KRTAP4-3

Summary

KRTAP4-3 (keratin associated protein 4-3, HGNC:18908) is a protein-coding gene on chromosome 17q21.2, encoding Keratin-associated protein 4-3 (Q9BYR4). In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-link…. It is a selective cancer dependency (DepMap: 22.6% of cell lines).

Involved in hair cycle. Predicted to be located in cytosol.

Source: NCBI Gene 85290 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 35 total
• Cancer dependency (DepMap): dependent in 22.6% of screened cell lines
• MANE Select transcript: NM_033187

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18908
Approved symbol	KRTAP4-3
Name	keratin associated protein 4-3
Location	17q21.2
Locus type	gene with protein product
Status	Approved
Aliases	KAP4.3
Ensembl gene	ENSG00000196156
Ensembl biotype	protein_coding
Entrez	85290

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000391356

RefSeq mRNA: 1 — MANE Select: NM_033187 NM_033187

CCDS: CCDS42331

Canonical transcript exons

ENST00000391356 — 1 exons

Exon	Start	End
ENSE00001509138	41167231	41168221

Expression profiles

Bgee: expression breadth broad, 18 present calls, max score 78.40.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0306 / max 35.9800, expressed in 3 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165879	0.0306	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper arm skin	UBERON:0004263	78.40	silver quality
ileal mucosa	UBERON:0000331	61.00	silver quality
upper leg skin	UBERON:0004262	58.63	gold quality
skin of hip	UBERON:0001554	58.04	gold quality
pancreatic ductal cell	CL:0002079	56.20	silver quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
epithelial cell of pancreas	CL:0000083	54.19	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
myocardium	UBERON:0002349	50.25	gold quality
quadriceps femoris	UBERON:0001377	47.46	gold quality
nasal cavity epithelium	UBERON:0005384	47.03	gold quality
lower lobe of lung	UBERON:0008949	46.88	silver quality
vastus lateralis	UBERON:0001379	45.40	gold quality
layer of synovial tissue	UBERON:0007616	43.55	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
middle temporal gyrus	UBERON:0002771	43.20	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
oviduct epithelium	UBERON:0004804	41.36	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
cartilage tissue	UBERON:0002418	40.77	gold quality
amniotic fluid	UBERON:0000173	40.69	gold quality
jejunal mucosa	UBERON:0000399	40.59	gold quality
biceps brachii	UBERON:0001507	40.57	gold quality
epithelium of nasopharynx	UBERON:0001951	40.45	gold quality
gingival epithelium	UBERON:0001949	40.43	gold quality
germinal epithelium of ovary	UBERON:0001304	40.33	gold quality
esophagus squamous epithelium	UBERON:0006920	40.29	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.32

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

39 targeting KRTAP4-3, 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-3924	100.00	72.09	2394
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-10393-5P	99.65	68.01	1368
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-4273	99.45	67.93	1206
HSA-MIR-183-3P	99.41	69.41	1598
HSA-MIR-4311	99.31	70.47	3041
HSA-MIR-3191-5P	99.24	66.52	1722
HSA-MIR-146A-3P	99.13	68.99	1881
HSA-MIR-10B-3P	99.04	66.98	988
HSA-MIR-140-3P	99.04	67.69	1324
HSA-MIR-4699-5P	98.99	67.50	1210
HSA-MIR-6512-5P	98.76	69.29	1195
HSA-MIR-2117	98.48	67.97	1307
HSA-MIR-943	97.81	64.42	694

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 22.6% of screened cell lines.

Cross-species orthologs

17 orthologs

Organism	Symbol	Gene ID
mus_musculus	Krtap4-2	ENSMUSG00000044649
mus_musculus	Krtap4-13	ENSMUSG00000048294
mus_musculus	Krtap4-1	ENSMUSG00000063251
mus_musculus	Krtap4-25	ENSMUSG00000069718
mus_musculus	Krtap4-6	ENSMUSG00000075566
mus_musculus	Krtap4-26	ENSMUSG00000078258
mus_musculus	Krtap4-20	ENSMUSG00000078259
mus_musculus	Krtap4-21	ENSMUSG00000078260
mus_musculus	Krtap4-23	ENSMUSG00000078261
mus_musculus	Krtap4-9	ENSMUSG00000078262
mus_musculus	Krtap4-22	ENSMUSG00000078668
mus_musculus	Krtap4-8	ENSMUSG00000089724
rattus_norvegicus	AABR07030464.1	ENSRNOG00000012973
rattus_norvegicus	AC099183.3	ENSRNOG00000058172
rattus_norvegicus	LOC100909494	ENSRNOG00000065268
rattus_norvegicus		ENSRNOG00000068861
rattus_norvegicus		ENSRNOG00000081031

