KRTAP5-3

Summary

KRTAP5-3 (keratin associated protein 5-3, HGNC:23598) is a protein-coding gene on chromosome 11p15.5, encoding Keratin-associated protein 5-3 (Q6L8H2). 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 387266 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 38 total
• MANE Select transcript: NM_001012708

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23598
Approved symbol	KRTAP5-3
Name	keratin associated protein 5-3
Location	11p15.5
Locus type	gene with protein product
Status	Approved
Aliases	KRTAP5.3, KRTAP5-9
Ensembl gene	ENSG00000196224
Ensembl biotype	protein_coding
Entrez	387266

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000399685

RefSeq mRNA: 1 — MANE Select: NM_001012708 NM_001012708

CCDS: CCDS41591

Canonical transcript exons

ENST00000399685 — 1 exons

Exon	Start	End
ENSE00001539621	1607565	1608463

Expression profiles

Bgee: expression breadth broad, 16 present calls, max score 40.73.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	40.73	silver quality
ventricular zone	UBERON:0003053	40.66	silver quality
skin of abdomen	UBERON:0001416	40.35	gold quality
zone of skin	UBERON:0000014	39.13	gold quality
duodenum	UBERON:0002114	38.86	silver quality
skin of leg	UBERON:0001511	38.75	gold quality
apex of heart	UBERON:0002098	38.52	silver quality
granulocyte	CL:0000094	38.13	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
mucosa of transverse colon	UBERON:0004991	36.31	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
hindlimb stylopod muscle	UBERON:0004252	36.11	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
muscle tissue	UBERON:0002385	32.30	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
prefrontal cortex	UBERON:0000451	30.51	gold quality
cortex of kidney	UBERON:0001225	30.39	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
right hemisphere of cerebellum	UBERON:0014890	29.69	gold quality
leukocyte	CL:0000738	29.03	gold quality
kidney	UBERON:0002113	28.62	gold quality
monocyte	CL:0000576	28.50	gold quality
urinary bladder	UBERON:0001255	28.23	gold quality
primary visual cortex	UBERON:0002436	28.20	gold quality
smooth muscle tissue	UBERON:0001135	28.04	gold quality
adult mammalian kidney	UBERON:0000082	27.98	gold quality
placenta	UBERON:0001987	27.67	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	27.60	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.07

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

4 targeting KRTAP5-3, 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-7162-3P	99.89	68.16	1682
HSA-MIR-10B-3P	99.04	66.98	988
HSA-MIR-7114-3P	98.42	66.53	569
HSA-MIR-3940-3P	84.90	61.31	32

Cross-species orthologs

0 orthologs

Paralogs (1): KRTAP5-4 (ENSG00000241598)

Protein

Protein identifiers

Keratin-associated protein 5-3 — Q6L8H2 (reviewed: Q6L8H2)

Alternative names: Keratin-associated protein 5-9, Keratin-associated protein 5.3, Keratin-associated protein 5.9, UHS KerB-like, Ultrahigh sulfur keratin-associated protein 5.3

All UniProt accessions (1): Q6L8H2

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_001012726* (*=MANE)

Domains & families (InterPro)

UniProt features (19 total): repeat 11, sequence variant 5, chain 1, region of interest 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6L8H2-F1	35.55	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: 40 (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, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, REACTOME_KERATINIZATION, JAK2_DN.V1_UP, GOCC_SUPRAMOLECULAR_POLYMER, MIR135A_3P, LOPEZ_MBD_TARGETS

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

0 interactions, top by confidence (×1000):

IntAct

141 interactions, top by confidence:

A	B	Type	Score
LCE5A	KRTAP5-3	psi-mi:“MI:0915”(physical association)	0.600
KRTAP5-3	LCE5A	psi-mi:“MI:0915”(physical association)	0.600
KRTAP5-3	NUFIP2	psi-mi:“MI:0915”(physical association)	0.560
POU4F2	KRTAP5-3	psi-mi:“MI:0915”(physical association)	0.560
KRTAP5-3	KRTAP9-3	psi-mi:“MI:0915”(physical association)	0.560
LCE2C	KRTAP5-3	psi-mi:“MI:0915”(physical association)	0.560
KRTAP5-3	CATSPER1	psi-mi:“MI:0915”(physical association)	0.560
NOTCH2NLC	KRTAP5-3	psi-mi:“MI:0915”(physical association)	0.560
HOXA1	KRTAP5-3	psi-mi:“MI:0915”(physical association)	0.560
SMCP	KRTAP5-3	psi-mi:“MI:0915”(physical association)	0.560
OTX1	KRTAP5-3	psi-mi:“MI:0915”(physical association)	0.560
KRTAP5-3	RGS17	psi-mi:“MI:0915”(physical association)	0.560
KRTAP5-3	KRTAP5-1	psi-mi:“MI:0915”(physical association)	0.560
MEOX2	KRTAP5-3	psi-mi:“MI:0915”(physical association)	0.560
KRTAP1-3	KRTAP5-3	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	KRTAP5-3	psi-mi:“MI:0915”(physical association)	0.560
KRTAP5-3	NR4A3	psi-mi:“MI:0915”(physical association)	0.560
KRTAP5-3	ADAMTSL4	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-8	KRTAP5-3	psi-mi:“MI:0915”(physical association)	0.560
LCE1D	KRTAP5-3	psi-mi:“MI:0915”(physical association)	0.560
KPRP	KRTAP5-3	psi-mi:“MI:0915”(physical association)	0.560
LCE3A	KRTAP5-3	psi-mi:“MI:0915”(physical association)	0.560
LCE1C	KRTAP5-3	psi-mi:“MI:0915”(physical association)	0.560
LCE3C	KRTAP5-3	psi-mi:“MI:0915”(physical association)	0.560
LCE1F	KRTAP5-3	psi-mi:“MI:0915”(physical association)	0.560
RAMP3	KRTAP5-3	psi-mi:“MI:0915”(physical association)	0.560
LCE4A	KRTAP5-3	psi-mi:“MI:0915”(physical association)	0.560
LCE1A	KRTAP5-3	psi-mi:“MI:0915”(physical association)	0.560
KRTAP5-3	KRTAP1-5	psi-mi:“MI:0915”(physical association)	0.560
LCE1B	KRTAP5-3	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (66): KRTAP5-3 (Two-hybrid), KRTAP5-3 (Two-hybrid), KRTAP5-3 (Two-hybrid), KRTAP5-3 (Two-hybrid), KRTAP5-3 (Two-hybrid), KRTAP5-3 (Two-hybrid), KRTAP5-3 (Two-hybrid), KRTAP5-3 (Two-hybrid), KRTAP5-3 (Two-hybrid), KRTAP5-3 (Two-hybrid), KRTAP5-3 (Two-hybrid), KRTAP5-3 (Two-hybrid), KRTAP5-3 (Two-hybrid), KRTAP5-3 (Two-hybrid), KRTAP5-3 (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 42 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	23	36.6×	4e-31
Formation of the cornified envelope	13	32.6×	4e-16

