KRT72

Summary

KRT72 (keratin 72, HGNC:28932) is a protein-coding gene on chromosome 12q13.13, encoding Keratin, type II cytoskeletal 72 (Q14CN4). Has a role in hair formation.

Keratins are intermediate filament proteins responsible for the structural integrity of epithelial cells. The type II keratins consist of basic or neutral proteins which are arranged in pairs of heterotypic keratin chains coexpressed during differentiation of simple and stratified epithelial tissues. This gene encodes a type II keratin that is specifically expressed in the inner root sheath of hair follicles. The type II keratins are clustered in a region of chromosome 12q12-q13. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 140807 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 95 total
• MANE Select transcript: NM_080747

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28932
Approved symbol	KRT72
Name	keratin 72
Location	12q13.13
Locus type	gene with protein product
Status	Approved
Aliases	K6IRS2, KRT6IRS2, KRT6, K6irs
Ensembl gene	ENSG00000170486
Ensembl biotype	protein_coding
OMIM	608246
Entrez	140807

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 nonsense_mediated_decay

ENST00000293745, ENST00000354310, ENST00000537672, ENST00000549979, ENST00000550829

RefSeq mRNA: 3 — MANE Select: NM_080747 NM_001146225, NM_001146226, NM_080747

CCDS: CCDS53795, CCDS8833

Canonical transcript exons

ENST00000293745 — 9 exons

Exon	Start	End
ENSE00001318769	52585589	52586172
ENSE00003498388	52587631	52587851
ENSE00003518899	52592396	52592491
ENSE00003574714	52598898	52599112
ENSE00003586705	52590836	52590961
ENSE00003664065	52592892	52592952
ENSE00003670652	52591464	52591628
ENSE00003680881	52586946	52586980
ENSE00003894114	52601027	52601463

Expression profiles

Bgee: expression breadth broad, 99 present calls, max score 87.29.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0475 / max 36.5379, expressed in 4 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
131100	0.0157	3
131097	0.0098	3
131098	0.0087	3
131101	0.0075	1
131099	0.0058	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	87.29	gold quality
left testis	UBERON:0004533	84.61	gold quality
right testis	UBERON:0004534	83.25	gold quality
testis	UBERON:0000473	81.92	gold quality
skin of leg	UBERON:0001511	80.08	gold quality
skin of abdomen	UBERON:0001416	77.00	gold quality
zone of skin	UBERON:0000014	76.23	gold quality
esophagus squamous epithelium	UBERON:0006920	70.18	gold quality
gingival epithelium	UBERON:0001949	69.80	gold quality
blood	UBERON:0000178	69.38	gold quality
secondary oocyte	CL:0000655	68.19	gold quality
lymph node	UBERON:0000029	65.73	gold quality
buccal mucosa cell	CL:0002336	65.68	gold quality
gingiva	UBERON:0001828	64.61	gold quality
amniotic fluid	UBERON:0000173	64.60	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	63.30	gold quality
spleen	UBERON:0002106	62.17	gold quality
vermiform appendix	UBERON:0001154	60.46	gold quality
bone marrow	UBERON:0002371	57.19	gold quality
skin of hip	UBERON:0001554	57.01	silver quality
jejunal mucosa	UBERON:0000399	56.81	gold quality
trabecular bone tissue	UBERON:0002483	56.64	gold quality
upper leg skin	UBERON:0004262	56.06	silver quality
caecum	UBERON:0001153	56.03	gold quality
tendon of biceps brachii	UBERON:0008188	56.00	gold quality
myocardium	UBERON:0002349	55.58	gold quality
adult organism	UBERON:0007023	55.38	silver quality
duodenum	UBERON:0002114	55.14	gold quality
small intestine Peyer’s patch	UBERON:0003454	55.08	gold quality
palpebral conjunctiva	UBERON:0001812	54.61	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.03

