KRT76

Summary

KRT76 (keratin 76, HGNC:24430) is a protein-coding gene on chromosome 12q13.13, encoding Keratin, type II cytoskeletal 2 oral (Q01546). Probably contributes to terminal cornification.

Keratins are intermediate filament proteins responsible for the structural integrity of epithelial cells and are subdivided into epithelial keratins and hair keratins. The type II keratins are clustered in a region of chromosome 12q13.

Source: NCBI Gene 51350 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 115 total
• MANE Select transcript: NM_015848

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24430
Approved symbol	KRT76
Name	keratin 76
Location	12q13.13
Locus type	gene with protein product
Status	Approved
Aliases	HUMCYT2A, KRT2B, KRT2P
Ensembl gene	ENSG00000185069
Ensembl biotype	protein_coding
OMIM	616671
Entrez	51350

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000332411

RefSeq mRNA: 1 — MANE Select: NM_015848 NM_015848

CCDS: CCDS8838

Canonical transcript exons

ENST00000332411 — 9 exons

Exon	Start	End
ENSE00001290056	52775388	52775602
ENSE00001294138	52768155	52769110
ENSE00001319852	52776692	52777345
ENSE00001321931	52772783	52772878
ENSE00001323177	52771871	52771996
ENSE00001620158	52769549	52769583
ENSE00001650813	52770999	52771219
ENSE00001679279	52772094	52772258
ENSE00001681343	52773582	52773642

Expression profiles

Bgee: expression breadth broad, 24 present calls, max score 95.98.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2151 / max 203.9119, expressed in 6 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
131123	0.2151	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gingiva	UBERON:0001828	95.98	gold quality
gingival epithelium	UBERON:0001949	94.71	gold quality
tongue squamous epithelium	UBERON:0006919	93.91	gold quality
tongue	UBERON:0001723	78.89	gold quality
body of tongue	UBERON:0011876	76.61	gold quality
superior surface of tongue	UBERON:0007371	70.34	gold quality
cervix epithelium	UBERON:0004801	61.85	silver quality
olfactory bulb	UBERON:0002264	61.83	gold quality
epithelium of nasopharynx	UBERON:0001951	60.55	gold quality
diaphragm	UBERON:0001103	59.60	gold quality
nephron tubule	UBERON:0001231	58.55	gold quality
metanephric glomerulus	UBERON:0004736	58.06	gold quality
squamous epithelium	UBERON:0006914	57.54	gold quality
oviduct epithelium	UBERON:0004804	55.42	silver quality
kidney epithelium	UBERON:0004819	53.36	gold quality
vastus lateralis	UBERON:0001379	52.78	gold quality
quadriceps femoris	UBERON:0001377	52.56	gold quality
buccal mucosa cell	CL:0002336	52.31	gold quality
cervix squamous epithelium	UBERON:0006922	50.98	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
hair follicle	UBERON:0002073	49.18	gold quality
epithelial cell of pancreas	CL:0000083	48.98	gold quality
myocardium	UBERON:0002349	48.87	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
tonsil	UBERON:0002372	48.55	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality
upper arm skin	UBERON:0004263	48.06	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	17.69

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

43 targeting KRT76, 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-4481	100.00	66.42	1669
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-1224-5P	99.48	65.59	803
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-4786-3P	99.36	68.35	1390
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-6876-3P	98.97	65.69	765
HSA-MIR-626	98.89	66.21	762
HSA-MIR-876-3P	98.76	68.23	945
HSA-MIR-4290	98.51	65.17	907
HSA-MIR-4518	98.12	66.82	1030
HSA-MIR-6511B-5P	97.98	65.64	823
HSA-MIR-6811-5P	97.98	64.96	848
HSA-MIR-7113-5P	97.88	67.33	1735
HSA-MIR-1266-5P	97.71	66.92	1052

Literature-anchored findings (GeneRIF, showing 2)

• Data shows that immunomodulatory role of Keratin 76 in oral and gastric cancer. (PMID:30143634)
• K2P2.1 is a regulator of inflammatory cell responses in idiopathic inflammatory myopathies. (PMID:37935063)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Krt76	ENSMUSG00000075402
rattus_norvegicus	Krt76	ENSRNOG00000031785

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 2 oral — Q01546 (reviewed: Q01546)

Alternative names: Cytokeratin-2P, Keratin-76, Type-II keratin Kb9

All UniProt accessions (1): Q01546

UniProt curated annotations — full annotation on UniProt →

Function. Probably contributes to terminal cornification.

