KRT2 (keratin 2)

Gene

• Entrez ID: 3849
• Gene name: Keratin 2
• Gene symbol: KRT2
• Synonyms (NCBI Gene): CK-2e, K2e, KRT2A, KRT2E, KRTE
• Chromosome: 12
• Chromosome location: 12q13.13
• Summary: 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 ep

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs56829062	C>T	Not-provided, pathogenic	Missense variant, coding sequence variant
rs57510142	T>A,G	Not-provided, pathogenic	Missense variant, coding sequence variant
rs137852628	C>A,T	Pathogenic, not-provided	Coding sequence variant, synonymous variant, missense variant
rs137852629	C>A,T	Pathogenic, not-provided	Coding sequence variant, stop gained, missense variant
rs137852630	T>C,G	Pathogenic, not-provided	Coding sequence variant, missense variant
rs137852631	T>A,C	Pathogenic, not-provided	Coding sequence variant, missense variant
rs137852632	G>T	Pathogenic, not-provided	Coding sequence variant, missense variant
rs1064795317	A>G	Likely-pathogenic	Missense variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT1101211	hsa-miR-1299	CLIP-seq
MIRT1101212	hsa-miR-3148	CLIP-seq
MIRT1101213	hsa-miR-323-5p	CLIP-seq
MIRT1101214	hsa-miR-3689a-3p	CLIP-seq
MIRT1101215	hsa-miR-3689c	CLIP-seq
MIRT1101216	hsa-miR-4447	CLIP-seq
MIRT1101217	hsa-miR-4472	CLIP-seq
MIRT1101218	hsa-miR-4488	CLIP-seq
MIRT1101219	hsa-miR-4643	CLIP-seq
MIRT1101220	hsa-miR-466	CLIP-seq
MIRT1101221	hsa-miR-4697-5p	CLIP-seq
MIRT1101222	hsa-miR-4785	CLIP-seq
MIRT1101223	hsa-miR-4789-3p	CLIP-seq
MIRT1101224	hsa-miR-541	CLIP-seq
MIRT1101225	hsa-miR-654-5p	CLIP-seq
MIRT1101226	hsa-miR-875-3p	CLIP-seq
MIRT1101227	hsa-miR-876-3p	CLIP-seq
MIRT2027566	hsa-miR-28-5p	CLIP-seq
MIRT2027567	hsa-miR-3139	CLIP-seq
MIRT2027568	hsa-miR-4633-3p	CLIP-seq
MIRT2027569	hsa-miR-708	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001533	Component	Cornified envelope	IDA	7543090
GO:0003334	Process	Keratinocyte development	IEA
GO:0005200	Function	Structural constituent of cytoskeleton	TAS	1380918
GO:0005515	Function	Protein binding	IPI	25416956, 25910212, 29892012, 31515488, 32296183
GO:0005615	Component	Extracellular space	HDA	23580065
GO:0005634	Component	Nucleus	HDA	21630459
GO:0005737	Component	Cytoplasm	IDA	32179842
GO:0005737	Component	Cytoplasm	IEA
GO:0005829	Component	Cytosol	IDA
GO:0005829	Component	Cytosol	IEA
GO:0005829	Component	Cytosol	TAS
GO:0005882	Component	Intermediate filament	IEA
GO:0005882	Component	Intermediate filament	TAS	1380918
GO:0008092	Function	Cytoskeletal protein binding	IEA
GO:0008544	Process	Epidermis development	IEA
GO:0008544	Process	Epidermis development	TAS	7524919
GO:0016020	Component	Membrane	HDA	19946888
GO:0018149	Process	Peptide cross-linking	IDA	7543090
GO:0030280	Function	Structural constituent of skin epidermis	IBA
GO:0030280	Function	Structural constituent of skin epidermis	IDA	7543090
GO:0030280	Function	Structural constituent of skin epidermis	IEA
GO:0031424	Process	Keratinization	IBA
GO:0031424	Process	Keratinization	IDA	12598329
GO:0032980	Process	Keratinocyte activation	IDA	12598329
GO:0043616	Process	Keratinocyte proliferation	IDA	12598329
GO:0045095	Component	Keratin filament	IBA
GO:0045095	Component	Keratin filament	IEA
GO:0045109	Process	Intermediate filament organization	IBA
GO:0045109	Process	Intermediate filament organization	IEA
GO:0045111	Component	Intermediate filament cytoskeleton	IDA
GO:0045684	Process	Positive regulation of epidermis development	IEA
GO:0045684	Process	Positive regulation of epidermis development	ISS
GO:0051546	Process	Keratinocyte migration	IDA	15737202
GO:0070062	Component	Extracellular exosome	HDA	19199708, 23533145

