KRT19

Summary

KRT19 (keratin 19, HGNC:6436) is a protein-coding gene on chromosome 17q21.2, encoding Keratin, type I cytoskeletal 19 (P08727). Involved in the organization of myofibers.

The protein encoded by this gene is a member of the keratin family. The keratins are intermediate filament proteins responsible for the structural integrity of epithelial cells and are subdivided into cytokeratins and hair keratins. The type I cytokeratins consist of acidic proteins which are arranged in pairs of heterotypic keratin chains. Unlike its related family members, this smallest known acidic cytokeratin is not paired with a basic cytokeratin in epithelial cells. It is specifically expressed in the periderm, the transiently superficial layer that envelopes the developing epidermis. The type I cytokeratins are clustered in a region of chromosome 17q12-q21.

Source: NCBI Gene 3880 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 89 total
• MANE Select transcript: NM_002276

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6436
Approved symbol	KRT19
Name	keratin 19
Location	17q21.2
Locus type	gene with protein product
Status	Approved
Aliases	K19, CK19, K1CS, MGC15366
Ensembl gene	ENSG00000171345
Ensembl biotype	protein_coding
OMIM	148020
Entrez	3880

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 10 protein_coding, 4 retained_intron

ENST00000361566, ENST00000455635, ENST00000462611, ENST00000468880, ENST00000471565, ENST00000479031, ENST00000593096, ENST00000868386, ENST00000868387, ENST00000912964, ENST00000912965, ENST00000946920, ENST00000946921, ENST00000946922

RefSeq mRNA: 1 — MANE Select: NM_002276 NM_002276

CCDS: CCDS11399

Canonical transcript exons

ENST00000361566 — 6 exons

Exon	Start	End
ENSE00000863524	41527828	41528308
ENSE00001300582	41523617	41523997
ENSE00001322749	41524143	41524268
ENSE00003460716	41525191	41525273
ENSE00003539860	41524843	41524999
ENSE00003605135	41524379	41524540

Expression profiles

Bgee: expression breadth ubiquitous, 236 present calls, max score 99.95.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 399.5992 / max 8380.8635, expressed in 1114 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165964	372.0832	1042
208190	14.2792	960
208186	4.7671	439
208185	1.8430	300
208184	1.8418	344
208188	1.0322	276
208189	1.0256	424
165962	0.7284	205
208187	0.7248	223
165961	0.4301	186

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
palpebral conjunctiva	UBERON:0001812	99.95	gold quality
lower esophagus mucosa	UBERON:0035834	99.82	gold quality
endometrium epithelium	UBERON:0004811	99.80	gold quality
mucosa of transverse colon	UBERON:0004991	99.74	gold quality
nasal cavity epithelium	UBERON:0005384	99.72	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.70	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.68	gold quality
colonic mucosa	UBERON:0000317	99.66	gold quality
nasal cavity mucosa	UBERON:0001826	99.66	gold quality
amniotic fluid	UBERON:0000173	99.64	gold quality
epithelium of nasopharynx	UBERON:0001951	99.56	gold quality
epithelium of bronchus	UBERON:0002031	99.40	gold quality
gall bladder	UBERON:0002110	99.40	gold quality
bronchus	UBERON:0002185	99.39	gold quality
bronchial epithelial cell	CL:0002328	99.32	gold quality
trachea	UBERON:0003126	99.31	gold quality
germinal epithelium of ovary	UBERON:0001304	99.30	gold quality
rectum	UBERON:0001052	99.29	gold quality
right uterine tube	UBERON:0001302	99.26	gold quality
ileal mucosa	UBERON:0000331	99.24	gold quality
urethra	UBERON:0000057	99.09	gold quality
esophagus mucosa	UBERON:0002469	99.05	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.97	gold quality
pharyngeal mucosa	UBERON:0000355	98.90	gold quality
mucosa of urinary bladder	UBERON:0001259	98.82	gold quality
minor salivary gland	UBERON:0001830	98.82	gold quality
saliva-secreting gland	UBERON:0001044	98.53	gold quality
esophagus squamous epithelium	UBERON:0006920	98.53	gold quality
upper lobe of left lung	UBERON:0008952	98.37	gold quality
upper lobe of lung	UBERON:0008948	98.35	gold quality

Single-cell (SCXA)

Detected in 50 experiment(s), a significant marker in 45.

