KRTAP4-5

Summary

KRTAP4-5 (keratin associated protein 4-5, HGNC:18899) is a protein-coding gene on chromosome 17q21.2, encoding Keratin-associated protein 4-5 (Q9BYR2). 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….

This protein is a member of the keratin-associated protein (KAP) family. The KAP proteins form a matrix of keratin intermediate filaments which contribute to the structure of hair fibers. KAP family members appear to have unique, family-specific amino- and carboxyl-terminal regions and are subdivided into three multi-gene families according to amino acid composition: the high sulfur, the ultrahigh sulfur, and the high tyrosine/glycine KAPs. This protein is a member of the ultrahigh sulfur KAP family and the gene is localized to a cluster of KAPs at 17q12-q21.

Source: NCBI Gene 85289 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 34 total
• MANE Select transcript: NM_033188

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18899
Approved symbol	KRTAP4-5
Name	keratin associated protein 4-5
Location	17q21.2
Locus type	gene with protein product
Status	Approved
Aliases	KAP4.5
Ensembl gene	ENSG00000198271
Ensembl biotype	protein_coding
Entrez	85289

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000343246

RefSeq mRNA: 1 — MANE Select: NM_033188 NM_033188

CCDS: CCDS32650

Canonical transcript exons

ENST00000343246 — 1 exons

Exon	Start	End
ENSE00001420899	41148924	41149825

Expression profiles

Bgee: expression breadth broad, 19 present calls, max score 87.21.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0124 / max 19.5680, expressed in 2 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165877	0.0124	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper arm skin	UBERON:0004263	87.21	silver quality
tibialis anterior	UBERON:0001385	80.33	silver quality
kidney epithelium	UBERON:0004819	77.37	gold quality
sperm	CL:0000019	76.97	gold quality
ileal mucosa	UBERON:0000331	76.53	silver quality
nasal cavity epithelium	UBERON:0005384	76.40	gold quality
pancreatic ductal cell	CL:0002079	74.55	silver quality
epithelial cell of pancreas	CL:0000083	74.19	gold quality
vena cava	UBERON:0004087	71.33	gold quality
mucosa of paranasal sinus	UBERON:0005030	68.78	gold quality
deltoid	UBERON:0001476	68.33	gold quality
inferior vagus X ganglion	UBERON:0005363	68.26	gold quality
cardia of stomach	UBERON:0001162	67.64	gold quality
superior surface of tongue	UBERON:0007371	67.42	gold quality
pericardium	UBERON:0002407	67.25	gold quality
cerebellar vermis	UBERON:0004720	67.05	gold quality
trachea	UBERON:0003126	67.03	gold quality
superior vestibular nucleus	UBERON:0007227	67.01	gold quality
substantia nigra pars reticulata	UBERON:0001966	66.97	gold quality
pharyngeal mucosa	UBERON:0000355	66.93	gold quality
nipple	UBERON:0002030	66.92	silver quality
pons	UBERON:0000988	66.82	gold quality
lateral globus pallidus	UBERON:0002476	66.82	gold quality
substantia nigra pars compacta	UBERON:0001965	66.76	gold quality
trigeminal ganglion	UBERON:0001675	66.63	gold quality
layer of synovial tissue	UBERON:0007616	66.63	gold quality
lateral nuclear group of thalamus	UBERON:0002736	66.61	gold quality
dorsal root ganglion	UBERON:0000044	66.49	gold quality
renal medulla	UBERON:0000362	65.95	gold quality
epithelium of nasopharynx	UBERON:0001951	65.60	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.99

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

37 targeting KRTAP4-5, 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-656-3P	100.00	72.15	2788
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
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-4255	99.72	67.70	1541
HSA-MIR-3685	99.62	68.83	1621
HSA-MIR-425-5P	99.59	67.67	900
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4687-3P	99.48	66.41	968
HSA-MIR-16-2-3P	99.29	70.60	1954
HSA-MIR-195-3P	99.29	70.61	1954
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-3160-3P	99.07	64.78	955
HSA-MIR-3127-3P	98.94	67.34	1055
HSA-MIR-6756-3P	98.94	66.79	1104
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-384	98.71	67.34	1229

