KRTAP5-6

Summary

KRTAP5-6 (keratin associated protein 5-6, HGNC:23600) is a protein-coding gene on chromosome 11p15.5, encoding Keratin-associated protein 5-6 (Q6L8G9). In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated protein (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linki….

Predicted to be located in cytosol.

Source: NCBI Gene 440023 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 20 total
• MANE Select transcript: NM_001012416

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23600
Approved symbol	KRTAP5-6
Name	keratin associated protein 5-6
Location	11p15.5
Locus type	gene with protein product
Status	Approved
Aliases	KRTAP5.6
Ensembl gene	ENSG00000205864
Ensembl biotype	protein_coding
Entrez	440023

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000382160

RefSeq mRNA: 1 — MANE Select: NM_001012416 NM_001012416

CCDS: CCDS31332

Canonical transcript exons

ENST00000382160 — 1 exons

Exon	Start	End
ENSE00001491080	1697195	1697755

Expression profiles

Bgee: expression breadth broad, 26 present calls, max score 75.27.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	75.27	gold quality
liver	UBERON:0002107	59.51	gold quality
placenta	UBERON:0001987	50.53	gold quality
stromal cell of endometrium	CL:0002255	42.17	silver quality
ventricular zone	UBERON:0003053	41.29	gold quality
sural nerve	UBERON:0015488	38.37	gold quality
ganglionic eminence	UBERON:0004023	37.70	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
gall bladder	UBERON:0002110	33.95	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	33.21	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
prefrontal cortex	UBERON:0000451	31.53	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
lymph node	UBERON:0000029	29.72	gold quality
skin of leg	UBERON:0001511	29.38	gold quality
skin of abdomen	UBERON:0001416	29.34	gold quality
zone of skin	UBERON:0000014	29.32	gold quality
frontal cortex	UBERON:0001870	28.99	gold quality
right lung	UBERON:0002167	28.94	silver quality
duodenum	UBERON:0002114	28.14	gold quality
cerebral cortex	UBERON:0000956	27.98	gold quality
islet of Langerhans	UBERON:0000006	27.61	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	27.50	gold quality
pancreas	UBERON:0001264	27.44	gold quality
kidney	UBERON:0002113	27.18	silver quality
tonsil	UBERON:0002372	27.05	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

10 targeting KRTAP5-6, 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-4648	99.91	67.00	710
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-363-5P	99.46	64.51	1015
HSA-MIR-3911	99.38	66.95	1087
HSA-MIR-4483	98.09	64.12	1642
HSA-MIR-3201	97.16	65.42	1044
HSA-MIR-4791	96.51	67.76	659
HSA-MIR-1293	96.16	64.69	916

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Krtap5-21	ENSMUSG00000073786
mus_musculus	Krtap5-25	ENSMUSG00000110061
mus_musculus	Krtap5-23	ENSMUSG00000110091

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), KRTAP5-2 (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 5-6 — Q6L8G9 (reviewed: Q6L8G9)

Alternative names: Keratin-associated protein 5.6, Ultrahigh sulfur keratin-associated protein 5.6

All UniProt accessions (1): Q6L8G9

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 protein (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 hair root and not in skin. Expressed also in liver and skeletal muscle.

Similarity. Belongs to the KRTAP type 5 family.

RefSeq proteins (1): NP_001012416* (*=MANE)

Domains & families (InterPro)

UniProt features (9 total): repeat 6, chain 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6L8G9-F1	45.89	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: 10 (showing top): GOCC_INTERMEDIATE_FILAMENT_CYTOSKELETON, GOCC_SUPRAMOLECULAR_COMPLEX, GOCC_POLYMERIC_CYTOSKELETAL_FIBER, REACTOME_KERATINIZATION, GOCC_SUPRAMOLECULAR_POLYMER, SNAPC4_TARGET_GENES, MIR4483, MIR1293, GSE32034_UNTREATED_VS_ROSIGLIZATONE_TREATED_LY6C_LOW_MONOCYTE_UP, chr11p15