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

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_056932* (*=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 (24 total): region of interest 8, compositionally biased region 6, sequence variant 4, modified residue 3, chain 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q01546-F1	65.30	0.37

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (3): 85, 110, 584

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: 77 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_INTERMEDIATE_FILAMENT_BASED_PROCESS, GOBP_INTERMEDIATE_FILAMENT_ORGANIZATION, PUJANA_CHEK2_PCC_NETWORK, GOBP_PIGMENTATION, GOBP_EPIDERMAL_CELL_DIFFERENTIATION, MODULE_99, GOBP_EPIDERMIS_DEVELOPMENT, MODULE_113, GOBP_KERATINIZATION, GOBP_SKIN_DEVELOPMENT, GOCC_INTERMEDIATE_FILAMENT_CYTOSKELETON, GOCC_KERATIN_FILAMENT

GO Biological Process (6): cytoskeleton organization (GO:0007010), keratinization (GO:0031424), pigmentation (GO:0043473), intermediate filament organization (GO:0045109), sebaceous gland development (GO:0048733), epidermis development (GO:0008544)

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), intermediate filament (GO:0005882), keratin filament (GO:0045095), extracellular exosome (GO:0070062)

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
organelle organization	1
keratinocyte differentiation	1
multicellular organismal process	1
biological_process	1
intermediate filament cytoskeleton organization	1
supramolecular fiber organization	1
skin development	1
gland development	1
tissue development	1
structural molecule activity	1
binding	1
intracellular membrane-bounded organelle	1
cytoplasm	1
cellular anatomical structure	1
intermediate filament cytoskeleton	1
polymeric cytoskeletal fiber	1
intermediate filament	1
extracellular vesicle	1

Protein interactions and networks

STRING

1349 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KRT76	KCNK18	Q7Z418	987
KRT76	KCNK6	Q9Y257	980
KRT76	KCNK1	O00180	975
KRT76	KCNK7	Q9Y2U2	952
KRT76	KCNK2	O95069	903
KRT76	MT-CO1	P00395	888
KRT76	KCNK10	P57789	883
KRT76	KCNK4	Q9NYG8	883
KRT76	KCNK9	Q9NPC2	880
KRT76	KCNK3	O14649	878
KRT76	KCNK5	O95279	799
KRT76	CSN3	P07498	722
KRT76	KCNK17	Q96T54	720
KRT76	KCNK16	Q96T55	720
KRT76	KCNK13	Q9HB14	716
KRT76	MT-CYB	P00156	716

IntAct

140 interactions, top by confidence:

A	B	Type	Score
KRT76	KRT31	psi-mi:“MI:0915”(physical association)	0.630
KRT31	KRT76	psi-mi:“MI:0915”(physical association)	0.630
TRIM27	KRT76	psi-mi:“MI:0915”(physical association)	0.560
KRT76	NFKBID	psi-mi:“MI:0915”(physical association)	0.560
HGS	KRT76	psi-mi:“MI:0915”(physical association)	0.560
KRT76	CCDC57	psi-mi:“MI:0915”(physical association)	0.560
KRT76	TRIM54	psi-mi:“MI:0915”(physical association)	0.560
KRT76	IQUB	psi-mi:“MI:0915”(physical association)	0.560
KRT76	IPO11	psi-mi:“MI:0915”(physical association)	0.560
KRT37	KRT76	psi-mi:“MI:0915”(physical association)	0.560
KRT76	DPPA3	psi-mi:“MI:0915”(physical association)	0.560
KRT76	TSGA10	psi-mi:“MI:0915”(physical association)	0.560
KRT76	MID2	psi-mi:“MI:0915”(physical association)	0.560
POLR1C	KRT76	psi-mi:“MI:0915”(physical association)	0.560
KRT76	C1orf216	psi-mi:“MI:0915”(physical association)	0.560
FRS3	KRT76	psi-mi:“MI:0915”(physical association)	0.560
KRT76	KRT27	psi-mi:“MI:0915”(physical association)	0.560
KRT76	KRT39	psi-mi:“MI:0915”(physical association)	0.560
KRT76	CDC37	psi-mi:“MI:0915”(physical association)	0.560
KRT76	KRT25	psi-mi:“MI:0915”(physical association)	0.560
LMO4	KRT76	psi-mi:“MI:0915”(physical association)	0.560
KRT75	KRT76	psi-mi:“MI:0915”(physical association)	0.560
KRT76	EXOC8	psi-mi:“MI:0915”(physical association)	0.560
KRT76	CFAP206	psi-mi:“MI:0915”(physical association)	0.560
KRT76	AIRIM	psi-mi:“MI:0915”(physical association)	0.560
KRT36	KRT76	psi-mi:“MI:0915”(physical association)	0.560
KRT76	RSPH14	psi-mi:“MI:0915”(physical association)	0.560
KRT76	FOXR2	psi-mi:“MI:0915”(physical association)	0.560
KRT76	MTUS2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (89): KRT76 (Affinity Capture-MS), KRT76 (Affinity Capture-MS), KRT76 (Affinity Capture-MS), KRT76 (Two-hybrid), KRT76 (Two-hybrid), KRT76 (Two-hybrid), KRT76 (Two-hybrid), KRT76 (Two-hybrid), KRT76 (Two-hybrid), KRT76 (Two-hybrid), KRT76 (Two-hybrid), KRT76 (Two-hybrid), KRT76 (Two-hybrid), KRT76 (Two-hybrid), KRT76 (Two-hybrid)

