KRTAP5-9

Summary

KRTAP5-9 (keratin associated protein 5-9, HGNC:23604) is a protein-coding gene on chromosome 11q13.4, encoding Keratin-associated protein 5-9 (P26371). 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….

Enables identical protein binding activity. Predicted to be involved in epidermis development. Predicted to be located in cytosol.

Source: NCBI Gene 3846 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 83 total
• MANE Select transcript: NM_005553

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23604
Approved symbol	KRTAP5-9
Name	keratin associated protein 5-9
Location	11q13.4
Locus type	gene with protein product
Status	Approved
Aliases	KRTAP5.9, KRTAP5-1
Ensembl gene	ENSG00000254997
Ensembl biotype	protein_coding
OMIM	148021
Entrez	3846

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000528743

RefSeq mRNA: 1 — MANE Select: NM_005553 NM_005553

CCDS: CCDS53677

Canonical transcript exons

ENST00000528743 — 1 exons

Exon	Start	End
ENSE00002152790	71548420	71549608

Expression profiles

Bgee: expression breadth ubiquitous, 141 present calls, max score 81.05.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cervix squamous epithelium	UBERON:0006922	81.05	gold quality
type B pancreatic cell	CL:0000169	75.28	gold quality
endometrium epithelium	UBERON:0004811	73.98	gold quality
olfactory bulb	UBERON:0002264	69.97	gold quality
cerebellar vermis	UBERON:0004720	67.46	gold quality
Brodmann (1909) area 10	UBERON:0013541	67.08	gold quality
squamous epithelium	UBERON:0006914	66.36	gold quality
cervix epithelium	UBERON:0004801	65.90	gold quality
esophagus squamous epithelium	UBERON:0006920	65.18	gold quality
frontal pole	UBERON:0002795	63.70	gold quality
mucosa of urinary bladder	UBERON:0001259	63.62	gold quality
middle frontal gyrus	UBERON:0002702	63.56	gold quality
paraflocculus	UBERON:0005351	63.39	gold quality
epithelium of esophagus	UBERON:0001976	63.17	gold quality
upper arm skin	UBERON:0004263	62.72	gold quality
diaphragm	UBERON:0001103	61.73	gold quality
tongue squamous epithelium	UBERON:0006919	61.73	gold quality
tibia	UBERON:0000979	60.82	gold quality
seminal vesicle	UBERON:0000998	60.58	gold quality
mucosa of transverse colon	UBERON:0004991	60.53	gold quality
left testis	UBERON:0004533	60.31	gold quality
pigmented layer of retina	UBERON:0001782	60.12	gold quality
palpebral conjunctiva	UBERON:0001812	60.11	gold quality
oral cavity	UBERON:0000167	59.95	gold quality
right testis	UBERON:0004534	59.89	gold quality
decidua	UBERON:0002450	58.87	gold quality
nucleus accumbens	UBERON:0001882	58.84	gold quality
endothelial cell	CL:0000115	58.60	gold quality
heart right ventricle	UBERON:0002080	58.59	gold quality
jejunal mucosa	UBERON:0000399	58.48	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.97

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

28 targeting KRTAP5-9, 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-4531	99.99	69.70	3181
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-3940-5P	99.14	65.26	493
HSA-MIR-4507	99.14	65.27	515
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-1286	99.09	66.23	1046
HSA-MIR-670-3P	99.03	68.88	2404
HSA-MIR-3154	98.94	66.55	1455
HSA-MIR-4764-5P	98.88	65.53	894
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-3184-5P	98.56	67.13	1491
HSA-MIR-3928-5P	98.50	67.48	980
HSA-MIR-6806-3P	98.50	67.31	980
HSA-MIR-3179	98.22	65.90	1445
HSA-MIR-1233-5P	98.19	66.71	1201
HSA-MIR-876-5P	97.99	68.49	1345
HSA-MIR-3167	96.81	67.09	1236
HSA-MIR-135A-3P	94.19	66.09	495

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

Keratin-associated protein 5-9 — P26371 (reviewed: P26371)

Alternative names: Keratin, cuticle, ultrahigh sulfur 1, Keratin, ultra high-sulfur matrix protein A, Keratin-associated protein 5.9, UHS keratin A, Ultrahigh sulfur keratin-associated protein 5.9

All UniProt accessions (1): P26371

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. Restricted to hair root, not detected in any other tissues. Expressed in cuticle layers of differentiating hair follicles.

Similarity. Belongs to the KRTAP type 5 family.

