KRT77

Summary

KRT77 (keratin 77, HGNC:20411) is a protein-coding gene on chromosome 12q13.13, encoding Keratin, type II cytoskeletal 1b (Q7Z794).

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 an epithelial keratin that is expressed in the skin and eccrine sweat glands. The type II keratins are clustered in a region of chromosome 12q13.

Source: NCBI Gene 374454 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 103 total
• MANE Select transcript: NM_175078

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20411
Approved symbol	KRT77
Name	keratin 77
Location	12q13.13
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000189182
Ensembl biotype	protein_coding
OMIM	611158
Entrez	374454

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 1 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000341809, ENST00000550823, ENST00000553168

RefSeq mRNA: 1 — MANE Select: NM_175078 NM_175078

CCDS: CCDS8837

Canonical transcript exons

ENST00000341809 — 9 exons

Exon	Start	End
ENSE00001378806	52689626	52691439
ENSE00003499806	52697682	52697896
ENSE00003512130	52694626	52694790
ENSE00003544434	52692755	52692880
ENSE00003553941	52695772	52695867
ENSE00003575423	52691938	52691972
ENSE00003636421	52696370	52696430
ENSE00003645174	52692421	52692641
ENSE00003895241	52702892	52703524

Expression profiles

Bgee: expression breadth ubiquitous, 102 present calls, max score 99.74.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1140 / max 94.9929, expressed in 9 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
131122	0.1140	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper arm skin	UBERON:0004263	99.74	gold quality
upper leg skin	UBERON:0004262	99.44	gold quality
nipple	UBERON:0002030	98.84	gold quality
skin of hip	UBERON:0001554	98.65	gold quality
skin of abdomen	UBERON:0001416	98.09	gold quality
zone of skin	UBERON:0000014	97.43	gold quality
skin of leg	UBERON:0001511	96.93	gold quality
mammalian vulva	UBERON:0000997	79.88	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.26	gold quality
pancreatic ductal cell	CL:0002079	73.50	silver quality
tibialis anterior	UBERON:0001385	70.98	silver quality
penis	UBERON:0000989	69.64	gold quality
ileal mucosa	UBERON:0000331	69.62	silver quality
deltoid	UBERON:0001476	59.03	gold quality
lower esophagus mucosa	UBERON:0035834	57.69	gold quality
epithelial cell of pancreas	CL:0000083	56.29	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	55.82	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
myocardium	UBERON:0002349	50.25	gold quality
gastrocnemius	UBERON:0001388	48.58	gold quality
nasal cavity epithelium	UBERON:0005384	47.03	gold quality
muscle of leg	UBERON:0001383	45.82	gold quality
subcutaneous adipose tissue	UBERON:0002190	45.62	gold quality
bone marrow cell	CL:0002092	45.44	gold quality
skeletal muscle tissue	UBERON:0001134	45.35	gold quality
esophagus mucosa	UBERON:0002469	44.69	gold quality
muscle tissue	UBERON:0002385	44.65	gold quality
heart left ventricle	UBERON:0002084	44.24	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.62

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ELF5

miRNA regulators (miRDB)

57 targeting KRT77, 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-548AW	99.99	72.57	3559
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-4658	99.77	64.94	514
HSA-MIR-6790-5P	99.77	65.24	505
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-642A-5P	99.51	65.10	1152
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-516A-3P	99.46	67.96	1378
HSA-MIR-516B-3P	99.46	67.96	1378
HSA-MIR-7162-5P	99.46	68.08	1368
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-1272	99.34	68.79	878
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-548V	99.29	69.47	1157
HSA-MIR-324-3P	99.26	66.31	1034
HSA-MIR-5690	99.25	67.58	1012

Literature-anchored findings (GeneRIF, showing 2)

• Epithelial keratin, K1b, is exclusively expressed in luminal duct cells of eccrine sweat glands. (PMID:16117782)
• Molecular Modeling of Pathogenic Mutations in the Keratin 1B Domain. (PMID:32927888)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Krt77	ENSMUSG00000067594
rattus_norvegicus	Krt77	ENSRNOG00000036865

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 1b — Q7Z794 (reviewed: Q7Z794)

Alternative names: Cytokeratin-1B, Keratin-77, Type-II keratin Kb39

All UniProt accessions (2): Q7Z794, F8VS61

UniProt curated annotations — full annotation on UniProt →

Tissue specificity. Expressed exclusively in skin.

Post-translational modifications. Undergoes deimination of some arginine residues (citrullination).