Experiment	Marker?	Max mean expression
E-MTAB-8221	yes	19543.51
E-HCAD-56	yes	7741.58
E-MTAB-6701	yes	5861.11
E-GEOD-125970	yes	5842.32
E-MTAB-7407	yes	5830.01
E-MTAB-10287	yes	5607.22
E-HCAD-24	yes	5445.56
E-HCAD-1	yes	5194.41
E-MTAB-8205	yes	5177.80
E-MTAB-6678	yes	4386.25
E-MTAB-8410	yes	4227.25
E-HCAD-15	yes	3762.54
E-MTAB-5061	yes	3574.71
E-HCAD-10	yes	3306.15
E-GEOD-124472	yes	3262.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BHLHA15, ESR1, ESR2, FOXO1, KLF4, MEIS1, MEIS2, PDX1, PRL, SALL4, SNAI2, SP1, TP53

miRNA regulators (miRDB)

8 targeting KRT19, 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-7150	99.62	66.80	1322
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-642A-5P	99.51	65.10	1152
HSA-MIR-1912-3P	99.32	67.40	936
HSA-MIR-4768-3P	98.16	66.02	2330
HSA-MIR-4736	97.96	65.89	1287
HSA-MIR-4776-5P	97.14	66.63	405
HSA-MIR-3619-3P	95.59	65.99	428

Literature-anchored findings (GeneRIF, showing 40)

