KRTAP9-4

Summary

KRTAP9-4 (keratin associated protein 9-4, HGNC:18902) is a protein-coding gene on chromosome 17q21.2, encoding Keratin-associated protein 9-4 (Q9BYQ2). 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….

This protein is a member of the keratin-associated protein (KAP) family. The KAP proteins form a matrix of keratin intermediate filaments which contribute to the structure of hair fibers. KAP family members appear to have unique, family-specific amino- and carboxyl-terminal regions and are subdivided into three multi-gene families according to amino acid composition: the high sulfur, the ultrahigh sulfur, and the high tyrosine/glycine KAPs. This protein is a member of the ultrahigh sulfur KAP family and the gene is localized to a cluster of KAPs at 17q12-q21.

Source: NCBI Gene 85280 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 28 total
• MANE Select transcript: NM_033191

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18902
Approved symbol	KRTAP9-4
Name	keratin associated protein 9-4
Location	17q21.2
Locus type	gene with protein product
Status	Approved
Aliases	KAP9.4
Ensembl gene	ENSG00000241595
Ensembl biotype	protein_coding
Entrez	85280

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000334109

RefSeq mRNA: 1 — MANE Select: NM_033191 NM_033191

CCDS: CCDS11386

Canonical transcript exons

ENST00000334109 — 1 exons

Exon	Start	End
ENSE00001384985	41249687	41250653

Expression profiles

Bgee: expression breadth broad, 22 present calls, max score 40.13.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skin of abdomen	UBERON:0001416	40.13	gold quality
zone of skin	UBERON:0000014	38.10	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
skin of leg	UBERON:0001511	36.83	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
right lung	UBERON:0002167	36.32	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
hindlimb stylopod muscle	UBERON:0004252	35.96	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
prefrontal cortex	UBERON:0000451	29.04	gold quality
blood	UBERON:0000178	29.03	silver quality
muscle of leg	UBERON:0001383	28.61	gold quality
right adrenal gland cortex	UBERON:0035827	28.51	gold quality
gastrocnemius	UBERON:0001388	28.14	gold quality
duodenum	UBERON:0002114	28.14	gold quality
lymph node	UBERON:0000029	27.57	gold quality
urinary bladder	UBERON:0001255	26.78	gold quality
islet of Langerhans	UBERON:0000006	26.55	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
pancreas	UBERON:0001264	26.11	gold quality
gall bladder	UBERON:0002110	25.98	gold quality
right adrenal gland	UBERON:0001233	25.97	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	25.89	gold quality
placenta	UBERON:0001987	25.81	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

miRNA regulators (miRDB)

44 targeting KRTAP9-4, 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-223-3P	99.99	70.14	1140
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-6832-5P	99.58	64.82	1132
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-2392	99.43	67.50	708
HSA-MIR-5697	99.39	67.74	1249
HSA-MIR-4311	99.31	70.47	3041
HSA-MIR-888-5P	99.30	70.15	1855
HSA-MIR-3692-5P	99.29	67.04	1421
HSA-MIR-892C-5P	99.16	70.56	2116
HSA-MIR-922	99.02	67.23	1838
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-520G-3P	98.91	67.38	1914
HSA-MIR-520H	98.91	67.38	1914
HSA-MIR-4451	98.82	68.17	1455
HSA-MIR-214-3P	98.71	68.12	2128
HSA-MIR-761	98.71	68.07	2051
HSA-MIR-6894-5P	98.70	63.78	809
HSA-MIR-6728-3P	98.63	67.63	1534
HSA-MIR-4290	98.51	65.17	907
HSA-MIR-3928-5P	98.50	67.48	980
HSA-MIR-6806-3P	98.50	67.31	980

Cross-species orthologs

0 orthologs

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), 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)

Protein

Protein identifiers

Keratin-associated protein 9-4 — Q9BYQ2 (reviewed: Q9BYQ2)

Alternative names: Keratin-associated protein 9.4, Ultrahigh sulfur keratin-associated protein 9.4

All UniProt accessions (1): Q9BYQ2

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.

Similarity. Belongs to the KRTAP type 9 family.