Cross-species orthologs

36 orthologs

Organism	Symbol	Gene ID
mus_musculus	Krtap5-2	ENSMUSG00000054759
mus_musculus	Krtap5-20	ENSMUSG00000056885
mus_musculus	Krtap10-4	ENSMUSG00000069582
mus_musculus	Krtap12-1	ENSMUSG00000069583
mus_musculus	Krtap12-23	ENSMUSG00000069584
mus_musculus	Krtap10-31	ENSMUSG00000071195
mus_musculus	Krtap12-22	ENSMUSG00000094012
mus_musculus	Krtap10-21	ENSMUSG00000094120
mus_musculus	Krtap12-21	ENSMUSG00000094146
mus_musculus	Krtap10-27	ENSMUSG00000094913
mus_musculus	Krtap10-26	ENSMUSG00000095593
mus_musculus	Krtap10-25	ENSMUSG00000095721
mus_musculus	Krtap10-22	ENSMUSG00000095817
mus_musculus	Krtap10-33	ENSMUSG00000095970
mus_musculus	Krtap10-29	ENSMUSG00000096131
mus_musculus	Krtap10-34	ENSMUSG00000096380
mus_musculus	Krtap12-20	ENSMUSG00000096421
mus_musculus	Krtap10-23	ENSMUSG00000096481
mus_musculus	Krtap5-26	ENSMUSG00000109859
mus_musculus	Krtap5-24	ENSMUSG00000110324
mus_musculus	Krtap10-24	ENSMUSG00000111915
mus_musculus	Krtap10-28	ENSMUSG00000112170
mus_musculus	Krtap10-10	ENSMUSG00000112223
mus_musculus	Krtap10-30	ENSMUSG00000112380
mus_musculus	Gm49918	ENSMUSG00000112600
mus_musculus	Krtap10-35	ENSMUSG00000112653
mus_musculus	Krtap10-32	ENSMUSG00000112864
rattus_norvegicus	Krtap10-8l1	ENSRNOG00000001218
rattus_norvegicus	Krtap5-8	ENSRNOG00000020131
rattus_norvegicus	Krtap10-10	ENSRNOG00000032530
rattus_norvegicus	Krtap10-9	ENSRNOG00000043302
rattus_norvegicus	Krtap10-1l1	ENSRNOG00000046538
rattus_norvegicus	AABR07006049.1	ENSRNOG00000046649
rattus_norvegicus	Krtap10-1	ENSRNOG00000047532
rattus_norvegicus	LOC120098854	ENSRNOG00000067436
rattus_norvegicus	Krtap10-10l2	ENSRNOG00000069553

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), KRTAP4-6 (ENSG00000198090), 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 4-5 — Q9BYR2 (reviewed: Q9BYR2)

Alternative names: Keratin-associated protein 4.5, Ultrahigh sulfur keratin-associated protein 4.5

All UniProt accessions (1): Q9BYR2

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 KAP4.5-v1.

Similarity. Belongs to the KRTAP type 4 family.

RefSeq proteins (1): NP_149445* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002494	KAP	Family

Pfam: PF13885

UniProt features (33 total): repeat 26, sequence variant 5, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BYR2-F1	35.75	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: 23 (showing top): MARTINEZ_RB1_TARGETS_DN, GOBP_MOLTING_CYCLE, GOCC_INTERMEDIATE_FILAMENT_CYTOSKELETON, GOCC_KERATIN_FILAMENT, GOCC_SUPRAMOLECULAR_COMPLEX, GOCC_POLYMERIC_CYTOSKELETAL_FIBER, REACTOME_KERATINIZATION, GOCC_SUPRAMOLECULAR_POLYMER, HMGA1_TARGET_GENES, MIR570_3P, MIR1207_5P, MIR195_3P, MIR16_2_3P, MIR4763_3P, MIR4687_3P

