KRT40

Summary

KRT40 (keratin 40, HGNC:26707) is a protein-coding gene on chromosome 17q21.2, encoding Keratin, type I cytoskeletal 40 (Q6A162). 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 125115 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 71 total
• MANE Select transcript: NM_001389244

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26707
Approved symbol	KRT40
Name	keratin 40
Location	17q21.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ36600, KA36
Ensembl gene	ENSG00000204889
Ensembl biotype	protein_coding
OMIM	616679
Entrez	125115

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 nonsense_mediated_decay

ENST00000377755, ENST00000398486, ENST00000461923, ENST00000684280

RefSeq mRNA: 3 — MANE Select: NM_001389244 NM_001385217, NM_001389244, NM_182497

CCDS: CCDS42320

Canonical transcript exons

ENST00000377755 — 7 exons

Exon	Start	End
ENSE00001700622	40983046	40983128
ENSE00001776595	40983827	40984326
ENSE00001784920	40980990	40981151
ENSE00002376849	40982307	40982463
ENSE00003464325	40978804	40979024
ENSE00003626578	40977715	40978296
ENSE00003632126	40980785	40980910

Expression profiles

Bgee: expression breadth broad, 41 present calls, max score 81.83.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0475 / max 40.3147, expressed in 9 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165859	0.0178	4
165858	0.0083	4
165855	0.0081	4
165856	0.0079	4
165857	0.0054	1

Top tissues by expression

114 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	81.83	gold quality
islet of Langerhans	UBERON:0000006	65.82	gold quality
adenohypophysis	UBERON:0002196	65.00	gold quality
pituitary gland	UBERON:0000007	64.73	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	58.98	gold quality
skin of abdomen	UBERON:0001416	55.88	gold quality
mucosa of transverse colon	UBERON:0004991	55.28	gold quality
zone of skin	UBERON:0000014	52.74	gold quality
duodenum	UBERON:0002114	52.37	gold quality
lower esophagus mucosa	UBERON:0035834	52.09	gold quality
skin of leg	UBERON:0001511	50.51	gold quality
saliva-secreting gland	UBERON:0001044	48.00	gold quality
pancreas	UBERON:0001264	47.61	gold quality
minor salivary gland	UBERON:0001830	47.52	gold quality
rectum	UBERON:0001052	44.47	gold quality
gall bladder	UBERON:0002110	40.64	gold quality
small intestine	UBERON:0002108	40.31	gold quality
esophagus mucosa	UBERON:0002469	39.96	gold quality
transverse colon	UBERON:0001157	39.84	gold quality
stromal cell of endometrium	CL:0002255	39.28	gold quality
small intestine Peyer’s patch	UBERON:0003454	39.11	silver quality
sural nerve	UBERON:0015488	37.68	gold quality
right lung	UBERON:0002167	37.44	silver quality
ganglionic eminence	UBERON:0004023	37.30	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
cortex of kidney	UBERON:0001225	36.74	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
intestine	UBERON:0000160	35.67	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.36

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

29 targeting KRT40, 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-8485	100.00	77.57	4731
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-12131	99.48	68.72	1673
HSA-MIR-6839-3P	99.39	68.86	1301
HSA-MIR-5580-5P	99.38	66.96	1139
HSA-MIR-4263	99.18	69.25	2236
HSA-MIR-3125	99.14	68.49	2269
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-670-3P	99.03	68.88	2404
HSA-MIR-3916	98.99	68.04	2155
HSA-MIR-6859-5P	98.99	68.07	2049
HSA-MIR-5590-5P	98.81	68.78	969
HSA-MIR-629-5P	98.78	68.72	1032
HSA-MIR-502-5P	98.77	66.51	906
HSA-MIR-4709-5P	98.51	67.25	1335
HSA-MIR-6841-3P	98.08	66.54	604
HSA-MIR-4659A-5P	98.03	66.42	819
HSA-MIR-3157-5P	97.41	67.61	998
HSA-MIR-4689	96.97	65.79	1209
HSA-MIR-34A-3P	96.80	67.70	805
HSA-MIR-3115	96.45	67.49	470
HSA-MIR-4653-3P	96.26	67.03	725
HSA-MIR-6858-5P	96.05	64.59	1020
HSA-MIR-584-5P	95.82	68.05	848
HSA-MIR-1915-5P	95.25	65.78	571
HSA-MIR-6125	95.17	67.26	91

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	Krt40	ENSMUSG00000059169
rattus_norvegicus	Krt40	ENSRNOG00000013896

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 40 — Q6A162 (reviewed: Q6A162)

Alternative names: Cytokeratin-40, Keratin-40, Type I hair keratin Ka36

All UniProt accessions (2): Q6A162, G3V1C2

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. Also very weakly expressed in tongue, breast, colon and small intestine. In the hair follicle, it is specifically present in the upper hair cuticle. Not present in the upper cortex (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 (3): NP_001372146, NP_001376173, NP_872303 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002957	Keratin_I	Family
IPR039008	IF_rod_dom	Domain