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

26 targeting KRT72, 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-5696	99.98	72.36	4487
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-1224-5P	99.48	65.59	803
HSA-MIR-3199	99.17	65.19	696
HSA-MIR-8052	99.17	65.01	719
HSA-MIR-3125	99.14	68.49	2269
HSA-MIR-1228-3P	99.00	66.53	857
HSA-MIR-3916	98.99	68.04	2155
HSA-MIR-4742-5P	98.89	68.41	1542
HSA-MIR-2467-3P	98.65	67.18	1969
HSA-MIR-6841-3P	98.08	66.54	604
HSA-MIR-6742-3P	97.95	64.50	1490
HSA-MIR-4733-5P	97.75	67.44	866
HSA-MIR-6828-3P	96.06	67.61	1155

Literature-anchored findings (GeneRIF, showing 5)

• we suggest that keratin 5/6 and bcl-2 should not be used to identify benign glands in prostate biopsy (PMID:20189848)
• the results of CK5/6 and p63 in CNBs of papillary neoplasms were mostly representative of the final results for CK5/6 and p63 in subsequent surgical excisions, excisional biopsy is required for definitive subtyping (PMID:22553810)
• the luminal cells of adenoid cystic carcinoma show a unique aberrant staining pattern for cytokeratin 5/6 that may aid in the differential diagnosis (PMID:27240462)
• Ozone therapy promotes the differentiation of basal keratinocytes via increasing Tp63-mediated transcription of KRT10 to improve psoriasis. (PMID:32168425)
• circ-Keratin 6c Promotes Malignant Progression and Immune Evasion of Colorectal Cancer through microRNA-485-3p/Programmed Cell Death Receptor Ligand 1 Axis. (PMID:33771844)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Krt72	ENSMUSG00000056605
rattus_norvegicus	Krt72	ENSRNOG00000030876

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), KRT83 (ENSG00000170523), BFSP2 (ENSG00000170819), KRT19 (ENSG00000171345), KRT15 (ENSG00000171346), KRT38 (ENSG00000171360), KRT13 (ENSG00000171401)

Protein

Protein identifiers

Keratin, type II cytoskeletal 72 — Q14CN4 (reviewed: Q14CN4)

Alternative names: Cytokeratin-72, Keratin-72, Type II inner root sheath-specific keratin-K6irs2, Type-II keratin Kb35

All UniProt accessions (3): Q14CN4, H0YHD9, H0YIG3

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 and eyebrow. Also expressed in palmoplantar epidermis. Not expressed in face skin despite the presence of fine hairs histologically. 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, its presence is delayed up to the height of the apex of the dermal papilla (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 (3)

UniProt ID	Names	Canonical?
Q14CN4-1	1	yes
Q14CN4-2	2
Q14CN4-3	3

RefSeq proteins (3): NP_001139697, NP_001139698, NP_542785* (*=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 (18 total): region of interest 8, sequence variant 5, splice variant 2, chain 1, domain 1, site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14CN4-F1	72.77	0.50

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): 376 (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): GOBP_EPITHELIUM_DEVELOPMENT, GOBP_INTERMEDIATE_FILAMENT_BASED_PROCESS, GOBP_INTERMEDIATE_FILAMENT_ORGANIZATION, GOBP_EPIDERMAL_CELL_DIFFERENTIATION, GATA3_01, MARTINEZ_RB1_TARGETS_DN, GOBP_EPIDERMIS_DEVELOPMENT, GATA1_03, GATA1_02, GOBP_KERATINIZATION, GOBP_SKIN_DEVELOPMENT, GATA_Q6, GOCC_INTERMEDIATE_FILAMENT_CYTOSKELETON, GOCC_KERATIN_FILAMENT, HMGIY_Q6

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 (4): 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
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