GO Biological Process (0):

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

GO Cellular Component (2): cytosol (GO:0005829), 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 cytoskeleton	1
polymeric cytoskeletal fiber	1

Protein interactions and networks

STRING

220 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KRTAP5-6	KRTAP5-7	Q6L8G8	479
KRTAP5-6	PRSS27	Q9BQR3	474
KRTAP5-6	STAC3	Q96MF2	431
KRTAP5-6	KRTAP25-1	Q3LHN0	431
KRTAP5-6	GRINA	Q7Z429	407
KRTAP5-6	MOB2	Q70IA6	348
KRTAP5-6	KRTAP21-2	Q3LI59	322
KRTAP5-6	SYT8	Q8NBV8	322
KRTAP5-6	ZIM2	Q9NZV7	311
KRTAP5-6	SCYGR1	A0A286YEY9	305
KRTAP5-6	KRTAP20-1	Q3LI63	293
KRTAP5-6	TSPAN32	Q96QS1	290
KRTAP5-6	KRTAP22-1	Q3MIV0	290
KRTAP5-6	INS-IGF2	F8WCM5	290
KRTAP5-6	STARD10	Q9Y365	278
KRTAP5-6	KRTAP13-3	Q3SY46	278

IntAct

338 interactions, top by confidence:

A	B	Type	Score
GLRX3	KRTAP5-6	psi-mi:“MI:0915”(physical association)	0.780
KRTAP5-6	GLRX3	psi-mi:“MI:0915”(physical association)	0.780
KRTAP5-6	NUFIP2	psi-mi:“MI:0915”(physical association)	0.720
KRTAP5-6	RGS20	psi-mi:“MI:0915”(physical association)	0.720
KRTAP5-6	KRTAP5-9	psi-mi:“MI:0915”(physical association)	0.720
KRTAP5-6	OTX1	psi-mi:“MI:0915”(physical association)	0.720
HOXA1	KRTAP5-6	psi-mi:“MI:0915”(physical association)	0.720
SMCP	KRTAP5-6	psi-mi:“MI:0915”(physical association)	0.720
KRTAP10-7	KRTAP5-6	psi-mi:“MI:0915”(physical association)	0.720
KRTAP5-6	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.720
CREB5	KRTAP5-6	psi-mi:“MI:0915”(physical association)	0.720
KRTAP26-1	KRTAP5-6	psi-mi:“MI:0915”(physical association)	0.720
KRTAP5-6	CATSPER1	psi-mi:“MI:0915”(physical association)	0.720
KRTAP4-12	KRTAP5-6	psi-mi:“MI:0915”(physical association)	0.720
KRTAP5-6	KRTAP9-2	psi-mi:“MI:0915”(physical association)	0.720
KRTAP5-6	KRTAP4-2	psi-mi:“MI:0915”(physical association)	0.720
RGS20	KRTAP5-6	psi-mi:“MI:0915”(physical association)	0.720
KRTAP5-9	KRTAP5-6	psi-mi:“MI:0915”(physical association)	0.720
KRTAP5-6	KRTAP26-1	psi-mi:“MI:0915”(physical association)	0.720
CATSPER1	KRTAP5-6	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (115): KRTAP5-6 (Two-hybrid), KRTAP5-6 (Two-hybrid), KRTAP5-6 (Two-hybrid), KRTAP5-6 (Two-hybrid), KRTAP5-6 (Two-hybrid), KRTAP5-6 (Two-hybrid), KRTAP5-6 (Two-hybrid), KRTAP5-6 (Two-hybrid), KRTAP5-6 (Two-hybrid), KRTAP5-6 (Two-hybrid), KRTAP5-6 (Two-hybrid), KRTAP5-6 (Two-hybrid), KRTAP5-6 (Two-hybrid), KRTAP5-6 (Two-hybrid), KRTAP5-6 (Two-hybrid)