Pfam: PF00038

UniProt features (22 total): sequence variant 9, region of interest 7, sequence conflict 3, chain 1, domain 1, site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6A162-F1	77.78	0.59

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): 338 (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: 44 (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, DODD_NASOPHARYNGEAL_CARCINOMA_DN, GOMF_STRUCTURAL_MOLECULE_ACTIVITY, CACTGCC_MIR34A_MIR34C_MIR449, GYORFFY_DOXORUBICIN_RESISTANCE, GOBP_SUPRAMOLECULAR_FIBER_ORGANIZATION, GOCC_SUPRAMOLECULAR_COMPLEX, GOCC_POLYMERIC_CYTOSKELETAL_FIBER, GOMF_STRUCTURAL_CONSTITUENT_OF_SKIN_EPIDERMIS

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

874 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KRT40	KRTAP3-1	Q9BYR8	455
KRT40	KRTAP15-1	Q3LI76	365
KRT40	KRTAP7-1	Q8IUC3	319
KRT40	OVCH1	Q7RTY7	309
KRT40	SPRR4	Q96PI1	305
KRT40	ARL5C	A6NH57	299
KRT40	PRSS45P	Q7RTY3	295
KRT40	C1orf159	Q96HA4	290
KRT40	C6orf141	Q5SZD1	288
KRT40	DSG4	Q86SJ6	280
KRT40	KRTAP9-2	Q9BYQ4	280
KRT40	FAM151A	Q8WW52	278
KRT40	CEACAM18	A8MTB9	271
KRT40	S100A3	P33764	268
KRT40	ACER1	Q8TDN7	264

IntAct

1369 interactions, top by confidence:

A	B	Type	Score
KRT6A	KRT40	psi-mi:“MI:0915”(physical association)	0.870
KRT40	KRT2	psi-mi:“MI:0915”(physical association)	0.810
KRT40	ZBTB16	psi-mi:“MI:0915”(physical association)	0.810
KRT4	KRT40	psi-mi:“MI:0915”(physical association)	0.780
TXLNA	KRT40	psi-mi:“MI:0915”(physical association)	0.780
KRT40	PSMC5	psi-mi:“MI:0915”(physical association)	0.740
KRT40	ATPAF2	psi-mi:“MI:0915”(physical association)	0.740
KRT40	PRPF31	psi-mi:“MI:0915”(physical association)	0.720
KRT40	HGS	psi-mi:“MI:0915”(physical association)	0.720
KRT40	PRKAB2	psi-mi:“MI:0915”(physical association)	0.720
KRT40	USP2	psi-mi:“MI:0915”(physical association)	0.720
KRT40	ZNF202	psi-mi:“MI:0915”(physical association)	0.720
KRT40	FARS2	psi-mi:“MI:0915”(physical association)	0.720
KRT8	KRT40	psi-mi:“MI:0915”(physical association)	0.720
KRT40	KRT5	psi-mi:“MI:0915”(physical association)	0.720
KRT40	ZNF250	psi-mi:“MI:0915”(physical association)	0.720
KRT6C	KRT40	psi-mi:“MI:0915”(physical association)	0.720
RWDD2B	KRT40	psi-mi:“MI:0915”(physical association)	0.720
KRT40	CYCS	psi-mi:“MI:0915”(physical association)	0.720
KRT40	CREB5	psi-mi:“MI:0915”(physical association)	0.720
ZNF844	KRT40	psi-mi:“MI:0915”(physical association)	0.720
BYSL	KRT40	psi-mi:“MI:0915”(physical association)	0.720
KRT40	BYSL	psi-mi:“MI:0915”(physical association)	0.720
KRT40	KRT81	psi-mi:“MI:0915”(physical association)	0.720
KRT40	LAGE3	psi-mi:“MI:0915”(physical association)	0.720
KRT40	JOSD1	psi-mi:“MI:0915”(physical association)	0.720
KRT40	KRT71	psi-mi:“MI:0915”(physical association)	0.720
KRT40	ZFP2	psi-mi:“MI:0915”(physical association)	0.720
FAM90A1	KRT40	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (510): KRT40 (Two-hybrid), KRT40 (Two-hybrid), KRT40 (Two-hybrid), KRT40 (Two-hybrid), KRT40 (Two-hybrid), KRT40 (Two-hybrid), KRT40 (Two-hybrid), KRT40 (Two-hybrid), KRT40 (Two-hybrid), KRT40 (Two-hybrid), KRT40 (Two-hybrid), KRT40 (Two-hybrid), KRT40 (Two-hybrid), KRT40 (Two-hybrid), KRT40 (Two-hybrid)

