KRTAP1-5

Summary

KRTAP1-5 (keratin associated protein 1-5, HGNC:16777) is a protein-coding gene on chromosome 17q21.2, encoding Keratin-associated protein 1-5 (Q9BYS1). 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 high sulfur KAP family and the gene is localized to a cluster of KAPs at 17q12-q21.

Source: NCBI Gene 83895 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 48 total
• MANE Select transcript: NM_031957

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16777
Approved symbol	KRTAP1-5
Name	keratin associated protein 1-5
Location	17q21.2
Locus type	gene with protein product
Status	Approved
Aliases	KAP1.5
Ensembl gene	ENSG00000221852
Ensembl biotype	protein_coding
OMIM	608822
Entrez	83895

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000361883

RefSeq mRNA: 1 — MANE Select: NM_031957 NM_031957

CCDS: CCDS42321

Canonical transcript exons

ENST00000361883 — 1 exons

Exon	Start	End
ENSE00001475002	41026026	41027208

Expression profiles

Bgee: expression breadth broad, 57 present calls, max score 90.18.

FANTOM5 (CAGE): breadth broad, TPM avg 4.7064 / max 636.3669, expressed in 344 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165865	4.7064	344

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.18	gold quality
stromal cell of endometrium	CL:0002255	71.02	gold quality
endocervix	UBERON:0000458	53.15	gold quality
ectocervix	UBERON:0012249	52.48	gold quality
uterine cervix	UBERON:0000002	51.33	gold quality
skin of abdomen	UBERON:0001416	50.27	gold quality
colonic epithelium	UBERON:0000397	49.57	gold quality
zone of skin	UBERON:0000014	49.05	gold quality
skin of leg	UBERON:0001511	48.55	gold quality
vagina	UBERON:0000996	45.55	gold quality
right lung	UBERON:0002167	41.09	gold quality
subcutaneous adipose tissue	UBERON:0002190	38.54	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
mucosa of transverse colon	UBERON:0004991	35.79	gold quality
mucosa of stomach	UBERON:0001199	35.62	silver quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
placenta	UBERON:0001987	35.45	silver quality
tibial artery	UBERON:0007610	34.58	gold quality
popliteal artery	UBERON:0002250	34.53	gold quality
prostate gland	UBERON:0002367	34.35	gold quality
smooth muscle tissue	UBERON:0001135	33.62	gold quality
adipose tissue	UBERON:0001013	33.49	gold quality
muscle tissue	UBERON:0002385	33.47	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
myometrium	UBERON:0001296	33.19	gold quality
adult mammalian kidney	UBERON:0000082	32.99	silver quality
gall bladder	UBERON:0002110	32.26	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.50

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

58 targeting KRTAP1-5, 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-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-2115-3P	99.31	69.68	2026
HSA-MIR-3614-5P	99.30	65.25	837
HSA-MIR-410-3P	99.27	69.98	2457

Literature-anchored findings (GeneRIF, showing 1)

• no polymorphic alleles were found for the hKAP1.4 and hKAP1.5 genes in Japanese and Caucasian individuals (PMID:12228244)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Krtap1-5	ENSMUSG00000047253
rattus_norvegicus	Krtap1-5	ENSRNOG00000084854

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), KRTAP4-5 (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), KRTAP10-10 (ENSG00000221859), KRTAP12-2 (ENSG00000221864), KRTAP1-3 (ENSG00000221880), KRTAP9-2 (ENSG00000239886), KRTAP9-1 (ENSG00000240542), KRTAP4-7 (ENSG00000240871)

Protein

Protein identifiers

Keratin-associated protein 1-5 — Q9BYS1 (reviewed: Q9BYS1)

Alternative names: High sulfur keratin-associated protein 1.5, Keratin-associated protein 1.5

All UniProt accessions (1): Q9BYS1

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 middle/upper portions of the hair cortex, in the region termed the keratogenous zone.

Similarity. Belongs to the KRTAP type 1 family.

RefSeq proteins (1): NP_114163* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002494	KAP	Family

Pfam: PF01500

UniProt features (2 total): chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BYS1-F1	39.52	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: 26 (showing top): RIGGI_EWING_SARCOMA_PROGENITOR_DN, GOCC_INTERMEDIATE_FILAMENT_CYTOSKELETON, GOCC_KERATIN_FILAMENT, YOSHIMURA_MAPK8_TARGETS_UP, CHICAS_RB1_TARGETS_CONFLUENT, MIYAGAWA_TARGETS_OF_EWSR1_ETS_FUSIONS_DN, GOCC_SUPRAMOLECULAR_COMPLEX, GOCC_POLYMERIC_CYTOSKELETAL_FIBER, REACTOME_KERATINIZATION, GOCC_SUPRAMOLECULAR_POLYMER, GSE14415_NATURAL_TREG_VS_FOXP3_KO_NATURAL_TREG_DN, GSE14386_UNTREATED_VS_IFNA_TREATED_ACT_PBMC_MS_PATIENT_UP, MIR4261, MIR5692B_MIR5692C, MIR4251