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_778253* (*=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, compositionally biased region 2, modified residue 2, sequence conflict 2, chain 1, domain 1, site 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z794-F1	68.73	0.42

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): 418 (stutter)

Post-translational modifications (2): 95, 523

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: 56 (showing top): GOBP_EPITHELIUM_DEVELOPMENT, GOBP_INTERMEDIATE_FILAMENT_BASED_PROCESS, GOBP_INTERMEDIATE_FILAMENT_ORGANIZATION, GOBP_EPIDERMAL_CELL_DIFFERENTIATION, MARTINEZ_RB1_TARGETS_UP, GATA6_01, GOBP_EPIDERMIS_DEVELOPMENT, GOBP_KERATINIZATION, GOBP_SKIN_DEVELOPMENT, MARTINEZ_RB1_AND_TP53_TARGETS_UP, CTAWWWATA_RSRFC4_Q2, GOCC_INTERMEDIATE_FILAMENT_CYTOSKELETON, GOCC_KERATIN_FILAMENT, GOCC_CORNIFIED_ENVELOPE, GOMF_STRUCTURAL_MOLECULE_ACTIVITY

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 (6): cornified envelope (GO:0001533), 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
keratinocyte differentiation	1
multicellular organismal process	1
intermediate filament cytoskeleton organization	1
supramolecular fiber organization	1
structural molecule activity	1
binding	1
plasma membrane	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

926 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KRT77	SPRR4	Q96PI1	474
KRT77	KRTDAP	P60985	473
KRT77	S100A7	P31151	467
KRT77	KLK6	Q92876	457
KRT77	S100A2	P29034	436
KRT77	LCE2C	Q5TA81	425
KRT77	KLK14	Q9P0G3	417
KRT77	S100A12	P80511	414
KRT77	ANXA1	P04083	411
KRT77	TCHHL1	Q5QJ38	410
KRT77	LARP1B	Q659C4	407
KRT77	SERPINB13	Q9UIV8	406
KRT77	SPRR2D	P22532	400
KRT77	LCE2D	Q5TA82	400
KRT77	LCE3C	Q5T5A8	396

IntAct

57 interactions, top by confidence:

A	B	Type	Score
KRT31	KRT77	psi-mi:“MI:0915”(physical association)	0.560
KRT77	MDFI	psi-mi:“MI:0915”(physical association)	0.560
KRT19	KRT77	psi-mi:“MI:0915”(physical association)	0.560
KRT27	KRT77	psi-mi:“MI:0915”(physical association)	0.560
KRT77	KRT35	psi-mi:“MI:0915”(physical association)	0.560
KRT15	KRT77	psi-mi:“MI:0915”(physical association)	0.560
KRT36	KRT77	psi-mi:“MI:0915”(physical association)	0.560
KRT17	KRT77	psi-mi:“MI:0915”(physical association)	0.400
HERC2	FTL	psi-mi:“MI:0914”(association)	0.350
WTAP	DDX39A	psi-mi:“MI:0914”(association)	0.350
METTL14	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
DCUN1D1	RGSL1	psi-mi:“MI:0914”(association)	0.350
CUL5	DDX3X	psi-mi:“MI:0914”(association)	0.350
WWC1	KRT6B	psi-mi:“MI:0914”(association)	0.350
YAP1	TEAD1	psi-mi:“MI:0914”(association)	0.350
	CLIC1	psi-mi:“MI:0914”(association)	0.350
CFTR	POTEF	psi-mi:“MI:0914”(association)	0.350
BMI1	MEIS3P1	psi-mi:“MI:0914”(association)	0.350
RYBP	PIPSL	psi-mi:“MI:0914”(association)	0.350
MAP1LC3B		psi-mi:“MI:0914”(association)	0.350
GABARAPL2		psi-mi:“MI:0914”(association)	0.350
GABARAPL1		psi-mi:“MI:0914”(association)	0.350
ATG101	FOXO3	psi-mi:“MI:0914”(association)	0.350
CACNA1C	IGLL5	psi-mi:“MI:0914”(association)	0.350
SMIM26	METTL15	psi-mi:“MI:0914”(association)	0.350
SULF2	IGLL5	psi-mi:“MI:0914”(association)	0.350
SULF2	IGKV2-29	psi-mi:“MI:0914”(association)	0.350
SULF2	HNRNPCL1	psi-mi:“MI:0914”(association)	0.350
SULF2	IGHA1	psi-mi:“MI:0914”(association)	0.350
LGALS3BP	IGHV3-64D	psi-mi:“MI:0914”(association)	0.350

BioGRID (96): KRT77 (Two-hybrid), KRT77 (Two-hybrid), KRT77 (Affinity Capture-MS), KRT77 (Co-fractionation), KRT77 (Co-fractionation), KRT77 (Co-fractionation), KRT77 (Affinity Capture-MS), KRT77 (Affinity Capture-MS), KRT77 (Affinity Capture-MS), KRT77 (Affinity Capture-MS), KRT77 (Affinity Capture-MS), KRT77 (Affinity Capture-MS), KRT77 (Affinity Capture-MS), KRT77 (Affinity Capture-MS), KRT77 (Affinity Capture-MS)

ESM2 similar proteins: A0JND2, A3KN27, A5A6N0, A6BLY7, A6H712, A6QNX5, A7YWK3, E1AB55, P07744, P08729, P19013, P25691, Q0P5J4, Q0P5J6, Q0P5J7, Q0VBK2, Q148H5, Q148H6, Q148H7, Q148H8, Q14CN4, Q3SY84, Q5XKE5, Q64291, Q6IFW8, Q6IFZ9, Q6IG00, Q6IG01, Q6IG03, Q6IG04, Q6IME9, Q6IMF0, Q6IMF1, Q6KB66, Q6NXH9, Q6R649, Q7RTS7, Q7Z3Y7, Q7Z3Y9, Q7Z794

