KRT39

Summary

KRT39 (keratin 39, HGNC:32971) is a protein-coding gene on chromosome 17q21.2, encoding Keratin, type I cytoskeletal 39 (Q6A163). May play a role in late hair differentiation.

This gene encodes a member of the type I (acidic) keratin family, which belongs to the superfamily of intermediate filament (IF) proteins. Keratins are heteropolymeric structural proteins which form the intermediate filament. These filaments, along with actin microfilaments and microtubules, compose the cytoskeleton of epithelial cells. The type I keratin genes are clustered in a region of chromosome 17q12-q21.

Source: NCBI Gene 390792 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 75 total
• MANE Select transcript: NM_213656

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32971
Approved symbol	KRT39
Name	keratin 39
Location	17q21.2
Locus type	gene with protein product
Status	Approved
Aliases	KA35
Ensembl gene	ENSG00000196859
Ensembl biotype	protein_coding
OMIM	616678
Entrez	390792

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 1 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000355612, ENST00000578029, ENST00000578078

RefSeq mRNA: 1 — MANE Select: NM_213656 NM_213656

CCDS: CCDS11382

Canonical transcript exons

ENST00000355612 — 7 exons

Exon	Start	End
ENSE00001629960	40966389	40966948
ENSE00001636575	40964446	40964528
ENSE00001667853	40958417	40958859
ENSE00003543528	40962162	40962287
ENSE00003545521	40963627	40963783
ENSE00003641096	40962402	40962563
ENSE00003663175	40960281	40960501

Expression profiles

Bgee: expression breadth broad, 45 present calls, max score 89.09.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0088 / max 12.1626, expressed in 2 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165854	0.0088	2

Top tissues by expression

102 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	89.09	gold quality
skin of abdomen	UBERON:0001416	59.06	gold quality
zone of skin	UBERON:0000014	56.33	gold quality
gall bladder	UBERON:0002110	55.01	gold quality
skin of leg	UBERON:0001511	54.62	gold quality
mucosa of transverse colon	UBERON:0004991	54.30	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	49.18	gold quality
islet of Langerhans	UBERON:0000006	45.01	gold quality
placenta	UBERON:0001987	44.37	gold quality
duodenum	UBERON:0002114	44.01	gold quality
right lung	UBERON:0002167	42.57	gold quality
rectum	UBERON:0001052	41.05	gold quality
adenohypophysis	UBERON:0002196	38.54	gold quality
pancreas	UBERON:0001264	38.50	gold quality
saliva-secreting gland	UBERON:0001044	38.38	gold quality
bone marrow cell	CL:0002092	37.99	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
sural nerve	UBERON:0015488	36.60	gold quality
minor salivary gland	UBERON:0001830	36.58	silver quality
ventricular zone	UBERON:0003053	36.48	gold quality
skeletal muscle tissue	UBERON:0001134	36.47	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
cortex of kidney	UBERON:0001225	36.19	gold quality
granulocyte	CL:0000094	35.52	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
small intestine	UBERON:0002108	34.42	silver quality
small intestine Peyer’s patch	UBERON:0003454	34.11	silver quality
endocervix	UBERON:0000458	34.02	silver quality
pituitary gland	UBERON:0000007	33.95	gold quality
vermiform appendix	UBERON:0001154	33.79	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.23

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

13 targeting KRT39, 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-6081	99.48	66.07	1446
HSA-MIR-4519	99.48	66.10	859
HSA-MIR-3191-3P	99.45	63.94	356
HSA-MIR-20B-3P	99.29	67.05	784
HSA-MIR-6878-3P	99.24	64.23	920
HSA-MIR-6744-3P	99.22	64.41	972
HSA-MIR-4757-5P	99.12	64.51	981
HSA-MIR-6868-5P	99.06	65.69	1284
HSA-MIR-4468	98.01	66.85	1187
HSA-MIR-3144-5P	97.64	65.45	646
HSA-MIR-7855-5P	97.39	67.18	925
HSA-MIR-4475	97.36	66.95	761
HSA-MIR-6892-5P	97.27	68.60	847

Literature-anchored findings (GeneRIF, showing 1)

• KRT39 and KRT40 expression patterns complete sequential expression of the 16 hair keratins in the human hair follicle (PMID:17301834)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Krt39	ENSMUSG00000064165
rattus_norvegicus	Krt39	ENSRNOG00000031422

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 I cytoskeletal 39 — Q6A163 (reviewed: Q6A163)

Alternative names: Cytokeratin-39, Keratin-39, Type I hair keratin Ka35

All UniProt accessions (2): Q6A163, J3QRE9

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in late hair differentiation.

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

Tissue specificity. Expressed in skin and scalp. In the hair follicle, it is present in the upper hair cuticle and the upper cortex. Also present in the in the upper portion of beard hairs (at protein level).

Miscellaneous. There are two types of cytoskeletal and microfibrillar keratin, I (acidic) and II (neutral to basic) (40-55 and 56-70 kDa, respectively).