• Cyfra 21-1 fragment is a sensitive marker in the diagnosis of distant metastases of head and neck carcinoma (PMID:12820323)
• CK19 expression is a predictor of early postoperative recurrence due to increased invasiveness (PMID:14556657)
• The results demonstrate that overexpression of CK19 in hepatocellular carcinoma cells is related to metastatic behavior. (PMID:14593079)
• CK19 expression is significantly higher in thyroid papillary carcinoma than benign thyroid tissue; and this characteristic can have important diagnostic value. (PMID:14761598)
• RET/PTC and CK19 have roles in progression of papillary thyroid carcinoma (PMID:15716612)
• SLUG levels in the cell regulated the function of cytokeratins 8 and 19 gene promoters. (PMID:15737616)
• Cytokeratin 19 is highly expressed in HER-2/neu-positive breast tumors when compared with HER-2/neu-negative breast tumors (PMID:15825149)
• High levels of serum CYFRA21-1 were correlated with the progression of thymic carcinoma (PMID:15870932)
• CEA and CK19 expression was higher in lung cancer patients than in patients with benign lung diseases and healthy controls. (PMID:16324274)
• The gene expression profile of hepatic stem cells throughout life consists of high levels of expression of cytokeratin 19 (CK19). (PMID:16627685)
• The large Paget cells uniformly expressed CK19 in 12/12 extramammary Paget’s disease. (PMID:16681689)
• CK19 is consistently expressed in the epithelial cells of pancreatic ducts. (PMID:16736556)
• Intensive follow-up by serial assay of CEA and cytokeratins (8, 18, 19) allows early detection of colorectal neoplasm recurrence. (PMID:16804977)
• The higher recurrence rate of CK19+ HCC (hepatocellular carcinomas) after transplantation suggests a worse prognosis for these HCCs compared with CK19- HCC. (PMID:16879391)
• [in] serum an independent prognostic factor for oral squamous cell carcinoma (PMID:16965897)
• Molecular staging of SLN using real-time RT-PCR for early breast cancer could serve as a useful complement to standard clinicopathological risk factors. (PMID:17071045)
• In conclusion, CYFRA 21-1 is a useful tumor marker before and after surgical treatment in lung cancer. (PMID:17450257)
• Detection of CK19 mRNA in the bone marrow of breast cancer patients is an independent predictor of relapse-free survival in operable breast cancer patients. (PMID:17492378)
• KRT19 variants are not overtransmitted or associated with familial IBD, although a potential role in sporadic IBD cannot be excluded. (PMID:17509943)
• Diffuse-type gastric cancer tissues at varying purities, were evaluated for the expression of a cancer-spec. gene, KRT19, by RT-PCR. Tissues of 70% purity for cancer cells, by microdissection, were of sufficient quality to proof the KRT19 gene expression. (PMID:17558891)
• CK19/CD99 immunoexpression did not correlate with extent of tumor invasion, mitotic activity, Ki-67 labeling index, presence of extracellular mucinous pools dissecting muscle, and angiolymphatic and perineural/neural invasion in goblet cell carcinoids. (PMID:17652531)
• serum Sialyl Lewisx and cytokeratin 19 fragment were prognostic markers for stage I non-small cell lung cancer (PMID:17697728)
• Comparing follicular variant of papillary carcinoma (FVPC) with follicular carcinoma (FC), the expression CK19 was significantly higher in FVPC. (PMID:17728499)
• There was a highly significant difference between overall survival time and lymph node metastasis with LOH and CK19 analysis. (PMID:17851895)
• A high serum CYFR21-1 concentration is associated with tumor progression and poor postoperative outcomes in patients with intrahepatic cholangiocarcinoma. (PMID:17955299)
• CK19 staining is a potential additional prognostic marker independent from the WHO criteria for pancreatic endocrine tumors. (PMID:18059224)
• Our results suggest that the degree of cytokeratin 19 expression could be a new prognostic factor in non-small cell lung cancer. (PMID:18080980)
• CK 19 expression can be helpful in differentiating sebaceous tumors from basal cell carcinomas. (PMID:18095993)
• Data indicate that expression of CK19 by qPCR is a quantitative method for distinguishing papillary carcinoma lesions from other types of thyroid lesions, in contrast to the more qualitative immunohistochemistry. (PMID:18308654)
• This preliminary study provides evidence that the CK19/EpCAM2 and/or CK19/P-cadherin ratio(s) may be a simple and accurate prognostic indicator of clinical outcome in early-stage adenocarcinoma of the lung. (PMID:18329483)
• The levels of CYFRA21-1 in pleural effusion of patients with lung cancer were much higher than those with benign lung disease. (PMID:18394347)
• Cyfra 21.1 may be regarded as a circulating marker of poorly differentiated and anaplastic thyroid carcinoma. (PMID:18409152)
• The detection of peripheral blood CK19mRNA+ and MGB1mRNA+ cells before adjuvant chemotherapy predicts poor DFS in women with early breast cancer. (PMID:18451221)
• CK10 alone, or in combination with CK19, can be a novel predictor for poor prognosis of hepatocellular carcinoma patients after curative resection. (PMID:18559605)
• Nucleosomes and CYFRA 21-1 have roles in tumor response to chemotherapy in recurrent non-small cell lung cancer (PMID:18571761)
• CK19 signal was occasionally observed in the peripheral blood of normal controls, and the HER2 signal was frequently present in the peripheral blood of both normal controls and breast cancer patients. (PMID:18577250)
• 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)
• mRNA expression of LUNX, CK19 and CEA genes in the regional lymph nodes of NSCLC was significantly higher than that in those of benign lung diseases. (PMID:18646695)
• Micrometastases of gastric cancer can be detected in circulating peripheral blood using quantitative real-time RT-PCR. CK19 is a better marker than CK18, CK20 and CEA. (PMID:18705345)
• Coexistence of strong CK19 positivity and p63-positive cells can enhance the cytologic diagnosis of PTC. (PMID:18833815)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	krt95	ENSDARG00000014356
danio_rerio	si:ch211-156l18.7	ENSDARG00000022334
danio_rerio	krt94	ENSDARG00000044975
danio_rerio	krt93	ENSDARG00000044976
mus_musculus	Krt19	ENSMUSG00000020911
rattus_norvegicus	Krt19	ENSRNOG00000071326

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), KRT15 (ENSG00000171346), KRT38 (ENSG00000171360), KRT13 (ENSG00000171401)

Protein

Protein identifiers

Keratin, type I cytoskeletal 19 — P08727 (reviewed: P08727)

Alternative names: Cytokeratin-19, Keratin-19

All UniProt accessions (3): C9JM50, P08727, K7EMS3

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the organization of myofibers. Together with KRT8, helps to link the contractile apparatus to dystrophin at the costameres of striated muscle.

