KRT2

Summary

KRT2 (keratin 2, HGNC:6439) is a protein-coding gene on chromosome 12q13.13, encoding Keratin, type II cytoskeletal 2 epidermal (P35908). Probably contributes to terminal cornification.

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. This type II cytokeratin is expressed largely in the upper spinous layer of epidermal keratinocytes and mutations in this gene have been associated with bullous congenital ichthyosiform erythroderma. The type II cytokeratins are clustered in a region of chromosome 12q12-q13.

Source: NCBI Gene 3849 — RefSeq curated summary.

At a glance

• Gene–disease (curated): superficial epidermolytic ichthyosis (Definitive, GenCC)
• Clinical variants (ClinVar): 242 total — 7 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 9
• MANE Select transcript: NM_000423

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6439
Approved symbol	KRT2
Name	keratin 2
Location	12q13.13
Locus type	gene with protein product
Status	Approved
Aliases	KRTE
Ensembl gene	ENSG00000172867
Ensembl biotype	protein_coding
OMIM	600194
Entrez	3849

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 retained_intron

ENST00000309680, ENST00000547106

RefSeq mRNA: 1 — MANE Select: NM_000423 NM_000423

CCDS: CCDS8835

Canonical transcript exons

ENST00000309680 — 9 exons

Exon	Start	End
ENSE00001192222	52645535	52645569
ENSE00001192233	52647730	52647855
ENSE00001192250	52650339	52650553
ENSE00001192257	52644558	52645434
ENSE00001192260	52651558	52652211
ENSE00001415508	52648173	52648337
ENSE00001649806	52646740	52646960
ENSE00003499848	52649007	52649102
ENSE00003680611	52649914	52649974

Expression profiles

Bgee: expression breadth ubiquitous, 162 present calls, max score 99.82.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.7926 / max 1126.3446, expressed in 13 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
131106	0.7926	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper arm skin	UBERON:0004263	99.82	gold quality
upper leg skin	UBERON:0004262	99.68	gold quality
skin of hip	UBERON:0001554	99.63	gold quality
skin of leg	UBERON:0001511	99.05	gold quality
zone of skin	UBERON:0000014	98.56	gold quality
skin of abdomen	UBERON:0001416	98.55	gold quality
nipple	UBERON:0002030	96.22	gold quality
penis	UBERON:0000989	92.67	gold quality
cervix squamous epithelium	UBERON:0006922	87.49	silver quality
cervix epithelium	UBERON:0004801	85.50	gold quality
gingival epithelium	UBERON:0001949	83.53	gold quality
gingiva	UBERON:0001828	82.12	gold quality
mammalian vulva	UBERON:0000997	80.75	gold quality
tongue squamous epithelium	UBERON:0006919	75.85	gold quality
palpebral conjunctiva	UBERON:0001812	74.22	gold quality
gastrocnemius	UBERON:0001388	72.04	gold quality
squamous epithelium	UBERON:0006914	71.45	gold quality
lower esophagus mucosa	UBERON:0035834	69.28	gold quality
apex of heart	UBERON:0002098	68.96	gold quality
oviduct epithelium	UBERON:0004804	68.21	gold quality
ileal mucosa	UBERON:0000331	67.83	gold quality
tibialis anterior	UBERON:0001385	67.59	silver quality
heart left ventricle	UBERON:0002084	67.06	gold quality
popliteal artery	UBERON:0002250	66.52	gold quality
tibial artery	UBERON:0007610	66.44	gold quality
cardiac ventricle	UBERON:0002082	66.18	gold quality
right lung	UBERON:0002167	66.10	gold quality
muscle of leg	UBERON:0001383	65.67	gold quality
right adrenal gland cortex	UBERON:0035827	65.53	gold quality
right atrium auricular region	UBERON:0006631	65.27	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.23

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

34 targeting KRT2, 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-548AW	99.99	72.57	3559
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-4756-3P	99.62	66.30	1319
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-12131	99.48	68.72	1673
HSA-MIR-548G-3P	99.48	68.67	2159
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-3138	98.41	67.53	744
HSA-MIR-92A-1-5P	98.28	64.51	631
HSA-MIR-6788-5P	97.80	66.41	1532
HSA-MIR-30C-1-3P	97.80	66.36	1499
HSA-MIR-30C-2-3P	97.80	66.45	1499
HSA-MIR-4308	97.56	67.13	1385
HSA-MIR-6859-3P	97.26	64.69	428
HSA-MIR-5192	96.89	63.35	879
HSA-MIR-582-3P	96.69	67.38	1019
HSA-MIR-3139	96.68	66.77	652

