KRT34

Summary

KRT34 (keratin 34, HGNC:6452) is a protein-coding gene on chromosome 17q21.2, encoding Keratin, type I cuticular Ha4 (O76011).

The protein encoded by this gene is a member of the keratin gene family. As a type I hair keratin, it is an acidic protein which heterodimerizes with type II keratins to form hair and nails. The type I hair keratins are clustered in a region of chromosome 17q12-q21 and have the same direction of transcription.

Source: NCBI Gene 3885 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 92 total
• MANE Select transcript: NM_001386014

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6452
Approved symbol	KRT34
Name	keratin 34
Location	17q21.2
Locus type	gene with protein product
Status	Approved
Aliases	Ha-4
Ensembl gene	ENSG00000131737
Ensembl biotype	protein_coding
OMIM	602763
Entrez	3885

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000394001

RefSeq mRNA: 1 — MANE Select: NM_001386014 NM_001386014

CCDS: CCDS11390

Canonical transcript exons

ENST00000394001 — 7 exons

Exon	Start	End
ENSE00001291288	41381899	41382306
ENSE00001517150	41377669	41378146
ENSE00002339765	41379570	41379731
ENSE00002366833	41378956	41379176
ENSE00002393174	41381713	41381795
ENSE00002400158	41379353	41379478
ENSE00002405353	41381056	41381212

Expression profiles

Bgee: expression breadth broad, 63 present calls, max score 96.36.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1911 / max 29.3866, expressed in 64 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165893	0.1493	55
165891	0.0418	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	96.36	gold quality
stromal cell of endometrium	CL:0002255	79.43	gold quality
cortical plate	UBERON:0005343	70.09	gold quality
placenta	UBERON:0001987	56.59	gold quality
skin of abdomen	UBERON:0001416	56.56	gold quality
zone of skin	UBERON:0000014	54.64	gold quality
ectocervix	UBERON:0012249	53.84	gold quality
skin of leg	UBERON:0001511	53.30	gold quality
vagina	UBERON:0000996	52.91	gold quality
endocervix	UBERON:0000458	51.86	gold quality
uterine cervix	UBERON:0000002	51.35	gold quality
right lung	UBERON:0002167	47.38	gold quality
esophagus mucosa	UBERON:0002469	47.23	gold quality
cerebellum	UBERON:0002037	46.87	silver quality
cerebellar cortex	UBERON:0002129	46.72	silver quality
cerebellar hemisphere	UBERON:0002245	46.61	silver quality
lower esophagus mucosa	UBERON:0035834	46.05	silver quality
right hemisphere of cerebellum	UBERON:0014890	44.94	silver quality
myometrium	UBERON:0001296	40.12	gold quality
ganglionic eminence	UBERON:0004023	39.05	gold quality
esophagus	UBERON:0001043	37.70	gold quality
right testis	UBERON:0004534	37.53	gold quality
smooth muscle tissue	UBERON:0001135	37.48	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
endometrium	UBERON:0001295	37.06	gold quality
left testis	UBERON:0004533	36.89	gold quality
testis	UBERON:0000473	36.86	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
tonsil	UBERON:0002372	36.05	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.74

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

24 targeting KRT34, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-520A-5P	99.35	66.72	1632
HSA-MIR-525-5P	99.35	66.85	1615
HSA-MIR-190B-3P	99.33	68.29	1382
HSA-MIR-873-5P	98.84	66.90	1348
HSA-MIR-198	98.70	67.32	920
HSA-MIR-6854-5P	96.77	65.96	848
HSA-MIR-6866-5P	96.64	68.06	624

Literature-anchored findings (GeneRIF, showing 6)

• Overexpressed in recurrent superficial urothelial carcinoma. (PMID:16286979)
• CK34betaE12 expression is a good indicator of lymph node metastasis, depth of tumor invasion, and differentiation in case of Esophageal squamous cell carcinoma (ESCC). (PMID:22790218)
• Keratin 34betaE12/K7 expression is a prognostic parameter in resected early stage NSCLC that allows identification of high-risk NSCLC patients with poor cancer-specific and overall survival (PMID:26057535)
• 95 of the prostate carcinoma biopsies demonstrated lack of cytokeratin 34betaE12 expression and only 3 cases showed weak patchy staining. (PMID:28384107)
• As an adjunct to biopsy, AMACR and HMWCK have value for resolving diagnostically challenging cases (PMID:28508828)
• Unveiling the genetic etiology of primary ciliary dyskinesia: When standard genetic approach is not enough. (PMID:31835165)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Krt34	ENSMUSG00000043485
rattus_norvegicus	Krt34	ENSRNOG00000051302

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), 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), KRT13 (ENSG00000171401)

Protein

Protein identifiers

Keratin, type I cuticular Ha4 — O76011 (reviewed: O76011)

Alternative names: Hair keratin, type I Ha4, Keratin-34

All UniProt accessions (1): O76011

UniProt curated annotations — full annotation on UniProt →

Tissue specificity. Expressed in the hair follicles.