ESM2 similar proteins: A5A6P5, A6QP35, A8MTY7, A8MVA2, A8MXZ3, O75690, P02438, P02441, P02442, P02443, P08131, P0C7H8, P26371, P59990, P59991, P60014, P60331, P60368, P60369, P60370, P60371, P60372, P60409, P60410, P60411, P60412, P60413, Q05B44, Q07627, Q3V2C1, Q6L8G4, Q6L8G8, Q6L8G9, Q6L8H2, Q701N4, Q8IUG1, Q9BQ66, Q9BYP9, Q9BYQ0, Q9BYQ2

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 81 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	42	37.7×	2e-58
Formation of the cornified envelope	18	25.5×	7e-20

GO biological processes:

GO term	Partners	Fold	FDR
keratinization	16	65.7×	3e-23

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	18
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

157 predictions. Top by Δscore:

Variant	Effect	Δscore
11:1697392:C:G	donor_gain	0.9500
11:1697416:GGG:G	donor_gain	0.8700
11:1697417:GGG:G	donor_gain	0.8700
11:1697418:G:T	donor_gain	0.8600
11:1697415:AGG:A	donor_gain	0.8200
11:1697422:C:CG	donor_gain	0.8000
11:1697268:G:GT	donor_gain	0.7800
11:1697353:GCCC:G	donor_gain	0.7800
11:1697414:AAGG:A	donor_gain	0.7600
11:1697417:G:A	donor_gain	0.7500
11:1697271:G:GT	donor_gain	0.7400
11:1697448:G:GT	donor_gain	0.7300
11:1697396:G:GA	donor_gain	0.7200
11:1697391:GCT:G	donor_gain	0.7100
11:1697421:G:A	donor_gain	0.6600
11:1697365:C:G	donor_gain	0.6200
11:1697656:GGTGA:G	acceptor_gain	0.6100
11:1697656:GGTG:G	donor_loss	0.5700
11:1697362:CTGCT:C	donor_gain	0.5600
11:1697657:G:GA	donor_loss	0.5600
11:1697658:T:A	donor_loss	0.5600
11:1697406:G:GT	donor_gain	0.5500
11:1697416:G:GT	donor_gain	0.5500
11:1697659:G:GC	acceptor_gain	0.5400
11:1697659:GA:G	donor_loss	0.5300
11:1697658:T:TC	acceptor_gain	0.5100
11:1697311:GGGCT:G	donor_gain	0.4900
11:1697312:GGCTG:G	donor_gain	0.4900
11:1697539:A:AG	acceptor_gain	0.4900
11:1697540:G:GG	acceptor_gain	0.4900

AlphaMissense

831 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:1697353:G:C	K36N	0.734
11:1697353:G:T	K36N	0.734
11:1697631:T:G	I129S	0.716
11:1697631:T:C	I129T	0.656
11:1697628:A:T	K128I	0.642
11:1697629:A:C	K128N	0.642
11:1697629:A:T	K128N	0.642
11:1697337:C:A	P31H	0.586
11:1697631:T:A	I129N	0.575
11:1697597:A:C	S118R	0.566
11:1697599:C:A	S118R	0.566
11:1697599:C:G	S118R	0.566

dbSNP variants (sampled 300 via entrez): RS1000452667 (11:1696875 T>A,C,G), RS1001241191 (11:1698019 C>G), RS1001962787 (11:1695206 A>C), RS1004269404 (11:1698050 C>A), RS1005856681 (11:1696282 T>C), RS1006215070 (11:1696716 G>A), RS1006721662 (11:1696437 G>A,C), RS1007723403 (11:1696385 G>A), RS1007816086 (11:1696000 T>C), RS1012066163 (11:1696755 C>A,G), RS1012587502 (11:1698147 C>A), RS1013308144 (11:1695718 C>T), RS1014079686 (11:1698206 A>G), RS1015991588 (11:1695937 G>A,T), RS1016317344 (11:1696463 A>G)

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
CGP 52608	affects binding, increases reaction	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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