Literature-anchored findings (GeneRIF, showing 7)

• influence of keratinocyte activation, proliferation, and keratinization on K2e expression in samples of cutaneous and oral lesions (keratin K2e) (PMID:12598329)
• novel H1 domain mutation in a family with icthyosis bullosa Siemens (PMID:17408392)
• We describe two children with superficial epidermolytic ichthyosis confirmed by genetic testing, including one with a novel mutation. (PMID:22612346)
• Report genetic/clinical spectrum of KRT2 mutations in keratinopathic ichthyosis. (PMID:26581228)
• Serum lipids, retinoic acid and phenol red differentially regulate expression of keratins K1, K10 and K2 in cultured keratinocytes. (PMID:32179842)
• First Case of KRT2 Epidermolytic Nevus and Novel Clinical and Genetic Findings in 26 Italian Patients with Keratinopathic Ichthyoses. (PMID:33081034)
• Acral lamellar ichthyosis with amino acid substitution in the C-terminus of keratin 2. (PMID:36331357)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Krt2	ENSMUSG00000064201
rattus_norvegicus	Krt2	ENSRNOG00000009563

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 2 epidermal — P35908 (reviewed: P35908)

Alternative names: Cytokeratin-2e, Epithelial keratin-2e, Keratin-2 epidermis, Keratin-2e, Type-II keratin Kb2

All UniProt accessions (1): P35908

UniProt curated annotations — full annotation on UniProt →

Function. Probably contributes to terminal cornification. Associated with keratinocyte activation, proliferation and keratinization. Required for maintenance of corneocytes and keratin filaments in suprabasal keratinocytes in the epidermis of the ear, potentially via moderation of expression and localization of keratins and their partner proteins. Plays a role in the establishment of the epidermal barrier on plantar skin.

Subunit / interactions. Heterotetramer of two type I and two type II keratins. Associates with KRT10.

Subcellular location. Cytoplasm.

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 carcinomas. Expression in hypertrophic and keloid scars begins in the deepest suprabasal layer. Weakly expressed in normal gingiva and tongue, however expression is induced in benign keratoses of lingual mucosa and in mild-to-moderate oral dysplasia with orthokeratinization.

Disease relevance. Ichthyosis bullosa of Siemens (IBS) [MIM:146800] A rare autosomal dominant skin disorder displaying a type of epidermolytic hyperkeratosis characterized by generalized erythema and extensive blistering from birth. Large, dark gray hyperkeratoses are observed in later weeks. The skin of IBS patients is unusually fragile and has a tendency to shed the outer layers of the epidermis, producing localized denuded areas (molting effect). IBS usually improves with age so that in most middle-aged patients the hyperkeratosis and keratotic lichenification is limited to the flexural folds of the major joints. The disease is caused by variants affecting the gene represented in this entry.

Induction. Induced in keratinocytes by all-trans retinoic acid (ATRA), via increase in mRNA stability.

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_000414* (*=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 (39 total): sequence variant 18, region of interest 9, modified residue 5, compositionally biased region 3, chain 1, domain 1, site 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P35908-F1	67.38	0.37

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): 429 (stutter)

Post-translational modifications (5): 12, 20, 23, 26, 62

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: 235 (showing top): MORF_ITGA2, SHEPARD_BMYB_MORPHOLINO_UP, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_INTERMEDIATE_FILAMENT_BASED_PROCESS, MORF_MSH3, GOBP_INTERMEDIATE_FILAMENT_ORGANIZATION, GOBP_REGULATION_OF_EPIDERMIS_DEVELOPMENT, GOBP_EPITHELIAL_CELL_DEVELOPMENT, GOBP_KERATINOCYTE_PROLIFERATION, GCANCTGNY_MYOD_Q6, MORF_BRCA1, DARWICHE_SKIN_TUMOR_PROMOTER_DN, DARWICHE_PAPILLOMA_RISK_LOW_DN, DARWICHE_PAPILLOMA_RISK_HIGH_DN, DARWICHE_SQUAMOUS_CELL_CARCINOMA_DN

GO Biological Process (10): keratinocyte development (GO:0003334), epidermis development (GO:0008544), keratinization (GO:0031424), keratinocyte activation (GO:0032980), keratinocyte proliferation (GO:0043616), intermediate filament organization (GO:0045109), positive regulation of epidermis development (GO:0045684), keratinocyte migration (GO:0051546), cornification (GO:0070268), peptide cross-linking (GO:0018149)

