KRTAP4-8

Summary

KRTAP4-8 (keratin associated protein 4-8, HGNC:17230) is a protein-coding gene on chromosome 17q21.2, encoding Keratin-associated protein 4-8 (Q9BYQ9). 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….

Involved in hair cycle. Predicted to be located in cytosol.

Source: NCBI Gene 728224 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 38 total
• MANE Select transcript: NM_031960

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17230
Approved symbol	KRTAP4-8
Name	keratin associated protein 4-8
Location	17q21.2
Locus type	gene with protein product
Status	Approved
Aliases	KAP4.8
Ensembl gene	ENSG00000204880
Ensembl biotype	protein_coding
Entrez	728224

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000333822

RefSeq mRNA: 1 — MANE Select: NM_031960 NM_031960

CCDS: CCDS45674

Canonical transcript exons

ENST00000333822 — 1 exons

Exon	Start	End
ENSE00001533292	41096981	41098142

Expression profiles

Bgee: expression breadth broad, 25 present calls, max score 38.59.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0692 / max 40.7113, expressed in 14 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165873	0.0692	14

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skin of abdomen	UBERON:0001416	38.59	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
zone of skin	UBERON:0000014	36.78	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
skin of leg	UBERON:0001511	35.65	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
sural nerve	UBERON:0015488	35.37	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	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
right lung	UBERON:0002167	30.62	silver quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
liver	UBERON:0002107	29.28	gold quality
prefrontal cortex	UBERON:0000451	29.21	gold quality
blood	UBERON:0000178	28.58	silver quality
cortex of kidney	UBERON:0001225	28.23	gold quality
duodenum	UBERON:0002114	28.14	gold quality
lymph node	UBERON:0000029	27.57	gold quality
muscle of leg	UBERON:0001383	27.27	gold quality
leukocyte	CL:0000738	27.16	gold quality
monocyte	CL:0000576	27.12	gold quality
tonsil	UBERON:0002372	27.05	gold quality
kidney	UBERON:0002113	26.93	gold quality
islet of Langerhans	UBERON:0000006	26.55	gold quality
gastrocnemius	UBERON:0001388	26.50	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
gall bladder	UBERON:0002110	25.98	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.20

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

60 targeting KRTAP4-8, 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-3646	100.00	73.56	5283
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-3681-5P	99.82	66.88	387
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-3618	99.69	68.57	1012
HSA-MIR-3660	99.68	67.33	1149
HSA-MIR-4526	99.68	67.07	1136
HSA-MIR-6849-5P	99.64	66.00	352
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-488-3P	99.61	68.79	1731
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-4437	99.52	65.29	1266

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
mus_musculus	Krtap5-2	ENSMUSG00000054759
mus_musculus	Krtap5-20	ENSMUSG00000056885
mus_musculus	Krtap5-26	ENSMUSG00000109859
mus_musculus	Krtap5-24	ENSMUSG00000110324
rattus_norvegicus	Krtap5-8	ENSRNOG00000020131
rattus_norvegicus	AABR07006049.1	ENSRNOG00000046649

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), KRTAP1-4 (ENSG00000204887), 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 4-8 — Q9BYQ9 (reviewed: Q9BYQ9)

Alternative names: Keratin-associated protein 4.8, Ultrahigh sulfur keratin-associated protein 4.8

All UniProt accessions (1): Q9BYQ9

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 hair follicles.

Polymorphism. Numerous size polymorphism are present in KRTAP4 gene family, which are mainly due to variations in the sequence encoding cysteine-rich repeat segments. The sequence shown corresponds to allele KAP4.8-v1.

Similarity. Belongs to the KRTAP type 4 family.

RefSeq proteins (1): NP_114166* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002494	KAP	Family

Pfam: PF13885

UniProt features (31 total): repeat 25, sequence conflict 4, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BYQ9-F1	34.97	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: 29 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, GOBP_MOLTING_CYCLE, GOCC_INTERMEDIATE_FILAMENT_CYTOSKELETON, GOCC_KERATIN_FILAMENT, GOCC_SUPRAMOLECULAR_COMPLEX, GOCC_POLYMERIC_CYTOSKELETAL_FIBER, REACTOME_KERATINIZATION, GOCC_SUPRAMOLECULAR_POLYMER, MIR3646, MIR4698, MIR3133, MIR338_5P, MIR655_3P, MIR374C_5P, MIR5196_5P

GO Biological Process (1): hair cycle (GO:0042633)

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
molting cycle	1
cytoplasm	1
cellular anatomical structure	1
intermediate filament	1
intermediate filament cytoskeleton	1
polymeric cytoskeletal fiber	1

