KRTAP5-4

Summary

KRTAP5-4 (keratin associated protein 5-4, HGNC:23599) is a protein-coding gene on chromosome 11p15.5, encoding Keratin-associated protein 5-4 (Q6L8H1). 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 387267 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 16 total
• MANE Select transcript: NM_001347674

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23599
Approved symbol	KRTAP5-4
Name	keratin associated protein 5-4
Location	11p15.5
Locus type	gene with protein product
Status	Approved
Aliases	KRTAP5.4
Ensembl gene	ENSG00000241598
Ensembl biotype	protein_coding
Entrez	387267

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000399682

RefSeq mRNA: 1 — MANE Select: NM_001347674 NM_001347674

CCDS: CCDS86161

Canonical transcript exons

ENST00000399682 — 1 exons

Exon	Start	End
ENSE00001539611	1620958	1622138

Expression profiles

Bgee: expression breadth broad, 19 present calls, max score 40.34.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skin of leg	UBERON:0001511	40.34	gold quality
zone of skin	UBERON:0000014	39.68	gold quality
skin of abdomen	UBERON:0001416	39.15	gold quality
bone marrow cell	CL:0002092	38.14	gold quality
mucosa of transverse colon	UBERON:0004991	37.50	silver quality
colonic epithelium	UBERON:0000397	37.20	gold quality
gall bladder	UBERON:0002110	36.60	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	35.31	gold quality
primary visual cortex	UBERON:0002436	34.99	silver quality
prefrontal cortex	UBERON:0000451	34.69	silver quality
muscle tissue	UBERON:0002385	33.74	gold quality
cerebellum	UBERON:0002037	33.64	gold quality
cerebellar cortex	UBERON:0002129	33.53	gold quality
superior frontal gyrus	UBERON:0002661	33.37	gold quality
cerebellar hemisphere	UBERON:0002245	33.21	gold quality
bone marrow	UBERON:0002371	32.76	gold quality
right hemisphere of cerebellum	UBERON:0014890	32.35	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
lymph node	UBERON:0000029	31.76	silver quality
leukocyte	CL:0000738	31.44	gold quality
monocyte	CL:0000576	31.26	gold quality
vermiform appendix	UBERON:0001154	30.31	silver quality
endocervix	UBERON:0000458	30.11	silver quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
duodenum	UBERON:0002114	28.14	gold quality
placenta	UBERON:0001987	27.78	gold quality
Brodmann (1909) area 9	UBERON:0013540	27.77	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.22

Regulation

Is transcription factor: no

Cross-species orthologs

0 orthologs

Paralogs (1): KRTAP5-3 (ENSG00000196224)

Protein

Protein identifiers

Keratin-associated protein 5-4 — Q6L8H1 (reviewed: Q6L8H1)

Alternative names: Keratin-associated protein 5.4, Ultrahigh sulfur keratin-associated protein 5.4

All UniProt accessions (1): A8MUN0

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.

Similarity. Belongs to the KRTAP type 5 family.

RefSeq proteins (1): NP_001334603* (*=MANE)

Domains & families (InterPro)

UniProt features (11 total): repeat 9, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6L8H1-F1	45.39	0.00

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6805567	Keratinization

MSigDB gene sets: 14 (showing top): MARTINEZ_RB1_TARGETS_DN, GOCC_INTERMEDIATE_FILAMENT_CYTOSKELETON, BYSTRYKH_HEMATOPOIESIS_STEM_CELL_QTL_TRANS, GOCC_SUPRAMOLECULAR_COMPLEX, GOCC_POLYMERIC_CYTOSKELETAL_FIBER, REACTOME_KERATINIZATION, GOCC_SUPRAMOLECULAR_POLYMER, MARTINEZ_RB1_AND_TP53_TARGETS_DN, WP_VITAMIN_D_RECEPTOR_PATHWAY, GSE5589_WT_VS_IL10_KO_LPS_AND_IL10_STIM_MACROPHAGE_180MIN_DN, MARTINEZ_TP53_TARGETS_DN, GSE37319_WT_VS_RC3H1_KO_CD44LOW_CD8_TCELL_DN, GSE32901_TH1_VS_TH17_NEG_CD4_TCELL_DN, chr11p15

GO Biological Process (0):

GO Molecular Function (0):

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
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

127 interactions, top by confidence:

A	B	Type	Score
HOXA1	KRTAP5-4	psi-mi:“MI:0915”(physical association)	0.600
LCE5A	KRTAP5-4	psi-mi:“MI:0915”(physical association)	0.600
KRTAP5-4	OTX1	psi-mi:“MI:0915”(physical association)	0.560
KRTAP5-4	GLRX3	psi-mi:“MI:0915”(physical association)	0.560
OTX1	KRTAP5-4	psi-mi:“MI:0915”(physical association)	0.560
LCE2C	KRTAP5-4	psi-mi:“MI:0915”(physical association)	0.560
GLRX3	KRTAP5-4	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	KRTAP5-4	psi-mi:“MI:0915”(physical association)	0.560
NOTCH2NLC	KRTAP5-4	psi-mi:“MI:0915”(physical association)	0.560
LCE1D	KRTAP5-4	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-8	KRTAP5-4	psi-mi:“MI:0915”(physical association)	0.560
KRTAP1-1	KRTAP5-4	psi-mi:“MI:0915”(physical association)	0.560
KRTAP5-9	KRTAP5-4	psi-mi:“MI:0915”(physical association)	0.560
KRTAP5-4	KRTAP9-3	psi-mi:“MI:0915”(physical association)	0.560
KRTAP5-4	CRCT1	psi-mi:“MI:0915”(physical association)	0.560
MEOX2	KRTAP5-4	psi-mi:“MI:0915”(physical association)	0.560
KRTAP1-3	KRTAP5-4	psi-mi:“MI:0915”(physical association)	0.560
POU4F2	KRTAP5-4	psi-mi:“MI:0915”(physical association)	0.560
LCE3B	KRTAP5-4	psi-mi:“MI:0915”(physical association)	0.560
KRTAP5-4	KRTAP5-2	psi-mi:“MI:0915”(physical association)	0.560
KRTAP5-4	CATSPER1	psi-mi:“MI:0915”(physical association)	0.560
LCE1B	KRTAP5-4	psi-mi:“MI:0915”(physical association)	0.560
LCE3C	KRTAP5-4	psi-mi:“MI:0915”(physical association)	0.560
KRTAP5-4	KRTAP11-1	psi-mi:“MI:0915”(physical association)	0.560
LCE1C	KRTAP5-4	psi-mi:“MI:0915”(physical association)	0.560
KRTAP5-4	PLEKHF2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (62): KRTAP5-4 (Two-hybrid), KRTAP5-4 (Two-hybrid), KRTAP5-4 (Two-hybrid), KRTAP5-4 (Two-hybrid), KRTAP5-4 (Two-hybrid), KRTAP5-4 (Two-hybrid), KRTAP5-4 (Two-hybrid), KRTAP5-4 (Two-hybrid), KRTAP5-4 (Two-hybrid), KRTAP5-4 (Two-hybrid), KRTAP5-4 (Two-hybrid), KRTAP5-4 (Two-hybrid), KRTAP5-4 (Two-hybrid), KRTAP5-4 (Two-hybrid), KRTAP5-4 (Two-hybrid)

ESM2 similar proteins: A0A286YEV6, A0A286YEX9, A0A286YF01, A0A286YF60, A0A286YF77, A0A286YFB4, A0A286YFG1, C0J7L8, O08884, P04459, P18165, P26371, P26372, Q01644, Q02957, Q02958, Q3LI54, Q3LI58, Q3LI59, Q3LI61, Q3LI63, Q3LI64, Q3LI66, Q3LI67, Q3LI70, Q3LI72, Q3SYF9, Q62220, Q64507, Q6L8G5, Q6L8H1, Q6L8H2, Q6L8H4, Q701N2, Q701N4, Q7Z4W3, Q8C1I6, Q8IUB9, Q925H2, Q925H3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 37 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	19	36.5×	3e-25
Formation of the cornified envelope	11	33.3×	2e-13

GO biological processes:

GO term	Partners	Fold	FDR
keratinization	11	92.0×	1e-17

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	13
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

421 predictions. Top by Δscore:

Variant	Effect	Δscore
11:1621858:C:A	donor_gain	0.9600
11:1621884:G:C	donor_gain	0.9500
11:1621853:AGCCC:A	donor_gain	0.9100
11:1622070:T:TA	donor_gain	0.8900
11:1621853:AGCC:A	donor_gain	0.8600
11:1621209:T:C	acceptor_gain	0.8300
11:1621222:T:C	acceptor_gain	0.8200
11:1622067:G:GA	donor_gain	0.7900
11:1621853:AGC:A	donor_gain	0.7800
11:1622066:AG:A	donor_gain	0.7800
11:1621879:C:CT	donor_gain	0.7700
11:1621642:CAGC:C	acceptor_gain	0.7600
11:1621882:CAG:C	donor_gain	0.7600
11:1621222:T:TC	acceptor_gain	0.7400
11:1621832:TGGA:T	donor_gain	0.7400
11:1621209:T:TC	acceptor_gain	0.7100
11:1621853:AG:A	donor_gain	0.7100
11:1621646:C:CC	acceptor_gain	0.6700
11:1621417:CA:C	donor_gain	0.6600
11:1620982:C:CT	acceptor_gain	0.6400
11:1621647:T:G	acceptor_loss	0.6400
11:1621911:G:C	donor_gain	0.6400
11:1621680:C:CC	acceptor_gain	0.6200
11:1621839:C:CA	donor_gain	0.6200
11:1621143:CT:C	acceptor_gain	0.6100
11:1621828:C:A	donor_gain	0.6100
11:1621854:G:C	donor_gain	0.6100
11:1621865:AGCC:A	donor_gain	0.6100
11:1621909:CAGCA:C	donor_gain	0.6100
11:1621870:C:T	donor_gain	0.6000

AlphaMissense

1462 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1002216026 (11:1623471 T>C,G), RS1003213810 (11:1623523 G>A), RS1004262125 (11:1623031 G>A), RS1004489764 (11:1622903 T>C), RS1004998507 (11:1624018 C>T), RS1006907532 (11:1621319 C>G), RS1007353803 (11:1620976 C>T), RS1008358930 (11:1622777 A>T), RS1008428479 (11:1623854 T>C), RS1010013370 (11:1622401 G>A), RS1010311350 (11:1622701 G>A), RS1010892750 (11:1622459 A>G), RS1011276798 (11:1623534 G>A), RS1012411160 (11:1622362 C>A,T), RS1012691502 (11:1623057 C>A,T)

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
CGP 52608	affects binding, increases reaction	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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