Subunit / interactions. Heterotetramer of two type I and two type II keratins. Interacts with PNN and the actin-binding domain of DMD. Interacts with HCV core protein. (Microbial infection) Interacts with hepatitis C virus/HCV core protein.

Tissue specificity. Expressed in a defined zone of basal keratinocytes in the deep outer root sheath of hair follicles. Also observed in sweat gland and mammary gland ductal and secretory cells, bile ducts, gastrointestinal tract, bladder urothelium, oral epithelia, esophagus, ectocervical epithelium (at protein level). Expressed in epidermal basal cells, in nipple epidermis and a defined region of the hair follicle. Also seen in a subset of vascular wall cells in both the veins and artery of human umbilical cord, and in umbilical cord vascular smooth muscle. Observed in muscle fibers accumulating in the costameres of myoplasm at the sarcolemma in structures that contain dystrophin and spectrin.

Domain organisation. This keratin differs from all other IF proteins in lacking the C-terminal tail domain.

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_002267* (*=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 (32 total): modified residue 16, region of interest 8, site 2, mutagenesis site 2, chain 1, domain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
8XTN	SOLUTION NMR
8XTO	SOLUTION NMR
8Y3S	SOLUTION NMR
8ZG2	SOLUTION NMR
8ZG3	SOLUTION NMR
8ZG4	SOLUTION NMR
8ZP3	SOLUTION NMR
8ZUG	SOLUTION NMR
9U4P	SOLUTION NMR
9U4Q	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P08727-F1	81.56	0.63

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 (2): 267 (stutter); 327 (stutter)

Post-translational modifications (16): 7, 14, 22, 24, 24, 32, 35, 40, 43, 51, 57, 72, 323, 391, 395, 397

Mutagenesis-validated functional residues (2):

Position	Phenotype
10	no effect on phosphorylation; no functional effect.
35	abolishes phosphorylation; induces perinuclear collapse or short cytoplasmic filaments.

Function

Pathways and Gene Ontology

Reactome pathways

8 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-9925563	Developmental Lineage of Pancreatic Ductal Cells
R-HSA-9927418	Developmental Lineage of Mammary Gland Luminal Epithelial Cells
R-HSA-9927426	Developmental Lineage of Mammary Gland Alveolar Cells
R-HSA-1266738	Developmental Biology
R-HSA-9734767	Developmental Cell Lineages

MSigDB gene sets: 294 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, MODULE_52, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, CHIBA_RESPONSE_TO_TSA_UP, GOBP_INTERMEDIATE_FILAMENT_BASED_PROCESS, GU_PDEF_TARGETS_DN, GOBP_INTERMEDIATE_FILAMENT_ORGANIZATION, MODULE_255, DORN_ADENOVIRUS_INFECTION_12HR_UP, JAEGER_METASTASIS_DN, GCANCTGNY_MYOD_Q6, MODULE_418, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, MODULE_317

GO Biological Process (7): morphogenesis of an epithelium (GO:0002009), Notch signaling pathway (GO:0007219), epithelial cell differentiation (GO:0030855), response to estrogen (GO:0043627), intermediate filament organization (GO:0045109), sarcomere organization (GO:0045214), cell differentiation involved in embryonic placenta development (GO:0060706)

GO Molecular Function (6): structural constituent of cytoskeleton (GO:0005200), structural constituent of muscle (GO:0008307), structural constituent of skin epidermis (GO:0030280), protein-containing complex binding (GO:0044877), structural molecule activity (GO:0005198), protein binding (GO:0005515)