RefSeq proteins (1): NP_005544* (*=MANE)

Domains & families (InterPro)

UniProt features (12 total): repeat 8, sequence variant 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P26371-F1	40.70	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: 43 (showing top): chr11q13, GOBP_EPIDERMIS_DEVELOPMENT, NIKOLSKY_BREAST_CANCER_11Q12_Q14_AMPLICON, MODULE_112, GOCC_INTERMEDIATE_FILAMENT_CYTOSKELETON, MODULE_220, FIGUEROA_AML_METHYLATION_CLUSTER_6_DN, GOCC_SUPRAMOLECULAR_COMPLEX, GOCC_POLYMERIC_CYTOSKELETAL_FIBER, REACTOME_KERATINIZATION, JAK2_DN.V1_UP, GSE13522_WT_VS_IFNG_KO_SKING_T_CRUZI_Y_STRAIN_INF_UP, GOCC_SUPRAMOLECULAR_POLYMER, GSE14415_INDUCED_TREG_VS_FOXP3_KO_INDUCED_TREG_IL2_CULTURE_DN, GSE14386_UNTREATED_VS_IFNA_TREATED_ACT_PBMC_MS_PATIENT_UP

GO Biological Process (1): epidermis development (GO:0008544)

GO Molecular Function (2): identical protein binding (GO:0042802), 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
tissue development	1
protein binding	1
binding	1
cytoplasm	1
cellular anatomical structure	1
intermediate filament cytoskeleton	1
polymeric cytoskeletal fiber	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

840 interactions, top by confidence:

A	B	Type	Score
KRTAP5-9	LCE1B	psi-mi:“MI:0915”(physical association)	0.830
KRTAP5-9	CTSZ	psi-mi:“MI:0915”(physical association)	0.830
LCE1B	KRTAP5-9	psi-mi:“MI:0915”(physical association)	0.830
SDC3	KRTAP5-9	psi-mi:“MI:0915”(physical association)	0.810
HOXA1	KRTAP5-9	psi-mi:“MI:0915”(physical association)	0.740
KRTAP5-9	HOXA1	psi-mi:“MI:0915”(physical association)	0.740
KRTAP5-9	TYRO3	psi-mi:“MI:0915”(physical association)	0.740
KRTAP5-9	LCE3C	psi-mi:“MI:0915”(physical association)	0.740
KRTAP5-9	RNF111	psi-mi:“MI:0915”(physical association)	0.740
LCE3C	KRTAP5-9	psi-mi:“MI:0915”(physical association)	0.740
RNF111	KRTAP5-9	psi-mi:“MI:0915”(physical association)	0.740
KRTAP5-9	SDCBP	psi-mi:“MI:0915”(physical association)	0.720
PRKAB2	KRTAP5-9	psi-mi:“MI:0915”(physical association)	0.720
KRTAP5-9	MAPKBP1	psi-mi:“MI:0915”(physical association)	0.720
GLRX3	KRTAP5-9	psi-mi:“MI:0915”(physical association)	0.720
ALPP	KRTAP5-9	psi-mi:“MI:0915”(physical association)	0.720
KRTAP5-9	PSMA1	psi-mi:“MI:0915”(physical association)	0.720
CXCL16	KRTAP5-9	psi-mi:“MI:0915”(physical association)	0.720
KRTAP5-9	RGS20	psi-mi:“MI:0915”(physical association)	0.720
KRTAP5-9	OTX1	psi-mi:“MI:0915”(physical association)	0.720
SMCP	KRTAP5-9	psi-mi:“MI:0915”(physical association)	0.720
KRTAP10-5	KRTAP5-9	psi-mi:“MI:0915”(physical association)	0.720
KRTAP5-9	KRTAP10-9	psi-mi:“MI:0915”(physical association)	0.720
KRTAP5-9	ADAMTSL4	psi-mi:“MI:0915”(physical association)	0.720
CATSPER1	KRTAP5-9	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (272): KRTAP5-9 (Two-hybrid), KRTAP5-9 (Two-hybrid), KRTAP5-9 (Two-hybrid), KRTAP5-9 (Two-hybrid), KRTAP5-9 (Two-hybrid), KRTAP5-9 (Two-hybrid), KRTAP5-9 (Two-hybrid), KRTAP5-9 (Two-hybrid), KRTAP5-9 (Two-hybrid), KRTAP5-9 (Two-hybrid), KRTAP5-9 (Two-hybrid), KRTAP5-9 (Two-hybrid), KRTAP5-9 (Two-hybrid), KRTAP5-9 (Two-hybrid), LY6H (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 98 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	17	14.6×	2e-13

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	79
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

1091 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:71548786:G:C	K43N	0.579
11:71548786:G:T	K43N	0.579

dbSNP variants (sampled 300 via entrez): RS1000214436 (11:71549771 A>G), RS1000456212 (11:71547944 G>C,T), RS1002175420 (11:71546670 C>T), RS1002716187 (11:71546901 C>A,G), RS1004152183 (11:71547208 G>A), RS1004226515 (11:71547603 C>T), RS1004745466 (11:71547392 C>T), RS1005148367 (11:71548605 C>G,T), RS1006248972 (11:71547438 G>T), RS1006662041 (11:71549572 A>T), RS1008041015 (11:71547886 C>T), RS1008329608 (11:71548247 G>A), RS1008662557 (11:71546932 G>A), RS1009632982 (11:71547980 C>T), RS1009714246 (11:71546615 T>C)

Disease associations

OMIM: gene MIM:148021 | disease phenotypes: MIM:605407

GenCC curated gene-disease

Mondo (1): TH-deficient dopa-responsive dystonia (MONDO:0011551)

Orphanet (1): Autosomal recessive dopa-responsive dystonia (Orphanet:101150)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010703_211	Brain morphology (MOSTest)	2.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation	2
bisphenol A	decreases expression	1
benzo(e)pyrene	increases methylation	1
CGP 52608	affects binding, increases reaction	1
Atrazine	increases expression	1
Methapyrilene	increases methylation	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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