KRT73

Summary

KRT73 (keratin 73, HGNC:28928) is a protein-coding gene on chromosome 12q13.13, encoding Keratin, type II cytoskeletal 73 (Q86Y46). Has a role in hair formation.

Keratins are intermediate filament proteins responsible for the structural integrity of epithelial cells and are subdivided into epithelial keratins and hair keratins. This gene encodes a protein that is expressed in the inner root sheath of hair follicles. The type II keratins are clustered in a region of chromosome 12q13.

Source: NCBI Gene 319101 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 111 total
• MANE Select transcript: NM_175068

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28928
Approved symbol	KRT73
Name	keratin 73
Location	12q13.13
Locus type	gene with protein product
Status	Approved
Aliases	KRT6IRS3, K6IRS3
Ensembl gene	ENSG00000186049
Ensembl biotype	protein_coding
OMIM	608247
Entrez	319101

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 retained_intron

ENST00000305748, ENST00000546934, ENST00000552855

RefSeq mRNA: 1 — MANE Select: NM_175068 NM_175068

CCDS: CCDS8834

Canonical transcript exons

ENST00000305748 — 9 exons

Exon	Start	End
ENSE00001270376	52607570	52608452
ENSE00001270422	52618078	52618559
ENSE00001720813	52610615	52610835
ENSE00001777807	52611204	52611329
ENSE00003539659	52615279	52615339
ENSE00003569369	52616166	52616380
ENSE00003586796	52613688	52613852
ENSE00003630974	52609247	52609281
ENSE00003650163	52614579	52614674

Expression profiles

Bgee: expression breadth broad, 73 present calls, max score 84.10.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skin of leg	UBERON:0001511	84.10	gold quality
zone of skin	UBERON:0000014	80.78	gold quality
skin of abdomen	UBERON:0001416	80.69	gold quality
granulocyte	CL:0000094	79.44	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	76.93	silver quality
sperm	CL:0000019	68.74	gold quality
blood	UBERON:0000178	63.41	gold quality
lymph node	UBERON:0000029	58.27	gold quality
skin of hip	UBERON:0001554	57.63	silver quality
vermiform appendix	UBERON:0001154	56.41	gold quality
jejunal mucosa	UBERON:0000399	54.52	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
caecum	UBERON:0001153	53.92	gold quality
endothelial cell	CL:0000115	53.81	gold quality
epithelial cell of pancreas	CL:0000083	53.46	gold quality
duodenum	UBERON:0002114	53.24	gold quality
amniotic fluid	UBERON:0000173	52.89	gold quality
cartilage tissue	UBERON:0002418	52.67	gold quality
gingival epithelium	UBERON:0001949	52.54	gold quality
nipple	UBERON:0002030	52.11	gold quality
spleen	UBERON:0002106	51.83	gold quality
quadriceps femoris	UBERON:0001377	50.92	gold quality
bone marrow	UBERON:0002371	50.91	gold quality
oocyte	CL:0000023	50.84	gold quality
vastus lateralis	UBERON:0001379	50.59	gold quality
myocardium	UBERON:0002349	50.25	gold quality
pancreatic ductal cell	CL:0002079	50.15	silver quality
bone marrow cell	CL:0002092	50.00	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.27

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SHH

miRNA regulators (miRDB)

42 targeting KRT73, 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-4692	100.00	67.32	2066
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-1260A	99.61	66.67	1098
HSA-MIR-1260B	99.61	66.67	1098
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-1224-5P	99.48	65.59	803
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-330-3P	99.41	69.95	2521
HSA-MIR-4434	99.10	67.01	1984
HSA-MIR-5703	99.10	67.09	2053
HSA-MIR-485-5P	99.10	64.78	1889
HSA-MIR-6884-5P	99.10	64.50	1987
HSA-MIR-4650-3P	99.01	68.39	1062
HSA-MIR-3926	98.95	69.26	1438
HSA-MIR-936	98.87	70.51	1124
HSA-MIR-222-5P	98.75	69.17	1242
HSA-MIR-384	98.71	67.34	1229
HSA-MIR-548S	98.50	67.17	1213

