KRT37

Summary

KRT37 (keratin 37, HGNC:6455) is a protein-coding gene on chromosome 17q21.2, encoding Keratin, type I cuticular Ha7 (O76014).

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 8688 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 90 total
• Dosage sensitivity (ClinGen): haploinsufficiency dosage sensitivity unlikely, triplosensitivity no evidence
• MANE Select transcript: NM_003770

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6455
Approved symbol	KRT37
Name	keratin 37
Location	17q21.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000108417
Ensembl biotype	protein_coding
OMIM	604541
Entrez	8688

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000225550

RefSeq mRNA: 1 — MANE Select: NM_003770 NM_003770

CCDS: CCDS32653

Canonical transcript exons

ENST00000225550 — 7 exons

Exon	Start	End
ENSE00001320577	41420547	41420986
ENSE00002329182	41422273	41422434
ENSE00002334247	41422778	41422934
ENSE00002353921	41423762	41423844
ENSE00002364214	41421367	41421587
ENSE00002407039	41422069	41422194
ENSE00002411621	41424032	41424585

Expression profiles

Bgee: expression breadth broad, 22 present calls, max score 84.51.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0134 / max 2.0786, expressed in 4 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
208182	0.0134	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.51	gold quality
lower esophagus mucosa	UBERON:0035834	52.03	gold quality
skin of abdomen	UBERON:0001416	46.70	gold quality
sural nerve	UBERON:0015488	45.10	gold quality
zone of skin	UBERON:0000014	44.74	gold quality
skin of leg	UBERON:0001511	43.06	gold quality
endocervix	UBERON:0000458	40.71	gold quality
stromal cell of endometrium	CL:0002255	40.04	gold quality
esophagus mucosa	UBERON:0002469	39.98	gold quality
ectocervix	UBERON:0012249	39.88	gold quality
uterine cervix	UBERON:0000002	39.77	gold quality
smooth muscle tissue	UBERON:0001135	37.35	gold quality
colonic epithelium	UBERON:0000397	37.20	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
vagina	UBERON:0000996	36.08	gold quality
hindlimb stylopod muscle	UBERON:0004252	35.56	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
muscle tissue	UBERON:0002385	34.25	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
placenta	UBERON:0001987	33.14	silver quality
esophagus	UBERON:0001043	31.75	silver quality
bone marrow	UBERON:0002371	31.74	gold quality
endometrium	UBERON:0001295	31.34	gold quality
tonsil	UBERON:0002372	30.39	gold quality
right lung	UBERON:0002167	30.34	silver quality
liver	UBERON:0002107	29.87	gold quality
prefrontal cortex	UBERON:0000451	29.52	gold quality
urinary bladder	UBERON:0001255	28.79	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.33

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1

miRNA regulators (miRDB)

25 targeting KRT37, 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-548N	99.98	71.94	4170
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-6757-3P	99.63	66.88	1089
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-12131	99.48	68.72	1673
HSA-MIR-8054	99.48	70.81	2084
HSA-MIR-6128	99.33	67.83	1581
HSA-MIR-4686	98.77	66.87	964
HSA-MIR-4635	98.74	67.63	1339
HSA-MIR-5197-3P	98.71	67.05	1905
HSA-MIR-302F	98.44	69.02	1776
HSA-MIR-3187-5P	98.36	65.74	1776
HSA-MIR-4733-3P	98.35	65.20	994
HSA-MIR-1285-3P	97.72	67.02	1932
HSA-MIR-5189-5P	97.72	66.96	1814
HSA-MIR-612	97.26	65.95	1597
HSA-MIR-6860	97.21	66.31	1656
HSA-MIR-1270	96.94	66.65	931
HSA-MIR-620	96.94	66.79	888
HSA-MIR-6866-5P	96.64	68.06	624
HSA-MIR-624-5P	96.00	68.88	728

Functional genomics

ClinGen dosage: haploinsufficiency 40 (dosage sensitivity unlikely), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Cross-species orthologs

0 orthologs

Paralogs (68): KRT33A (ENSG00000006059), VIM (ENSG00000026025), KRT31 (ENSG00000094796), NEFM (ENSG00000104722), KRT23 (ENSG00000108244), 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), KRT13 (ENSG00000171401)

Protein

Protein identifiers

Keratin, type I cuticular Ha7 — O76014 (reviewed: O76014)

Alternative names: Hair keratin, type I Ha7, Keratin-37

All UniProt accessions (1): O76014

UniProt curated annotations — full annotation on UniProt →

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_003761* (*=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 (19 total): sequence variant 9, region of interest 7, chain 1, domain 1, site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O76014-F1	76.14	0.53