GO Cellular Component (13): cytosol (GO:0005829), cytoskeleton (GO:0005856), intermediate filament (GO:0005882), plasma membrane (GO:0005886), dystrophin-associated glycoprotein complex (GO:0016010), apicolateral plasma membrane (GO:0016327), Z disc (GO:0030018), sarcolemma (GO:0042383), costamere (GO:0043034), keratin filament (GO:0045095), extracellular exosome (GO:0070062), cell periphery (GO:0071944), terminal web (GO:1990357)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Developmental Biology	2
Developmental Lineages of the Mammary Gland	2
Keratinization	1
Developmental Cell Lineages of the Integumentary System	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	4
structural molecule activity	3
epithelium development	2
cell differentiation	2
binding	2
tissue morphogenesis	1
cell surface receptor signaling pathway	1
response to hormone	1
intermediate filament cytoskeleton organization	1
supramolecular fiber organization	1
myofibril assembly	1
actomyosin structure organization	1
embryonic placenta development	1
developmental process involved in reproduction	1
cytoskeleton	1
cytoskeleton organization	1
molecular_function	1
cytoplasm	1
intracellular membraneless organelle	1
intermediate filament cytoskeleton	1
polymeric cytoskeletal fiber	1
membrane	1
cell periphery	1
glycoprotein complex	1
plasma membrane protein complex	1
plasma membrane region	1
I band	1
plasma membrane	1
myofibril	1
intermediate filament	1
extracellular vesicle	1
cortical actin cytoskeleton	1

Protein interactions and networks

STRING

3430 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KRT19	LIAT1	Q6ZQX7	877
KRT19	CEACAM5	P06731	871
KRT19	AFP	P02771	851
KRT19	EPCAM	P16422	811
KRT19	PROM1	O43490	803
KRT19	PECAM1	P16284	776
KRT19	GPC3	P51654	775
KRT19	ENO2	P09104	771
KRT19	KRT18	P05783	761
KRT19	LGALS3	P17931	739
KRT19	THY1	P04216	727
KRT19	MUC1	P13931	720
KRT19	SOX9	P48436	698
KRT19	CDH1	P12830	692
KRT19	ALB	P02768	671

IntAct

316 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
GFAP	KRT19	psi-mi:“MI:0915”(physical association)	0.810
KRT19	GFAP	psi-mi:“MI:0915”(physical association)	0.810
TBC1D7	KRT19	psi-mi:“MI:0915”(physical association)	0.780
KRT19	TBC1D7	psi-mi:“MI:0915”(physical association)	0.780
AIRIM	KRT19	psi-mi:“MI:0915”(physical association)	0.720
KRT19	AIRIM	psi-mi:“MI:0915”(physical association)	0.720
KRT19	PRPH	psi-mi:“MI:0915”(physical association)	0.720
CARD9	KRT19	psi-mi:“MI:0915”(physical association)	0.670
KRT19	CARD9	psi-mi:“MI:0915”(physical association)	0.670
KRT6B	KRT19	psi-mi:“MI:0915”(physical association)	0.670
KRT19	EXOC8	psi-mi:“MI:0915”(physical association)	0.670
KRT19	KRT80	psi-mi:“MI:0915”(physical association)	0.630
KRT19	POLR1C	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (351): KRT19 (Two-hybrid), KRT19 (Two-hybrid), KRT19 (Two-hybrid), UBE2I (Two-hybrid), EIF4E2 (Two-hybrid), POLR1C (Two-hybrid), IKZF3 (Two-hybrid), TFPT (Two-hybrid), TBC1D7 (Two-hybrid), AMOTL2 (Two-hybrid), C1orf109 (Two-hybrid), EIF4ENIF1 (Two-hybrid), CCDC146 (Two-hybrid), CARD9 (Two-hybrid), FAM124B (Two-hybrid)

ESM2 similar proteins: A1KQY9, A1L595, A5A6M0, A6QQQ9, O57607, O57611, O77727, O93256, P02533, P05781, P05783, P05784, P05786, P05787, P08727, P08728, P08730, P08776, P08777, P08778, P08802, P11679, P19001, P19012, P25030, P35900, P51856, Q04695, Q07427, Q10758, Q5BJY9, Q5K2N3, Q5K2N9, Q5K2P6, Q5R8S9, Q61414, Q63279, Q6IFU7, Q6IFU8, Q6IFV1

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

2 interactions.