Literature-anchored findings (GeneRIF, showing 1)

• report on the cloning of two novel human type II keratin cDNAs, K6irs3 and K6irs4, which were specifically expressed in the inner root sheath of the hair follicle (PMID:12648212)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Krt73	ENSMUSG00000063661
rattus_norvegicus	Krt73	ENSRNOG00000025087

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 II cytoskeletal 73 — Q86Y46 (reviewed: Q86Y46)

Alternative names: Cytokeratin-73, Keratin-73, Type II inner root sheath-specific keratin-K6irs3, Type-II keratin Kb36

All UniProt accessions (2): Q86Y46, H0YIC5

UniProt curated annotations — full annotation on UniProt →

Function. Has a role in hair formation. Specific component of keratin intermediate filaments in the inner root sheath (IRS) of the hair follicle.

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

Tissue specificity. Highly expressed in hair follicles from scalp. In hair, it is specifically present in the inner root sheath (IRS) of the hair follicle. Present in the IRS cuticle, but not in Henle or Huxley layers of the IRS. In the IRS cuticle, it is expressed between the lowermost bulb region of the cuticle and the region where Henle cells undergo abrupt terminal differentiation. Detected up to the uppermost cortex region where cuticle cells terminally differentiate (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.

Isoforms (2)

UniProt ID	Names	Canonical?
Q86Y46-1	1	yes
Q86Y46-2	2

RefSeq proteins (1): NP_778238* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003054	Keratin_II	Family
IPR018039	IF_conserved	Conserved_site
IPR032444	Keratin_2_head	Domain
IPR039008	IF_rod_dom	Domain

Pfam: PF00038, PF16208

UniProt features (20 total): region of interest 8, sequence variant 5, splice variant 2, chain 1, domain 1, compositionally biased region 1, site 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86Y46-F1	70.92	0.47

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): 383 (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: 79 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_UP, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_INTERMEDIATE_FILAMENT_BASED_PROCESS, GOBP_INTERMEDIATE_FILAMENT_ORGANIZATION, GOBP_EPIDERMAL_CELL_DIFFERENTIATION, GOBP_EPIDERMIS_DEVELOPMENT, AML1_01, GOBP_KERATINIZATION, GOBP_SKIN_DEVELOPMENT, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, HOXA4_Q2, ZHONG_SECRETOME_OF_LUNG_CANCER_AND_FIBROBLAST, TAATTA_CHX10_01, GOCC_INTERMEDIATE_FILAMENT_CYTOSKELETON, GOCC_KERATIN_FILAMENT

GO Biological Process (2): keratinization (GO:0031424), intermediate filament organization (GO:0045109)

GO Molecular Function (2): structural constituent of skin epidermis (GO:0030280), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), cytosol (GO:0005829), 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
keratinocyte differentiation	1
multicellular organismal process	1
intermediate filament cytoskeleton organization	1
supramolecular fiber organization	1
structural molecule activity	1
binding	1
intracellular membrane-bounded organelle	1
cytoplasm	1
cellular anatomical structure	1
intermediate filament	1
extracellular vesicle	1
intermediate filament cytoskeleton	1
polymeric cytoskeletal fiber	1

Protein interactions and networks

STRING

424 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KRT73	KRTAP3-3	Q9BYR6	511
KRT73	S100A3	P33764	459
KRT73	CCHCR1	Q8TD31	445
KRT73	KRTAP16-1	A8MUX0	417
KRT73	SPINK8	P0C7L1	398
KRT73	TTC16	Q8NEE8	354
KRT73	KRTAP3-2	Q9BYR7	353
KRT73	TMEM74B	Q9NUR3	322
KRT73	USP43	Q70EL4	307
KRT73	CAMSAP2	Q08AD1	304
KRT73	CPNE9	Q8IYJ1	297
KRT73	ADAMTS14	Q8WXS8	296
KRT73	VWC2	Q2TAL6	294
KRT73	A8MUN0	A8MUN0	287
KRT73	CALCOCO1	Q9P1Z2	278