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): 353 (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, MORF_EPHA7, MORF_RAB3A, TANAKA_METHYLATED_IN_ESOPHAGEAL_CARCINOMA, MORF_WNT1, MORF_IL9, GOBP_TISSUE_MORPHOGENESIS, MORF_DCC, GOCC_INTERMEDIATE_FILAMENT_CYTOSKELETON, GOCC_KERATIN_FILAMENT, MORF_FRK, CAMPS_COLON_CANCER_COPY_NUMBER_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 molecule activity (GO:0005198), structural constituent of skin epidermis (GO:0030280), protein binding (GO:0005515)

GO Cellular Component (5): cytosol (GO:0005829), cytoskeleton (GO:0005856), keratin filament (GO:0045095), extracellular exosome (GO:0070062), 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
molecular_function	1
structural molecule activity	1
binding	1
cytoplasm	1
cellular anatomical structure	1
intracellular membraneless organelle	1
intermediate filament	1
extracellular vesicle	1
intermediate filament cytoskeleton	1
polymeric cytoskeletal fiber	1

Protein interactions and networks

STRING

366 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KRT37	C6orf163	Q5TEZ5	415
KRT37	CFAP107	Q8N1D5	396
KRT37	NFAM1	Q8NET5	385
KRT37	NDUFA2	O43678	370
KRT37	ZNF431	Q8TF32	370
KRT37	WFDC10B	Q8IUB3	365
KRT37	PRRT1	Q99946	349
KRT37	LCE3A	Q5TA76	336
KRT37	OR1J1	Q8NGS3	325
KRT37	LCE3D	Q9BYE3	322
KRT37	NBPF20	P0DPF2	303
KRT37	THEMIS2	Q5TEJ8	302
KRT37	C17orf50	Q8WW18	297
KRT37	OR2H2	O95918	288
KRT37	ZNF768	Q9H5H4	279

IntAct

138 interactions, top by confidence:

A	B	Type	Score
KRT37	KRT85	psi-mi:“MI:0915”(physical association)	0.630
KRT37	KRT81	psi-mi:“MI:0915”(physical association)	0.630
KRT37	KRT74	psi-mi:“MI:0915”(physical association)	0.630
KRT74	KRT37	psi-mi:“MI:0915”(physical association)	0.630
KRT85	KRT37	psi-mi:“MI:0915”(physical association)	0.630
KRT37	TXLNB	psi-mi:“MI:0915”(physical association)	0.560
KRT86	KRT37	psi-mi:“MI:0915”(physical association)	0.560
KRT37	KRT6C	psi-mi:“MI:0915”(physical association)	0.560
KRT37	USHBP1	psi-mi:“MI:0915”(physical association)	0.560
KRT37	PSMA1	psi-mi:“MI:0915”(physical association)	0.560
HGS	KRT37	psi-mi:“MI:0915”(physical association)	0.560
KRT37	KRT76	psi-mi:“MI:0915”(physical association)	0.560
KRT37	KRT71	psi-mi:“MI:0915”(physical association)	0.560
KRT37	GNG13	psi-mi:“MI:0915”(physical association)	0.560
BCAS2	KRT37	psi-mi:“MI:0915”(physical association)	0.560
KRT37	MTG1	psi-mi:“MI:0915”(physical association)	0.560
KRT37	PKN1	psi-mi:“MI:0915”(physical association)	0.560
KRT37	SMARCE1	psi-mi:“MI:0915”(physical association)	0.560
KRT37	SMARCD1	psi-mi:“MI:0915”(physical association)	0.560
KRT37	HOXA1	psi-mi:“MI:0915”(physical association)	0.560
KRT37	AQP1	psi-mi:“MI:0915”(physical association)	0.560
KRT37	AGXT	psi-mi:“MI:0915”(physical association)	0.560
KRT37	KRT1	psi-mi:“MI:0915”(physical association)	0.560
KRT37	KRT75	psi-mi:“MI:0915”(physical association)	0.560
KRT37	DES	psi-mi:“MI:0915”(physical association)	0.560
KRT37	HSF4	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (99): KRT37 (Affinity Capture-MS), KRT37 (Two-hybrid), KRT37 (Two-hybrid), KRT37 (Two-hybrid), KRT37 (Two-hybrid), KRT37 (Two-hybrid), KRT37 (Two-hybrid), OTX1 (Two-hybrid), BCAS2 (Two-hybrid), PKN1 (Two-hybrid), FAM110A (Two-hybrid), PIN1 (Two-hybrid), GNG13 (Two-hybrid), PSMA1 (Two-hybrid), USHBP1 (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: 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 48 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	13	32.6×	1e-14
Keratinization	13	20.7×	2e-12

GO biological processes:

GO term	Partners	Fold	FDR
intermediate filament organization	15	86.0×	1e-23
keratinization	13	72.5×	2e-19