ESM2 similar proteins: A0JND2, A3KN27, A6BLY7, A6H712, A6QNX5, A6QQJ3, A7YWK3, D3ZER2, E1AB55, O76014, O76015, P08552, P15331, P21807, P35617, P41219, P46660, P48670, Q0VBK2, Q13515, Q148H5, Q148H6, Q148H8, Q14CN4, Q28177, Q3SY84, Q3TRJ4, Q6A162, Q6IFW3, Q6IFW8, Q6IFX0, Q6IFX4, Q6IFZ9, Q6IG04, Q6IME9, Q6IMF1, Q6KB66, Q6NVD9, Q6NXH9, Q7RTS7

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 181 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	9.0×	2e-05
Keratinization	11	5.7×	9e-04

GO biological processes:

GO term	Partners	Fold	FDR
intermediate filament organization	9	14.2×	8e-06
keratinization	9	13.9×	8e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

71 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	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

873 predictions. Top by Δscore:

Variant	Effect	Δscore
17:40979021:CTGT:C	acceptor_gain	1.0000
17:40980251:G:C	donor_gain	1.0000
17:40980748:T:C	donor_gain	1.0000
17:40980774:G:A	donor_gain	1.0000
17:40980780:CGCA:C	donor_gain	1.0000
17:40980781:GCACC:G	donor_loss	1.0000
17:40980782:CA:C	donor_loss	1.0000
17:40980783:A:AC	donor_gain	1.0000
17:40980784:C:CC	donor_gain	1.0000
17:40980784:C:G	donor_loss	1.0000
17:40980784:CCAGG:C	donor_gain	1.0000
17:40980907:CTGT:C	acceptor_gain	1.0000
17:40980908:TGT:T	acceptor_gain	1.0000
17:40980910:TCTG:T	acceptor_loss	1.0000
17:40980911:C:CC	acceptor_gain	1.0000
17:40980911:C:CG	acceptor_loss	1.0000
17:40980986:TGA:T	donor_loss	1.0000
17:40980987:GAC:G	donor_loss	1.0000
17:40981148:CTTC:C	acceptor_gain	1.0000
17:40982301:CCTTA:C	donor_loss	1.0000
17:40982302:CTTA:C	donor_loss	1.0000
17:40982303:TTA:T	donor_loss	1.0000
17:40982304:TACCT:T	donor_loss	1.0000
17:40982305:A:C	donor_loss	1.0000
17:40982306:C:T	donor_loss	1.0000
17:40982306:CCT:C	donor_gain	1.0000
17:40982462:ACCT:A	acceptor_loss	1.0000
17:40982463:CC:C	acceptor_loss	1.0000
17:40982464:C:A	acceptor_loss	1.0000
17:40982465:T:A	acceptor_loss	1.0000

AlphaMissense

2832 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:40983912:A:G	I121T	0.921
17:40983113:C:G	A155P	0.919
17:40983837:A:G	L146P	0.916
17:40980804:A:G	L319P	0.914
17:40983973:C:G	A101P	0.905
17:40978900:C:G	R367P	0.897
17:40983984:T:A	N97I	0.897
17:40983951:C:G	R108P	0.896
17:40978863:C:A	K379N	0.894
17:40978863:C:G	K379N	0.894
17:40978927:A:G	L358P	0.888
17:40983963:A:G	L104P	0.886
17:40978939:A:G	L354P	0.885
17:40983975:A:G	L100P	0.885
17:40978906:A:G	L365P	0.881
17:40980799:C:G	A321P	0.875
17:40978915:C:G	R362P	0.865
17:40983104:A:G	S158P	0.865
17:40983924:A:G	L117P	0.860
17:40978855:A:G	L382P	0.858
17:40983975:A:T	L100H	0.857
17:40978843:A:G	I386T	0.852
17:40983983:A:C	N97K	0.852
17:40983983:A:T	N97K	0.852
17:40983987:A:G	L96P	0.847
17:40983945:A:G	L110P	0.846
17:40978988:C:G	A338P	0.845
17:40983995:C:A	M93I	0.845
17:40983995:C:G	M93I	0.845
17:40983995:C:T	M93I	0.845

dbSNP variants (sampled 300 via entrez): RS1000039296 (17:40986462 C>T), RS1000665381 (17:40986688 A>G), RS1000739496 (17:40977452 G>A,T), RS1000944830 (17:40982046 T>G), RS1001078957 (17:40978746 C>A), RS1002007622 (17:40988998 C>A,G,T), RS1002211692 (17:40983254 C>A,T), RS1002413897 (17:40978674 G>A,C), RS1002687251 (17:40979329 C>A), RS1002749301 (17:40979570 A>G), RS1002866543 (17:40986200 G>A), RS1002921001 (17:40980614 C>A), RS1002954080 (17:40984745 G>T), RS1004444522 (17:40982973 G>T), RS1004734101 (17:40988723 G>A,T)

Disease associations

OMIM: gene MIM:616679 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010397_78	Gut microbiota (bacterial taxa, rank normal transformation method)	6.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
beta-lapachone	decreases expression	1
CGP 52608	affects binding, increases reaction	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Estradiol	decreases expression	1
Silver	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	increases expression	1
Permethrin	decreases expression	1

Clinical trials (associated diseases)

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