GO Biological Process (0):

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

Protein interactions and networks

STRING

302 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KRTAP1-5	KRTAP3-2	Q9BYR7	538
KRTAP1-5	A0A3B3IRQ3	A0A3B3IRQ3	506
KRTAP1-5	KRTAP3-1	Q9BYR8	484
KRTAP1-5	KRTAP9-4	Q9BYQ2	469
KRTAP1-5	KRTAP2-3	P0C7H8	446
KRTAP1-5	SLC35G6	P0C7Q6	419
KRTAP1-5	KRTAP17-1	Q9BYP8	409
KRTAP1-5	ZNF808	Q8N4W9	400
KRTAP1-5	KRTAP19-1	Q8IUB9	400
KRTAP1-5	KRT34	O76011	397
KRTAP1-5	KRTAP5-7	Q6L8G8	396
KRTAP1-5	LHFPL7	Q6ICI0	384
KRTAP1-5	KRTAP5-11	Q6L8G4	379
KRTAP1-5	KRT27	Q7Z3Y8	377
KRTAP1-5	KRTAP5-5	Q701N2	374

IntAct

130 interactions, top by confidence:

A	B	Type	Score
KRTAP1-5	LCE1D	psi-mi:“MI:0915”(physical association)	0.700
KRTAP1-5	OTX1	psi-mi:“MI:0915”(physical association)	0.700
LCE1D	KRTAP1-5	psi-mi:“MI:0915”(physical association)	0.700
OTX1	KRTAP1-5	psi-mi:“MI:0915”(physical association)	0.700
LCE3A	KRTAP1-5	psi-mi:“MI:0915”(physical association)	0.600
LCE1B	KRTAP1-5	psi-mi:“MI:0915”(physical association)	0.600
KRTAP1-5	LCE1B	psi-mi:“MI:0915”(physical association)	0.600
KRTAP1-5	LCE3A	psi-mi:“MI:0915”(physical association)	0.600
FADS6	KRTAP1-5	psi-mi:“MI:0915”(physical association)	0.560
KRTAP4-11	KRTAP1-5	psi-mi:“MI:0915”(physical association)	0.560
CREB5	KRTAP1-5	psi-mi:“MI:0915”(physical association)	0.560
NUFIP2	KRTAP1-5	psi-mi:“MI:0915”(physical association)	0.560
HOXB9	KRTAP1-5	psi-mi:“MI:0915”(physical association)	0.560
KPRP	KRTAP1-5	psi-mi:“MI:0915”(physical association)	0.560
KRTAP9-2	KRTAP1-5	psi-mi:“MI:0915”(physical association)	0.560
LCE2D	KRTAP1-5	psi-mi:“MI:0915”(physical association)	0.560
KRTAP4-4	KRTAP1-5	psi-mi:“MI:0915”(physical association)	0.560
KRTAP1-5	SHFL	psi-mi:“MI:0915”(physical association)	0.560
GRN	KRTAP1-5	psi-mi:“MI:0915”(physical association)	0.560
ADAMTSL4	KRTAP1-5	psi-mi:“MI:0915”(physical association)	0.560
KRTAP5-11	KRTAP1-5	psi-mi:“MI:0915”(physical association)	0.560
LCE1E	KRTAP1-5	psi-mi:“MI:0915”(physical association)	0.560
GUCD1	KRTAP1-5	psi-mi:“MI:0915”(physical association)	0.560
SDCBP	KRTAP1-5	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (49): LCE1D (Two-hybrid), OTX1 (Two-hybrid), KRTAP1-5 (Two-hybrid), KRTAP1-5 (Two-hybrid), KRTAP1-5 (Two-hybrid), KRTAP1-5 (Two-hybrid), KRTAP1-5 (Two-hybrid), KRTAP1-5 (Two-hybrid), KRTAP1-5 (Two-hybrid), KRTAP1-5 (Two-hybrid), KRTAP1-5 (Two-hybrid), KRTAP1-5 (Two-hybrid), KRTAP1-5 (Two-hybrid), KRTAP1-5 (Two-hybrid), KRTAP1-5 (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

Diamond homologs: P02438, P02439, P02440, P08131, P0C5Y4, Q07627, Q3V2C1, Q8IUG1, Q9BYS1

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 39 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	16	30.7×	2e-19
Formation of the cornified envelope	9	27.3×	4e-10

