KRTAP4-6

Summary

KRTAP4-6 (keratin associated protein 4-6, HGNC:18909) is a protein-coding gene on chromosome 17q21.2, encoding Keratin-associated protein 4-6 (Q9BYQ5). 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….

Predicted to be located in cytosol.

Source: NCBI Gene 81871 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 63 total
• MANE Select transcript: NM_030976

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18909
Approved symbol	KRTAP4-6
Name	keratin associated protein 4-6
Location	17q21.2
Locus type	gene with protein product
Status	Approved
Aliases	KAP4.6, KAP4.15
Ensembl gene	ENSG00000198090
Ensembl biotype	protein_coding
Entrez	81871

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000345847

RefSeq mRNA: 1 — MANE Select: NM_030976 NM_030976

CCDS: CCDS54125

Canonical transcript exons

ENST00000345847 — 1 exons

Exon	Start	End
ENSE00003978143	41139433	41140544

Expression profiles

Bgee: expression breadth broad, 25 present calls, max score 82.74.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0556 / max 47.4965, expressed in 10 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165876	0.0556	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper arm skin	UBERON:0004263	82.74	silver quality
pancreatic ductal cell	CL:0002079	72.80	silver quality
kidney epithelium	UBERON:0004819	67.47	gold quality
ileal mucosa	UBERON:0000331	66.22	silver quality
tibialis anterior	UBERON:0001385	65.48	silver quality
upper leg skin	UBERON:0004262	57.08	silver quality
deltoid	UBERON:0001476	57.05	gold quality
epithelial cell of pancreas	CL:0000083	56.20	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	54.09	gold quality
skin of hip	UBERON:0001554	52.83	silver quality
myocardium	UBERON:0002349	50.25	gold quality
quadriceps femoris	UBERON:0001377	48.00	gold quality
nasal cavity epithelium	UBERON:0005384	47.03	gold quality
lateral nuclear group of thalamus	UBERON:0002736	46.14	gold quality
sural nerve	UBERON:0015488	45.46	gold quality
vastus lateralis	UBERON:0001379	45.40	gold quality
cardia of stomach	UBERON:0001162	45.24	gold quality
ventral tegmental area	UBERON:0002691	43.70	gold quality
layer of synovial tissue	UBERON:0007616	43.55	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
buccal mucosa cell	CL:0002336	43.27	gold quality
penis	UBERON:0000989	43.26	gold quality
amniotic fluid	UBERON:0000173	42.77	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
pylorus	UBERON:0001166	42.56	gold quality
dorsal plus ventral thalamus	UBERON:0001897	42.44	gold quality
skeletal muscle tissue	UBERON:0001134	42.29	gold quality
right lung	UBERON:0002167	42.20	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.98

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

55 targeting KRTAP4-6, 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-6740-5P	100.00	65.64	932
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-3913-5P	99.78	67.26	968
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-4527	99.66	67.43	714
HSA-MIR-6503-5P	99.62	66.96	597
HSA-MIR-4762-5P	99.57	68.54	1424
HSA-MIR-7159-3P	99.51	70.17	1920
HSA-MIR-3122	99.50	66.33	821
HSA-MIR-4677-3P	99.49	67.91	1246
HSA-MIR-3182	99.40	68.15	2454

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
mus_musculus	Krtap4-7	ENSMUSG00000045109
mus_musculus	Krtap4-24	ENSMUSG00000078130
rattus_norvegicus	Krtap9-7	ENSRNOG00000026803
rattus_norvegicus		ENSRNOG00000077385
rattus_norvegicus		ENSRNOG00000080465

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), KRTAP4-3 (ENSG00000196156), KRTAP9-9 (ENSG00000198083), 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 4-6 — Q9BYQ5 (reviewed: Q9BYQ5)

Alternative names: Keratin-associated protein 4-15, Keratin-associated protein 4.15, Keratin-associated protein 4.6, Ultrahigh sulfur keratin-associated protein 4.15

All UniProt accessions (1): Q9BYQ5

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 in the hair follicles.

Polymorphism. Numerous size polymorphism are present in KRTAP4 gene family, which are mainly due to variations in the sequence encoding cysteine-rich repeat segments. Allele shown is KAP4.15.

Similarity. Belongs to the KRTAP type 4 family.

