KRT28

Summary

KRT28 (keratin 28, HGNC:30842) is a protein-coding gene on chromosome 17q21.2, encoding Keratin, type I cytoskeletal 28 (Q7Z3Y7). Essential for the proper assembly of types I and II keratin protein complexes and the formation of keratin intermediate filaments in the inner root sheath (irs).

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 162605 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 83 total
• MANE Select transcript: NM_181535

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30842
Approved symbol	KRT28
Name	keratin 28
Location	17q21.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000173908
Ensembl biotype	protein_coding
OMIM	616677
Entrez	162605

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000306658

RefSeq mRNA: 1 — MANE Select: NM_181535 NM_181535

CCDS: CCDS11376

Canonical transcript exons

ENST00000306658 — 8 exons

Exon	Start	End
ENSE00001181861	40793155	40793210
ENSE00001181868	40792196	40792569
ENSE00001181874	40793829	40794046
ENSE00001213485	40796916	40797041
ENSE00001332372	40798917	40798999
ENSE00001332417	40799444	40799959
ENSE00002377083	40797120	40797281
ENSE00002392066	40798235	40798391

Expression profiles

Bgee: expression breadth broad, 13 present calls, max score 85.65.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0979 / max 152.6260, expressed in 2 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165810	0.0979	2

Top tissues by expression

130 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	85.65	gold quality
thymus	UBERON:0002370	63.16	silver quality
quadriceps femoris	UBERON:0001377	61.63	gold quality
cerebellar vermis	UBERON:0004720	58.50	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	54.26	gold quality
skin of abdomen	UBERON:0001416	39.80	gold quality
zone of skin	UBERON:0000014	39.25	gold quality
skin of leg	UBERON:0001511	39.04	gold quality
granulocyte	CL:0000094	37.95	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
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	34.04	gold quality
mucosa of stomach	UBERON:0001199	32.49	gold quality
bone marrow	UBERON:0002371	32.21	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
muscle tissue	UBERON:0002385	31.57	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
prefrontal cortex	UBERON:0000451	30.92	gold quality
liver	UBERON:0002107	30.74	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
leukocyte	CL:0000738	29.61	gold quality
monocyte	CL:0000576	29.15	gold quality
tonsil	UBERON:0002372	28.59	gold quality
right lobe of liver	UBERON:0001114	28.49	gold quality
duodenum	UBERON:0002114	28.14	gold quality
uterine cervix	UBERON:0000002	27.80	gold quality
lymph node	UBERON:0000029	27.57	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.28

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

46 targeting KRT28, 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-6873-3P	100.00	71.42	2626
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Krt28	ENSMUSG00000055937
rattus_norvegicus	Krt28	ENSRNOG00000011846

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 28 — Q7Z3Y7 (reviewed: Q7Z3Y7)

Alternative names: Cytokeratin-28, Keratin-25D, Keratin-28, Type I inner root sheath-specific keratin-K25irs4

All UniProt accessions (1): Q7Z3Y7

UniProt curated annotations — full annotation on UniProt →

Function. Essential for the proper assembly of types I and II keratin protein complexes and the formation of keratin intermediate filaments in the inner root sheath (irs).

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

Subcellular location. Cytoplasm.

Tissue specificity. Strongly expressed in skin and scalp, and weak expression observed in thymus. In the hair follicle, expressed in Henle layer, Huxley layer and in the irs cuticle. Expression extends from the bulb region up to the point of differentiation into the three layers. Also present in the medulla of beard hair (at protein level).

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

Similarity. Belongs to the intermediate filament family.

RefSeq proteins (1): NP_853513* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002957	Keratin_I	Family
IPR039008	IF_rod_dom	Domain

Pfam: PF00038

UniProt features (13 total): region of interest 8, sequence variant 3, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z3Y7-F1	76.92	0.54

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: 74 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_EPIDERMIS_MORPHOGENESIS, GOBP_INTERMEDIATE_FILAMENT_BASED_PROCESS, GOBP_INTERMEDIATE_FILAMENT_ORGANIZATION, GOBP_MOLTING_CYCLE, GOBP_EPIDERMIS_DEVELOPMENT, POU3F2_02, GOBP_SKIN_DEVELOPMENT, GOBP_TISSUE_MORPHOGENESIS, HOXA4_Q2, MEF2_03, GOCC_INTERMEDIATE_FILAMENT_CYTOSKELETON, GOCC_KERATIN_FILAMENT, YATGNWAAT_OCT_C