GO biological processes:

GO term	Partners	Fold	FDR
keratinization	9	63.8×	3e-12

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	41
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

319 predictions. Top by Δscore:

Variant	Effect	Δscore
17:41026470:T:TC	acceptor_gain	0.8300
17:41026468:CAT:C	acceptor_gain	0.8000
17:41026273:T:TC	acceptor_gain	0.7900
17:41026396:AT:A	donor_gain	0.7700
17:41026470:T:C	acceptor_gain	0.7700
17:41026273:T:C	acceptor_gain	0.7500
17:41026396:ATC:A	donor_gain	0.7400
17:41026398:C:A	donor_gain	0.7400
17:41026370:T:TA	donor_gain	0.7300
17:41026397:T:TA	donor_gain	0.7100
17:41026802:C:CT	donor_gain	0.7000
17:41026261:T:TC	acceptor_gain	0.6900
17:41026368:AAT:A	donor_gain	0.6900
17:41026803:C:CT	donor_gain	0.6900
17:41026286:A:C	acceptor_gain	0.6800
17:41026472:G:C	acceptor_gain	0.6700
17:41026271:T:TC	acceptor_gain	0.6500
17:41026272:T:C	acceptor_gain	0.6500
17:41026472:G:GC	acceptor_gain	0.6500
17:41026270:A:AC	acceptor_gain	0.6400
17:41026282:CAAGA:C	acceptor_gain	0.6300
17:41026394:ATAT:A	donor_gain	0.6200
17:41026397:T:C	donor_gain	0.5800
17:41026264:C:CT	acceptor_gain	0.5700
17:41026954:T:TA	donor_gain	0.5700
17:41026270:A:C	acceptor_gain	0.5600
17:41026271:T:C	acceptor_gain	0.5600
17:41027062:T:TA	donor_gain	0.5500
17:41026261:T:C	acceptor_gain	0.5400
17:41026265:A:T	acceptor_gain	0.5400

AlphaMissense

1160 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:41026802:C:A	W118C	0.853
17:41026802:C:G	W118C	0.853
17:41026804:A:G	W118R	0.845
17:41026804:A:T	W118R	0.845
17:41026679:A:C	C159W	0.813
17:41026729:A:G	C143R	0.812
17:41026680:C:G	C159S	0.810
17:41026681:A:T	C159S	0.810
17:41026727:G:C	C143W	0.802
17:41026694:G:C	C154W	0.795
17:41026724:G:C	C144W	0.789
17:41026726:A:G	C144R	0.789
17:41026725:C:G	C144S	0.786
17:41026726:A:T	C144S	0.786
17:41026696:A:G	C154R	0.781
17:41026681:A:G	C159R	0.770
17:41026684:A:C	Y158D	0.768
17:41026680:C:T	C159Y	0.766
17:41026695:C:G	C154S	0.766
17:41026696:A:T	C154S	0.766
17:41026745:G:C	S137R	0.761
17:41026745:G:T	S137R	0.761
17:41026747:T:G	S137R	0.761
17:41026664:G:C	C164W	0.760
17:41026666:A:G	C164R	0.747
17:41026652:G:C	C168W	0.741
17:41026654:A:G	C168R	0.741
17:41026649:G:C	C169W	0.733
17:41027024:G:C	F44L	0.730
17:41027024:G:T	F44L	0.730

dbSNP variants (sampled 300 via entrez): RS1000752837 (17:41028407 C>T), RS1002311197 (17:41028265 A>G), RS1002477294 (17:41027921 G>A), RS1003221303 (17:41026836 C>A,T), RS1004211538 (17:41027897 G>A), RS1004542832 (17:41029205 G>A), RS1004709342 (17:41027583 T>G), RS1006992553 (17:41027766 C>T), RS1007698002 (17:41028832 A>G), RS1008359665 (17:41027509 G>A,T), RS1008819530 (17:41028612 C>T), RS1008913396 (17:41027244 G>C,T), RS1009140730 (17:41028813 G>A), RS1009407457 (17:41028755 G>T), RS1009808533 (17:41028451 A>G)

Disease associations

OMIM: gene MIM:608822 | 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

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression	1
diallyl trisulfide	increases expression	1
pentanal	increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
incobotulinumtoxinA	decreases expression	1
Air Pollutants	increases abundance, decreases expression	1
Mercuric Chloride	affects cotreatment, decreases expression	1
Silicon Dioxide	increases expression	1
8-Bromo Cyclic Adenosine Monophosphate	decreases expression	1
Aflatoxin B1	decreases methylation	1
Copper Sulfate	increases expression	1
Particulate Matter	increases abundance, decreases expression	1

Clinical trials (associated diseases)

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