RefSeq proteins (1): NP_149461* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002494	KAP	Family

Pfam: PF13885

UniProt features (18 total): repeat 15, chain 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BYQ2-F1	37.45	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: 20 (showing top): MARTINEZ_RB1_TARGETS_DN, GOCC_INTERMEDIATE_FILAMENT_CYTOSKELETON, GOCC_KERATIN_FILAMENT, GOCC_SUPRAMOLECULAR_COMPLEX, GOCC_POLYMERIC_CYTOSKELETAL_FIBER, REACTOME_KERATINIZATION, GOCC_SUPRAMOLECULAR_POLYMER, MIR570_3P, MIR4311, MIR892C_5P, MIR3123, MIR518A_5P_MIR527, MIR6894_5P, NIKOLSKY_BREAST_CANCER_17Q11_Q21_AMPLICON, MARTINEZ_RB1_AND_TP53_TARGETS_DN

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

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
binding	1
cytoplasm	1
cellular anatomical structure	1
intermediate filament	1
intermediate filament cytoskeleton	1
polymeric cytoskeletal fiber	1

Protein interactions and networks

STRING

232 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KRTAP9-4	KRTAP3-1	Q9BYR8	576
KRTAP9-4	KRTAP13-3	Q3SY46	524
KRTAP9-4	KRTAP17-1	Q9BYP8	479
KRTAP9-4	KRTAP1-5	Q9BYS1	469
KRTAP9-4	KRTAP3-3	Q9BYR6	434
KRTAP9-4	KRTCAP3	Q53RY4	431
KRTAP9-4	KRT33B	Q14525	399
KRTAP9-4	KPRP	Q5T749	395
KRTAP9-4	PRB4	P02813	370
KRTAP9-4	KRT83	P78385	358
KRTAP9-4	MARVELD1	Q9BSK0	354
KRTAP9-4	KRT27	Q7Z3Y8	348
KRTAP9-4	PRB2	P02811	348
KRTAP9-4	KRT86	P78387	348
KRTAP9-4	KRT6C	P48666	339

IntAct

98 interactions, top by confidence:

A	B	Type	Score
KRTAP9-4	LCE1B	psi-mi:“MI:0915”(physical association)	0.670
LCE1B	KRTAP9-4	psi-mi:“MI:0915”(physical association)	0.670
KRTAP9-4	PRKAB2	psi-mi:“MI:0915”(physical association)	0.560
KRTAP9-4	MAPKBP1	psi-mi:“MI:0915”(physical association)	0.560
OTX1	KRTAP9-4	psi-mi:“MI:0915”(physical association)	0.560
KRTAP9-4	SMCP	psi-mi:“MI:0915”(physical association)	0.560
KRTAP9-4	KRTAP10-5	psi-mi:“MI:0915”(physical association)	0.560
KRTAP9-4	CREB5	psi-mi:“MI:0915”(physical association)	0.560
KRTAP9-4	LCE3C	psi-mi:“MI:0915”(physical association)	0.560
LCE3E	KRTAP9-4	psi-mi:“MI:0915”(physical association)	0.560
LCE4A	KRTAP9-4	psi-mi:“MI:0915”(physical association)	0.560
KRTAP5-6	KRTAP9-4	psi-mi:“MI:0915”(physical association)	0.560
DHX57	KRTAP9-4	psi-mi:“MI:0915”(physical association)	0.560
KRTAP9-4	DOCK2	psi-mi:“MI:0915”(physical association)	0.560
KRTAP9-4	FBXW5	psi-mi:“MI:0915”(physical association)	0.560
NTAQ1	KRTAP9-4	psi-mi:“MI:0915”(physical association)	0.560
NUFIP2	KRTAP9-4	psi-mi:“MI:0915”(physical association)	0.560
KRTAP9-4		psi-mi:“MI:0915”(physical association)	0.560
SPRY2	KRTAP9-4	psi-mi:“MI:0915”(physical association)	0.560
KRTAP9-4	KRTAP5-9	psi-mi:“MI:0915”(physical association)	0.560
KRTAP9-4	HOXA1	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-5	KRTAP9-4	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-8	KRTAP9-4	psi-mi:“MI:0915”(physical association)	0.560
KRTAP9-4	KRTAP10-9	psi-mi:“MI:0915”(physical association)	0.560
REL	KRTAP9-4	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (32): KRTAP9-4 (Two-hybrid), KRTAP9-4 (Two-hybrid), KRTAP9-4 (Two-hybrid), KRTAP9-4 (Two-hybrid), KRTAP9-4 (Two-hybrid), KRTAP9-4 (Two-hybrid), KRTAP9-4 (Two-hybrid), KRTAP9-4 (Two-hybrid), KRTAP9-4 (Two-hybrid), KRTAP9-4 (Two-hybrid), KRTAP9-4 (Two-hybrid), KRTAP9-4 (Two-hybrid), KRTAP9-4 (Two-hybrid), KRTAP9-4 (Two-hybrid), KRTAP9-4 (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