A	Effect	B	Mechanism
SRC	unknown	KRT19	phosphorylation
PRL	“up-regulates quantity by expression”	KRT19	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 72 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	22	37.9×	8e-28
Keratinization	22	24.0×	1e-23

GO biological processes:

GO term	Partners	Fold	FDR
intermediate filament organization	22	84.1×	2e-35
keratinization	20	74.3×	5e-31

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	68
Likely benign	2
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

515 predictions. Top by Δscore:

Variant	Effect	Δscore
17:41523994:CTTT:C	acceptor_gain	1.0000
17:41523995:TTT:T	acceptor_gain	1.0000
17:41523996:TT:T	acceptor_gain	1.0000
17:41523998:C:CC	acceptor_gain	1.0000
17:41524004:A:AC	acceptor_gain	1.0000
17:41524004:A:C	acceptor_gain	1.0000
17:41524138:CATA:C	donor_loss	1.0000
17:41524140:TA:T	donor_loss	1.0000
17:41524141:A:AC	donor_gain	1.0000
17:41524141:A:T	donor_loss	1.0000
17:41524141:AC:A	donor_gain	1.0000
17:41524142:C:CT	donor_gain	1.0000
17:41524142:CC:C	donor_gain	1.0000
17:41524142:CCATG:C	donor_gain	1.0000
17:41524151:G:C	donor_gain	1.0000
17:41524173:AAGAC:A	donor_gain	1.0000
17:41524264:TCAGT:T	acceptor_gain	1.0000
17:41524265:CAGT:C	acceptor_gain	1.0000
17:41524265:CAGTC:C	acceptor_gain	1.0000
17:41524266:AGT:A	acceptor_gain	1.0000
17:41524266:AGTC:A	acceptor_gain	1.0000
17:41524267:GT:G	acceptor_gain	1.0000
17:41524267:GTC:G	acceptor_gain	1.0000
17:41524268:TC:T	acceptor_gain	1.0000
17:41524269:C:CC	acceptor_gain	1.0000
17:41524269:C:CG	acceptor_gain	1.0000
17:41524270:T:C	acceptor_gain	1.0000
17:41524272:C:CT	acceptor_gain	1.0000
17:41524273:A:T	acceptor_gain	1.0000
17:41524367:C:A	donor_gain	1.0000

AlphaMissense

2588 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:41527988:A:G	L87P	0.997
17:41525222:C:G	A158P	0.995
17:41527976:A:T	L91Q	0.995
17:41527979:C:G	R90P	0.995
17:41527988:A:T	L87H	0.995
17:41527913:A:G	I112T	0.994
17:41527976:A:G	L91P	0.994
17:41527838:A:G	L137P	0.993
17:41527938:C:G	A104P	0.993
17:41524999:C:A	K168N	0.991
17:41524999:C:G	K168N	0.991
17:41527964:A:G	L95P	0.991
17:41527974:C:G	A92P	0.991
17:41527985:T:A	N88I	0.991
17:41525210:C:G	A162P	0.990
17:41527984:G:C	N88K	0.990
17:41527984:G:T	N88K	0.990
17:41523849:A:G	L366P	0.989
17:41527980:G:T	R90S	0.989
17:41523828:A:G	L373P	0.988
17:41523836:C:A	K370N	0.988
17:41523836:C:G	K370N	0.988
17:41524162:A:G	L310P	0.988
17:41527946:A:G	L101P	0.988
17:41527989:G:A	L87F	0.988
17:41527996:C:A	M84I	0.988
17:41527996:C:G	M84I	0.988
17:41527996:C:T	M84I	0.988
17:41527925:A:G	L108P	0.987
17:41525236:A:G	L153P	0.986

