KRT7

Summary

KRT7 (keratin 7, HGNC:6445) is a protein-coding gene on chromosome 12q13.13, encoding Keratin, type II cytoskeletal 7 (P08729). Blocks interferon-dependent interphase and stimulates DNA synthesis in cells.

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 specifically expressed in the simple epithelia lining the cavities of the internal organs and in the gland ducts and blood vessels. The genes encoding the type II cytokeratins are clustered in a region of chromosome 12q12-q13. Alternative splicing may result in several transcript variants; however, not all variants have been fully described.

Source: NCBI Gene 3855 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 113 total
• MANE Select transcript: NM_005556

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6445
Approved symbol	KRT7
Name	keratin 7
Location	12q13.13
Locus type	gene with protein product
Status	Approved
Aliases	K7, CK7, CK-7, K2C7, SCL
Ensembl gene	ENSG00000135480
Ensembl biotype	protein_coding
OMIM	148059
Entrez	3855

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 12 protein_coding, 9 protein_coding_CDS_not_defined, 3 retained_intron

ENST00000331817, ENST00000546666, ENST00000546856, ENST00000547613, ENST00000548088, ENST00000548657, ENST00000549127, ENST00000549638, ENST00000550153, ENST00000551130, ENST00000552183, ENST00000552322, ENST00000552400, ENST00000888037, ENST00000888038, ENST00000888039, ENST00000888040, ENST00000888041, ENST00000955639, ENST00000955640, ENST00000955641, ENST00000955642, ENST00000955643, ENST00000955644

RefSeq mRNA: 1 — MANE Select: NM_005556 NM_005556

CCDS: CCDS8822

Canonical transcript exons

ENST00000331817 — 9 exons

Exon	Start	End
ENSE00000939323	52245412	52245632
ENSE00001652750	52237509	52237569
ENSE00002373298	52233243	52233620
ENSE00003512967	52241472	52241636
ENSE00003519392	52235155	52235366
ENSE00003629789	52243012	52243137
ENSE00003638188	52248177	52248211
ENSE00003638211	52248591	52248921
ENSE00003688832	52238680	52238775

Expression profiles

Bgee: expression breadth ubiquitous, 212 present calls, max score 99.70.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 239.7803 / max 14193.0254, expressed in 1166 samples.

FANTOM5 promoters (16 alternative TSS)

Promoter ID	TPM avg	Samples expressed
125591	231.2620	857
125601	1.7607	373
125599	1.3493	254
125588	1.3111	378
125602	1.1002	250
125606	0.7479	224
125589	0.4385	188
125604	0.3102	82
125603	0.2651	78
125590	0.2440	108

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left lobe of thyroid gland	UBERON:0001120	99.70	gold quality
right lobe of thyroid gland	UBERON:0001119	99.64	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.50	gold quality
thyroid gland	UBERON:0002046	99.45	gold quality
upper lobe of left lung	UBERON:0008952	99.39	gold quality
metanephros cortex	UBERON:0010533	99.30	gold quality
upper lobe of lung	UBERON:0008948	99.26	gold quality
right lung	UBERON:0002167	99.06	gold quality
lower esophagus mucosa	UBERON:0035834	98.51	gold quality
islet of Langerhans	UBERON:0000006	98.48	gold quality
right uterine tube	UBERON:0001302	98.38	gold quality
gall bladder	UBERON:0002110	98.29	gold quality
minor salivary gland	UBERON:0001830	98.22	gold quality
saliva-secreting gland	UBERON:0001044	98.05	gold quality
nasal cavity mucosa	UBERON:0001826	97.80	gold quality
placenta	UBERON:0001987	97.35	gold quality
nasal cavity epithelium	UBERON:0005384	96.71	gold quality
parotid gland	UBERON:0001831	96.56	gold quality
body of pancreas	UBERON:0001150	96.50	gold quality
palpebral conjunctiva	UBERON:0001812	95.91	gold quality
skin of leg	UBERON:0001511	95.45	gold quality
pancreas	UBERON:0001264	95.44	gold quality
trachea	UBERON:0003126	95.40	gold quality
lung	UBERON:0002048	94.44	gold quality
decidua	UBERON:0002450	94.05	gold quality
seminal vesicle	UBERON:0000998	93.89	gold quality
esophagus mucosa	UBERON:0002469	93.68	gold quality
lower lobe of lung	UBERON:0008949	93.57	gold quality
mouth mucosa	UBERON:0003729	93.45	gold quality
right coronary artery	UBERON:0001625	93.30	gold quality

Single-cell (SCXA)

Detected in 33 experiment(s), a significant marker in 29.