ESM2 similar proteins: A5A6M6, A5A6M8, O95678, P02535, P02537, P02538, P04104, P04259, P04264, P06394, P07744, P08776, P12035, P13645, P13647, P16878, P18520, P19013, P35527, P35908, P48668, P50446, Q01546, Q08D91, Q148H7, Q29426, Q2M2I5, Q3TTY5, Q3UV17, Q4FZU2, Q5XQN5, Q6EIY9, Q6EIZ0, Q6EIZ1, Q6IFW6, Q6IFZ6, Q6IG00, Q6IG01, Q6IG02, Q6IG05

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 63 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	28.5×	9e-13
Keratinization	12	18.1×	1e-10
Neddylation	8	10.2×	6e-05

GO biological processes:

GO term	Partners	Fold	FDR
morphogenesis of an epithelium	10	61.4×	9e-14
intermediate filament organization	12	51.6×	2e-15
epithelial cell differentiation	9	28.2×	3e-09
G1/S transition of mitotic cell cycle	5	17.9×	6e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	102
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1196 predictions. Top by Δscore:

Variant	Effect	Δscore
12:52769547:A:AC	donor_gain	1.0000
12:52769548:C:CC	donor_gain	1.0000
12:52770993:CCTCA:C	donor_loss	1.0000
12:52770994:CTCA:C	donor_loss	1.0000
12:52770997:A:T	donor_loss	1.0000
12:52770998:C:CA	donor_loss	1.0000
12:52771011:C:CA	donor_gain	1.0000
12:52771215:GCATT:G	acceptor_gain	1.0000
12:52771216:CATT:C	acceptor_gain	1.0000
12:52771216:CATTC:C	acceptor_gain	1.0000
12:52771217:ATT:A	acceptor_gain	1.0000
12:52771218:TT:T	acceptor_gain	1.0000
12:52771220:C:CC	acceptor_gain	1.0000
12:52771225:G:C	acceptor_gain	1.0000
12:52771225:G:GC	acceptor_gain	1.0000
12:52771902:AG:A	donor_gain	1.0000
12:52772088:TCCCA:T	donor_loss	1.0000
12:52772089:CCCAC:C	donor_loss	1.0000
12:52772090:CCACC:C	donor_loss	1.0000
12:52772091:CACCT:C	donor_loss	1.0000
12:52772092:A:T	donor_loss	1.0000
12:52772093:C:CG	donor_loss	1.0000
12:52772116:G:C	donor_gain	1.0000
12:52772254:AGCTC:A	acceptor_gain	1.0000
12:52772256:CTC:C	acceptor_gain	1.0000
12:52772257:TC:T	acceptor_gain	1.0000
12:52772257:TCC:T	acceptor_loss	1.0000
12:52772258:CC:C	acceptor_gain	1.0000
12:52772258:CCT:C	acceptor_loss	1.0000
12:52772259:C:CC	acceptor_gain	1.0000

AlphaMissense

4235 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:52773619:C:G	R280P	0.995
12:52773585:C:A	K291N	0.993
12:52773585:C:G	K291N	0.993
12:52771923:A:G	L404P	0.991
12:52771953:A:G	L394P	0.991
12:52771902:A:G	L411P	0.990
12:52772117:C:G	A372P	0.988
12:52773620:G:T	R280S	0.988
12:52773597:A:C	F287L	0.986
12:52773597:A:T	F287L	0.986
12:52773599:A:G	F287L	0.986
12:52772844:A:G	L304P	0.985
12:52773611:C:G	A283P	0.982
12:52776710:A:C	F194L	0.982
12:52776710:A:T	F194L	0.982
12:52776712:A:G	F194L	0.982
12:52771071:A:G	L471P	0.979
12:52771986:A:G	L383P	0.979
12:52771020:A:G	L488P	0.972
12:52771156:C:G	A443P	0.972
12:52771189:C:G	A432P	0.972
12:52771026:C:G	R486P	0.971
12:52771058:C:A	K475N	0.971
12:52771058:C:G	K475N	0.971
12:52772804:G:C	F317L	0.971
12:52772804:G:T	F317L	0.971
12:52772806:A:G	F317L	0.971
12:52771036:C:G	A483P	0.967
12:52772872:C:G	D295H	0.966
12:52773586:T:G	K291T	0.966

dbSNP variants (sampled 300 via entrez): RS1000072395 (12:52776846 C>T), RS1000087726 (12:52770480 A>C,G), RS1001286085 (12:52774693 C>A,G), RS1001367305 (12:52776209 C>G), RS1001612626 (12:52771431 C>G,T), RS1002069329 (12:52770528 G>A), RS1002125826 (12:52771748 C>G,T), RS1002393494 (12:52775721 T>A,C), RS1002496698 (12:52778340 A>G), RS1003020712 (12:52772568 C>T), RS1003204255 (12:52778793 G>A), RS1003360202 (12:52773468 C>A), RS1003433630 (12:52772993 G>A), RS1003875313 (12:52778995 C>T), RS1004711257 (12:52778551 T>G)

Disease associations

OMIM: gene MIM:616671 | 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

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	affects expression, decreases expression	2
beauvericin	affects cotreatment, decreases expression	1
sodium arsenite	increases expression	1
enniatins	affects cotreatment, decreases expression	1
corosolic acid	increases expression	1
Aerosols	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression, increases abundance	1
Dinitrochlorobenzene	affects binding	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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