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	85
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

679 predictions. Top by Δscore:

Variant	Effect	Δscore
17:41421363:GTA:G	donor_loss	1.0000
17:41421364:TA:T	donor_loss	1.0000
17:41421365:A:AC	donor_gain	1.0000
17:41421365:A:C	donor_loss	1.0000
17:41421366:C:CG	donor_gain	1.0000
17:41421366:C:T	donor_loss	1.0000
17:41421366:CTTG:C	donor_gain	1.0000
17:41421583:TCCTT:T	acceptor_gain	1.0000
17:41421584:CCTTC:C	acceptor_gain	1.0000
17:41421585:CTT:C	acceptor_gain	1.0000
17:41421586:TT:T	acceptor_gain	1.0000
17:41421588:C:CC	acceptor_gain	1.0000
17:41421588:C:CG	acceptor_loss	1.0000
17:41421589:T:G	acceptor_loss	1.0000
17:41421590:G:C	acceptor_gain	1.0000
17:41422066:TAC:T	donor_loss	1.0000
17:41422067:A:AC	donor_gain	1.0000
17:41422067:A:T	donor_loss	1.0000
17:41422067:AC:A	donor_gain	1.0000
17:41422068:C:CG	donor_gain	1.0000
17:41422068:CC:C	donor_gain	1.0000
17:41422068:CCA:C	donor_gain	1.0000
17:41422068:CCAA:C	donor_gain	1.0000
17:41422068:CCAAG:C	donor_gain	1.0000
17:41422190:TCAGA:T	acceptor_gain	1.0000
17:41422191:CAGA:C	acceptor_gain	1.0000
17:41422191:CAGAC:C	acceptor_gain	1.0000
17:41422192:AGA:A	acceptor_gain	1.0000
17:41422193:GA:G	acceptor_gain	1.0000
17:41422195:C:CC	acceptor_gain	1.0000

AlphaMissense

2953 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:41423793:C:G	A182P	0.952
17:41424183:C:G	R114P	0.946
17:41421478:C:G	R377P	0.944
17:41421418:A:G	L397S	0.940
17:41421394:C:G	R405P	0.938
17:41421469:A:G	L380P	0.933
17:41422282:G:C	F295L	0.932
17:41422282:G:T	F295L	0.932
17:41422284:A:G	F295L	0.932
17:41421388:A:G	L407P	0.927
17:41421463:C:G	R382P	0.920
17:41423781:C:G	A186P	0.915
17:41424042:A:G	L161P	0.913
17:41421398:A:G	Y404H	0.911
17:41421460:T:G	Q383P	0.911
17:41421426:C:A	K394N	0.908
17:41421426:C:G	K394N	0.908
17:41421439:A:G	L390P	0.905
17:41422083:C:G	A336P	0.897
17:41421398:A:C	Y404D	0.894
17:41424156:C:G	R123P	0.893
17:41421514:A:G	L365P	0.883
17:41421409:T:A	E400V	0.882
17:41421577:A:G	L344P	0.881
17:41421490:A:G	L373S	0.870
17:41422088:C:G	R334P	0.869
17:41421406:A:C	I401S	0.864
17:41422121:A:G	L323P	0.862
17:41424189:T:A	N112I	0.862
17:41424059:G:C	F155L	0.859

dbSNP variants (sampled 300 via entrez): RS1000243811 (17:41423586 T>G), RS1001060879 (17:41422593 G>C), RS1001318303 (17:41424601 CCCAA>C), RS1002839701 (17:41424854 C>T), RS1003201509 (17:41426113 C>G,T), RS1003663062 (17:41425992 T>A,C), RS1003987987 (17:41420822 G>A,T), RS1004329587 (17:41425270 T>G), RS1005000514 (17:41424829 A>C,G,T), RS1005282167 (17:41425912 G>A,T), RS1005747243 (17:41426065 C>A,T), RS1006465836 (17:41421786 C>T), RS1008058946 (17:41424672 C>T), RS1008131236 (17:41424919 C>A,T), RS1009033591 (17:41424073 A>T)

Disease associations

OMIM: gene MIM:604541 | 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
GCST004750_12	Squamous cell lung carcinoma	9.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tetrachlorodibenzodioxin	increases expression	3
Benzo(a)pyrene	increases expression, increases methylation	2
sodium arsenate	decreases expression, increases abundance	1
tris(2-butoxyethyl) phosphate	affects expression	1
CGP 52608	affects binding, increases reaction	1
Arsenic	decreases expression, increases abundance	1
Calcitriol	increases expression	1
Sodium Dodecyl Sulfate	increases expression	1
Urethane	increases expression	1
Vitallium	increases expression	1
Cadmium Chloride	increases expression	1
Copper Sulfate	increases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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