Experiment	Marker?	Max mean expression
E-GEOD-130473	yes	3669.61
E-MTAB-8495	yes	3633.33
E-MTAB-6701	yes	3524.71
E-HCAD-15	yes	3296.48
E-CURD-126	yes	3003.53
E-MTAB-6108	yes	2596.65
E-MTAB-10287	yes	2165.69
E-HCAD-1	yes	2102.52
E-MTAB-6308	yes	1828.72
E-CURD-114	yes	1786.73
E-MTAB-10283	yes	1748.88
E-MTAB-10553	yes	1453.85
E-MTAB-8221	yes	1386.43
E-MTAB-8142	yes	1280.75
E-HCAD-38	yes	911.46

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXA1, TAL1

miRNA regulators (miRDB)

18 targeting KRT7, 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-6748-5P	100.00	65.81	1057
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-1911-3P	99.15	66.17	528
HSA-MIR-485-5P	99.10	64.78	1889
HSA-MIR-6884-5P	99.10	64.50	1987
HSA-MIR-8070	99.07	69.30	1303
HSA-MIR-1304-3P	98.29	66.44	1207
HSA-MIR-3652	97.71	65.43	1890
HSA-MIR-4430	97.47	65.61	1813
HSA-MIR-6760-3P	96.35	68.31	1001
HSA-MIR-12115	94.19	66.37	738

Literature-anchored findings (GeneRIF, showing 40)