Paralogs (47): KRTAP4-4 (ENSG00000171396), KRTAP9-7 (ENSG00000180386), KRTAP5-5 (ENSG00000185940), KRTAP12-1 (ENSG00000187175), KRTAP9-8 (ENSG00000187272), KRTAP10-8 (ENSG00000187766), KRTAP10-6 (ENSG00000188155), KRTAP1-1 (ENSG00000188581), KRTAP10-12 (ENSG00000189169), KRTAP9-9 (ENSG00000198083), KRTAP4-6 (ENSG00000198090), KRTAP4-5 (ENSG00000198271), KRTAP4-1 (ENSG00000198443), KRTAP9-3 (ENSG00000204873), KRTAP4-8 (ENSG00000204880), KRTAP1-4 (ENSG00000204887), KRTAP12-3 (ENSG00000205439), KRTAP10-2 (ENSG00000205445), KRTAP5-6 (ENSG00000205864), KRTAP5-2 (ENSG00000205867), KRTAP16-1 (ENSG00000212657), KRTAP9-6 (ENSG00000212659), KRTAP4-11 (ENSG00000212721), KRTAP4-9 (ENSG00000212722), KRTAP2-3 (ENSG00000212724), KRTAP2-1 (ENSG00000212725), KRTAP10-3 (ENSG00000212935), KRTAP4-12 (ENSG00000213416), KRTAP2-4 (ENSG00000213417), KRTAP2-2 (ENSG00000214518), KRTAP10-4 (ENSG00000215454), KRTAP10-1 (ENSG00000215455), KRTAP10-9 (ENSG00000221837), KRTAP1-5 (ENSG00000221852), KRTAP10-10 (ENSG00000221859), KRTAP12-2 (ENSG00000221864), KRTAP1-3 (ENSG00000221880), KRTAP9-2 (ENSG00000239886), KRTAP9-1 (ENSG00000240542), KRTAP4-7 (ENSG00000240871)

Protein

Protein identifiers

Keratin-associated protein 4-3 — Q9BYR4 (reviewed: Q9BYR4)

Alternative names: Keratin-associated protein 4.3, Ultrahigh sulfur keratin-associated protein 4.3

All UniProt accessions (1): Q9BYR4

UniProt curated annotations — full annotation on UniProt →

Function. In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins.

Subunit / interactions. Interacts with hair keratins.

Tissue specificity. Expressed specifically in the middle/uper portions of the hair cortex. Not detected in the hair matrix or cuticle.

Polymorphism. Numerous size polymorphism are present in KRTAP4 gene family, which are mainly due to variations in the sequence encoding cysteine-rich repeat segments.

Similarity. Belongs to the KRTAP type 4 family.

RefSeq proteins (1): NP_149443* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002494	KAP	Family

Pfam: PF13885

UniProt features (34 total): repeat 28, sequence variant 4, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BYR4-F1	31.04	0.00

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-6805567	Keratinization
R-HSA-1266738	Developmental Biology

MSigDB gene sets: 27 (showing top): GOBP_MOLTING_CYCLE, GOCC_INTERMEDIATE_FILAMENT_CYTOSKELETON, GOCC_KERATIN_FILAMENT, GOCC_SUPRAMOLECULAR_COMPLEX, GOCC_POLYMERIC_CYTOSKELETAL_FIBER, REACTOME_KERATINIZATION, GOCC_SUPRAMOLECULAR_POLYMER, MIR3924, MIR4699_5P, MIR3928_3P, MIR10B_3P, MIR6826_5P, MIR943, NIKOLSKY_BREAST_CANCER_17Q11_Q21_AMPLICON, GSE17721_PAM3CSK4_VS_CPG_6H_BMDC_DN

GO Biological Process (1): hair cycle (GO:0042633)

GO Molecular Function (0):

GO Cellular Component (3): cytosol (GO:0005829), keratin filament (GO:0045095), intermediate filament (GO:0005882)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
molting cycle	1
cytoplasm	1
cellular anatomical structure	1
intermediate filament	1
intermediate filament cytoskeleton	1
polymeric cytoskeletal fiber	1

Protein interactions and networks

STRING

292 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KRTAP4-3	KRTAP5-11	Q6L8G4	600
KRTAP4-3	A8MUN0	A8MUN0	598
KRTAP4-3	KRTAP6-1	Q3LI64	576
KRTAP4-3	KRTAP3-1	Q9BYR8	570
KRTAP4-3	KRTAP3-2	Q9BYR7	541
KRTAP4-3	A0A3B3IRQ3	A0A3B3IRQ3	540
KRTAP4-3	KRTAP22-1	Q3MIV0	511
KRTAP4-3	KRTAP13-3	Q3SY46	493
KRTAP4-3	KRTAP6-3	Q3LI67	480
KRTAP4-3	KRTAP3-3	Q9BYR6	480
KRTAP4-3	KRTAP6-2	Q3LI66	479
KRTAP4-3	KRTAP24-1	Q3LI83	476
KRTAP4-3	KRT27	Q7Z3Y8	475
KRTAP4-3	SLC35G6	P0C7Q6	447
KRTAP4-3	FRG2B	Q96QU4	447
KRTAP4-3	KRTAP2-2	Q9BYT5	447