Diamond homologs: A5A6P5, Q9BYP9, Q9BYQ0, Q9BYQ2, Q9BYQ3, Q9BYQ4, A8MTY7, A8MVA2

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 28 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	11	30.6×	5e-13

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	27
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

228 predictions. Top by Δscore:

Variant	Effect	Δscore
17:41249792:G:GT	donor_gain	0.8300
17:41250390:T:TA	acceptor_gain	0.8000
17:41250384:A:AG	acceptor_gain	0.7600
17:41250481:G:GT	donor_gain	0.7300
17:41250391:G:A	acceptor_gain	0.7100
17:41250385:C:G	acceptor_gain	0.7000
17:41250384:ACTTT:A	acceptor_gain	0.6600
17:41249780:G:GT	donor_gain	0.6500
17:41250454:TC:T	donor_gain	0.6400
17:41250345:G:T	donor_gain	0.6200
17:41250344:G:GT	donor_gain	0.6000
17:41250472:GCTTC:G	donor_gain	0.5800
17:41249927:C:G	donor_gain	0.5700
17:41250578:T:G	acceptor_gain	0.5700
17:41250535:A:AG	acceptor_gain	0.5500
17:41250585:G:A	acceptor_gain	0.5400
17:41250476:C:G	donor_gain	0.5200
17:41249980:G:A	donor_gain	0.5100
17:41250423:T:G	donor_gain	0.5100
17:41250482:A:T	donor_gain	0.5100
17:41249977:G:GG	donor_gain	0.5000
17:41250168:C:A	donor_gain	0.5000
17:41250124:G:GG	donor_gain	0.4900
17:41250476:C:CG	donor_gain	0.4800
17:41250553:CTT:C	donor_gain	0.4800
17:41249765:G:GT	donor_gain	0.4700
17:41250020:C:CG	donor_gain	0.4700
17:41250065:T:TA	donor_gain	0.4700
17:41250405:C:G	donor_gain	0.4700
17:41250485:T:G	donor_gain	0.4700

AlphaMissense

1017 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:41249856:A:C	S46R	0.575
17:41249858:C:A	S46R	0.575
17:41249858:C:G	S46R	0.575

dbSNP variants (sampled 300 via entrez): RS1002346051 (17:41250515 G>A,C), RS1002796673 (17:41250986 G>T), RS1003465831 (17:41247898 A>G), RS1003759415 (17:41247682 G>A,T), RS1004908119 (17:41250959 A>G), RS1007008298 (17:41249242 A>G), RS1007193063 (17:41248722 A>G), RS1007542772 (17:41248746 A>G), RS1007902767 (17:41251137 A>G), RS1008003238 (17:41250910 GAAGT>G), RS1009470172 (17:41249201 T>C,G), RS1009869734 (17:41250397 T>C), RS1010592986 (17:41249392 C>T), RS1011649758 (17:41250685 A>G), RS1011939952 (17:41247935 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

3 total (human), top 3 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
2-palmitoylglycerol	increases expression	1
Aflatoxin B1	decreases methylation	1
Copper Sulfate	increases expression	1

Clinical trials (associated diseases)

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