• Changing pattern of cytokeratin 7 and 20 expression from normal epithelium to intestinal metaplasia of the gastric mucosa and gastroesophageal junction (PMID:11962749)
• HPV16 E7 mRNA-cytokeratin 7 binding in squamous cervical cancer SiHa cells occurs through the 6-mer peptide SEQIKA present in human cytokeratin 7 protein (PMID:12072504)
• cloning and expression of the gene (PMID:12359226)
• altered expression and transcription of SCL in patients’ hematopoietic cells emphasizes the possible contribution of this regulatory nuclear factor to the hematopoietic dysregulation, which is a feature of myelofibrosis with myeloid metaplasia (PMID:14513050)
• The combined expression of CK7 and CK20 has a low specificity in the distinction between esophageal and cardiac (stomach) adenocarcinomas. (PMID:14631371)
• Alteration of CK7 and CK20 expression profile that occurs early in small intestinal tumorigenesis. (PMID:15371952)
• Cytokeratin 7 and epithelial membrane antigen are essentially negative in yolk sac tumors but are diffusely positive in clear cell carcinomas and endometriod adenocarcinomas making them useful markers for differentiating YSTs from both CCCs and EACs. (PMID:15489654)
• Cytokeratin 7 was found in the majority of type 1 papillary renal cell carcinomas and chromophobe renal cell carcinomas. (PMID:15502805)
• expressed in sinonasal intestinal-type adenocarcinoma less frequently than in colonic adenocarcinoma (PMID:15894926)
• In peripheral blood mononuclear cells, sarcolectin induced CD4+ T cell growth and expression of inflammatory cytokine genes, including TNF-alpha, IL-1beta, IL-6 and IL-8 (PMID:16483709)
• Results showed that 28% of hepatocellular carcinomas contained cells expressing CK7. (PMID:16879391)
• salivary gland neoplasms showed a CK7+/CK20- immunoprofile ranging from 5 to 100%; squamous carcinoma showed negative CK7/20 immunoexpression (PMID:17593078)
• CK7 is a possible marker for colorectal carcinogenesis. (PMID:17715023)
• an immunohistochemical panel including CK7,CD10 and mesothelin is optimal for distinguishing between ovarian and renal clear cell carcinoma. (PMID:18042078)
• Possible relationship between expression of CK7 and CK20 and neoplastic development of colorectal mucosa in patients with ulcerative colitis. (PMID:18092953)
• In ovarian metastases from undiagnosed colorectal adenocarcinomas, elevated CA-125 levels and frequent coexpression of cytokeratin 7 are features that can contribute to misclassification of these metastases as primary ovarian neoplasms. (PMID:18317225)
• The variability of CK expression in clear cell renal cell carcinoma (ccRCC) can be explained by genetic heterogeneity. The CK7/CK19 expressing subtype is associated with better outcome. (PMID:18478571)
• Distinct cytokeratin 7, cytokeratin 19, & neuronal cell adhesion molecule staining patterns are seen in hepatic adenoma & focal nodular hyperplasia possibly suggest activation of different subsets of hepatic progenitor/stem cell. (PMID:18602664)
• Clear cell renal cell carcinoma characterised by diffuse CK7 positivity represents a distinct type of CRCC with characteristic histopathological and immunohistochemical features (PMID:18604734)
• CK7, bax, CCND1, and HER2 represent marker proteins and frequently amplified genes in carcinomas of the ampulla of Vater. (PMID:18936968)
• CK7 expression was a useful biomarker for predicting the outcome of stage I/IIA/IIB Squamous cell carcinoma of the esophagus (PMID:18949396)
• Human eccrine sweat glands express CK7, CK8, CK14, CK18, CK19, CEA, EMA, Ki67, p63, EGF and EGFR. In skin, CEA can be used as a specific immunological marker of sweat glands. (PMID:19032382)
• It can be helpful in cases with metastatic rectal carcinoma, especially those with CK7+/CK20+ or CK20-/CK7- immunophenotype. (PMID:19098678)
• cytokeratins 7 and 19, are very helpful in distinguishing normal from lesional tissue, as well as hepatic adenoma from focal nodular hyperplasia (PMID:19157505)
• the combination of CK7, S100A1 and claudin 8 immunohistochemistry can be useful for classifying tumours of overlapping histology as chromophobe renal cell carcinoma or renal oncocytomas. (PMID:19302533)
• expression of KRT7 might help to explain the pathological, reflux-related nature of columnar-lined esophagus, as aberrant expression in a very early stage of the multistep Barrett esophagus progression (PMID:19396034)
• There was a significant difference between AP, CK 7 and CK 8 expressions in primary lung adenocarcinomas (P=0.02; Chi-squared test). (PMID:19419944)
• Unlike Paget’s disease, breast Toker cells have small bland nuclei and are characterized by CK7 positivity. (PMID:19601945)
• The presence of microcystic, elongated and fragmented (‘MELF’) gland invasion was characterized by strong CK7 expression, sometimes in contrast to adjacent unstained tumour glands. (PMID:19614771)
• Toker cells and mammmary Paget cells share immunoreactivity to CK7. (PMID:20001343)
• FOXA1 induces not only KRT7 but also LOXL2 in a subset of poor prognostic esophageal squamous cell carcinomas with metastatic lymph nodes (PMID:20043065)
• the expression of Cytokeratins 7, 8, 18, and 19 may serve as differential diagnostic markers for pulmonary large cell neuroendocrine carcinoma and small cell lung carcinoma (PMID:20398190)
• Immunohistochemistry for cytokeratins 7 and 19, which mark biliary epithelium, is helpful in the diagnosis of biliary diseases. (PMID:20538416)
• Endometrial adenocarcinomas show micro-anatomical variations in Ki67 expression and this is often inversely correlated with CK7 immunoreactivity. (PMID:20557372)
• Case Report: CK7+/CK20- Merkel cell carcinoma presenting as inguinal subcutaneous nodules with subsequent epidermotropic metastasis. (PMID:20574624)
• Case Report: Primary pulmonary adenocarcinoma with enteric differentiation resembling metastatic colorectal carcinoma, negative for cytokeratin 7. (PMID:20727680)
• Hepatocyte CK7 expression is frequently noted in chronic allograft rejection, and it would appear to reflect ductopenia. (PMID:21228364)
• A considerable number of colorectal carcinomas showed immunoreactivity to CK7. (PMID:21282015)
• Our results reveal that menopause influences the adipose tissue expression of many genes, especially of neurexin 3, metallothionein 1E, and keratyn 7, which are associated with the alteration of several key biological processes. (PMID:21358552)
• Our results along with the data from the literature indicate that CK7/CK20 expression may be of clinical significance. (PMID:21574103)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Krt7	ENSMUSG00000023039
rattus_norvegicus	Krt7	ENSRNOG00000008057