IntAct

2 interactions, top by confidence:

A	B	Type	Score
FHIP1A	ILVBL	psi-mi:“MI:2364”(proximity)	0.270

ESM2 similar proteins: A0A286YEV6, A0A286YEX9, A0A286YEY9, A0A286YF01, A0A286YF46, A0A286YF60, A0A286YF77, A0A286YFB4, A0A286YFG1, O14633, P02438, P04459, P05687, P05688, P08131, P08175, P0DSO2, P20730, Q01642, Q01643, Q01644, Q01645, Q07627, Q3LI58, Q3LI59, Q3V2C1, Q5T750, Q5T752, Q5T754, Q5TA78, Q5TA79, Q5TA81, Q5TA82, Q5TCM9, Q8IUC1, Q8IUG1, Q9BQ66, Q9BYP8, Q9BYQ5, Q9BYQ6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	31
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

134 predictions. Top by Δscore:

Variant	Effect	Δscore
17:41167447:A:AC	donor_gain	0.6900
17:41167448:C:CC	donor_gain	0.6900
17:41167462:T:A	donor_gain	0.5800
17:41167477:G:A	donor_gain	0.5600
17:41167444:CATA:C	donor_gain	0.5400
17:41167448:CTA:C	donor_gain	0.5400
17:41167448:CTAAT:C	donor_gain	0.5400
17:41167445:ATAC:A	donor_loss	0.5300
17:41167446:TACT:T	donor_loss	0.5300
17:41167447:A:T	donor_loss	0.5300
17:41167448:C:CA	donor_loss	0.5300
17:41167884:T:TA	donor_gain	0.5100
17:41167588:G:C	donor_gain	0.4900
17:41167448:CT:C	donor_gain	0.4800
17:41167280:A:C	acceptor_gain	0.4600
17:41167974:T:TA	donor_gain	0.4600
17:41167448:CTAA:C	donor_gain	0.4400
17:41167532:G:A	donor_gain	0.4300
17:41167458:ATTTT:A	donor_gain	0.4200
17:41167774:G:C	donor_gain	0.3900
17:41167527:TCTG:T	donor_gain	0.3800
17:41167587:A:AC	donor_gain	0.3800
17:41167587:AG:A	donor_gain	0.3800
17:41167277:CACA:C	acceptor_gain	0.3700
17:41167587:AGCAG:A	donor_gain	0.3600
17:41167939:A:C	donor_gain	0.3600
17:41168023:G:GT	acceptor_gain	0.3600
17:41168064:T:TA	donor_gain	0.3600
17:41167253:T:TC	acceptor_gain	0.3500
17:41167581:T:TA	donor_gain	0.3500

AlphaMissense

1318 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:41167939:A:C	S78R	0.921
17:41167939:A:T	S78R	0.921
17:41167941:T:G	S78R	0.921
17:41167999:G:C	S58R	0.898
17:41167999:G:T	S58R	0.898
17:41168001:T:G	S58R	0.898
17:41167849:A:C	S108R	0.890
17:41167849:A:T	S108R	0.890
17:41167851:T:G	S108R	0.890
17:41167909:G:C	S88R	0.880
17:41167909:G:T	S88R	0.880
17:41167911:T:G	S88R	0.880
17:41168029:A:C	S48R	0.862
17:41168029:A:T	S48R	0.862
17:41168031:T:G	S48R	0.862
17:41167819:G:C	S118R	0.857
17:41167819:G:T	S118R	0.857
17:41167821:T:G	S118R	0.857
17:41167948:G:C	C75W	0.821
17:41167918:A:C	C85W	0.819
17:41168008:A:C	C55W	0.811
17:41167858:G:C	C105W	0.797
17:41167954:G:C	S73R	0.794
17:41167954:G:T	S73R	0.794
17:41167956:T:G	S73R	0.794
17:41168011:G:C	C54W	0.791
17:41167923:A:G	C84R	0.788
17:41168013:A:G	C54R	0.786
17:41168038:G:C	C45W	0.783
17:41167951:G:C	C74W	0.781

dbSNP variants (sampled 300 via entrez): RS1000517607 (17:41169708 A>G), RS1001255974 (17:41166997 C>G,T), RS1001372201 (17:41167260 G>T), RS1002971113 (17:41169613 A>C), RS1003376166 (17:41168123 T>G), RS1003434054 (17:41169347 C>T), RS1003881453 (17:41167960 G>A), RS1005335376 (17:41169253 C>T), RS1005488682 (17:41169419 G>A,C), RS1005585492 (17:41168163 A>C), RS1007894691 (17:41167077 G>A), RS1009167284 (17:41167308 G>A), RS1009729599 (17:41167279 C>T), RS1010013946 (17:41167316 C>T), RS1010741048 (17:41168744 T>C)

Disease associations

OMIM: gene `` | 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

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	increases methylation	1
Lead	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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