GO Biological Process (4): morphogenesis of an epithelium (GO:0002009), epithelial cell differentiation (GO:0030855), hair follicle morphogenesis (GO:0031069), 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 (6): cytosol (GO:0005829), cytoskeleton (GO:0005856), keratin filament (GO:0045095), extracellular exosome (GO:0070062), cytoplasm (GO:0005737), 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
cellular anatomical structure	2
tissue morphogenesis	1
cell differentiation	1
hair follicle development	1
anatomical structure morphogenesis	1
hair cycle process	1
epidermis morphogenesis	1
intermediate filament cytoskeleton organization	1
supramolecular fiber organization	1
structural molecule activity	1
molecular_function	1
binding	1
cytoplasm	1
intracellular membraneless organelle	1
intermediate filament	1
extracellular vesicle	1
intracellular anatomical structure	1
intermediate filament cytoskeleton	1
polymeric cytoskeletal fiber	1

Protein interactions and networks

STRING

514 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KRT28	DNASE1L2	Q92874	296
KRT28	KNTC1	P50748	244
KRT28	OTUD6B	Q8N6M0	240
KRT28	INPP5J	Q15735	236
KRT28	MBOAT2	Q6ZWT7	233
KRT28	CNN3	Q15417	220
KRT28	ARHGEF2	Q92974	204
KRT28	PDHX	O00330	203
KRT28	KRT71	Q3SY84	203
KRT28	NAA25	Q14CX7	201
KRT28	LGALS8	O00214	201
KRT28	TPD52L1	Q16890	191
KRT28	MAPRE2	Q15555	188
KRT28	KRT74	Q7RTS7	186
KRT28	SWAP70	Q9UH65	183

IntAct

70 interactions, top by confidence:

A	B	Type	Score
KRT28		psi-mi:“MI:0915”(physical association)	0.560
KRT6A	KRT28	psi-mi:“MI:0915”(physical association)	0.560
KRT5	KRT28	psi-mi:“MI:0915”(physical association)	0.560
KRT79	KRT28	psi-mi:“MI:0915”(physical association)	0.560
KRT3	KRT28	psi-mi:“MI:0915”(physical association)	0.560
KRT8	KRT28	psi-mi:“MI:0915”(physical association)	0.560
KRT6B	KRT28	psi-mi:“MI:0915”(physical association)	0.560
KRT1	KRT28	psi-mi:“MI:0915”(physical association)	0.560
KRT71	KRT28	psi-mi:“MI:0915”(physical association)	0.560
KRT81	KRT28	psi-mi:“MI:0915”(physical association)	0.560
KRT28	NUP58	psi-mi:“MI:0915”(physical association)	0.560
KRT80	KRT28	psi-mi:“MI:0915”(physical association)	0.560
KRT28	USHBP1	psi-mi:“MI:0915”(physical association)	0.560
DEUP1	KRT28	psi-mi:“MI:0915”(physical association)	0.560
KRT28	ABI3	psi-mi:“MI:0915”(physical association)	0.560
KRT4	KRT28	psi-mi:“MI:0915”(physical association)	0.560
KRT86	KRT28	psi-mi:“MI:0915”(physical association)	0.560
CCDC196	KRT28	psi-mi:“MI:0915”(physical association)	0.560
	KRT28	psi-mi:“MI:0915”(physical association)	0.560
KRT28	PPIB	psi-mi:“MI:0915”(physical association)	0.400
YAP1	TEAD1	psi-mi:“MI:0914”(association)	0.350
SLC16A11	PABPC4	psi-mi:“MI:0914”(association)	0.350
KRT6A	KRT28	psi-mi:“MI:0915”(physical association)	0.000
KRT28	KRT5	psi-mi:“MI:0915”(physical association)	0.000
KRT28	KRT79	psi-mi:“MI:0915”(physical association)	0.000
KRT3	KRT28	psi-mi:“MI:0915”(physical association)	0.000
KRT5	KRT28	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (29): KRT28 (Affinity Capture-MS), KRT28 (Affinity Capture-MS), KRT28 (Affinity Capture-MS), KRT28 (Affinity Capture-MS), KRT28 (Two-hybrid), KRT28 (Two-hybrid), KRT28 (Two-hybrid), KRT28 (Two-hybrid), KRT28 (Two-hybrid), KRT28 (Two-hybrid), KRT28 (Two-hybrid), KRT28 (Two-hybrid), KRT28 (Two-hybrid), KRT28 (Two-hybrid), WASH1 (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: A1KQY9, A1L317, A1L595, A5A6M0, A5A6M5, A5A6N2, A5A6P3, A6BLY7, A6QQQ9, A7YWM2, B0LKP1, B1AQ75, O57607, O57611, O76009, O76013, O77727, O93256, P02533, P02534, P02535, P02537, P05781, P05783, P05784, P06394, P08727, P08728, P08730, P08777, P08778, P08779, P08802, P13645, P13646, P19001, P19012, P25030, P25690, P35527

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 22 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	12	65.9×	3e-19
Keratinization	12	41.8×	5e-17

GO biological processes:

GO term	Partners	Fold	FDR
intermediate filament organization	11	132.4×	4e-20
keratinization	11	128.7×	4e-20