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 61 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	8	19.0×	2e-06
Keratinization	8	12.0×	3e-05

GO biological processes:

GO term	Partners	Fold	FDR
morphogenesis of an epithelium	7	51.2×	1e-08
intermediate filament organization	8	41.0×	6e-09
epithelial cell differentiation	7	26.1×	1e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	91
Likely benign	9
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1275 predictions. Top by Δscore:

Variant	Effect	Δscore
12:52691437:CGG:C	acceptor_gain	1.0000
12:52691440:C:CC	acceptor_gain	1.0000
12:52691936:A:AC	donor_gain	1.0000
12:52691937:C:CC	donor_gain	1.0000
12:52692417:CCA:C	donor_loss	1.0000
12:52692418:CA:C	donor_loss	1.0000
12:52692420:CCTG:C	donor_gain	1.0000
12:52692427:T:A	donor_gain	1.0000
12:52692648:C:CT	acceptor_gain	1.0000
12:52692881:C:CC	acceptor_gain	1.0000
12:52692888:C:CT	acceptor_gain	1.0000
12:52692889:A:T	acceptor_gain	1.0000
12:52694622:CCACC:C	donor_loss	1.0000
12:52694623:CACCT:C	donor_loss	1.0000
12:52694624:ACCT:A	donor_loss	1.0000
12:52694625:C:A	donor_loss	1.0000
12:52694654:T:TA	donor_gain	1.0000
12:52696364:CCTCA:C	donor_loss	1.0000
12:52696365:CTCA:C	donor_loss	1.0000
12:52696366:TCAC:T	donor_loss	1.0000
12:52696367:CACCT:C	donor_loss	1.0000
12:52696368:ACCT:A	donor_loss	1.0000
12:52697654:C:A	donor_gain	1.0000
12:52697680:A:AC	donor_gain	1.0000
12:52697681:C:CA	donor_gain	1.0000
12:52697681:CTTG:C	donor_gain	1.0000
12:52697706:T:TA	donor_gain	1.0000
12:52702887:CTCA:C	donor_loss	1.0000
12:52702888:TCACC:T	donor_loss	1.0000
12:52702889:CACCT:C	donor_loss	1.0000

AlphaMissense

3790 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:52702910:A:C	F175L	0.989
12:52702910:A:T	F175L	0.989
12:52702912:A:G	F175L	0.989
12:52696373:C:A	K272N	0.988
12:52696373:C:G	K272N	0.988
12:52694649:C:G	A353P	0.982
12:52702911:A:C	F175C	0.977
12:52702911:A:G	F175S	0.976
12:52692870:A:G	L364P	0.975
12:52697856:T:A	K195I	0.974
12:52692807:A:G	L385P	0.971
12:52697877:T:G	Q188P	0.970
12:52702920:T:A	N172I	0.970
12:52692611:C:G	A413P	0.963
12:52694690:C:G	R339P	0.963
12:52692859:C:G	A368P	0.961
12:52696385:A:C	F268L	0.960
12:52696385:A:T	F268L	0.960
12:52696387:A:G	F268L	0.960
12:52697775:A:G	L222P	0.959
12:52702901:G:C	F178L	0.958
12:52702901:G:T	F178L	0.958
12:52702903:A:G	F178L	0.958
12:52697855:T:A	K195N	0.955
12:52697855:T:G	K195N	0.955
12:52702919:G:C	N172K	0.955
12:52702919:G:T	N172K	0.955
12:52696377:A:G	L271P	0.953
12:52697880:T:G	Q187P	0.953
12:52702908:G:T	A176D	0.953

dbSNP variants (sampled 300 via entrez): RS1000048299 (12:52698222 G>A,T), RS1000141410 (12:52697950 C>A,G), RS1000999236 (12:52692107 A>G), RS1001188245 (12:52702455 T>C), RS1001862973 (12:52693757 T>C), RS1001954129 (12:52695126 C>A,T), RS1002172113 (12:52690762 G>T), RS1002347221 (12:52696946 C>T), RS1002392829 (12:52699497 C>T), RS1002399069 (12:52693494 T>C), RS1002457104 (12:52705226 T>C), RS1002504224 (12:52689404 GAGAAGA>G,GAGA,GAGAAGAAGA), RS1002553550 (12:52696516 T>C), RS1002812662 (12:52701072 C>A,T), RS1002863693 (12:52701329 C>T)

Disease associations

OMIM: gene MIM:611158 | 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

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	2
Nickel	decreases expression	2
sodium arsenate	decreases expression, increases abundance	1
pyrogallol 1,3-dimethyl ether	decreases expression, affects cotreatment, affects localization	1
butyraldehyde	increases expression	1
epigallocatechin gallate	increases expression	1
pentanal	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression	1
bromovanin	decreases expression	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Furaldehyde	affects localization, increases expression, affects cotreatment	1
Sodium Chloride	affects cotreatment, affects localization, increases expression, decreases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	decreases expression	1
Aflatoxin B1	increases expression	1

Clinical trials (associated diseases)

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