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), KRT71 (ENSG00000139648), INA (ENSG00000148798), LMNTD1 (ENSG00000152936), LMNA (ENSG00000160789), KRT84 (ENSG00000161849), KRT82 (ENSG00000161850), KRT80 (ENSG00000167767), KRT1 (ENSG00000167768), KRT24 (ENSG00000167916), KRT8 (ENSG00000170421), KRT78 (ENSG00000170423), KRT86 (ENSG00000170442), KRT75 (ENSG00000170454), KRT6C (ENSG00000170465), KRT4 (ENSG00000170477), KRT74 (ENSG00000170484), KRT72 (ENSG00000170486), KRT83 (ENSG00000170523), BFSP2 (ENSG00000170819), KRT19 (ENSG00000171345), KRT15 (ENSG00000171346), KRT38 (ENSG00000171360), KRT13 (ENSG00000171401)

Protein

Protein identifiers

Keratin, type II cytoskeletal 7 — P08729 (reviewed: P08729)

Alternative names: Cytokeratin-7, Keratin-7, Sarcolectin, Type-II keratin Kb7

All UniProt accessions (1): P08729

UniProt curated annotations — full annotation on UniProt →

Function. Blocks interferon-dependent interphase and stimulates DNA synthesis in cells. Involved in the translational regulation of the human papillomavirus type 16 E7 mRNA (HPV16 E7).

Subunit / interactions. Heterotetramer of two type I and two type II keratins. Interacts with eukaryotic translation initiator factor 3 (eIF3) subunit EIF3S10. Interacts with GPER1. (Microbial infection) Interacts with human papillomavirus 16/HPV16 protein E7.

Subcellular location. Cytoplasm.

Tissue specificity. Expressed in cultured epidermal, bronchial and mesothelial cells but absent in colon, ectocervix and liver. Observed throughout the glandular cells in the junction between stomach and esophagus but is absent in the esophagus.

Post-translational modifications. Arg-20 is dimethylated, probably to asymmetric dimethylarginine.

Induction. Up-regulated by retinoic acid.

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_005547* (*=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 (44 total): modified residue 14, sequence conflict 10, region of interest 8, cross-link 5, sequence variant 2, initiator methionine 1, chain 1, site 1, domain 1, glycosylation site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4XIF	X-RAY DIFFRACTION	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P08729-F1	75.57	0.56

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): 343 (stutter)

Post-translational modifications (19): 2, 2, 6, 7, 20, 20, 53, 71, 83, 97, 179, 252, 254, 289, 130, 265, 286, 296, 331

Glycosylation sites (1): 12

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

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

MSigDB gene sets: 215 (showing top): MODULE_52, GOBP_EPITHELIUM_DEVELOPMENT, CHIBA_RESPONSE_TO_TSA_UP, GOBP_INTERMEDIATE_FILAMENT_BASED_PROCESS, GU_PDEF_TARGETS_DN, GOBP_INTERMEDIATE_FILAMENT_ORGANIZATION, ENK_UV_RESPONSE_KERATINOCYTE_UP, KENNY_CTNNB1_TARGETS_UP, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_1, RIZKI_TUMOR_INVASIVENESS_3D_DN, HINATA_NFKB_TARGETS_KERATINOCYTE_UP, GOBP_EPIDERMAL_CELL_DIFFERENTIATION, KIM_RESPONSE_TO_TSA_AND_DECITABINE_UP, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, MODULE_298

GO Biological Process (2): keratinization (GO:0031424), intermediate filament organization (GO:0045109)

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

GO Cellular Component (7): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), intermediate filament (GO:0005882), keratin filament (GO:0045095), intermediate filament cytoskeleton (GO:0045111), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-3 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
keratinocyte differentiation	1
multicellular organismal process	1
intermediate filament cytoskeleton organization	1
supramolecular fiber organization	1
structural molecule activity	1
molecular_function	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
intermediate filament cytoskeleton	1
polymeric cytoskeletal fiber	1
intermediate filament	1
cytoskeleton	1
extracellular vesicle	1

Protein interactions and networks

STRING

2394 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KRT7	LIAT1	Q6ZQX7	960
KRT7	CDX2	Q99626	886
KRT7	CEACAM5	P06731	883
KRT7	NAPSA	O96009	881
KRT7	PAX8	Q06710	872
KRT7	NKX2-1	P43699	871
KRT7	PIP	P12273	845
KRT7	SYP	P08247	840
KRT7	WT1	P19544	822
KRT7	AMACR	Q9UHK6	811
KRT7	MME	P08473	801
KRT7	TP53	P04637	785
KRT7	CALB2	P22676	773
KRT7	CDH1	P12830	770
KRT7	MIF	P14174	759