Other IDs

• MIM: 600194
• HGNC: 6439
• e!Ensembl: ENSG00000172867

Protein

• UniProt ID: P35908
• Protein name: Keratin, type II cytoskeletal 2 epidermal (Cytokeratin-2e) (CK-2e) (Epithelial keratin-2e) (Keratin-2 epidermis) (Keratin-2e) (K2e) (Type-II keratin Kb2)
• Protein function: Probably contributes to terminal cornification (PubMed:1380918). Associated with keratinocyte activation, proliferation and keratinization (PubMed:12598329). Required for maintenance of corneocytes and keratin filaments in suprabasal keratinocyt
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF16208	Keratin_2_head	21 → 174	Keratin type II head	Family
  PF00038	Filament	177 → 490	Intermediate filament protein	Coiled-coil

• Tissue specificity: TISSUE SPECIFICITY: Expressed in the upper spinous and granular suprabasal layers of normal adult epidermal tissues from most body sites including thigh, breast nipple, foot sole, penile shaft and axilla. Not present in foreskin, squamous metaplasias and
• Sequence:

  MSCQISCKSRGRGGGGGGFRGFSSGSAVVSGGSRRSTSSFSCLSRHGGGGGGFGGGGFGS
  RSLVGLGGTKSISISVAGGGGGFGAAGGFGGRGGGFGGGSSFGGGSGFSGGGFGGGGFGG
  GRFGGFGGPGGVGGLGGPGGFGPGGYPGGIHEVSVNQSLLQPLNVKVDPEIQNVKAQERE
  QIKTLNNKFASFIDKVRFLEQQNQVLQTKWELLQQMNVGTRPINLEPIFQGYIDSLKRYL
  DGLTAERTSQNSELNNMQDLVEDYKKKYEDEINKRTAAENDFVTLKKDVDNAYMIKVELQ
  SKVDLLNQEIEFLKVLYDAEISQIHQSVTDTNVILSMDNSRNLDLDSIIAEVKAQYEEIA
  QRSKEEAEALYHSKYEELQVTVGRHGDSLKEIKIEISELNRVIQRLQGEIAHVKKQCKNV
  QDAIADAEQRGEHALKDARNKLNDLEEALQQAKEDLARLLRDYQELMNVKLALDVEIATY
  RKLLEGEECRMSGDLSSNVTVSVTSSTISSNVASKAAFGGSGGRGSSSGGGYSSGSSSYG
  SGGRQSGSRGGSGGGGSISGGGYGSGGGSGGRYGSGGGSKGGSISGGGYGSGGGKHSSGG
  GSRGGSSSGGGYGSGGGGSSSVKGSSGEAFGSSVTFSFR

• Sequence length: 639

Pathways

Reactome:

Keratinization
Formation of the cornified envelope

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Exfoliative ichthyosis	Pathogenic	rs137852629	RCV000009895	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Ichthyosis bullosa of Siemens	Pathogenic; Likely pathogenic	rs137852628, rs137852629, rs57510142, rs137852630, rs137852631, rs56829062, rs137852632, rs2498607356, rs61726452	RCV000009893 RCV000009894 RCV000009896 RCV000009897 RCV000009898 RCV000009899 RCV000009900 RCV000009901 RCV004586429 RCV005007985	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Clear cell carcinoma of kidney	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colorectal cancer	Benign	ClinVar GWAS catalog	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
CONTACT DERMATITIS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DERMATITIS, CONTACT	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ICHTHYOSES	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
KRT2-related disorder	Uncertain significance; Benign; Conflicting classifications of pathogenicity; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
XERODERMA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Autosomal dominant ichthyosis	Ichthyosis	GENOMICS_ENGLAND_DG			★☆☆☆☆ Found in Text Mining only
Blister	Blister	Pubtator	32881395	Associate	★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	22228641		★☆☆☆☆ Found in Text Mining only
Congenital reticular ichthyosiform erythroderma	Congenital Reticular Ichthyosiform Erythroderma	BEFREE	26581228		★☆☆☆☆ Found in Text Mining only
Contact Dermatitis	Dermatitis	CTD_human_DG	25724174		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Diabetic Retinopathy	Diabetic retinopathy	Pubtator	39619568	Associate	★☆☆☆☆ Found in Text Mining only
Epidermolysis Bullosa Simplex	Epidermolysis bullosa	Pubtator	9036937	Associate	★☆☆☆☆ Found in Text Mining only
Hyperkeratosis Epidermolytic	Epidermolytic hyperkeratosis	Pubtator	26581228, 32881395, 33081034, 35887135, 7521371, 8077693	Associate	★☆☆☆☆ Found in Text Mining only
Hyperkeratosis, Epidermolytic	Hyperkeratosis, Epidermolytic	BEFREE	10564334, 11531804, 26581228, 7524919, 8077693		★☆☆☆☆ Found in Text Mining only
Hyperkeratosis, Epidermolytic	Hyperkeratosis, Epidermolytic	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ichthyoses	Ichthyosis	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ichthyosiform Erythroderma Congenital	Congenital ichthyosiform erythroderma	Pubtator	32881395	Associate	★☆☆☆☆ Found in Text Mining only
Ichthyosis	Ichthyosis	Pubtator	10620137, 26581228, 32881395, 33081034, 7521372, 8077693, 9036937, 9204966, 9804344, 9833038	Associate	★☆☆☆☆ Found in Text Mining only
Ichthyosis Bullosa of Siemens	Ichthyosis Bullosa Of Siemens	BEFREE	10084318, 10564334, 10620137, 10688369, 11167982, 11531804, 7521371, 7521372, 7524919, 8077693, 8820401, 9036937, 9036938, 9204966, 9804344, 9833038		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Ichthyosis Bullosa of Siemens	Ichthyosis Bullosa Of Siemens	UNIPROT_DG	10084318, 10233323, 10564334, 10620137, 10688369, 11167982, 11531804, 15949009, 7521371, 7524919, 8077693, 9036938, 9204966, 9804344, 9833038		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Ichthyosis Bullosa of Siemens	Junctional epidermolysis bullosa	Pubtator	10084318, 7521371, 9036938	Associate	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Ichthyosis Bullosa of Siemens	Ichthyosis Bullosa Of Siemens	ORPHANET_DG	15949009		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Ichthyosis Bullosa of Siemens	Ichthyosis Bullosa Of Siemens	GENOMICS_ENGLAND_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Ichthyosis Bullosa of Siemens	Ichthyosis Bullosa Of Siemens	CLINVAR_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Ichthyosis Bullosa of Siemens	Ichthyosis Bullosa Of Siemens	CTD_human_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
ICHTHYOSIS EXFOLIATIVA	Ichthyosis Exfoliativa	BEFREE	7521372		★☆☆☆☆ Found in Text Mining only
ICHTHYOSIS EXFOLIATIVA	Ichthyosis Exfoliativa	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Keratoderma, Palmoplantar	Palmoplantar keratoderma	BEFREE	26603179		★☆☆☆☆ Found in Text Mining only
Keratoderma, Palmoplantar	Palmoplantar keratoderma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Lupus Erythematosus Systemic	Systemic lupus erythematosus	Pubtator	19089296	Associate	★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	22228641		★☆☆☆☆ Found in Text Mining only
Melanoma	Melanoma	Pubtator	33441834	Associate	★☆☆☆☆ Found in Text Mining only
Myasthenia Gravis	Myasthenia gravis	Pubtator	35802752	Associate	★☆☆☆☆ Found in Text Mining only
Periodontitis	Periodontitis	Pubtator	27531006	Inhibit	★☆☆☆☆ Found in Text Mining only
Skin Diseases	Skin disease	Pubtator	32045015	Associate	★☆☆☆☆ Found in Text Mining only
Superficial epidermolytic ichthyosis	Superficial Epidermolytic Ichthyosis	Orphanet			★☆☆☆☆ Found in Text Mining only