GO Molecular Function (4): structural constituent of cytoskeleton (GO:0005200), cytoskeletal protein binding (GO:0008092), structural constituent of skin epidermis (GO:0030280), protein binding (GO:0005515)

GO Cellular Component (10): cornified envelope (GO:0001533), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), intermediate filament (GO:0005882), membrane (GO:0016020), keratin filament (GO:0045095), intermediate filament cytoskeleton (GO:0045111), extracellular exosome (GO:0070062)

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
cellular anatomical structure	3
keratinocyte differentiation	2
structural molecule activity	2
cytoskeleton	2
epithelial cell development	1
tissue development	1
multicellular organismal process	1
cell activation	1
epithelial cell proliferation	1
intermediate filament cytoskeleton organization	1
supramolecular fiber organization	1
epidermis development	1
regulation of epidermis development	1
positive regulation of developmental process	1
epithelial cell migration	1
programmed cell death	1
keratinization	1
cornified envelope assembly	1
protein modification process	1
cytoskeleton organization	1
protein binding	1
binding	1
plasma membrane	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
intermediate filament cytoskeleton	1
polymeric cytoskeletal fiber	1
intermediate filament	1
extracellular vesicle	1

Protein interactions and networks

STRING

1321 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KRT2	SOAT2	O75908	736
KRT2	IGFBP6	P24592	660
KRT2	RARG	P13631	558
KRT2	FLG2	Q5D862	523
KRT2	DSG1	Q02413	519
KRT2	KRTDAP	P60985	496
KRT2	SBSN	Q6UWP8	489
KRT2	TGM1	P22735	485
KRT2	FLG	P20930	480
KRT2	LORICRIN	P23490	479
KRT2	NIPAL4	Q0D2K0	479
KRT2	KRT9	P35527	475
KRT2	CYP4F22	Q6NT55	453
KRT2	PNPLA1	Q8N8W4	446
KRT2	KRT6B	P04259	443

IntAct

146 interactions, top by confidence:

A	B	Type	Score
KRT19	KRT2	psi-mi:“MI:0915”(physical association)	0.850
KRT2	KRT19	psi-mi:“MI:0915”(physical association)	0.850
KRT38	KRT2	psi-mi:“MI:0915”(physical association)	0.840
KRT2	KRT38	psi-mi:“MI:0915”(physical association)	0.840
KRT31	KRT2	psi-mi:“MI:0915”(physical association)	0.810
KRT40	KRT2	psi-mi:“MI:0915”(physical association)	0.810
KRT2	KRT31	psi-mi:“MI:0915”(physical association)	0.810
KRT2	KRT40	psi-mi:“MI:0915”(physical association)	0.810

BioGRID (316): KRT13 (Two-hybrid), KRT19 (Two-hybrid), KRT31 (Two-hybrid), KRT38 (Two-hybrid), KRT40 (Two-hybrid), KRT2 (Affinity Capture-RNA), KRT2 (Affinity Capture-MS), KRT2 (Affinity Capture-MS), KRT2 (Affinity Capture-MS), KRT10 (Co-fractionation), KRT2 (Co-fractionation), KRT5 (Co-fractionation), KRT77 (Co-fractionation), PRSS1 (Co-fractionation), KRT2 (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: A0A125S9M6, A0JND2, A4FUZ0, A5A6M8, A6NCN2, A7YWK3, O43790, P02542, P02545, P02547, P02548, P04104, P04260, P04261, P04262, P04263, P07196, P07744, P08551, P08928, P09010, P10999, P12035, P12036, P13647, P13648, P15241, P16884, P19013, P19246, P19527, P21619, P21910, P25691, P35908, P48671, P48672, P48678, P48679, P78385

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 95 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	13	16.6×	3e-10
Regulation of RAS by GAPs	5	14.0×	3e-04
Keratinization	13	10.5×	5e-08
Macroautophagy	6	10.0×	3e-04
Neddylation	12	8.2×	3e-06
Cargo recognition for clathrin-mediated endocytosis	5	7.6×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
morphogenesis of an epithelium	13	55.9×	4e-17
intermediate filament organization	14	42.1×	5e-17
intrinsic apoptotic signaling pathway	7	31.4×	3e-07
epithelial cell differentiation	11	24.1×	2e-10
autophagosome maturation	5	21.9×	2e-04
mitophagy	5	19.9×	3e-04
autophagosome assembly	6	16.9×	1e-04
G1/S transition of mitotic cell cycle	6	15.1×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	4
Uncertain significance	117
Likely benign	29
Benign	58