IntAct

38 interactions, top by confidence:

A	B	Type	Score
GRB2	EGFR	psi-mi:“MI:0914”(association)	0.980
HMGB1	KRT7	psi-mi:“MI:0915”(physical association)	0.740
HMGB1	KRT7	psi-mi:“MI:0403”(colocalization)	0.740
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
EIF3A	KRT7	psi-mi:“MI:0915”(physical association)	0.580
KRT7	EIF3A	psi-mi:“MI:0915”(physical association)	0.580
KRT7		psi-mi:“MI:0915”(physical association)	0.400
SDC1	ILVBL	psi-mi:“MI:0915”(physical association)	0.400
PCNA	KRT7	psi-mi:“MI:0915”(physical association)	0.400
KDM1A	KRT7	psi-mi:“MI:0915”(physical association)	0.370
NES	RPL10	psi-mi:“MI:0914”(association)	0.350
IGHG1	PDPK1	psi-mi:“MI:0914”(association)	0.350
METTL14	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
L1TD1	MYO1C	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
RYBP	PIPSL	psi-mi:“MI:0914”(association)	0.350
DCAF4	IGLL5	psi-mi:“MI:0914”(association)	0.350

BioGRID (94): KRT7 (Affinity Capture-MS), KRT7 (Reconstituted Complex), KRT7 (Affinity Capture-MS), KRT7 (Affinity Capture-MS), KRT7 (Affinity Capture-MS), KRT7 (Affinity Capture-MS), KRT7 (Affinity Capture-MS), KRT7 (Affinity Capture-MS), KRT7 (Affinity Capture-MS), KRT7 (Affinity Capture-MS), KRT7 (Affinity Capture-MS), KRT7 (Affinity Capture-MS), KRT7 (Affinity Capture-MS), KRT7 (Affinity Capture-RNA), KRT7 (Affinity Capture-MS)

ESM2 similar proteins: A0JND2, A3KN27, A5A6N0, A6BLY7, A6H712, A6QNX5, A7YWK3, E1AB55, P07744, P08729, P19013, P25691, Q0P5J4, Q0P5J6, Q0P5J7, Q0VBK2, Q148H5, Q148H6, Q148H7, Q148H8, Q14CN4, Q3SY84, Q5XKE5, Q64291, Q6IFW8, Q6IFZ9, Q6IG00, Q6IG01, Q6IG03, Q6IG04, Q6IME9, Q6IMF0, Q6IMF1, Q6KB66, Q6NXH9, Q6R649, Q7RTS7, Q7Z3Y7, Q7Z3Y9, Q7Z794

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

1 interactions.

A	Effect	B	Mechanism
FOXA1	“up-regulates quantity by expression”	KRT7	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 30 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
PIP3 activates AKT signaling	5	18.6×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	86
Likely benign	5
Benign	7

Top pathogenic / likely-pathogenic (0)

SpliceAI

1338 predictions. Top by Δscore:

Variant	Effect	Δscore
12:52233617:CAAGG:C	donor_loss	1.0000
12:52233618:AAGG:A	donor_loss	1.0000
12:52233619:AGGT:A	donor_loss	1.0000
12:52233620:GGTG:G	donor_loss	1.0000
12:52233621:G:C	donor_loss	1.0000
12:52233622:T:G	donor_loss	1.0000
12:52235153:AGGT:A	acceptor_gain	1.0000
12:52235154:G:A	acceptor_loss	1.0000
12:52235154:GGT:G	acceptor_gain	1.0000
12:52235154:GGTG:G	acceptor_gain	1.0000
12:52235154:GGTGC:G	acceptor_gain	1.0000
12:52235341:G:GT	donor_gain	1.0000
12:52235353:G:GT	donor_gain	1.0000
12:52235361:GAA:G	donor_gain	1.0000
12:52235363:A:AG	donor_gain	1.0000
12:52235367:G:GG	donor_gain	1.0000
12:52238661:ATCTT:A	acceptor_gain	1.0000
12:52238665:T:A	acceptor_gain	1.0000
12:52238671:A:AG	acceptor_gain	1.0000
12:52238677:CAG:C	acceptor_loss	1.0000
12:52238678:AGGA:A	acceptor_loss	1.0000
12:52238679:G:A	acceptor_loss	1.0000
12:52238772:GACG:G	donor_gain	1.0000
12:52238774:CGGTG:C	donor_loss	1.0000
12:52238776:G:GG	donor_gain	1.0000
12:52238777:T:G	donor_loss	1.0000
12:52241460:T:A	acceptor_gain	1.0000
12:52241461:G:A	acceptor_gain	1.0000
12:52241468:ACAG:A	acceptor_gain	1.0000
12:52241469:C:G	acceptor_gain	1.0000