RefSeq proteins (1): NP_112238* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002494	KAP	Family

Pfam: PF13885

UniProt features (32 total): repeat 30, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BYQ5-F1	36.11	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: 31 (showing top): GOCC_INTERMEDIATE_FILAMENT_CYTOSKELETON, GOCC_KERATIN_FILAMENT, GOCC_SUPRAMOLECULAR_COMPLEX, GOCC_POLYMERIC_CYTOSKELETAL_FIBER, REACTOME_KERATINIZATION, GOCC_SUPRAMOLECULAR_POLYMER, MIR15A_5P, MIR195_5P, MIR15B_5P, MIR16_5P, MIR6838_5P, MIR424_5P, MIR497_5P, MIR3686, MIR6761_5P

GO Biological Process (0):

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
cytoplasm	1
cellular anatomical structure	1
intermediate filament	1
intermediate filament cytoskeleton	1
polymeric cytoskeletal fiber	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

0 interactions, top by confidence:

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	62
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

242 predictions. Top by Δscore:

Variant	Effect	Δscore
17:41140236:G:C	donor_gain	0.8300
17:41140259:T:TA	donor_gain	0.8200
17:41140199:A:AC	donor_gain	0.7100
17:41140200:C:CC	donor_gain	0.7100
17:41140149:G:C	donor_gain	0.6500
17:41140331:A:AC	donor_gain	0.6300
17:41140332:C:CC	donor_gain	0.6300
17:41140363:A:T	donor_gain	0.6300
17:41140224:G:C	donor_gain	0.6000
17:41140226:TGGA:T	donor_gain	0.5900
17:41140196:CAGA:C	donor_gain	0.5800
17:41140121:TGGAC:T	donor_gain	0.5700
17:41139492:CATTG:C	acceptor_gain	0.5500
17:41140391:T:TA	donor_gain	0.5500
17:41139497:C:CC	acceptor_gain	0.5400
17:41139873:G:C	donor_gain	0.5400
17:41139957:TCGGC:T	donor_gain	0.5300
17:41139958:CGGCC:C	donor_gain	0.5300
17:41139835:AGCTG:A	acceptor_gain	0.5200
17:41139495:TG:T	acceptor_gain	0.5100
17:41139735:ATAT:A	donor_gain	0.5100
17:41140014:G:C	donor_gain	0.5100
17:41140164:G:C	donor_gain	0.5100
17:41139494:TTG:T	acceptor_gain	0.5000
17:41139496:GC:G	acceptor_loss	0.4900
17:41139498:T:A	acceptor_loss	0.4900
17:41139836:GCTGA:G	acceptor_gain	0.4900
17:41139966:G:T	donor_gain	0.4900
17:41140059:G:C	donor_gain	0.4900
17:41140104:CTG:C	donor_gain	0.4900

AlphaMissense

1351 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:41140400:A:G	C30R	0.778
17:41140479:G:C	S3R	0.778
17:41140479:G:T	S3R	0.778
17:41140481:T:G	S3R	0.778
17:41140356:G:C	S44R	0.761
17:41140356:G:T	S44R	0.761
17:41140358:T:G	S44R	0.761
17:41140472:A:G	C6R	0.740
17:41139921:A:C	C189W	0.739
17:41140397:A:G	C31R	0.738
17:41139938:A:G	C184R	0.733
17:41139923:A:G	C189R	0.723
17:41140398:G:C	C30W	0.722
17:41140370:A:G	C40R	0.717
17:41140390:G:A	T33I	0.717
17:41140385:A:G	C35R	0.714
17:41140383:G:C	C35W	0.713
17:41139936:G:C	C184W	0.705
17:41140368:G:C	C40W	0.700
17:41139916:A:G	I191T	0.689
17:41139950:A:G	C180R	0.687
17:41140224:G:C	S88R	0.681
17:41140224:G:T	S88R	0.681
17:41140226:T:G	S88R	0.681
17:41140460:A:G	C10R	0.674
17:41140470:A:C	C6W	0.671
17:41140475:A:G	C5R	0.669
17:41140413:G:C	C25W	0.668
17:41140392:C:A	R32S	0.666
17:41140392:C:G	R32S	0.666

dbSNP variants (sampled 300 via entrez): RS1000814468 (17:41139108 G>A), RS1001352617 (17:41141013 C>T), RS1002537611 (17:41140611 T>A), RS1002650342 (17:41141121 T>C), RS1004440012 (17:41139729 G>A), RS1004721773 (17:41141065 C>G,T), RS1006435152 (17:41142347 G>A,C), RS1006898400 (17:41142149 G>A,T), RS1008569816 (17:41140935 A>G,T), RS1009695267 (17:41139164 T>C), RS1010439616 (17:41139181 C>T), RS1011860588 (17:41140565 T>C), RS1014658524 (17:41139131 C>T), RS1016405721 (17:41141928 C>G), RS1017255897 (17:41139454 G>A,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

2 total (human), top 2 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cadmium	decreases expression, increases abundance	1
Cadmium Chloride	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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