Top pathogenic / likely-pathogenic (11)

Variant ID	HGVS	Classification
9309	NM_000423.3(KRT2):c.1461G>T (p.Glu487Asp)	Pathogenic
9310	NM_000423.3(KRT2):c.1459G>A (p.Glu487Lys)	Pathogenic
9312	NM_000423.3(KRT2):c.1435A>C (p.Thr479Pro)	Pathogenic
9313	NM_000423.3(KRT2):c.556A>T (p.Asn186Tyr)	Pathogenic
9314	NM_000423.3(KRT2):c.1426G>A (p.Glu476Lys)	Pathogenic
9315	NM_000423.3(KRT2):c.556A>G (p.Asn186Asp)	Pathogenic
9316	NM_000423.3(KRT2):c.558C>A (p.Asn186Lys)	Pathogenic
1700990	NM_000423.3(KRT2):c.1430T>A (p.Ile477Asn)	Likely pathogenic
3251985	NM_000423.3(KRT2):c.557A>G (p.Asn186Ser)	Likely pathogenic
66192	NM_000423.3(KRT2):c.1462G>A (p.Glu488Lys)	Likely pathogenic
9311	NM_000423.3(KRT2):c.542A>C (p.Gln181Pro)	Likely pathogenic

SpliceAI

1538 predictions. Top by Δscore:

Variant	Effect	Δscore
12:52645432:CAG:C	acceptor_gain	1.0000
12:52645529:A:AC	donor_gain	1.0000
12:52645530:C:CC	donor_gain	1.0000
12:52645533:A:AC	donor_gain	1.0000
12:52645534:C:CC	donor_gain	1.0000
12:52645534:CA:C	donor_gain	1.0000
12:52645534:CACA:C	donor_gain	1.0000
12:52645566:CATC:C	acceptor_gain	1.0000
12:52645568:TC:T	acceptor_gain	1.0000
12:52645569:CCTG:C	acceptor_gain	1.0000
12:52645569:CCTGT:C	acceptor_loss	1.0000
12:52645570:C:CC	acceptor_gain	1.0000
12:52645570:CTGT:C	acceptor_loss	1.0000
12:52646734:CCTCA:C	donor_loss	1.0000
12:52646735:CTCA:C	donor_loss	1.0000
12:52646736:TCAC:T	donor_loss	1.0000
12:52646738:A:AC	donor_gain	1.0000
12:52646739:C:CC	donor_gain	1.0000
12:52646739:C:T	donor_loss	1.0000
12:52646956:TTACA:T	acceptor_gain	1.0000
12:52646958:ACAC:A	acceptor_loss	1.0000
12:52646959:CA:C	acceptor_gain	1.0000
12:52646960:ACTA:A	acceptor_loss	1.0000
12:52646961:C:CC	acceptor_gain	1.0000
12:52646967:C:CT	acceptor_gain	1.0000
12:52647725:CTCA:C	donor_loss	1.0000
12:52647726:TCA:T	donor_loss	1.0000
12:52647727:CACC:C	donor_loss	1.0000
12:52647728:ACCT:A	donor_loss	1.0000
12:52647729:CCTG:C	donor_gain	1.0000

AlphaMissense

4134 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:52646791:A:G	L473P	0.999
12:52649917:T:A	K286N	0.999
12:52649917:T:G	K286N	0.999
12:52651576:A:C	F189L	0.999
12:52651576:A:T	F189L	0.999
12:52651578:A:G	F189L	0.999
12:52646930:C:G	A427P	0.998
12:52648196:C:G	A367P	0.998
12:52649918:T:A	K286I	0.998
12:52650513:T:A	K209I	0.998
12:52651577:A:C	F189C	0.998
12:52651577:A:G	F189S	0.998
12:52646761:A:G	L483P	0.997
12:52646799:C:A	K470N	0.997
12:52646799:C:G	K470N	0.997
12:52646812:A:G	L466P	0.997
12:52647845:A:G	L378P	0.997
12:52650534:T:G	Q202P	0.997
12:52651585:G:C	N186K	0.997
12:52651585:G:T	N186K	0.997
12:52651586:T:A	N186I	0.997
12:52651589:A:G	L185P	0.997
12:52646767:C:G	R481P	0.996
12:52646771:A:G	Y480H	0.996
12:52646777:C:G	A478P	0.996
12:52646782:T:A	E476V	0.996
12:52646897:C:G	A438P	0.996
12:52649919:T:C	K286E	0.996
12:52649951:C:G	R275P	0.996
12:52650543:A:G	L199S	0.996

