KRT33B

Summary

KRT33B (keratin 33B, HGNC:6451) is a protein-coding gene on chromosome 17q21.2, encoding Keratin, type I cuticular Ha3-II (Q14525).

This gene encodes a member of the keratin gene family. This gene is one of multiple type I hair keratin genes that are clustered in a region of chromosome 17q12-q21 and have the same direction of transcription. As a type I hair keratin, the encoded protein is an acidic protein which heterodimerizes with type II keratins to form hair and nails. There are two isoforms of this protein, encoded by two separate genes, keratin 33A and keratin 33B.

Source: NCBI Gene 3884 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 85 total
• MANE Select transcript: NM_002279

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6451
Approved symbol	KRT33B
Name	keratin 33B
Location	17q21.2
Locus type	gene with protein product
Status	Approved
Aliases	Ha-3II
Ensembl gene	ENSG00000131738
Ensembl biotype	protein_coding
OMIM	602762
Entrez	3884

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000251646

RefSeq mRNA: 1 — MANE Select: NM_002279 NM_002279

CCDS: CCDS11389

Canonical transcript exons

ENST00000251646 — 7 exons

Exon	Start	End
ENSE00001810585	41363498	41363953
ENSE00002438381	41369403	41369813
ENSE00002458105	41365175	41365300
ENSE00002486034	41367908	41367990
ENSE00002491252	41364779	41364999
ENSE00002517762	41365392	41365553
ENSE00002528182	41366470	41366626

Expression profiles

Bgee: expression breadth broad, 59 present calls, max score 48.94.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0502 / max 12.5852, expressed in 29 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165889	0.0502	29

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
prefrontal cortex	UBERON:0000451	48.94	gold quality
anterior cingulate cortex	UBERON:0009835	46.85	gold quality
frontal cortex	UBERON:0001870	44.13	gold quality
sural nerve	UBERON:0015488	43.13	gold quality
skin of abdomen	UBERON:0001416	42.69	gold quality
zone of skin	UBERON:0000014	42.18	gold quality
skin of leg	UBERON:0001511	42.05	gold quality
cerebral cortex	UBERON:0000956	41.81	gold quality
Brodmann (1909) area 9	UBERON:0013540	40.95	gold quality
cortical plate	UBERON:0005343	40.23	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	39.94	gold quality
lower esophagus mucosa	UBERON:0035834	39.39	gold quality
right lung	UBERON:0002167	38.95	gold quality
esophagus mucosa	UBERON:0002469	37.40	silver quality
right frontal lobe	UBERON:0002810	37.23	silver quality
colonic epithelium	UBERON:0000397	37.20	gold quality
vagina	UBERON:0000996	37.20	gold quality
cerebellum	UBERON:0002037	36.95	gold quality
cerebellar cortex	UBERON:0002129	36.94	gold quality
cerebellar hemisphere	UBERON:0002245	36.74	gold quality
right hemisphere of cerebellum	UBERON:0014890	36.71	gold quality
Ammon’s horn	UBERON:0001954	36.37	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
hindlimb stylopod muscle	UBERON:0004252	35.62	gold quality
granulocyte	CL:0000094	35.60	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
brain	UBERON:0000955	33.62	gold quality
minor salivary gland	UBERON:0001830	33.41	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
saliva-secreting gland	UBERON:0001044	33.03	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.18

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

15 targeting KRT33B, 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-2110	99.96	66.68	1930
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-1251-3P	99.64	67.21	1408
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-3125	99.14	68.49	2269
HSA-MIR-3916	98.99	68.04	2155
HSA-MIR-6859-5P	98.99	68.07	2049
HSA-MIR-450A-2-3P	97.91	67.56	1459
HSA-MIR-410-5P	96.55	66.28	459
HSA-MIR-591	96.29	68.16	611
HSA-MIR-323B-5P	96.12	66.39	472
HSA-MIR-494-5P	95.31	66.29	463

Cross-species orthologs

0 orthologs

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), 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), KRT13 (ENSG00000171401)

Protein

Protein identifiers

Keratin, type I cuticular Ha3-II — Q14525 (reviewed: Q14525)

Alternative names: Hair keratin, type I Ha3-II, Keratin-33B

All UniProt accessions (1): Q14525

UniProt curated annotations — full annotation on UniProt →

Miscellaneous. There are two types of hair/microfibrillar keratin, I (acidic) and II (neutral to basic).

Similarity. Belongs to the intermediate filament family.

