KRTAP5-1

Summary

KRTAP5-1 (keratin associated protein 5-1, HGNC:23596) is a protein-coding gene on chromosome 11p15.5, encoding Keratin-associated protein 5-1 (Q6L8H4). 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 387264 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 62 total
• MANE Select transcript: NM_001005922

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23596
Approved symbol	KRTAP5-1
Name	keratin associated protein 5-1
Location	11p15.5
Locus type	gene with protein product
Status	Approved
Aliases	KRTAP5.1
Ensembl gene	ENSG00000205869
Ensembl biotype	protein_coding
OMIM	148022
Entrez	387264

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000382171

RefSeq mRNA: 1 — MANE Select: NM_001005922 NM_001005922

CCDS: CCDS31330

Canonical transcript exons

ENST00000382171 — 1 exons

Exon	Start	End
ENSE00001491105	1584342	1585283

Expression profiles

Bgee: expression breadth ubiquitous, 122 present calls, max score 82.42.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar hemisphere	UBERON:0002245	82.42	gold quality
cerebellum	UBERON:0002037	82.38	gold quality
cerebellar cortex	UBERON:0002129	82.34	gold quality
right hemisphere of cerebellum	UBERON:0014890	82.10	gold quality
mucosa of transverse colon	UBERON:0004991	72.58	gold quality
apex of heart	UBERON:0002098	72.49	gold quality
pituitary gland	UBERON:0000007	71.44	gold quality
adenohypophysis	UBERON:0002196	71.24	gold quality
primary visual cortex	UBERON:0002436	70.33	gold quality
right frontal lobe	UBERON:0002810	68.04	gold quality
superior frontal gyrus	UBERON:0002661	66.63	gold quality
brain	UBERON:0000955	66.34	gold quality
putamen	UBERON:0001874	66.05	gold quality
caudate nucleus	UBERON:0001873	65.56	gold quality
anterior cingulate cortex	UBERON:0009835	65.41	gold quality
nucleus accumbens	UBERON:0001882	65.18	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	64.70	gold quality
Brodmann (1909) area 9	UBERON:0013540	64.37	gold quality
heart left ventricle	UBERON:0002084	64.29	gold quality
body of pancreas	UBERON:0001150	63.41	gold quality
frontal cortex	UBERON:0001870	63.35	gold quality
cerebral cortex	UBERON:0000956	63.34	gold quality
hindlimb stylopod muscle	UBERON:0004252	63.31	gold quality
transverse colon	UBERON:0001157	63.22	gold quality
right atrium auricular region	UBERON:0006631	62.98	gold quality
minor salivary gland	UBERON:0001830	62.62	gold quality
temporal lobe	UBERON:0001871	62.13	gold quality
amygdala	UBERON:0001876	61.97	gold quality
saliva-secreting gland	UBERON:0001044	61.28	gold quality
hypothalamus	UBERON:0001898	61.14	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.17

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 2)

• A novel mutation designated as E477K of K1 was identified in epidermolytic hyperkeratosis. (PMID:12234709)
• KAP5 gene expression in human hair follicles is regulated by Runx1 (PMID:16442267)

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

Keratin-associated protein 5-1 — Q6L8H4 (reviewed: Q6L8H4)

Alternative names: Keratin, cuticle, ultrahigh sulphur 1-like, Keratin-associated protein 5.1, Ultrahigh sulfur keratin-associated protein 5.1

All UniProt accessions (1): Q6L8H4

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 but not in skin. Expressed also in lung, pancreas, ovary, testis.

Similarity. Belongs to the KRTAP type 5 family.