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

GO Molecular Function (1): protein binding (GO:0005515)

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

Protein interactions and networks

STRING

270 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KRTAP4-5	GOLGA8B	A8MQT2	603
KRTAP4-5	TMPRSS13	Q9BYE2	543
KRTAP4-5	GOLGA8A	A7E2F4	445
KRTAP4-5	ERICH6B	Q5W0A0	434
KRTAP4-5	ZNF772	Q68DY9	434
KRTAP4-5	OR2T35	Q8NGX2	417
KRTAP4-5	KRTAP17-1	Q9BYP8	398
KRTAP4-5	OR1E1	P30953	395
KRTAP4-5	CT47B1	P0C2W7	394
KRTAP4-5	KRTAP3-3	Q9BYR6	354
KRTAP4-5	KRTAP5-11	Q6L8G4	350
KRTAP4-5	LURAP1L	Q8IV03	348
KRTAP4-5	KRTAP2-3	P0C7H8	348
KRTAP4-5	C9JR48	C9JR48	339
KRTAP4-5	KRT38	O76015	323

IntAct

216 interactions, top by confidence:

A	B	Type	Score
LCE2C	KRTAP4-5	psi-mi:“MI:0915”(physical association)	0.600
LCE3C	KRTAP4-5	psi-mi:“MI:0915”(physical association)	0.600
KRTAP4-5	POTEB3	psi-mi:“MI:0915”(physical association)	0.560
KRTAP4-5	RORB	psi-mi:“MI:0915”(physical association)	0.560
GLRX3	KRTAP4-5	psi-mi:“MI:0915”(physical association)	0.560
LCE3B	KRTAP4-5	psi-mi:“MI:0915”(physical association)	0.560
NUFIP2	KRTAP4-5	psi-mi:“MI:0915”(physical association)	0.560
NOTCH2NLC	KRTAP4-5	psi-mi:“MI:0915”(physical association)	0.560
LCE1F	KRTAP4-5	psi-mi:“MI:0915”(physical association)	0.560
KRTAP5-2	KRTAP4-5	psi-mi:“MI:0915”(physical association)	0.560
KRTAP1-1	KRTAP4-5	psi-mi:“MI:0915”(physical association)	0.560
SMCP	KRTAP4-5	psi-mi:“MI:0915”(physical association)	0.560
KRTAP5-9	KRTAP4-5	psi-mi:“MI:0915”(physical association)	0.560
KRTAP4-5	ZNF552	psi-mi:“MI:0915”(physical association)	0.560
KRTAP4-5	AXIN2	psi-mi:“MI:0915”(physical association)	0.560
KPRP	KRTAP4-5	psi-mi:“MI:0915”(physical association)	0.560
TRIM42	KRTAP4-5	psi-mi:“MI:0915”(physical association)	0.560
KRTAP9-3	KRTAP4-5	psi-mi:“MI:0915”(physical association)	0.560
HOXA1	KRTAP4-5	psi-mi:“MI:0915”(physical association)	0.560
KRTAP4-5	KRTAP4-4	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-7	KRTAP4-5	psi-mi:“MI:0915”(physical association)	0.560
KRTAP4-5	ZNF835	psi-mi:“MI:0915”(physical association)	0.560
KRTAP1-3	KRTAP4-5	psi-mi:“MI:0915”(physical association)	0.560
LCE1C	KRTAP4-5	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-6	KRTAP4-5	psi-mi:“MI:0915”(physical association)	0.560
LCE1B	KRTAP4-5	psi-mi:“MI:0915”(physical association)	0.560
GATA1	KRTAP4-5	psi-mi:“MI:0915”(physical association)	0.560
ZNF837	KRTAP4-5	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (76): KRTAP4-5 (Two-hybrid), KRTAP4-5 (Two-hybrid), KRTAP4-5 (Two-hybrid), KRTAP4-5 (Two-hybrid), KRTAP4-5 (Two-hybrid), KRTAP4-5 (Two-hybrid), KRTAP4-5 (Two-hybrid), KRTAP4-5 (Two-hybrid), KRTAP4-5 (Two-hybrid), KRTAP4-5 (Two-hybrid), KRTAP4-5 (Two-hybrid), KRTAP4-5 (Two-hybrid), KRTAP4-5 (Two-hybrid), KRTAP4-5 (Two-hybrid), KRTAP4-5 (Two-hybrid)