IntAct

21 interactions, top by confidence:

A	B	Type	Score
KRT73	KRT15	psi-mi:“MI:0915”(physical association)	0.560
KRT15	KRT73	psi-mi:“MI:0915”(physical association)	0.560
Nup107	POM121C	psi-mi:“MI:0914”(association)	0.350
Tmed10	TARS3	psi-mi:“MI:0914”(association)	0.350
Smc1a	PDS5B	psi-mi:“MI:0914”(association)	0.350
Ttll7	TK2	psi-mi:“MI:0914”(association)	0.350
CCNB2	SCAF4	psi-mi:“MI:0914”(association)	0.350
ILK	ELOC	psi-mi:“MI:0914”(association)	0.350
MKI67	ARHGAP10	psi-mi:“MI:0914”(association)	0.350
TPT1	EIF3F	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
SQSTM1	CHEK1	psi-mi:“MI:0914”(association)	0.350
KRT73	EPPK1	psi-mi:“MI:0914”(association)	0.350
KRT73	IPO13	psi-mi:“MI:0914”(association)	0.350
ARMC9	PRMT5	psi-mi:“MI:0914”(association)	0.350
	PSMD12	psi-mi:“MI:0914”(association)	0.350
FHIP2A	MED19	psi-mi:“MI:2364”(proximity)	0.270
KRT73	tdk	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (63): KRT73 (Two-hybrid), KRT73 (Affinity Capture-MS), KRT73 (Affinity Capture-MS), KRT73 (Affinity Capture-MS), KRT73 (Affinity Capture-MS), KRT73 (Affinity Capture-MS), KRT73 (Affinity Capture-MS), KRT73 (Affinity Capture-MS), KRT73 (Affinity Capture-MS), KRT73 (Affinity Capture-MS), KRT73 (Affinity Capture-MS), KRT73 (Two-hybrid), KRT73 (Two-hybrid), KRT73 (Two-hybrid), KRT16 (Two-hybrid)

ESM2 similar proteins: A1L317, A1L595, A5A6N2, A6BLY7, B1AQ75, E1AB55, O76013, P02533, P08730, P08779, P13646, P19012, Q0P5J4, Q0P5J6, Q0P5J7, Q148H5, Q148H6, Q148H8, Q2M2I5, Q3UV17, Q497I4, Q61414, Q61781, Q64291, Q6IFU7, Q6IFU8, Q6IFV1, Q6IFV3, Q6IFV4, Q6IFW6, Q6IFW8, Q6IFX0, Q6IFX1, Q6IFX2, Q6NXH9, Q6R649, Q6R650, Q7Z3Y7, Q7Z3Y8, Q7Z3Y9

Diamond homologs: A0A125S9M6, A0JND2, A4FUZ0, A5A6M8, A6NCN2, A7YWK3, O43790, P02542, P02545, P02547, P02548, P04104, P04260, P04261, P04262, P04263, P07196, P07744, P08551, P08928, P09010, P10999, P12035, P12036, P13647, P13648, P15241, P16884, P19013, P19246, P19527, P21619, P21910, P25691, P35908, P48671, P48672, P48678, P48679, P78385

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	104
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1075 predictions. Top by Δscore:

Variant	Effect	Δscore
12:52608450:CCG:C	acceptor_gain	1.0000
12:52608451:CGC:C	acceptor_gain	1.0000
12:52609245:A:AC	donor_gain	1.0000
12:52609246:C:CC	donor_gain	1.0000
12:52609246:CAA:C	donor_gain	1.0000
12:52609278:CATC:C	acceptor_gain	1.0000
12:52609280:TC:T	acceptor_gain	1.0000
12:52609281:CC:C	acceptor_gain	1.0000
12:52609282:C:CC	acceptor_gain	1.0000
12:52611325:TGGAA:T	acceptor_gain	1.0000
12:52611327:GAA:G	acceptor_gain	1.0000
12:52611328:AA:A	acceptor_gain	1.0000
12:52611330:C:CC	acceptor_gain	1.0000
12:52613685:CACC:C	donor_loss	1.0000
12:52613686:A:AC	donor_gain	1.0000
12:52613687:C:CC	donor_gain	1.0000
12:52613848:GTCTC:G	acceptor_gain	1.0000
12:52613849:TCTCC:T	acceptor_gain	1.0000
12:52613850:CTC:C	acceptor_gain	1.0000
12:52613851:TC:T	acceptor_gain	1.0000
12:52613851:TCCTG:T	acceptor_loss	1.0000
12:52613852:CC:C	acceptor_gain	1.0000
12:52613853:C:CC	acceptor_gain	1.0000
12:52613853:C:T	acceptor_gain	1.0000
12:52613853:CT:C	acceptor_loss	1.0000
12:52613856:C:CT	acceptor_gain	1.0000
12:52614577:AC:A	donor_gain	1.0000
12:52614577:ACC:A	donor_gain	1.0000
12:52614577:ACCC:A	donor_gain	1.0000
12:52614578:CC:C	donor_gain	1.0000

AlphaMissense

3532 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:52618096:G:C	F143L	0.990
12:52618096:G:T	F143L	0.990
12:52618098:A:G	F143L	0.990
12:52610805:C:G	A381P	0.987
12:52615282:C:A	K240N	0.986
12:52615282:C:G	K240N	0.986
12:52615294:A:C	F236L	0.983
12:52615294:A:T	F236L	0.983
12:52615296:A:G	F236L	0.983
12:52615316:C:G	R229P	0.983
12:52618097:A:G	F143S	0.983
12:52610636:A:G	L437P	0.981
12:52615308:C:G	A232P	0.981
12:52610642:C:G	R435P	0.978
12:52618097:A:C	F143C	0.978
12:52610772:C:G	A392P	0.977
12:52618105:G:C	N140K	0.973
12:52618105:G:T	N140K	0.973
12:52616361:T:G	Q156P	0.972
12:52610817:C:G	A377P	0.971
12:52613711:C:G	A321P	0.970
12:52610646:A:C	Y434D	0.969
12:52610666:A:G	L427P	0.969
12:52616370:A:G	L153P	0.969
12:52611256:A:G	L353P	0.968
12:52618087:G:C	F146L	0.968
12:52618087:G:T	F146L	0.968
12:52618089:A:G	F146L	0.968
12:52618094:G:T	A144D	0.966
12:52618106:T:A	N140I	0.966

dbSNP variants (sampled 300 via entrez): RS1000063353 (12:52624037 A>G), RS1000072587 (12:52620816 T>C), RS1000354026 (12:52632244 G>A,C), RS1000472907 (12:52622857 G>A,C), RS1000742683 (12:52631471 G>A), RS1000875914 (12:52610198 C>T), RS1000891100 (12:52619092 A>C,G), RS1001067997 (12:52611998 G>A,T), RS1001167818 (12:52622337 T>A), RS1001239711 (12:52622583 C>T), RS1001325963 (12:52607270 C>T), RS1001375308 (12:52629097 G>A,C), RS1001392892 (12:52615964 G>T), RS1001804985 (12:52629411 C>A,T), RS1001807279 (12:52612997 A>C)

Disease associations

OMIM: gene MIM:608247 | 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

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

Chemical	Actions (top 5)	PubMed papers
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
terbufos	increases methylation	1
(+)-JQ1 compound	decreases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression	1
Dinitrochlorobenzene	affects binding	1
Fonofos	increases methylation	1
Parathion	increases methylation	1
Dihydrotestosterone	increases expression	1
Tobacco Smoke Pollution	affects expression	1
Lactic Acid	increases expression	1

Clinical trials (associated diseases)

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