Miscellaneous. There are two types of hair/microfibrillar keratin, I (acidic) and II (neutral to basic).

Similarity. Belongs to the intermediate filament family.

RefSeq proteins (1): NP_001372943* (*=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 (13 total): region of interest 7, sequence variant 2, chain 1, domain 1, sequence conflict 1, site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O76011-F1	81.30	0.64

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): 305 (stutter)

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: 119 (showing top): MORF_ITGA2, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_INTERMEDIATE_FILAMENT_BASED_PROCESS, GU_PDEF_TARGETS_DN, GOBP_INTERMEDIATE_FILAMENT_ORGANIZATION, ENK_UV_RESPONSE_KERATINOCYTE_UP, DAZARD_UV_RESPONSE_CLUSTER_G4, MORF_RAD51L3, MARTINEZ_RB1_TARGETS_DN, MORF_CTSB, MORF_IL4, MORF_PRKCA, GOBP_EPIDERMIS_DEVELOPMENT, MORF_THPO

GO Biological Process (4): morphogenesis of an epithelium (GO:0002009), epidermis development (GO:0008544), epithelial cell differentiation (GO:0030855), intermediate filament organization (GO:0045109)

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

GO Cellular Component (5): obsolete extracellular space (GO:0005615), cytosol (GO:0005829), cytoskeleton (GO:0005856), keratin filament (GO:0045095), intermediate filament (GO:0005882)

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
epithelium development	2
tissue morphogenesis	1
tissue development	1
cell differentiation	1
intermediate filament cytoskeleton organization	1
supramolecular fiber organization	1
molecular_function	1
structural molecule activity	1
binding	1
cytoplasm	1
cellular anatomical structure	1
intracellular membraneless organelle	1
intermediate filament	1
intermediate filament cytoskeleton	1
polymeric cytoskeletal fiber	1

Protein interactions and networks

STRING

962 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KRT34	KRTAP2-3	P0C7H8	507
KRT34	KRTAP16-1	A8MUX0	479
KRT34	KRTAP3-3	Q9BYR6	464
KRT34	KRTAP3-1	Q9BYR8	414
KRT34	KRTAP1-5	Q9BYS1	397
KRT34	TMEM171	Q8WVE6	388
KRT34	TEX19	Q8NA77	383
KRT34	TNFRSF10D	Q9UBN6	374
KRT34	S100A3	P33764	374
KRT34	KRTAP13-1	Q8IUC0	372
KRT34	CCHCR1	Q8TD31	367
KRT34	SECTM1	Q8WVN6	364
KRT34	DSG4	Q86SJ6	361
KRT34	KRTAP9-3	Q9BYQ3	359
KRT34	KRTAP7-1	Q8IUC3	351

IntAct

816 interactions, top by confidence:

A	B	Type	Score
YWHAG	KRT34	psi-mi:“MI:0915”(physical association)	0.000
	KRT34	psi-mi:“MI:0915”(physical association)	0.000
DLG3	KRT34	psi-mi:“MI:0915”(physical association)	0.000
PLEKHB2	KRT34	psi-mi:“MI:0915”(physical association)	0.000
DISC1	KRT34	psi-mi:“MI:0915”(physical association)	0.000
KRT6A	KRT34	psi-mi:“MI:0915”(physical association)	0.000
CFAP206	KRT34	psi-mi:“MI:0915”(physical association)	0.000
SEC14L4	KRT34	psi-mi:“MI:0915”(physical association)	0.000
TRIML2	KRT34	psi-mi:“MI:0915”(physical association)	0.000
LMO4	KRT34	psi-mi:“MI:0915”(physical association)	0.000
AIMP2	KRT34	psi-mi:“MI:0915”(physical association)	0.000
TLX3	KRT34	psi-mi:“MI:0915”(physical association)	0.000
ICAM4	KRT34	psi-mi:“MI:0915”(physical association)	0.000
HGS	KRT34	psi-mi:“MI:0915”(physical association)	0.000
KRT80	KRT34	psi-mi:“MI:0915”(physical association)	0.000
RIPPLY1	KRT34	psi-mi:“MI:0915”(physical association)	0.000
C1orf216	KRT34	psi-mi:“MI:0915”(physical association)	0.000
MNS1	KRT34	psi-mi:“MI:0915”(physical association)	0.000
INIP	KRT34	psi-mi:“MI:0915”(physical association)	0.000
PITX1	KRT34	psi-mi:“MI:0915”(physical association)	0.000
KLK8	KRT34	psi-mi:“MI:0915”(physical association)	0.000
CCDC24	KRT34	psi-mi:“MI:0915”(physical association)	0.000
FAM83A	KRT34	psi-mi:“MI:0915”(physical association)	0.000
MAPKBP1	KRT34	psi-mi:“MI:0915”(physical association)	0.000
TLE5	KRT34	psi-mi:“MI:0915”(physical association)	0.000
HBA1	KRT34	psi-mi:“MI:0915”(physical association)	0.000
DDX6	KRT34	psi-mi:“MI:0915”(physical association)	0.000
DMRT3	KRT34	psi-mi:“MI:0915”(physical association)	0.000
PKN1	KRT34	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (293): KRT34 (Affinity Capture-MS), KRT34 (Affinity Capture-MS), KRT34 (Affinity Capture-MS), KRT34 (Affinity Capture-MS), KRT34 (Affinity Capture-MS), KRT34 (Affinity Capture-MS), KRT34 (Two-hybrid), KRT34 (Two-hybrid), KRT34 (Two-hybrid), KRT34 (Two-hybrid), KRT34 (Two-hybrid), KRT34 (Two-hybrid), KRT34 (Two-hybrid), KRT34 (Two-hybrid), KRT34 (Two-hybrid)

ESM2 similar proteins: A4FUZ0, A5A6M5, A5A6N2, A5A6P3, A7YWM2, B0LKP1, B1AQ75, O43790, O76009, O76011, O76013, O76014, O76015, P02534, P08730, P13646, P15241, P25690, P78385, P97861, Q0P5J4, Q0P5J7, Q14525, Q14532, Q14533, Q148H4, Q15323, Q497I4, Q61765, Q61897, Q62168, Q6A162, Q6A163, Q6IFV4, Q6IFW2, Q6IFW3, Q6IFW8, Q6IFX0, Q6IFX1, Q6IFX3

Diamond homologs: A1L317, A1L595, A5A6M0, A5A6M5, A5A6N2, A5A6P3, A6BLY7, A6H712, A6QQQ9, A7YWM2, B0LKP1, B1AQ75, O18740, O57611, O76009, O76011, O76013, O76015, O77727, O93256, P02533, P02534, P02535, P02537, P05781, P06394, P08727, P08728, P08730, P08777, P08778, P08779, P13645, P13646, P19001, P19012, P25030, P25690, P35527, P35900

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 116 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	14	18.4×	5e-12
Keratinization	14	11.6×	1e-09

GO biological processes:

GO term	Partners	Fold	FDR
intermediate filament organization	12	27.5×	8e-12
keratinization	11	24.5×	2e-10

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	81
Likely benign	9
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

713 predictions. Top by Δscore:

Variant	Effect	Δscore
17:41378950:A:AC	donor_gain	1.0000
17:41378951:C:CC	donor_gain	1.0000
17:41378951:CTCA:C	donor_gain	1.0000
17:41378952:TCA:T	donor_loss	1.0000
17:41378953:CA:C	donor_loss	1.0000
17:41378954:A:AC	donor_gain	1.0000
17:41378954:ACTTG:A	donor_gain	1.0000
17:41378955:C:CA	donor_gain	1.0000
17:41378955:CT:C	donor_gain	1.0000
17:41378955:CTT:C	donor_gain	1.0000
17:41378955:CTTG:C	donor_gain	1.0000
17:41378955:CTTGC:C	donor_gain	1.0000
17:41379173:CTCG:C	acceptor_gain	1.0000
17:41379174:TCG:T	acceptor_gain	1.0000
17:41379175:CG:C	acceptor_gain	1.0000
17:41379175:CGC:C	acceptor_gain	1.0000
17:41379176:GCT:G	acceptor_loss	1.0000
17:41379177:C:CC	acceptor_gain	1.0000
17:41379177:CTGT:C	acceptor_loss	1.0000
17:41379179:G:C	acceptor_gain	1.0000
17:41379179:G:GC	acceptor_gain	1.0000
17:41379182:G:C	acceptor_gain	1.0000
17:41379182:G:GC	acceptor_gain	1.0000
17:41379347:AC:A	donor_loss	1.0000
17:41379349:ACACC:A	donor_loss	1.0000
17:41379350:CA:C	donor_loss	1.0000
17:41379351:A:AC	donor_gain	1.0000
17:41379352:C:CC	donor_gain	1.0000
17:41379474:TCGGT:T	acceptor_gain	1.0000
17:41379475:CGGT:C	acceptor_gain	1.0000

AlphaMissense

2866 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:41382050:C:G	R108P	0.990
17:41378995:A:G	I395T	0.984
17:41382047:A:G	L109P	0.984
17:41381744:C:G	A176P	0.980
17:41379372:A:G	L328P	0.979
17:41382047:A:T	L109Q	0.979
17:41379007:A:G	L391P	0.978
17:41382017:A:G	L119P	0.978
17:41382035:A:G	L113P	0.978
17:41382045:C:G	A110P	0.978
17:41382055:G:C	N106K	0.978
17:41382055:G:T	N106K	0.978
17:41382056:T:A	N106I	0.978
17:41381909:A:G	L155P	0.977
17:41378977:A:G	L401P	0.976
17:41381996:A:G	L126P	0.975
17:41378995:A:C	I395S	0.974
17:41382051:G:T	R108S	0.974
17:41382067:C:A	M102I	0.974
17:41382067:C:G	M102I	0.974
17:41382067:C:T	M102I	0.974
17:41382059:A:G	L105P	0.972
17:41379052:C:G	R376P	0.970
17:41379058:A:G	L374P	0.970
17:41379067:C:G	R371P	0.970
17:41379028:A:G	L384P	0.969
17:41378998:T:A	E394V	0.968
17:41379121:A:G	L353P	0.968
17:41382023:C:G	R117P	0.967
17:41382076:C:A	K99N	0.967

dbSNP variants (sampled 300 via entrez): RS1000333785 (17:41385418 T>C), RS1000339690 (17:41384268 T>C), RS1000543844 (17:41378326 T>A,C), RS1001032574 (17:41375998 A>T), RS1001056170 (17:41383382 G>A,C,T), RS1001076589 (17:41383052 C>T), RS1001179349 (17:41380572 T>C), RS1001215546 (17:41380967 C>A,T), RS1001347861 (17:41377307 T>C), RS1001598783 (17:41382326 A>G), RS1002841869 (17:41383366 G>A), RS1003109655 (17:41382958 G>A), RS1003242605 (17:41383165 C>T), RS1003584386 (17:41384695 C>A), RS1003751017 (17:41376015 C>A)

Disease associations

OMIM: gene MIM:602763 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cadmium Chloride	decreases expression, increases abundance, increases expression	3
bisphenol A	increases expression, affects cotreatment, decreases expression	2
sodium arsenite	affects cotreatment, increases abundance, increases expression	2
Estradiol	increases expression, affects cotreatment	2
Silicon Dioxide	increases expression	2
bisphenol F	decreases expression, affects cotreatment	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
2-butenal	increases expression	1
3,4-dichloroaniline	increases expression	1
arsenite	affects binding, increases reaction	1
mono-(2-ethylhexyl)phthalate	increases expression	1
butyraldehyde	increases expression	1
zinc chromate	decreases expression, increases abundance	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
potassium chromate(VI)	increases expression	1
1-nitropyrene	increases expression	1
dicyclohexyl phthalate	increases expression	1
S-(1,2-dichlorovinyl)cysteine	increases expression	1
diallyl trisulfide	increases expression	1
pentanal	increases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
perfluorooctane sulfonic acid	increases expression	1
dimethylarsinous acid	increases expression	1
abrine	increases expression	1
bisphenol S	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1
NSC 689534	affects binding, increases expression	1
(+)-JQ1 compound	decreases expression	1
NSC668394	increases expression	1

Clinical trials (associated diseases)

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