dbSNP variants (sampled 300 via entrez): RS1000402045 (17:41529869 C>G), RS1002146230 (17:41526633 G>A), RS1002186994 (17:41525621 C>A), RS1002498695 (17:41527001 A>C), RS1002846655 (17:41528122 G>A), RS1004374120 (17:41526446 G>A), RS1005001417 (17:41527983 C>A,T), RS1005720040 (17:41530099 C>A), RS1005940180 (17:41523670 G>C,T), RS1006017334 (17:41524758 C>G,T), RS1006052262 (17:41528856 G>A,C), RS1006226862 (17:41523949 C>A,T), RS1006256734 (17:41527866 T>G), RS1006608455 (17:41525974 T>C), RS1007071925 (17:41525738 G>A,C)

Disease associations

OMIM: gene MIM:148020 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): hereditary breast ovarian cancer syndrome (MONDO:0003582)

Orphanet (1): Hereditary breast and/or ovarian cancer syndrome (Orphanet:145)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, increases methylation, affects cotreatment	7
Benzo(a)pyrene	affects expression, affects methylation, increases expression, increases methylation	6
Estradiol	decreases reaction, affects reaction, affects expression, decreases expression, increases reaction (+3 more)	6
bisphenol A	decreases expression, increases expression, affects expression	5
Tobacco Smoke Pollution	affects expression, decreases expression	5
Arsenic Trioxide	decreases expression, decreases response to substance	4
Tetrachlorodibenzodioxin	decreases reaction, increases expression, decreases expression	4
Tretinoin	increases expression	4
Cyclosporine	increases expression, decreases expression	4
methylmercuric chloride	decreases expression	3
Alitretinoin	increases expression	3
Cisplatin	affects cotreatment, increases expression, decreases expression	3
Doxorubicin	increases expression	3
4-oxoretinoic acid	increases expression	2
trichostatin A	increases expression	2
3,3’-diindolylmethane	increases reaction, affects reaction, decreases reaction, increases expression, affects binding	2
sodium arsenite	decreases expression, increases expression	2
cobaltous chloride	decreases expression, increases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	2
Air Pollutants	decreases expression, increases abundance	2
Drugs, Chinese Herbal	affects binding, increases reaction, decreases expression	2
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Quercetin	increases expression	2
Smoke	decreases expression	2
Aflatoxin B1	increases expression	2
Particulate Matter	increases abundance, affects cotreatment, increases expression, decreases expression	2
aristolochic acid I	increases expression	1
dicrotophos	decreases expression	1
chloroacetaldehyde	increases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A5UD	SACC-LM-KRT19-KD	Cancer cell line	Female
CVCL_D1X9	Abcam A-549 KRT19 KO	Cancer cell line	Male
CVCL_D2BI	Abcam HCT 116 KRT19 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02562170	PHASE4	COMPLETED	Protexa® Versus TiLoopBra® in Immediate Breast Reconstruction- A Pilot Study
NCT00673335	PHASE3	COMPLETED	Letrozole in Preventing Breast Cancer in Postmenopausal Women With a BRCA1 or BRCA2 Mutation
NCT00685256	PHASE3	COMPLETED	Standard Genetic Counseling With or Without a Decision Guide in Improving Communication Between Mothers Undergoing BRCA1/2 Testing and Their Minor-Age Children
NCT03162276	PHASE3	UNKNOWN	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00253539	PHASE2	COMPLETED	Arzoxifene or Tamoxifen in Preventing Breast Cancer in Premenopausal Women at High Risk for Breast Cancer
NCT00305695	PHASE2	COMPLETED	Zoledronate or Observation in Maintaining Bone Mineral Density in Patients Who Are Undergoing Surgery to Remove Both Ovaries
NCT00321633	PHASE2	COMPLETED	Carboplatin or Docetaxel in Treating Women With Metastatic Genetic Breast Cancer