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	76
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

968 predictions. Top by Δscore:

Variant	Effect	Δscore
17:40793207:TGAA:T	acceptor_gain	1.0000
17:40793211:C:CC	acceptor_gain	1.0000
17:40793823:A:AC	donor_gain	1.0000
17:40793824:C:CC	donor_gain	1.0000
17:40793824:CTTA:C	donor_gain	1.0000
17:40793825:TTA:T	donor_loss	1.0000
17:40793826:TA:T	donor_loss	1.0000
17:40793827:A:AC	donor_gain	1.0000
17:40793827:ACTTT:A	donor_gain	1.0000
17:40793828:C:CC	donor_gain	1.0000
17:40793828:CT:C	donor_gain	1.0000
17:40793828:CTT:C	donor_gain	1.0000
17:40793828:CTTT:C	donor_gain	1.0000
17:40793828:CTTTC:C	donor_gain	1.0000
17:40793831:T:A	donor_gain	1.0000
17:40794042:TGTTT:T	acceptor_gain	1.0000
17:40794057:C:CT	acceptor_gain	1.0000
17:40796910:ACCT:A	donor_loss	1.0000
17:40796911:CCTA:C	donor_loss	1.0000
17:40797038:CGCT:C	acceptor_gain	1.0000
17:40797040:CT:C	acceptor_gain	1.0000
17:40797042:C:CC	acceptor_gain	1.0000
17:40797115:CTCA:C	donor_loss	1.0000
17:40797116:TCAC:T	donor_loss	1.0000
17:40797118:A:C	donor_loss	1.0000
17:40797119:CCTT:C	donor_gain	1.0000
17:40797277:ATCTC:A	acceptor_gain	1.0000
17:40797278:TCTCC:T	acceptor_gain	1.0000
17:40797279:CTC:C	acceptor_gain	1.0000
17:40797279:CTCCT:C	acceptor_gain	1.0000

AlphaMissense

3021 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:40799604:A:G	L97S	0.991
17:40799616:A:G	L93P	0.982
17:40799607:C:G	R96P	0.976
17:40799616:A:T	L93H	0.965
17:40799602:C:G	A98P	0.964
17:40797129:G:C	F281L	0.962
17:40797129:G:T	F281L	0.962
17:40797131:A:G	F281L	0.962
17:40798948:C:G	A168P	0.960
17:40799624:C:A	M90I	0.960
17:40799624:C:G	M90I	0.960
17:40799624:C:T	M90I	0.960
17:40799592:A:G	L101P	0.959
17:40799566:C:G	A110P	0.955
17:40799574:A:G	L107P	0.952
17:40793898:A:G	L376P	0.950
17:40799612:A:C	N94K	0.946
17:40799612:A:T	N94K	0.946
17:40799613:T:A	N94I	0.944
17:40797151:C:G	R274P	0.943
17:40799541:A:G	I118T	0.941
17:40793949:A:G	L359P	0.940
17:40799454:A:G	L147P	0.939
17:40797143:C:G	A277P	0.936
17:40799604:A:C	L97W	0.936
17:40793847:A:G	L393P	0.934
17:40798925:G:C	F175L	0.932
17:40798925:G:T	F175L	0.932
17:40798927:A:G	F175L	0.932
17:40793877:A:G	L383S	0.931

dbSNP variants (sampled 300 via entrez): RS1000240254 (17:40793632 T>G), RS1000977923 (17:40800140 A>G), RS1001062447 (17:40800071 A>C), RS1001160426 (17:40795269 T>C), RS1001450563 (17:40801707 T>C), RS1001506060 (17:40794895 T>C), RS1001556953 (17:40794590 T>C), RS1001708643 (17:40801811 T>G), RS1001734758 (17:40801386 T>C), RS1003343122 (17:40792277 C>T), RS1003824560 (17:40792004 A>T), RS1003972781 (17:40795885 A>G), RS1005123125 (17:40796653 G>T), RS1005359395 (17:40791752 T>A), RS1005502146 (17:40797048 G>A)

Disease associations

OMIM: gene MIM:616677 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002726_32	Glucose homeostasis traits	4.000000e-06
GCST003075_45	Cognitive decline rate in late mild cognitive impairment	2.000000e-06
GCST003075_59	Cognitive decline rate in late mild cognitive impairment	2.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004471	insulin sensitivity measurement
EFO:0007710	cognitive decline measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
CGP 52608	increases reaction, affects binding	1
clothianidin	increases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression, increases abundance	1
Estradiol	affects binding, increases reaction	1
Furaldehyde	affects cotreatment, affects localization, increases expression	1
Lead	affects methylation	1
Sodium Chloride	increases expression, decreases expression, affects cotreatment, affects localization	1
Cadmium Chloride	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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