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.

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
Keratinization	30	38.0×	4e-41
Formation of the cornified envelope	17	33.9×	5e-21

GO biological processes:

GO term	Partners	Fold	FDR
keratinization	17	84.7×	4e-27

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	28
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

159 predictions. Top by Δscore:

Variant	Effect	Δscore
17:41149626:A:AC	donor_gain	0.7100
17:41149627:C:CC	donor_gain	0.7100
17:41149671:T:TA	donor_gain	0.6600
17:41149506:T:TA	donor_gain	0.6400
17:41149491:T:TA	donor_gain	0.6200
17:41149471:G:C	donor_gain	0.6000
17:41149552:T:C	donor_gain	0.5700
17:41149076:T:A	donor_gain	0.5500
17:41149328:A:AC	donor_gain	0.5300
17:41149329:C:CC	donor_gain	0.5300
17:41149623:CAGA:C	donor_gain	0.5200
17:41149381:G:C	donor_gain	0.5100
17:41148950:A:C	acceptor_gain	0.4900
17:41149329:CGCAG:C	donor_gain	0.4900
17:41149329:CG:C	donor_gain	0.4800
17:41149635:A:AC	donor_gain	0.4800
17:41149636:C:CC	donor_gain	0.4800
17:41149013:T:C	donor_gain	0.4700
17:41149351:G:C	donor_gain	0.4700
17:41149617:A:AC	donor_gain	0.4700
17:41149762:G:T	donor_gain	0.4700
17:41149468:G:C	donor_gain	0.4600
17:41149645:G:A	donor_gain	0.4600
17:41149225:G:C	donor_gain	0.4500
17:41149208:A:AC	donor_gain	0.4400
17:41149396:G:C	donor_gain	0.4400
17:41149440:A:AC	donor_gain	0.4400
17:41149441:C:CC	donor_gain	0.4400
17:41149615:G:T	acceptor_gain	0.4400
17:41149456:G:C	donor_gain	0.4300

AlphaMissense

1197 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:41149576:G:C	S64R	0.631
17:41149576:G:T	S64R	0.631
17:41149578:T:G	S64R	0.631
17:41149381:G:C	S129R	0.620
17:41149381:G:T	S129R	0.620
17:41149383:T:G	S129R	0.620
17:41149273:A:C	C165W	0.601
17:41149456:G:C	S104R	0.591
17:41149456:G:T	S104R	0.591
17:41149458:T:G	S104R	0.591
17:41149288:G:C	C160W	0.574
17:41149275:A:G	C165R	0.572

dbSNP variants (sampled 300 via entrez): RS1001605779 (17:41150681 T>A,G), RS1001947988 (17:41149337 C>T), RS1002008136 (17:41150258 A>T), RS1002125988 (17:41150584 A>T), RS1002608876 (17:41151810 G>A,T), RS1004129433 (17:41150027 A>G,T), RS1004580657 (17:41151433 C>A), RS1006213648 (17:41151233 C>T), RS1007646855 (17:41149046 A>G,T), RS1008467775 (17:41151000 C>T), RS1008597410 (17:41150948 T>G), RS1008651164 (17:41150337 T>C), RS1008711877 (17:41151179 A>G), RS1008831481 (17:41151202 A>T), RS1009369515 (17:41149705 G>A)

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
Plant Extracts	affects cotreatment, decreases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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