RefSeq proteins (1): NP_001005922* (*=MANE)

Domains & families (InterPro)

UniProt features (10 total): repeat 8, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6L8H4-F1	38.74	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: 15 (showing top): GOCC_INTERMEDIATE_FILAMENT_CYTOSKELETON, GOCC_SUPRAMOLECULAR_COMPLEX, GOCC_POLYMERIC_CYTOSKELETAL_FIBER, REACTOME_KERATINIZATION, 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, GSE13547_WT_VS_ZFX_KO_BCELL_ANTI_IGM_STIM_12H_DN, BLANCO_MELO_COVID19_SARS_COV_2_INFECTION_A594_ACE2_EXPRESSING_CELLS_RUXOLITINIB_UP, WP_VITAMIN_D_RECEPTOR_PATHWAY, KANNAN_BLOOD_2012_2013_TIV_AGE_65PLS_REVACCINATED_IN_6_9_MO_VS_REVACCINATED_IN_12_13_MO_UP, GSE13887_ACT_CD4_VS_NO_TREATED_CD4_TCELL_UP, GSE3920_UNTREATED_VS_IFNA_TREATED_ENDOTHELIAL_CELL_DN, 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

62 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KRTAP5-1	KRTAP10-1	P60331	657
KRTAP5-1	KRTAP5-5	Q701N2	571
KRTAP5-1	MOB2	Q70IA6	477
KRTAP5-1	EVI2A	P22794	447
KRTAP5-1	IFITM10	A6NMD0	444
KRTAP5-1	EVI2B	P34910	432
KRTAP5-1	ANGPTL7	O43827	368
KRTAP5-1	OMG	P23515	322
KRTAP5-1	DUSP8	Q13202	318
KRTAP5-1	TCHH	Q07283	308
KRTAP5-1	LY6G5B	Q8NDX9	292
KRTAP5-1	LORICRIN	P23490	238
KRTAP5-1	S100A3	P33764	186
KRTAP5-1	DBR1	Q9UK59	177
KRTAP5-1	SRA1	Q9HD15	174

IntAct

34 interactions, top by confidence:

A	B	Type	Score
KRTAP5-1	SMOC2	psi-mi:“MI:0915”(physical association)	0.560
KRTAP5-1	MT1M	psi-mi:“MI:0915”(physical association)	0.560
	KRTAP5-1	psi-mi:“MI:0915”(physical association)	0.560
KRTAP5-1	KRTAP4-12	psi-mi:“MI:0915”(physical association)	0.560
KRTAP5-1	CST9L	psi-mi:“MI:0915”(physical association)	0.560
KRTAP5-1	DHRS1	psi-mi:“MI:0915”(physical association)	0.560
KRTAP5-3	KRTAP5-1	psi-mi:“MI:0915”(physical association)	0.560
PHLDA1	KRTAP5-1	psi-mi:“MI:0915”(physical association)	0.560
CRY2	KRTAP5-1	psi-mi:“MI:0915”(physical association)	0.560
KRTAP5-1	ZNF575	psi-mi:“MI:0915”(physical association)	0.560
KRTAP5-6	KRTAP5-1	psi-mi:“MI:0915”(physical association)	0.560
SMOC2	KRTAP5-1	psi-mi:“MI:0915”(physical association)	0.000
MT1M	KRTAP5-1	psi-mi:“MI:0915”(physical association)	0.000
	KRTAP5-1	psi-mi:“MI:0915”(physical association)	0.000
KRTAP4-12	KRTAP5-1	psi-mi:“MI:0915”(physical association)	0.000
KRTAP5-6	KRTAP5-1	psi-mi:“MI:0915”(physical association)	0.000
CST9L	KRTAP5-1	psi-mi:“MI:0915”(physical association)	0.000
DHRS1	KRTAP5-1	psi-mi:“MI:0915”(physical association)	0.000
KRTAP5-3	KRTAP5-1	psi-mi:“MI:0915”(physical association)	0.000
PHLDA1	KRTAP5-1	psi-mi:“MI:0915”(physical association)	0.000
CRY2	KRTAP5-1	psi-mi:“MI:0915”(physical association)	0.000
ZNF575	KRTAP5-1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (12): KRTAP5-1 (Two-hybrid), KRTAP5-1 (Two-hybrid), KRTAP5-1 (Two-hybrid), KRTAP5-1 (Two-hybrid), KRTAP5-1 (Two-hybrid), KRTAP5-1 (Two-hybrid), KRTAP5-1 (Two-hybrid), KRTAP5-1 (Two-hybrid), KRTAP5-1 (Two-hybrid), KRTAP4-12 (Two-hybrid), KRTAP10-1 (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.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	59
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