GO biological processes:

GO term	Partners	Fold	FDR
keratinization	12	90.6×	3e-19

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	33
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

733 predictions. Top by Δscore:

Variant	Effect	Δscore
11:1608192:C:CA	donor_gain	0.9800
11:71548538:A:T	donor_gain	0.9700
11:1608189:ACCC:A	donor_gain	0.9600
11:1608190:CCCC:C	donor_gain	0.9600
11:1608218:G:C	donor_gain	0.9600
11:1608060:C:CA	donor_gain	0.8700
11:1608213:C:CT	donor_gain	0.8700
11:1608253:CGGG:C	donor_gain	0.8200
11:1608216:CAG:C	donor_gain	0.8000
11:71548831:C:T	donor_gain	0.7800
11:71548537:G:GT	donor_gain	0.7600
11:1608362:T:TA	donor_gain	0.7400
11:71548517:GAGC:G	donor_gain	0.7400
11:1607968:C:CC	acceptor_gain	0.7300
11:1608064:TGGA:T	donor_gain	0.7300
11:1607964:CAGC:C	acceptor_gain	0.7200
11:1608243:CAGCA:C	donor_gain	0.7200
11:1608345:CAG:C	donor_gain	0.7200
11:1607798:C:CC	acceptor_gain	0.6900
11:1608202:C:A	donor_gain	0.6900
11:1608203:C:CA	donor_gain	0.6900
11:1608245:G:C	donor_gain	0.6900
11:1607968:C:A	acceptor_loss	0.6800
11:1608206:A:AC	donor_gain	0.6800
11:1608207:C:CC	donor_gain	0.6800
11:1608359:G:GA	donor_gain	0.6800
11:1608273:G:C	donor_gain	0.6700
11:1607966:GC:G	acceptor_gain	0.6600
11:1607967:CC:C	acceptor_gain	0.6600
11:1608214:C:CT	donor_gain	0.6600

AlphaMissense

1541 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:1607879:G:C	S169R	0.746
11:1607879:G:T	S169R	0.746
11:1607881:T:G	S169R	0.746
11:1608257:C:A	K43N	0.712
11:1608257:C:G	K43N	0.712
11:1607909:G:C	S159R	0.682
11:1607909:G:T	S159R	0.682
11:1607911:T:G	S159R	0.682
11:1607822:G:C	S188R	0.643
11:1607822:G:T	S188R	0.643
11:1607824:T:G	S188R	0.643
11:1607939:G:C	S149R	0.635
11:1607939:G:T	S149R	0.635
11:1607941:T:G	S149R	0.635
11:1607673:A:C	I238S	0.634
11:1607705:G:C	S227R	0.631
11:1607705:G:T	S227R	0.631
11:1607707:T:G	S227R	0.631
11:1607792:G:C	S198R	0.629
11:1607792:G:T	S198R	0.629
11:1607794:T:G	S198R	0.629
11:1607673:A:G	I238T	0.617
11:1607675:C:A	K237N	0.614
11:1607675:C:G	K237N	0.614
11:1608047:A:C	F113L	0.613
11:1608047:A:T	F113L	0.613
11:1608049:A:G	F113L	0.613
11:1607789:G:C	C199W	0.609
11:1607735:G:C	S217R	0.601
11:1607735:G:T	S217R	0.601

dbSNP variants (sampled 300 via entrez): RS1002018975 (11:1607313 G>T), RS1002081205 (11:1607133 G>A), RS1003554553 (11:1608375 G>A,C), RS1005482515 (11:1608029 C>T), RS1006046959 (11:1609559 T>C), RS1008665574 (11:1607345 C>G,T), RS1009646061 (11:1609857 A>C), RS1010769100 (11:1607325 G>A,C), RS1012563493 (11:1609631 T>C,G), RS1012782003 (11:1609779 A>G), RS1014753445 (11:1607113 A>G), RS1015564780 (11:1607662 C>G,T), RS1016504081 (11:1609360 C>A,T), RS1018594591 (11:1607578 C>G,T), RS1019080536 (11:1607346 G>A)

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

1 total (human), top 1 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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