KRTAP4-9

Summary

KRTAP4-9 (keratin associated protein 4-9, HGNC:18910) is a protein-coding gene on chromosome 17q21.2, encoding Keratin-associated protein 4-9 (Q9BYQ8). 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 100132386 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 49 total — 1 pathogenic
• MANE Select transcript: NM_001146041

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18910
Approved symbol	KRTAP4-9
Name	keratin associated protein 4-9
Location	17q21.2
Locus type	gene with protein product
Status	Approved
Aliases	KAP4.9
Ensembl gene	ENSG00000212722
Ensembl biotype	protein_coding
Entrez	100132386

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000391415

RefSeq mRNA: 1 — MANE Select: NM_001146041 NM_001146041

CCDS: CCDS54124

Canonical transcript exons

ENST00000391415 — 1 exons

Exon	Start	End
ENSE00003978170	41105389	41106488

Expression profiles

Bgee: expression breadth broad, 27 present calls, max score 42.88.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	42.88	gold quality
skin of abdomen	UBERON:0001416	40.97	gold quality
zone of skin	UBERON:0000014	39.12	gold quality
skin of leg	UBERON:0001511	38.05	gold quality
right lung	UBERON:0002167	37.95	gold 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
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
stromal cell of endometrium	CL:0002255	29.87	gold quality
blood	UBERON:0000178	29.58	gold quality
muscle of leg	UBERON:0001383	29.37	gold quality
prefrontal cortex	UBERON:0000451	29.21	gold quality
gastrocnemius	UBERON:0001388	29.15	gold quality
lymph node	UBERON:0000029	29.01	gold quality
leukocyte	CL:0000738	28.28	gold quality
duodenum	UBERON:0002114	28.14	gold quality
monocyte	CL:0000576	27.75	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
pancreas	UBERON:0001264	26.38	gold quality
kidney	UBERON:0002113	26.21	silver quality
gall bladder	UBERON:0002110	25.98	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	25.89	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.06

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

43 targeting KRTAP4-9, 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-3662	99.99	73.82	5684
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-4728-5P	99.85	69.39	4718
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-3681-5P	99.82	66.88	387
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-7156-5P	99.64	68.81	1369
HSA-MIR-6849-5P	99.64	66.00	352
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-4273	99.45	67.93	1206
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-330-3P	99.41	69.95	2521
HSA-MIR-5190	99.15	67.76	1234
HSA-MIR-4777-3P	99.15	68.92	626
HSA-MIR-1253	99.12	67.08	1688

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), KRTAP4-8 (ENSG00000204880), KRTAP1-4 (ENSG00000204887), KRTAP12-3 (ENSG00000205439), KRTAP10-2 (ENSG00000205445), KRTAP5-6 (ENSG00000205864), KRTAP5-2 (ENSG00000205867), KRTAP16-1 (ENSG00000212657), KRTAP9-6 (ENSG00000212659), KRTAP4-11 (ENSG00000212721), 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 4-9 — Q9BYQ8 (reviewed: Q9BYQ8)

Alternative names: Keratin-associated protein 4.9, Ultrahigh sulfur keratin-associated protein 4.9

All UniProt accessions (1): Q9BYQ8

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.

Similarity. Belongs to the KRTAP type 4 family.

RefSeq proteins (1): NP_001139513* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002494	KAP	Family

Pfam: PF01500, PF13885

UniProt features (32 total): repeat 28, chain 1, region of interest 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BYQ8-F1	36.86	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: 24 (showing top): GOBP_MOLTING_CYCLE, RIGGI_EWING_SARCOMA_PROGENITOR_UP, GOCC_INTERMEDIATE_FILAMENT_CYTOSKELETON, GOCC_KERATIN_FILAMENT, GOCC_SUPRAMOLECULAR_COMPLEX, GOCC_POLYMERIC_CYTOSKELETAL_FIBER, REACTOME_KERATINIZATION, GOCC_SUPRAMOLECULAR_POLYMER, LHX9_TARGET_GENES, MIR330_3P, LET_7A_2_3P, LET_7G_3P, MIR4276, MIR3915, MIR6505_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

0 interactions, top by confidence (×1000):

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

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	45
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3242217	GRCh37/hg19 17q12-22(chr17:41196270-41277589)	Pathogenic

