETED	The ASCEND Study: Evaluating TMB-001 in the Treatment of RXLI or ARCI Ichthyosis
NCT03041038	PHASE2	COMPLETED	The Efficacy and Safety of Secukinumab in Patients With Ichthyoses
NCT02864082	PHASE2	COMPLETED	A Safety and Tolerability Study of Topical PAT-001 in Congenital Ichthyosis
NCT04154293	PHASE2	COMPLETED	A Vehicle Controlled Study to Evaluate Safety and Efficacy of Topical TMB-001 for Treatment of Congenital Ichthyosis
NCT04697056	PHASE2	TERMINATED	A Study to Evaluate the Efficacy and Safety of Imsidolimab (ANB019) in the Treatment of Participants With Ichthyosis
NCT06136403	PHASE2	RECRUITING	A 44-week Monocentric Open Study Assessing the Efficacy and Safety of Deucravacitinib in Adults With Inflammatory Genodermatoses
NCT06362447	PHASE2	NOT_YET_RECRUITING	Efficacy of Injectable Gentamicin in Hereditary Ichthyosis
NCT06545695	PHASE1/PHASE2	NOT_YET_RECRUITING	Epidermal Growth Factor Receptor Inhibition for Keratinopathies
NCT05312073	Not specified	COMPLETED	Study of in Vivo and in Vitro Transcriptomic and Proteomic Signatures in Unhereditary Ichtyosis
NCT04549792	EARLY_PHASE1	COMPLETED	An Open-Label and Long-Term Extension Study to Evaluate the Efficacy and Safety of Ustekinumab in the Treatment of Patients With Ichthyoses
NCT07050810	EARLY_PHASE1	ENROLLING_BY_INVITATION	Thera-Clean® Microbubbles System in Patients With Skin Diseases
NCT00074685	Not specified	COMPLETED	National Registry for Ichthyosis and Related Disorders
NCT02655861	Not specified	TERMINATED	A Multi-center, Prospective Evaluation of Infants and Children With Congenital Ichthyosis
NCT03051347	Not specified	COMPLETED	Asthma and Atopic Dermatitis Validation of PROMIS Pediatric Instruments
NCT03417856	Not specified	ENROLLING_BY_INVITATION	Defining the Skin and Blood Biomarkers of Ichthyosis
NCT03464994	Not specified	COMPLETED	Ophthalmological Abnormalities in Hereditary Ichthyosis (ICHTYO-KERATO)
NCT03641261	Not specified	COMPLETED	Therapeutic Education Using an Internet Application in Hereditary Ichthyosis
NCT03796052	Not specified	COMPLETED	Study Determining Safety and Efficacy of Avena Sativa (Oat) Skincare Products for Treating Skin Dryness and Itching in Cancer Patients
NCT05610306	Not specified	COMPLETED	Quality of Life in Middle-aged and Older Patients With Congenital Ichthyosis
NCT05954416	Not specified	RECRUITING	FARD (RaDiCo Cohort) (RaDiCo-FARD)
NCT06123091	Not specified	UNKNOWN	Exploring Patient Reported Outcomes in Inherited Ichthyosis
NCT06330324	Not specified	ENROLLING_BY_INVITATION	Reproductive Options in Inherited Skin Diseases
NCT06330350	Not specified	RECRUITING	Qualitative Study in Patients With Genodermatoses and Healthcare Professionals on Reproductive Counselling
NCT07066150	Not specified	COMPLETED	A Clinical Evaluation of Marula-Derived Ceramide Cream on Skin Barrier Function Enhancement