Similarity. Belongs to the intermediate filament family.

RefSeq proteins (1): NP_998821* (*=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 3, chain 1, domain 1, site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6A163-F1	75.29	0.54

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): 345 (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: 29 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_INTERMEDIATE_FILAMENT_BASED_PROCESS, GOBP_INTERMEDIATE_FILAMENT_ORGANIZATION, GOBP_TISSUE_MORPHOGENESIS, GOCC_INTERMEDIATE_FILAMENT_CYTOSKELETON, GOCC_KERATIN_FILAMENT, GOMF_STRUCTURAL_MOLECULE_ACTIVITY, GOBP_SUPRAMOLECULAR_FIBER_ORGANIZATION, GOCC_SUPRAMOLECULAR_COMPLEX, GOCC_POLYMERIC_CYTOSKELETAL_FIBER, GOMF_STRUCTURAL_CONSTITUENT_OF_SKIN_EPIDERMIS, REACTOME_KERATINIZATION, REACTOME_FORMATION_OF_THE_CORNIFIED_ENVELOPE, GSE13522_CTRL_VS_T_CRUZI_Y_STRAIN_INF_SKIN_129_MOUSE_UP

GO Biological Process (3): morphogenesis of an epithelium (GO:0002009), epithelial cell differentiation (GO:0030855), 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 (4): 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
cell differentiation	1
intermediate filament cytoskeleton organization	1
supramolecular fiber organization	1
structural molecule activity	1
molecular_function	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

344 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KRT39	KRTAP9-2	Q9BYQ4	479
KRT39	KRTAP3-1	Q9BYR8	479
KRT39	CERT1	Q9Y5P4	410
KRT39	CDA	P32320	388
KRT39	GAREM1	Q9H706	386
KRT39	GFUS	Q13630	380
KRT39	PLCD1	P51178	353
KRT39	NEGR1	Q7Z3B1	345
KRT39	RASGRP4	Q8TDF6	341
KRT39	DCAF11	Q8TEB1	336
KRT39	XRRA1	Q6P2D8	320
KRT39	MZT2A	Q6P582	316
KRT39	S100A3	P33764	309
KRT39	KLHL33	A6NCF5	308
KRT39	CHST1	O43916	307

IntAct

110 interactions, top by confidence:

A	B	Type	Score
KRT86	KRT39	psi-mi:“MI:0915”(physical association)	0.630
PPL	KRT39	psi-mi:“MI:0915”(physical association)	0.600
KRT39	PPL	psi-mi:“MI:0915”(physical association)	0.600
ANKS1A	KRT39	psi-mi:“MI:0915”(physical association)	0.560
KRT39	SMARCE1	psi-mi:“MI:0915”(physical association)	0.560
KRT39	C1orf216	psi-mi:“MI:0915”(physical association)	0.560
KRT1	KRT39	psi-mi:“MI:0915”(physical association)	0.560
KRT39	KRT74	psi-mi:“MI:0915”(physical association)	0.560
HGS	KRT39	psi-mi:“MI:0915”(physical association)	0.560
KRT39	ZNF417	psi-mi:“MI:0915”(physical association)	0.560
KRT3	KRT39	psi-mi:“MI:0915”(physical association)	0.560
KRT76	KRT39	psi-mi:“MI:0915”(physical association)	0.560
KRT39	SCNM1	psi-mi:“MI:0915”(physical association)	0.560
KRT85	KRT39	psi-mi:“MI:0915”(physical association)	0.560
CCDC196	KRT39	psi-mi:“MI:0915”(physical association)	0.560
KLHL38	KRT39	psi-mi:“MI:0915”(physical association)	0.560
KRT39	BEX2	psi-mi:“MI:0915”(physical association)	0.560
KRT39	VPS9D1	psi-mi:“MI:0915”(physical association)	0.560
KRT39	ARMC7	psi-mi:“MI:0915”(physical association)	0.560
KRT83	KRT39	psi-mi:“MI:0915”(physical association)	0.560
KDM1A	KRT39	psi-mi:“MI:0915”(physical association)	0.560
CLCNKA	KRT39	psi-mi:“MI:0915”(physical association)	0.560
KRT81	KRT39	psi-mi:“MI:0915”(physical association)	0.560
KRT39	PRPF18	psi-mi:“MI:0915”(physical association)	0.560
KRT6B	KRT39	psi-mi:“MI:0915”(physical association)	0.560
KRT39	KRT78	psi-mi:“MI:0915”(physical association)	0.560
KRT39	TGM7	psi-mi:“MI:0915”(physical association)	0.560
GFAP	KRT39	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (60): KRT39 (Affinity Capture-MS), KRT39 (Two-hybrid), KRT39 (Two-hybrid), KRT39 (Two-hybrid), KRT39 (Two-hybrid), KRT39 (Two-hybrid), KRT39 (Two-hybrid), KRT39 (Two-hybrid), KRT39 (Two-hybrid), KRT39 (Two-hybrid), KRT39 (Two-hybrid), KRT39 (Two-hybrid), KRT39 (Two-hybrid), KRT39 (Two-hybrid), KRT39 (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: A1L595, A5A6M0, A5A6M5, A5A6N2, A5A6P3, A6BLY7, A6QQQ9, A7YWM2, B0LKP1, B1AQ75, O76009, O76011, O76013, O76014, O76015, O77727, O93256, P02533, P02534, P02535, P02537, P05781, P05783, P05784, P06394, P08727, P08728, P08730, P08777, P08778, P08779, P13645, P13646, P19001, P19012, P25030, P25690, P35900, P51856, Q04695