AlphaMissense

3065 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:52237566:G:C	K198N	0.980
12:52237566:G:T	K198N	0.980
12:52245442:G:C	A339P	0.977
12:52237552:T:C	F194L	0.974
12:52237554:T:A	F194L	0.974
12:52237554:T:G	F194L	0.974
12:52233600:T:C	F102L	0.963
12:52233602:T:A	F102L	0.963
12:52233602:T:G	F102L	0.963
12:52241613:G:C	A279P	0.962
12:52237532:G:C	R187P	0.960
12:52245475:G:C	A350P	0.959
12:52245605:G:C	R393P	0.958
12:52245573:G:C	K382N	0.957
12:52245573:G:T	K382N	0.957
12:52235361:G:C	K177N	0.954
12:52235361:G:T	K177N	0.954
12:52235174:A:C	Q115P	0.946
12:52245611:T:C	L395P	0.943
12:52233601:T:G	F102C	0.940
12:52245591:G:C	E388D	0.939
12:52245591:G:T	E388D	0.939
12:52245542:T:C	L372P	0.936
12:52233609:T:C	F105L	0.934
12:52233611:C:A	F105L	0.934
12:52233611:C:G	F105L	0.934
12:52245595:G:C	A390P	0.933
12:52245590:A:T	E388V	0.932
12:52233601:T:C	F102S	0.930
12:52243055:T:C	L301P	0.929

dbSNP variants (sampled 300 via entrez): RS1000006176 (12:52231343 G>C), RS1001094111 (12:52241366 C>G,T), RS1001323622 (12:52235133 T>C), RS1001351270 (12:52231703 G>A), RS1001379511 (12:52252254 G>A,C), RS1001395242 (12:52234959 C>T), RS1001402318 (12:52231985 C>A,T), RS1001644111 (12:52238292 G>C), RS1001766001 (12:52244080 A>G), RS1001854721 (12:52243107 G>A,T), RS1001925294 (12:52236510 T>A,C), RS1002107844 (12:52250277 T>C,G), RS1002123480 (12:52253849 C>G), RS1002304226 (12:52239626 A>T), RS1002540704 (12:52239488 C>T)

Disease associations

OMIM: gene MIM:148059 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002875_139	Diisocyanate-induced asthma	1.000000e-06
GCST006988_173	Blond vs. brown/black hair color	2.000000e-12

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006995	response to diisocyanate
EFO:0003924	hair color

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression	5
sodium arsenite	increases expression, affects acetylation, affects methylation, decreases expression, increases abundance	4
monomethylarsonous acid	affects acetylation, affects methylation, decreases expression, increases methylation	4
Tobacco Smoke Pollution	increases expression, affects expression, decreases expression	4
Tretinoin	increases expression	4
bisphenol A	decreases expression, increases expression	3
Air Pollutants	increases oxidation, decreases expression, affects cotreatment, increases abundance	3
Cadmium	increases methylation, decreases expression, increases abundance, increases expression	3
Cadmium Chloride	decreases expression, increases abundance, increases expression, increases methylation	3
4-oxoretinoic acid	increases expression	2
cobaltous chloride	decreases expression	2
perfluorooctane sulfonic acid	decreases expression, increases expression	2
chloropicrin	decreases expression	2
entinostat	increases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	2
Alitretinoin	increases expression	2
Acrolein	increases abundance, affects cotreatment, increases oxidation, increases metabolic processing	2
Benzo(a)pyrene	affects methylation, decreases methylation, affects cotreatment, increases expression	2
Estradiol	affects cotreatment, increases expression	2
Nickel	decreases expression	2
Ozone	affects cotreatment, increases oxidation, increases abundance, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Silicon Dioxide	affects secretion, increases expression	2
Smoke	decreases expression, increases abundance, increases metabolic processing	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	increases expression	1
3,19-(2-bromobenzylidene)andrographolide	decreases response to substance, increases expression	1
bisphenol F	increases expression	1
fluorene-9-bisphenol	increases expression	1
sotorasib	affects cotreatment, increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2NQ	Abcam A-549 KRT7 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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