NCT01333748	PHASE2	COMPLETED	Search Allelic Imbalance of Expression of BRCA Genes in Hereditary Risk of Breast and/or Ovarian Cancer
NCT01367639	PHASE2	COMPLETED	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00535119	PHASE1	COMPLETED	Veliparib, Carboplatin, and Paclitaxel in Treating Patients With Advanced Solid Cancer
NCT00892736	PHASE1	COMPLETED	Veliparib in Treating Patients With Malignant Solid Tumors That Do Not Respond to Previous Therapy
NCT03832985	EARLY_PHASE1	COMPLETED	Pediatric Reporting of Adult-Onset Genomic Results
NCT00005095	Not specified	RECRUITING	Specimen and Data Study for Ovarian Cancer Early Detection and Prevention
NCT00609505	Not specified	COMPLETED	Telemedicine vs. Face-to-Face Cancer Genetic Counseling
NCT01273909	Not specified	UNKNOWN	Outcomes After Perforator Flap Reconstruction for Breast Reconstruction and/or Lymphedema Treatment
NCT01445275	Not specified	WITHDRAWN	Cost of Cancer Risk Management in Women at Elevated Genetic Risk for Ovarian Cancer Who Participated on GOG-0199
NCT01608074	Not specified	ACTIVE_NOT_RECRUITING	Radical Fimbriectomy for Young BRCA Mutation Carriers
NCT02087592	Not specified	COMPLETED	Feasibility of Lifestyle Intervention in BRCA1/2 Mutation Carriers
NCT02302742	Not specified	RECRUITING	Triple Negative Breast Cancer and Germline Hereditary Breast and Ovarian Cancer Mutation Carrier Registry
NCT02324062	Not specified	COMPLETED	Cancer Genetics Hereditary Cancer Panel Testing
NCT02516540	Not specified	UNKNOWN	Efficacy of Lifestyle Intervention in BRCA1/2 Mutation Carriers
NCT02653105	Not specified	ACTIVE_NOT_RECRUITING	Women at Risk of Breast Cancer and OLFM4
NCT02705924	Not specified	TERMINATED	Impact of a Psychoeducational Intervention on Expectations and Coping in Young Women Exposed to a High HBOC Risk
NCT02760849	Not specified	ACTIVE_NOT_RECRUITING	Surgery in Preventing Ovarian Cancer in Patients With Genetic Mutations
NCT02786147	Not specified	COMPLETED	Identification and Referral of Women at Risk for Hereditary Breast/Ovarian Cancer
NCT02956681	Not specified	COMPLETED	Statewide Communication to Reach Diverse Low Income Women
NCT03015376	Not specified	UNKNOWN	Inherited Susceptible Genes Among Epithelial Ovarian Cancer
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition
NCT03075540	Not specified	COMPLETED	Enhancing At-risk Latina Women’s Use of Genetic Counseling for Hereditary Breast and Ovarian Cancer
NCT03124212	Not specified	RECRUITING	Cascade Genetic Testing for Hereditary Breast/Ovarian Cancer and Lynch Syndrome in Switzerland
NCT03246841	Not specified	ACTIVE_NOT_RECRUITING	Investigation of Tumour Spectrum of Germline Mutations in Breast and Ovarian Cancer Genes.
NCT03294343	Not specified	UNKNOWN	Risk-Reducing Surgeries for Hereditary Ovarian Cancer
NCT03421327	Not specified	COMPLETED	Genetic Risk: Whether, When, and How to Tell Adolescents
NCT03510689	Not specified	COMPLETED	Genetics and Heart Health After Cancer Therapy
NCT03511690	Not specified	COMPLETED	Testing an Intelligent Tutoring System to Enhance Genetic Risk Assessment
NCT03784859	Not specified	COMPLETED	Tissue Expansion in Breast Reconstruction Without Drains
NCT03979612	Not specified	UNKNOWN	Evaluation of the Adhesion to the GENEPY Network
NCT04197856	Not specified	ACTIVE_NOT_RECRUITING	Direct Information to At-risk Relatives
NCT04407611	Not specified	COMPLETED	Scalable Communication Modalities for Returning Genetic Research Results
NCT04508764	Not specified	TERMINATED	Implementation of the Families Accelerating Cascade Testing Toolkit (FACTT) for Hereditary Breast and Ovarian Cancer and Lynch Syndrome