SpliceAI

292 predictions. Top by Δscore:

Variant	Effect	Δscore
17:41106104:G:GT	donor_gain	0.8300
17:41105496:G:GT	donor_gain	0.7800
17:41105810:A:AG	donor_gain	0.7600
17:41105811:G:GG	donor_gain	0.7600
17:41105520:T:G	donor_gain	0.7500
17:41105616:G:GT	donor_gain	0.7300
17:41105481:G:GT	donor_gain	0.7200
17:41105721:G:GT	donor_gain	0.7200
17:41105556:GTCT:G	donor_gain	0.7000
17:41106233:G:GA	donor_gain	0.7000
17:41105862:C:G	donor_gain	0.6800
17:41105772:C:G	donor_gain	0.6600
17:41106104:G:T	donor_gain	0.6600
17:41105555:A:AG	donor_gain	0.6200
17:41105909:GCTGC:G	donor_gain	0.6100
17:41105526:ATCC:A	donor_gain	0.6000
17:41106018:C:G	donor_gain	0.5900
17:41105394:C:A	donor_gain	0.5700
17:41106097:G:GT	donor_gain	0.5700
17:41106105:A:T	donor_gain	0.5700
17:41106177:T:G	donor_gain	0.5700
17:41105914:G:GG	donor_gain	0.5600
17:41106113:TTG:T	donor_gain	0.5600
17:41106229:C:CA	acceptor_gain	0.5600
17:41105757:C:G	donor_gain	0.5500
17:41105738:C:CG	donor_gain	0.5400
17:41105738:C:G	donor_gain	0.5300
17:41105886:A:G	donor_gain	0.5300
17:41105912:GC:G	donor_gain	0.5300
17:41105982:C:G	donor_gain	0.5300

AlphaMissense

1394 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:41105968:T:C	C194R	0.777
17:41105953:T:C	C189R	0.774
17:41105970:T:G	C194W	0.767
17:41105975:T:C	I196T	0.755
17:41105941:T:C	C185R	0.741
17:41105956:T:G	Y190D	0.734
17:41105955:C:G	C189W	0.730
17:41105943:C:G	C185W	0.709
17:41105983:T:C	C199R	0.694
17:41105985:C:G	C199W	0.689
17:41105975:T:A	I196N	0.677
17:41105969:G:A	C194Y	0.660
17:41105975:T:G	I196S	0.657
17:41105498:C:T	T37I	0.654
17:41105959:C:A	R191S	0.653
17:41105972:T:A	V195D	0.651
17:41105530:A:C	S48R	0.650
17:41105532:C:A	S48R	0.650
17:41105532:C:G	S48R	0.650
17:41105960:G:C	R191P	0.647
17:41105954:G:A	C189Y	0.644
17:41105941:T:A	C185S	0.637
17:41105942:G:C	C185S	0.637
17:41105650:A:C	S88R	0.632
17:41105652:C:A	S88R	0.632
17:41105652:C:G	S88R	0.632
17:41105926:T:C	C180R	0.631
17:41105755:A:C	S123R	0.627
17:41105757:C:A	S123R	0.627
17:41105757:C:G	S123R	0.627

dbSNP variants (sampled 300 via entrez): RS1000639948 (17:41104357 T>G), RS1000704701 (17:41103452 G>A), RS1004669474 (17:41106722 T>C), RS1007211380 (17:41105457 C>G,T), RS1007336617 (17:41104098 A>C), RS1008936753 (17:41106685 T>TGC), RS1009286778 (17:41104809 G>A), RS1014658997 (17:41106754 A>T), RS1014711487 (17:41106985 T>C), RS1018566554 (17:41105460 C>T), RS1018926687 (17:41105077 G>C), RS1020915367 (17:41106112 GT>G), RS1023434574 (17:41104349 G>A), RS1023561008 (17:41103434 A>C), RS1025054624 (17:41105803 T>G)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:604370

GenCC curated gene-disease

Mondo (1): breast-ovarian cancer, familial, susceptibility to, 1 (MONDO:0011450)

Orphanet (1): Hereditary breast and/or ovarian cancer syndrome (Orphanet:145)

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
bisphenol A	decreases methylation	1
Resveratrol	affects cotreatment, decreases expression	1
Formaldehyde	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	increases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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