dbSNP variants (sampled 300 via entrez): RS1001004301 (12:52647155 C>A,T), RS1001108406 (12:52646741 T>A), RS1001841552 (12:52653956 C>A), RS1001959077 (12:52653712 G>A), RS1002510295 (12:52647784 C>G), RS1002822063 (12:52648516 G>A), RS1002895092 (12:52649829 T>C), RS1003610000 (12:52645350 C>G), RS1004235173 (12:52650595 C>T), RS1004739004 (12:52644750 G>A), RS1005026443 (12:52649270 C>T), RS1005663001 (12:52646613 T>A,C), RS1005784766 (12:52652458 G>T), RS1005858176 (12:52651284 C>A,T), RS1005940283 (12:52652667 G>A,T)

Disease associations

OMIM: gene MIM:600194 | disease phenotypes: MIM:146800

GenCC curated gene-disease

Disease	Classification	Inheritance
superficial epidermolytic ichthyosis	Definitive	Autosomal dominant

Mondo (2): superficial epidermolytic ichthyosis (MONDO:0007813), exfoliative ichthyosis (MONDO:0017339)

Orphanet (2): Superficial epidermolytic ichthyosis (Orphanet:455), Exfoliative ichthyosis (Orphanet:289586)

HPO phenotypes

9 total (9 of 9 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000963	Thin skin
HP:0000969	Edema
HP:0000982	Palmoplantar keratoderma
HP:0007475	Congenital bullous ichthyosiform erythroderma
HP:0008064	Ichthyosis
HP:0008066	Abnormal blistering of the skin
HP:0010783	Erythema
HP:0100792	Acantholysis

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D053560	Ichthyosis Bullosa of Siemens	C16.131.831.512.408; C16.320.850.402; C16.614.492.410; C17.800.428.333.330; C17.800.804.512.405; C17.800.827.403

