KRTAP1-4

Summary

KRTAP1-4 (keratin associated protein 1-4, HGNC:18904) is a protein-coding gene on chromosome 17q21.2, encoding Keratin-associated protein 1-4 (P0C5Y4). In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-link….

The main structural proteins of mammalian hair fiber are the hair keratins (see MIM 601077) and the keratin-associated proteins (KAPs), which form a rigid and resistant hair shaft through extensive disulfide bond crosslinking with the abundant cysteines of hair keratins (Shimomura et al., 2002 [PubMed 12228244]).

Source: NCBI Gene 728255 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_001257305

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18904
Approved symbol	KRTAP1-4
Name	keratin associated protein 1-4
Location	17q21.2
Locus type	gene with protein product
Status	Approved
Aliases	KAP1.4
Ensembl gene	ENSG00000204887
Ensembl biotype	protein_coding
OMIM	608821
Entrez	728255

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000377747

RefSeq mRNA: 1 — MANE Select: NM_001257305 NM_001257305

CCDS: CCDS58548

Canonical transcript exons

ENST00000377747 — 1 exons

Exon	Start	End
ENSE00001475011	41029351	41030195

Expression profiles

Bgee: expression breadth broad, 16 present calls, max score 37.20.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
skin of abdomen	UBERON:0001416	33.07	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
zone of skin	UBERON:0000014	31.05	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
skin of leg	UBERON:0001511	29.52	gold quality
prefrontal cortex	UBERON:0000451	29.04	gold quality
cortex of kidney	UBERON:0001225	28.41	silver quality
duodenum	UBERON:0002114	28.14	gold quality
liver	UBERON:0002107	28.04	gold quality
lymph node	UBERON:0000029	27.57	gold quality
tonsil	UBERON:0002372	27.05	gold quality
islet of Langerhans	UBERON:0000006	26.55	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
gall bladder	UBERON:0002110	25.98	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	25.89	gold quality
placenta	UBERON:0001987	25.81	gold quality
urinary bladder	UBERON:0001255	25.72	gold quality
muscle of leg	UBERON:0001383	25.64	silver quality
kidney	UBERON:0002113	25.18	silver quality
leukocyte	CL:0000738	24.80	gold quality
primary visual cortex	UBERON:0002436	24.61	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

Literature-anchored findings (GeneRIF, showing 1)

• no polymorphic alleles were found for the hKAP1.4 and hKAP1.5 genes in Japanese and Caucasian individuals (PMID:12228244)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Krtap1-5	ENSMUSG00000047253
rattus_norvegicus	Krtap1-5	ENSRNOG00000084854

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), KRTAP12-3 (ENSG00000205439), KRTAP10-2 (ENSG00000205445), KRTAP5-6 (ENSG00000205864), 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 1-4 — P0C5Y4 (reviewed: P0C5Y4)

Alternative names: High sulfur keratin-associated protein 1.4, Keratin-associated protein 1.4

All UniProt accessions (1): P0C5Y4

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 proteins (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 the middle/upper portions of the hair cortex, in the region termed the keratogenous zone.

Similarity. Belongs to the KRTAP type 1 family.

RefSeq proteins (1): NP_001244234* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002494	KAP	Family

Pfam: PF01500

UniProt features (1 total): chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0C5Y4-F1	46.47	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: 9 (showing top): GOCC_INTERMEDIATE_FILAMENT_CYTOSKELETON, GOCC_KERATIN_FILAMENT, GOCC_SUPRAMOLECULAR_COMPLEX, GOCC_POLYMERIC_CYTOSKELETAL_FIBER, REACTOME_KERATINIZATION, GOCC_SUPRAMOLECULAR_POLYMER, ALKBH3_TARGET_GENES, GSE27241_WT_VS_RORGT_KO_TH17_POLARIZED_CD4_TCELL_TREATED_WITH_DIGOXIN_UP, chr17q21

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (3): cytosol (GO:0005829), keratin filament (GO:0045095), 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	1
intermediate filament cytoskeleton	1
polymeric cytoskeletal fiber	1