418 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KRT72	KRT16	P08779	538
KRT72	NDUFV2	P19404	438
KRT72	KRT78	Q8N1N4	426
KRT72	PRMT1	Q99873	401
KRT72	LGALS9	O00182	388
KRT72	MYSM1	Q5VVJ2	378
KRT72	CD44	P16070	369
KRT72	DSG4	Q86SJ6	365
KRT72	GATAD2A	Q86YP4	351
KRT72	ACER1	Q8TDN7	335
KRT72	LORICRIN	P23490	310
KRT72	SPRR3	Q9UBC9	308
KRT72	TP63	Q9H3D4	305
KRT72	FOXA1	P55317	299
KRT72	S100A7	P31151	294

IntAct

61 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
KRT72	KRT40	psi-mi:“MI:0915”(physical association)	0.560
KRT40	KRT72	psi-mi:“MI:0915”(physical association)	0.560
BLOC1S6	KRT72	psi-mi:“MI:0915”(physical association)	0.560
KRT13	KRT72	psi-mi:“MI:0915”(physical association)	0.560
KRT72	KRT27	psi-mi:“MI:0915”(physical association)	0.560
KRT16	KRT72	psi-mi:“MI:0915”(physical association)	0.560
KRT15	KRT72	psi-mi:“MI:0915”(physical association)	0.560
KRT38	KRT72	psi-mi:“MI:0915”(physical association)	0.560
KRT72	KRT31	psi-mi:“MI:0915”(physical association)	0.560
KRT72	KRT25	psi-mi:“MI:0915”(physical association)	0.560
KRT72	KRT35	psi-mi:“MI:0915”(physical association)	0.560
KRT32	KRT72	psi-mi:“MI:0915”(physical association)	0.560
KRT33B	KRT72	psi-mi:“MI:0915”(physical association)	0.560
KRT72	KRT24	psi-mi:“MI:0915”(physical association)	0.560
KRT14	KRT72	psi-mi:“MI:0915”(physical association)	0.560
KRT20	KRT72	psi-mi:“MI:0915”(physical association)	0.560
KRT72	BLOC1S6	psi-mi:“MI:0915”(physical association)	0.560
KRT19	KRT72	psi-mi:“MI:0915”(physical association)	0.560
HSPB1	KRT72	psi-mi:“MI:0915”(physical association)	0.370
MYO19	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
TF	IGKV2D-40	psi-mi:“MI:0914”(association)	0.350
METTL3	TUBAL3	psi-mi:“MI:0914”(association)	0.350
METTL14	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
CFTR	MYH7B	psi-mi:“MI:0914”(association)	0.350

BioGRID (60): KRT72 (Two-hybrid), KRT72 (Two-hybrid), KRT72 (Affinity Capture-MS), KRT72 (Affinity Capture-MS), KRT72 (Affinity Capture-MS), KRT72 (Affinity Capture-MS), KRT72 (Affinity Capture-MS), KRT72 (Affinity Capture-MS), KRT72 (Affinity Capture-MS), KRT72 (Affinity Capture-MS), KRT72 (Affinity Capture-MS), KRT72 (Two-hybrid), KRT72 (Two-hybrid), KRT72 (Two-hybrid), KRT72 (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: 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.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 31 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	15	48.8×	1e-20
Keratinization	15	30.9×	6e-18

GO biological processes:

GO term	Partners	Fold	FDR
morphogenesis of an epithelium	15	177.9×	8e-30
intermediate filament organization	16	132.8×	8e-30
epithelial cell differentiation	13	78.7×	1e-20

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	83
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

987 predictions. Top by Δscore:

Variant	Effect	Δscore
12:52586944:A:AC	donor_gain	1.0000
12:52586945:C:CC	donor_gain	1.0000
12:52587626:CTCA:C	donor_loss	1.0000
12:52587629:A:AC	donor_gain	1.0000
12:52587629:ACCTG:A	donor_loss	1.0000
12:52587630:C:CC	donor_gain	1.0000
12:52587847:GCACA:G	acceptor_gain	1.0000
12:52587848:CACA:C	acceptor_gain	1.0000
12:52587848:CACAC:C	acceptor_gain	1.0000
12:52587849:ACA:A	acceptor_gain	1.0000
12:52587849:ACAC:A	acceptor_loss	1.0000
12:52587850:CA:C	acceptor_gain	1.0000
12:52587850:CAC:C	acceptor_gain	1.0000
12:52587851:ACTG:A	acceptor_loss	1.0000
12:52587852:C:CC	acceptor_gain	1.0000
12:52587852:CT:C	acceptor_loss	1.0000
12:52587853:T:G	acceptor_loss	1.0000
12:52587860:C:CT	acceptor_gain	1.0000
12:52590831:CCCA:C	donor_loss	1.0000
12:52590832:CCA:C	donor_loss	1.0000
12:52590833:CA:C	donor_loss	1.0000
12:52590834:ACCT:A	donor_loss	1.0000
12:52590835:C:CT	donor_loss	1.0000
12:52590835:CCTG:C	donor_gain	1.0000
12:52590972:G:GC	acceptor_gain	1.0000
12:52591459:CTCA:C	donor_loss	1.0000
12:52591460:TCACC:T	donor_loss	1.0000
12:52591461:CA:C	donor_loss	1.0000
12:52591462:ACCTT:A	donor_loss	1.0000
12:52591463:C:T	donor_loss	1.0000

AlphaMissense

3361 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:52601045:G:C	F136L	0.975
12:52601045:G:T	F136L	0.975
12:52601047:A:G	F136L	0.975
12:52592895:C:A	K233N	0.969
12:52592895:C:G	K233N	0.969
12:52592907:A:C	F229L	0.965
12:52592907:A:T	F229L	0.965
12:52592909:A:G	F229L	0.965
12:52591487:C:G	A314P	0.942
12:52590918:A:G	L336P	0.940
12:52601046:A:C	F136C	0.936
12:52592457:A:G	L246P	0.935
12:52592485:C:G	D237H	0.930
12:52592921:C:G	A225P	0.930
12:52601046:A:G	F136S	0.926
12:52592483:A:C	D237E	0.921
12:52592483:A:T	D237E	0.921
12:52599093:T:G	Q149P	0.921
12:52601036:G:C	F139L	0.917
12:52601036:G:T	F139L	0.917
12:52601038:A:G	F139L	0.917
12:52592929:C:G	R222P	0.911
12:52587821:C:G	A374P	0.910
12:52592417:G:C	F259L	0.910
12:52592417:G:T	F259L	0.910
12:52592419:A:G	F259L	0.910
12:52599070:A:G	W157R	0.910
12:52599070:A:T	W157R	0.910
12:52601055:T:A	N133I	0.910
12:52587658:C:G	R428P	0.909

dbSNP variants (sampled 300 via entrez): RS1000149131 (12:52599770 C>A,G,T), RS1000193964 (12:52590480 C>A,T), RS1000458877 (12:52594404 C>A), RS1000712260 (12:52598991 A>G), RS1000713326 (12:52594755 T>A), RS1000744148 (12:52593279 C>T), RS1000930120 (12:52589178 G>A,T), RS1000997826 (12:52600532 A>G), RS1001137683 (12:52600880 C>T), RS1001170343 (12:52601166 C>A,G), RS1001199270 (12:52593107 C>A,G,T), RS1001399572 (12:52595996 T>A), RS1001458026 (12:52604093 G>A), RS1001776148 (12:52601136 A>G), RS1001826580 (12:52601299 G>C)

Disease associations

OMIM: gene MIM:608246 | 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
GCST007202_4	High density lipoprotein cholesterol levels	3.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects binding, increases reaction	1
hydroxyhydroquinone	decreases expression	1
CGP 52608	affects binding, increases reaction	1
bromovanin	decreases expression	1
bisphenol S	decreases methylation	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Endosulfan	decreases expression	1
Estradiol	affects expression, increases reaction	1
Folic Acid	increases expression	1
Aflatoxin B1	decreases methylation	1
Sodium Selenite	increases expression	1

Clinical trials (associated diseases)

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