RefSeq proteins (1): NP_002270* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002957	Keratin_I	Family
IPR018039	IF_conserved	Conserved_site
IPR039008	IF_rod_dom	Domain

Pfam: PF00038

UniProt features (11 total): region of interest 7, chain 1, domain 1, sequence conflict 1, site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14525-F1	80.40	0.61

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): 305 (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: 83 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_EPITHELIUM_DEVELOPMENT, MORF_FLT1, GOBP_INTERMEDIATE_FILAMENT_BASED_PROCESS, GOBP_INTERMEDIATE_FILAMENT_ORGANIZATION, ENK_UV_RESPONSE_KERATINOCYTE_UP, MARTINEZ_RB1_TARGETS_DN, MODULE_298, MODULE_157, GOBP_MOLTING_CYCLE, NRF2_Q4, MORF_ETV3, TANAKA_METHYLATED_IN_ESOPHAGEAL_CARCINOMA, GOBP_TISSUE_MORPHOGENESIS, MODULE_104

GO Biological Process (4): morphogenesis of an epithelium (GO:0002009), epithelial cell differentiation (GO:0030855), hair cycle (GO:0042633), 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): obsolete extracellular space (GO:0005615), 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
epithelium development	2
tissue morphogenesis	1
cell differentiation	1
molting cycle	1
intermediate filament cytoskeleton organization	1
supramolecular fiber organization	1
structural molecule activity	1
molecular_function	1
binding	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

684 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KRT33B	KRTAP3-1	Q9BYR8	489
KRT33B	KRTAP3-2	Q9BYR7	466
KRT33B	C22orf31	O95567	446
KRT33B	KRTAP3-3	Q9BYR6	434
KRT33B	KRTAP9-3	Q9BYQ3	431
KRT33B	KRTAP13-1	Q8IUC0	411
KRT33B	TEX19	Q8NA77	403
KRT33B	KRTAP9-4	Q9BYQ2	399
KRT33B	TCHH	Q07283	394
KRT33B	SECTM1	Q8WVN6	377
KRT33B	KRTAP13-3	Q3SY46	353
KRT33B	ZNF664	Q8N3J9	337
KRT33B	HERC2	O95714	333
KRT33B	KRTAP11-1	Q8IUC1	330
KRT33B	ARL5C	A6NH57	316
KRT33B	PRR9	Q5T870	316

IntAct

286 interactions, top by confidence:

A	B	Type	Score
KRT4	KRT33B	psi-mi:“MI:0915”(physical association)	0.780
KRT33B	KRT79	psi-mi:“MI:0915”(physical association)	0.780
KRT79	KRT33B	psi-mi:“MI:0915”(physical association)	0.780
KRT33B	KRT4	psi-mi:“MI:0915”(physical association)	0.780
KRT1	KRT33B	psi-mi:“MI:0915”(physical association)	0.740
HGS	KRT33B	psi-mi:“MI:0915”(physical association)	0.720
KRT33B	NUP58	psi-mi:“MI:0915”(physical association)	0.720
KDM1A	KRT33B	psi-mi:“MI:0915”(physical association)	0.670
KRT33B	KRT78	psi-mi:“MI:0915”(physical association)	0.630
KRT33B	AQP1	psi-mi:“MI:0915”(physical association)	0.560
ABI2	KRT33B	psi-mi:“MI:0915”(physical association)	0.560
AQP1	KRT33B	psi-mi:“MI:0915”(physical association)	0.560
KRT33B	ABI2	psi-mi:“MI:0915”(physical association)	0.560
KRT33B	KRT71	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (111): KRT33B (Two-hybrid), KRT33B (Two-hybrid), ABI2 (Two-hybrid), KRT79 (Two-hybrid), KRT33B (Affinity Capture-MS), KRT33B (Two-hybrid), KRT33B (Affinity Capture-MS), KRT33B (Affinity Capture-MS), KRT33B (Affinity Capture-MS), KRT33B (Affinity Capture-MS), KRT33B (Affinity Capture-MS), KRT33B (Two-hybrid), KRT33B (Affinity Capture-MS), KRT33B (Two-hybrid), KRT33B (Two-hybrid)

ESM2 similar proteins: A4FUZ0, A5A6M5, A5A6P3, A6QNX5, A7YWK3, B0LKP1, B1AQ75, E1AB55, O43790, O76009, O76013, P02534, P15241, P19013, P25690, P25691, P78385, P78386, P97861, Q0P5J7, Q14525, Q14532, Q14533, Q148H4, Q148H5, Q148H7, Q148H8, Q14CN4, Q15323, Q3SY84, Q497I4, Q61765, Q61897, Q62168, Q6IG03, Q6IG04, Q6IME9, Q6IMF0, Q6NXH9, Q86Y46

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 72 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	19	34.1×	1e-22
Keratinization	19	21.6×	5e-19

GO biological processes:

GO term	Partners	Fold	FDR
intermediate filament organization	19	66.3×	8e-28
keratinization	16	54.3×	8e-22

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	81
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

542 predictions. Top by Δscore:

Variant	Effect	Δscore
17:41364777:A:AC	donor_gain	1.0000
17:41364778:C:CC	donor_gain	1.0000
17:41364995:TATCG:T	acceptor_gain	1.0000
17:41364996:ATCG:A	acceptor_gain	1.0000
17:41364997:TCG:T	acceptor_gain	1.0000
17:41364998:CG:C	acceptor_gain	1.0000
17:41364998:CGC:C	acceptor_gain	1.0000
17:41365000:C:A	acceptor_loss	1.0000
17:41365000:C:CC	acceptor_gain	1.0000
17:41365002:G:C	acceptor_gain	1.0000
17:41365002:G:GC	acceptor_gain	1.0000
17:41365005:G:C	acceptor_gain	1.0000
17:41365005:G:GC	acceptor_gain	1.0000
17:41365296:TCGGT:T	acceptor_gain	1.0000
17:41365297:CGGT:C	acceptor_gain	1.0000
17:41365297:CGGTC:C	acceptor_gain	1.0000
17:41365298:GGT:G	acceptor_gain	1.0000
17:41365298:GGTC:G	acceptor_loss	1.0000
17:41365299:GT:G	acceptor_gain	1.0000
17:41365299:GTC:G	acceptor_loss	1.0000
17:41365300:TCT:T	acceptor_loss	1.0000
17:41365301:C:CC	acceptor_gain	1.0000
17:41365302:T:A	acceptor_loss	1.0000
17:41365307:C:CT	acceptor_gain	1.0000
17:41365310:C:CT	acceptor_gain	1.0000
17:41365311:C:CT	acceptor_gain	1.0000
17:41365311:C:T	acceptor_gain	1.0000
17:41365312:A:T	acceptor_gain	1.0000
17:41365388:CCACC:C	donor_loss	1.0000
17:41365417:T:TA	donor_gain	1.0000

AlphaMissense

2643 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:41369554:C:G	R66P	0.997
17:41364890:C:G	R329P	0.992
17:41365194:A:G	L286P	0.992
17:41369551:A:G	L67P	0.992
17:41364818:A:G	I353T	0.991
17:41364902:A:G	L325P	0.991
17:41364830:A:G	L349P	0.990
17:41369521:A:G	L77P	0.990
17:41364800:A:G	L359P	0.988
17:41364818:A:C	I353S	0.988
17:41364881:A:G	L332P	0.988
17:41369413:A:G	L113P	0.988
17:41369549:C:G	A68P	0.988
17:41365189:C:G	A288P	0.987
17:41369555:G:T	R66S	0.987
17:41369563:A:G	L63P	0.987
17:41364851:A:G	L342P	0.986
17:41364872:T:G	Q335P	0.986
17:41364977:A:G	L300P	0.986
17:41369539:A:G	L71P	0.986
17:41369551:A:T	L67Q	0.986
17:41364806:C:G	R357P	0.985
17:41364944:A:G	L311P	0.985
17:41367939:C:G	A134P	0.985
17:41364810:A:C	Y356D	0.984
17:41364821:T:A	E352V	0.983
17:41364875:C:G	R334P	0.983
17:41365227:A:G	L275P	0.983
17:41369500:A:G	L84P	0.983
17:41369560:T:A	N64I	0.983

dbSNP variants (sampled 300 via entrez): RS1001513582 (17:41364885 C>T), RS1001533348 (17:41370098 C>T), RS1001534485 (17:41371770 A>G), RS1001546133 (17:41365070 C>G,T), RS1001847099 (17:41366085 T>C), RS1002279077 (17:41369172 T>C), RS1003282446 (17:41370434 C>A,G), RS1003524738 (17:41367682 T>A,C), RS1003555947 (17:41367945 C>T), RS1003972730 (17:41366034 C>T), RS1004305164 (17:41370386 A>T), RS1004491286 (17:41366524 G>C,T), RS1005084450 (17:41364119 A>G), RS1005103621 (17:41370673 A>G), RS1005609430 (17:41367387 A>G)

Disease associations

OMIM: gene MIM:602762 | 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

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
2-methyl-4-isothiazolin-3-one	increases expression	1
sodium arsenite	increases expression	1
potassium chromate(VI)	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
Benzo(a)pyrene	increases methylation	1
Diethylhexyl Phthalate	decreases expression	1
Estradiol	affects binding, increases reaction	1
Folic Acid	decreases expression	1
Silicon Dioxide	increases expression	1
Smoke	increases expression	1
1-Methyl-4-phenylpyridinium	increases expression	1
Asbestos, Crocidolite	increases expression	1
Antirheumatic Agents	increases expression	1
Lactic Acid	decreases expression	1
Particulate Matter	decreases expression	1

Clinical trials (associated diseases)

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