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	affects expression, decreases expression	3
apocarotenal	increases expression	1
sodium arsenate	decreases expression, increases abundance	1
microcystin RR	decreases expression	1
CGP 52608	affects binding, increases reaction	1
bisphenol B	increases expression	1
abrine	increases expression	1
bromovanin	decreases expression	1
Aerosols	decreases expression	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Cadmium	affects binding	1
Calcitriol	increases expression, affects cotreatment	1
Copper	affects binding	1
Dinitrochlorobenzene	affects binding	1
Doxorubicin	affects expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ivermectin	decreases expression	1
Lead	affects binding	1
Nickel	affects binding	1
Phenytoin	increases expression	1
Silicon Dioxide	affects secretion	1
Sodium Dodecyl Sulfate	increases expression	1
Testosterone	affects cotreatment, increases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Tretinoin	increases expression	1
Zinc	affects binding	1
beta Carotene	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01667627	PHASE4	COMPLETED	Probiotic in Irritable Bowel Syndrome (IBS) Patients With Diarrhea
NCT01779765	PHASE4	UNKNOWN	The Efficacy of Hydrolyzed Guar Gum ( PHGG) in the Treatment of Patients With Irritable Bowel Syndrome (IBS)
NCT02937506	PHASE4	COMPLETED	Patient Satisfaction With Propofol for Out Patient Colonoscopy
NCT05995899	PHASE4	COMPLETED	Effect of Tenapanor on the Metagenomics and Metabolomics of Patients With Irritable Bowel Syndrome With Constipation
NCT07426705	PHASE4	NOT_YET_RECRUITING	Effect of Multispecies Probiotic Supplementation on the Efficacy of Rifaximin α Therapy in Patients With Small Intestinal Bacterial Overgrowth (SIBO): a Randomized Placebo-controlled Trial
NCT05815602	PHASE3	RECRUITING	Ebastine Versus Mebeverine in IBS Patients
NCT07168434	PHASE3	RECRUITING	Saccharomyces Boulardii CNCM I-745 in Irritable Bowel Syndrome
NCT06727422	PHASE2	RECRUITING	Efficacy of Rifaximin With NAC in IBS-D
NCT01717404	PHASE1	COMPLETED	Effects of Mexiletine on Colonic Transit in a Patient With Irritable Bowel Syndrome - Constipation (IBS-C)
NCT01276626	PHASE1/PHASE2	COMPLETED	Study of Bacteria on Mood and Bowel Symptoms in Patients With Irritable Bowel Syndrome
NCT07238790	EARLY_PHASE1	NOT_YET_RECRUITING	Use of A Complex Gut Bacterial Consortium (MITI 001) for the Treatment of Irritable Bowel Syndrome With Diarrhea
NCT00179582	Not specified	TERMINATED	Dose Ranging Study With the Probiotic Combination (VSL#3) in Diarrhea IBS
NCT00248586	Not specified	COMPLETED	Development of Limited Contact CBT Treatment for IBS
NCT01912313	Not specified	RECRUITING	Measuring Nerve Activity in Small Human Intestinal Biopsies in IBS (Irritable Bowel Syndrome)
NCT02009618	Not specified	COMPLETED	The Effects of Rifaximin Therapy in Irritable Bowel Syndrome
NCT02293343	Not specified	COMPLETED	24 Hrs Histamine Profile in Healthy Persons and Patients With Food Intolerance
NCT02313207	Not specified	WITHDRAWN	Confocal Laser Endomicroscopy in IBS Patients
NCT02419963	Not specified	COMPLETED	Analyzing IBS to Identify Biomarkers and Microbiome Signatures
NCT02421705	Not specified	RECRUITING	Visceral Sensitivity in IBD (Irritable Bowel Disease) and IBS (Irritable Bowel Syndrome)
NCT02436603	Not specified	COMPLETED	Integrative Approaches to Managing Irritable Bowel Syndrome (IBS)
NCT02536131	Not specified	COMPLETED	Intestinal Microbiome and Psychological Correlates in Irritable Bowel Syndrome and Inflammatory Bowel Disease
NCT02681666	Not specified	COMPLETED	Mindfulness-Based Eating in Patients With Irritable Bowel Syndrome
NCT02920268	Not specified	COMPLETED	Just in TIME - Intervention With Dance and Yoga for Girls With Recurrent Abdominal Pain
NCT02981888	Not specified	COMPLETED	Fecal Metabolome and the Intestinal Microbiota in Irritable Bowel Syndrome
NCT03482765	Not specified	COMPLETED	A Study of Probiotics in IBS Subjects
NCT03986476	Not specified	COMPLETED	The Effect of Two Probiotic Products on the Intestinal Barrier Function in Patients With Irritable Bowel Syndrome
NCT04031469	Not specified	SUSPENDED	A Non-Interventional Pilot Study to Explore the Role of Gut Flora in Disease
NCT04122586	Not specified	UNKNOWN	Mechanism of PERK - eIF2a Pathways in Intestinal Mucosal Barrier of IBS-D and the Role Metabolism Ingredients of Tongxieyaofang
NCT04677881	Not specified	COMPLETED	Health Effects of Different Types of Bread
NCT04953728	Not specified	COMPLETED	Optimization of Transcutaneous Electrical Acustimulation (TEA) Modalities for Treatment of IBS-C
NCT05579444	Not specified	TERMINATED	Systems Biology of Gastrointestinal and Related Diseases
NCT05718505	Not specified	UNKNOWN	Comparison of the Atmo Motility Gas Capsule System to the Reference Standard
NCT05737277	Not specified	UNKNOWN	Gabapral in Pediatric IBS
NCT06072287	Not specified	UNKNOWN	The Living With a Long-Term Condition Study
NCT06275906	Not specified	COMPLETED	Influence of a Mediterranean Diet Combined With a Physical Activity Intervention, on NAFLD and Inflammation Parameters.
NCT06389851	Not specified	COMPLETED	Effects of Tomato Consumption on Steatosis, Intestinal Function and Glucose and Lipid Metabolism in Subjects With NAFLD
NCT06618677	Not specified	COMPLETED	Efficacy of a Low FODMAP Diet in IBS Children and Impact on Urinary and Faecal Metabolome
NCT06757491	Not specified	RECRUITING	Lf-rTMS Attenuates Visceral Pain in Irritable Bowel Syndrome With Diarrhea
NCT06889779	Not specified	RECRUITING	Study Evaluating the Efficacy of Different Mixes of HMO-2FL + Humiome® Post LB on IBS Gastrointestinal Symptoms
NCT06945302	Not specified	COMPLETED	The Effect of Inulin Supplementation in Individuals With IBS-C