Protein interactions and networks

STRING

166 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KRTAP1-4	KRTAP27-1	Q3LI81	676
KRTAP1-4	KRTAP24-1	Q3LI83	654
KRTAP1-4	KRTAP6-2	Q3LI66	643
KRTAP1-4	KRTAP6-3	Q3LI67	643
KRTAP1-4	KRTAP13-3	Q3SY46	640
KRTAP1-4	KRTAP3-2	Q9BYR7	630
KRTAP1-4	KRTAP26-1	Q6PEX3	624
KRTAP1-4	KRTAP8-1	Q8IUC2	608
KRTAP1-4	SCYGR1	A0A286YEY9	608
KRTAP1-4	KRTAP22-1	Q3MIV0	602
KRTAP1-4	A8MUN0	A8MUN0	597
KRTAP1-4	KRTAP6-1	Q3LI64	581
KRTAP1-4	KRTAP20-2	Q3LI61	574
KRTAP1-4	KRTAP2-1	Q9BYU5	544
KRTAP1-4	KRTAP7-1	Q8IUC3	541

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A5A6P5, A6QP35, A8MTY7, A8MVA2, A8MXZ3, P02438, P02439, P02440, P02441, P02442, P02443, P08131, P0C5Y4, P59990, P59991, P60014, P60328, P60329, P60331, P60368, P60369, P60370, P60371, P60372, P60409, P60410, P60411, P60412, P60413, Q05B44, Q07627, Q3V2C1, Q8IUG1, Q9BQ66, Q9BYP9, Q9BYQ2, Q9BYQ3, Q9BYQ4, Q9BYQ5, Q9BYQ6

Diamond homologs: P02438, P02439, P02440, P08131, P0C5Y4, Q07627, Q3V2C1, Q8IUG1, Q9BYS1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

56 predictions. Top by Δscore:

Variant	Effect	Δscore
17:41029951:C:CT	donor_gain	0.8400
17:41029952:C:CT	donor_gain	0.8000
17:41029894:C:CT	donor_gain	0.7500
17:41029893:C:CT	donor_gain	0.7300
17:41029930:T:TA	donor_gain	0.7300
17:41029892:A:AC	donor_gain	0.7100
17:41029948:C:CT	donor_gain	0.7100
17:41029835:AGCTT:A	donor_loss	0.6700
17:41029836:GCTTA:G	donor_loss	0.6700
17:41029837:CTTAC:C	donor_loss	0.6700
17:41029838:TTAC:T	donor_loss	0.6700
17:41029839:TAC:T	donor_loss	0.6700
17:41029841:C:A	donor_loss	0.6700
17:41029908:G:A	donor_gain	0.6600
17:41029895:A:AA	donor_gain	0.6500
17:41029834:CAGCT:C	donor_loss	0.6400
17:41029840:A:AC	donor_gain	0.6100
17:41029841:C:CC	donor_gain	0.6100
17:41029912:A:AC	donor_gain	0.6100
17:41029913:C:CC	donor_gain	0.6100
17:41029949:C:CT	donor_gain	0.6100
17:41029914:A:C	donor_gain	0.5700
17:41029950:A:AC	donor_gain	0.5300
17:41029891:CA:C	donor_gain	0.5200
17:41029971:T:TA	donor_gain	0.5000
17:41029842:C:A	donor_loss	0.4900
17:41029833:GCAGC:G	donor_loss	0.4300
17:41030025:G:C	donor_gain	0.4300
17:41030058:A:AC	donor_gain	0.4200
17:41030059:C:CC	donor_gain	0.4200

AlphaMissense

792 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:41029893:C:A	W62C	0.650
17:41029893:C:G	W62C	0.650
17:41029895:A:G	W62R	0.595
17:41029895:A:T	W62R	0.595
17:41029836:G:C	S81R	0.569
17:41029836:G:T	S81R	0.569
17:41029838:T:G	S81R	0.569

dbSNP variants (sampled 300 via entrez): RS1000117288 (17:41031136 G>A), RS1002382858 (17:41029515 C>G), RS1002765845 (17:41031021 T>C), RS1003740623 (17:41029303 C>A), RS1004542832 (17:41029205 G>A), RS1004846595 (17:41029236 C>A,T), RS1005209998 (17:41031881 C>T), RS1006216202 (17:41030310 T>C), RS1006653205 (17:41031437 A>T), RS1009465886 (17:41030258 G>A,C), RS1011405583 (17:41031040 C>A), RS1012368741 (17:41029617 T>C), RS1012702808 (17:41030707 A>G), RS1014372497 (17:41031992 A>G), RS1014715414 (17:41029255 T>C)

Disease associations

OMIM: gene MIM:608821 | 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)

Clinical trials (associated diseases)

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