322 predictions. Top by Δscore:

Variant	Effect	Δscore
11:1585049:C:CA	donor_gain	0.9800
11:1585061:G:C	donor_gain	0.9700
11:1585045:AGCCC:A	donor_gain	0.9600
11:1585055:G:A	donor_gain	0.9300
11:1585059:CAG:C	donor_gain	0.9200
11:1585226:T:TA	donor_gain	0.9200
11:1585047:C:A	donor_gain	0.9100
11:1585096:CGGG:C	donor_gain	0.9000
11:1585020:C:CA	donor_gain	0.8700
11:1585142:T:TA	donor_gain	0.8700
11:1584990:C:A	donor_gain	0.8600
11:1585053:TTGCC:T	donor_gain	0.8600
11:1585056:C:CT	donor_gain	0.8500
11:1585209:CAG:C	donor_gain	0.8500
11:1585031:C:CA	donor_gain	0.8400
11:1585223:G:GA	donor_gain	0.8300
11:1585046:G:GA	donor_gain	0.8000
11:1585127:G:C	donor_gain	0.8000
11:1585001:T:TA	donor_gain	0.7900
11:1585045:AGC:A	donor_gain	0.7900
11:1585086:CGGCA:C	donor_gain	0.7900
11:1585087:GGCAG:G	donor_gain	0.7900
11:1585211:G:C	donor_gain	0.7900
11:1584960:C:A	donor_gain	0.7800
11:1585045:AGCC:A	donor_gain	0.7600
11:1585138:A:T	donor_gain	0.7300
11:1585222:AG:A	donor_gain	0.7300
11:1585072:A:AT	donor_gain	0.6800
11:1585083:A:T	donor_gain	0.6700
11:1585103:G:A	donor_gain	0.6700

AlphaMissense

1775 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:1584479:G:C	S257R	0.761
11:1584479:G:T	S257R	0.761
11:1584481:T:G	S257R	0.761
11:1584448:A:G	C268R	0.758
11:1584417:A:C	I278S	0.753
11:1584419:C:A	K277N	0.742
11:1584419:C:G	K277N	0.742
11:1584433:A:G	C273R	0.736
11:1584431:G:C	C273W	0.725
11:1584470:C:A	K260N	0.708
11:1584470:C:G	K260N	0.708
11:1584417:A:G	I278T	0.702
11:1584438:G:T	P271H	0.701
11:1584446:G:C	C268W	0.698
11:1584449:A:C	S267R	0.692
11:1584449:A:T	S267R	0.692
11:1584451:T:G	S267R	0.692
11:1584443:A:C	C269W	0.685
11:1584527:C:A	K241N	0.684
11:1584527:C:G	K241N	0.684
11:1584461:G:C	C263W	0.675
11:1584420:T:A	K277M	0.663
11:1584463:A:G	C263R	0.645
11:1584441:A:T	V270D	0.641
11:1584836:C:A	K138N	0.637
11:1584836:C:G	K138N	0.637
11:1584432:C:G	C273S	0.634
11:1584433:A:T	C273S	0.634
11:1584478:A:G	C258R	0.632
11:1584797:G:C	S151R	0.632

dbSNP variants (sampled 300 via entrez): RS1000104507 (11:1586645 T>G), RS1002597005 (11:1584172 T>TG), RS1003205905 (11:1585882 T>C), RS1004434355 (11:1584145 G>A), RS1005223616 (11:1585520 G>GC), RS1005365311 (11:1586169 A>G), RS1005621718 (11:1584500 C>T), RS1005852044 (11:1585819 C>T), RS1005957267 (11:1586190 C>T), RS1006226099 (11:1587017 C>G), RS1007139056 (11:1583879 G>A,T), RS1007473122 (11:1585479 T>C), RS1007505634 (11:1585745 C>T), RS1007940835 (11:1583880 G>C,T), RS1009369919 (11:1585406 C>A,T)

Disease associations

OMIM: gene MIM:148022 | 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

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
jinfukang	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Atrazine	increases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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