Protein interactions and networks

STRING

210 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KRTAP4-8	A0A3B3IRQ3	A0A3B3IRQ3	583
KRTAP4-8	DEPDC4	Q8N2C3	581
KRTAP4-8	SLC35G6	P0C7Q6	507
KRTAP4-8	LYSET	Q8N6I4	492
KRTAP4-8	NPIPB12	F8W0I5	479
KRTAP4-8	POTEC	B2RU33	447
KRTAP4-8	NPIPB4	C9JG80	447
KRTAP4-8	VCF2	Q5XKR9	447
KRTAP4-8	KRTAP17-1	Q9BYP8	447
KRTAP4-8	NPIPB5	A8MRT5	446
KRTAP4-8	POTEM	A6NI47	445
KRTAP4-8	PWWP2B	Q6NUJ5	444
KRTAP4-8	NPIPB13	A6NJU9	444
KRTAP4-8	RGPD3	A6NKT7	432
KRTAP4-8	DTD2	Q96FN9	431

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A286YEV6, A0A286YEX9, A0A286YEY9, A0A286YF01, A0A286YF46, A0A286YF60, A0A286YF77, A0A286YFB4, A0A286YFG1, O14633, P02438, P04459, P05687, P05688, P08131, P08175, P0DSO2, P20730, Q01642, Q01643, Q01644, Q01645, Q07627, Q3LI58, Q3LI59, Q3V2C1, Q5T750, Q5T752, Q5T754, Q5TA78, Q5TA79, Q5TA81, Q5TA82, Q5TCM9, Q8IUC1, Q8IUG1, Q9BQ66, Q9BYP8, Q9BYQ5, Q9BYQ6

SIGNOR signaling

0 interactions.

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	31
Likely benign	6
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

282 predictions. Top by Δscore:

Variant	Effect	Δscore
17:41097956:G:C	donor_gain	0.8000
17:41097950:A:AC	donor_gain	0.7900
17:41097951:C:CC	donor_gain	0.7900
17:41097916:A:AC	donor_gain	0.7700
17:41097917:C:CC	donor_gain	0.7700
17:41097976:T:TA	donor_gain	0.7300
17:41097317:C:CC	acceptor_gain	0.7200
17:41097314:TGA:T	acceptor_gain	0.6800
17:41097948:A:T	donor_gain	0.6800
17:41097686:G:C	donor_gain	0.6700
17:41097913:CAGA:C	donor_gain	0.6700
17:41097353:T:C	donor_gain	0.6600
17:41097355:A:T	donor_gain	0.6600
17:41097433:AAAT:A	donor_gain	0.6500
17:41097662:T:C	donor_gain	0.6400
17:41097359:A:T	donor_gain	0.6200
17:41097370:A:AC	donor_gain	0.6200
17:41097371:C:CC	donor_gain	0.6200
17:41097841:A:AC	donor_gain	0.6200
17:41097842:C:CC	donor_gain	0.6200
17:41097433:AAATC:A	donor_gain	0.6100
17:41097366:TCTCA:T	donor_loss	0.6000
17:41097367:CTCA:C	donor_loss	0.6000
17:41097368:TCA:T	donor_loss	0.6000
17:41097369:CA:C	donor_loss	0.6000
17:41097370:AC:A	donor_loss	0.6000
17:41097371:C:G	donor_loss	0.6000
17:41097873:A:T	donor_gain	0.6000
17:41097736:A:AC	donor_gain	0.5900
17:41097737:C:CC	donor_gain	0.5900

AlphaMissense

1225 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:41097791:G:C	S98R	0.659
17:41097791:G:T	S98R	0.659
17:41097793:T:G	S98R	0.659
17:41097532:A:G	C185R	0.636
17:41097573:A:G	I171T	0.629
17:41097595:A:G	C164R	0.609
17:41097593:G:C	C164W	0.595
17:41097866:G:C	S73R	0.595
17:41097866:G:T	S73R	0.595
17:41097868:T:G	S73R	0.595
17:41097589:G:T	R166S	0.587
17:41097580:A:G	C169R	0.573

dbSNP variants (sampled 300 via entrez): RS1000410672 (17:41098540 T>C,G), RS1000744926 (17:41099552 A>G,T), RS1000794265 (17:41099694 T>A), RS1002899235 (17:41097216 A>G), RS1003250645 (17:41098181 A>T), RS1003302546 (17:41098373 C>T), RS1004979716 (17:41097028 G>C), RS1006983642 (17:41098740 C>A), RS1007313556 (17:41099818 T>C), RS1007774815 (17:41099962 T>C), RS1007808596 (17:41096948 A>G,T), RS1009390993 (17:41099613 T>G), RS1009503417 (17:41098833 C>A,G,T), RS1009853939 (17:41099731 A>G), RS1009887120 (17:41096673 C>A,G,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

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
2-methyl-4-isothiazolin-3-one	increases expression	1
diallyl trisulfide	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Polystyrenes	increases expression	1
Smoke	increases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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