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 36 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	11	48.3×	3e-15
Keratinization	10	27.9×	2e-11

GO biological processes:

GO term	Partners	Fold	FDR
intermediate filament organization	11	88.3×	2e-17
keratinization	11	85.8×	2e-17

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	67
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1087 predictions. Top by Δscore:

Variant	Effect	Δscore
17:40958857:CGC:C	acceptor_gain	1.0000
17:40960276:CATA:C	donor_gain	1.0000
17:40960279:A:AC	donor_gain	1.0000
17:40960279:ACT:A	donor_loss	1.0000
17:40960280:C:CA	donor_gain	1.0000
17:40960280:CTTG:C	donor_gain	1.0000
17:40960498:CTCT:C	acceptor_gain	1.0000
17:40960500:CT:C	acceptor_gain	1.0000
17:40960506:CA:C	acceptor_gain	1.0000
17:40960507:A:C	acceptor_gain	1.0000
17:40962092:A:AC	donor_gain	1.0000
17:40962093:C:CC	donor_gain	1.0000
17:40962121:T:TA	donor_gain	1.0000
17:40962414:C:CT	donor_gain	1.0000
17:40962418:TGTTC:T	donor_gain	1.0000
17:40962560:TTTC:T	acceptor_gain	1.0000
17:40962561:TTC:T	acceptor_gain	1.0000
17:40962562:TC:T	acceptor_gain	1.0000
17:40962563:CC:C	acceptor_gain	1.0000
17:40962564:C:CC	acceptor_gain	1.0000
17:40963624:CACC:C	donor_loss	1.0000
17:40963626:CCT:C	donor_gain	1.0000
17:40963779:CGTAT:C	acceptor_gain	1.0000
17:40963784:C:CC	acceptor_gain	1.0000
17:40963786:T:C	acceptor_gain	1.0000
17:40963786:T:TC	acceptor_gain	1.0000
17:40963794:C:T	acceptor_gain	1.0000
17:40963794:CAGA:C	acceptor_gain	1.0000
17:40964444:A:AC	donor_gain	1.0000
17:40964445:C:CC	donor_gain	1.0000

AlphaMissense

3222 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:40964513:C:G	A162P	0.960
17:40966399:A:G	L153P	0.955
17:40964465:C:G	A178P	0.950
17:40966540:C:G	R106P	0.947
17:40964504:A:G	S165P	0.946
17:40962181:A:G	L326P	0.938
17:40962214:A:G	L315P	0.926
17:40962411:G:C	F287L	0.918
17:40962411:G:T	F287L	0.918
17:40962413:A:G	F287L	0.918
17:40964497:A:G	L167P	0.915
17:40962176:C:G	A328P	0.910
17:40960320:A:G	I393T	0.907
17:40960446:A:G	L351P	0.899
17:40963760:C:G	R192P	0.899
17:40964488:T:G	Q170P	0.890
17:40966486:A:G	L124P	0.885
17:40966535:C:G	A108P	0.884
17:40966537:A:G	L107P	0.884
17:40960332:A:G	L389P	0.883
17:40960416:A:G	L361P	0.882
17:40960340:C:A	K386N	0.878
17:40960340:C:G	K386N	0.878
17:40962172:T:G	Q329P	0.878
17:40966525:A:G	L111P	0.877
17:40966474:A:G	I128T	0.875
17:40964514:C:A	K161N	0.874
17:40964514:C:G	K161N	0.874
17:40964470:A:G	L176P	0.872
17:40966396:T:G	Q154P	0.872

dbSNP variants (sampled 300 via entrez): RS1000154345 (17:40960815 CTT>C), RS1001415640 (17:40965501 C>T), RS1002052016 (17:40968029 T>A), RS1002343409 (17:40961384 G>A), RS1002452908 (17:40963456 A>G), RS1002508034 (17:40958726 A>C), RS1002539079 (17:40958951 G>A), RS1002966717 (17:40968367 A>G), RS1003719327 (17:40964813 C>T), RS1003841445 (17:40961324 T>C), RS1004068519 (17:40963095 G>T), RS1004630172 (17:40958263 G>A), RS1004933007 (17:40964762 T>C), RS1005534086 (17:40962748 T>C), RS1005980557 (17:40963888 T>A)

Disease associations

OMIM: gene MIM:616678 | 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

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
propionaldehyde	decreases expression	1
beta-lapachone	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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