KRTAP4-11

Summary

KRTAP4-11 (keratin associated protein 4-11, HGNC:18911) is a protein-coding gene on chromosome 17q21.2, encoding Keratin-associated protein 4-11 (Q9BYQ6). 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…. It is a selective cancer dependency (DepMap: 68.0% of cell lines).

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 653240 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 65 total
• Cancer dependency (DepMap): dependent in 68.0% of screened cell lines
• MANE Select transcript: NM_033059

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18911
Approved symbol	KRTAP4-11
Name	keratin associated protein 4-11
Location	17q21.2
Locus type	gene with protein product
Status	Approved
Aliases	KAP4.11, KAP4.14
Ensembl gene	ENSG00000212721
Ensembl biotype	protein_coding
Entrez	653240

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000391413

RefSeq mRNA: 1 — MANE Select: NM_033059 NM_033059

CCDS: CCDS45675

Canonical transcript exons

ENST00000391413 — 1 exons

Exon	Start	End
ENSE00001509197	41117181	41118373

Expression profiles

Bgee: expression breadth broad, 11 present calls, max score 38.72.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0197 / max 16.4119, expressed in 3 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165874	0.0197	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lymph node	UBERON:0000029	38.72	silver quality
colonic epithelium	UBERON:0000397	37.20	gold quality
granulocyte	CL:0000094	36.86	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
skin of abdomen	UBERON:0001416	34.83	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
zone of skin	UBERON:0000014	32.81	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
skin of leg	UBERON:0001511	31.50	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
leukocyte	CL:0000738	29.62	gold quality
right lung	UBERON:0002167	29.24	silver quality
monocyte	CL:0000576	29.20	gold quality
liver	UBERON:0002107	29.17	gold quality
prefrontal cortex	UBERON:0000451	29.04	gold quality
gall bladder	UBERON:0002110	28.81	silver quality
duodenum	UBERON:0002114	28.14	gold quality
blood	UBERON:0000178	27.36	gold quality
cortex of kidney	UBERON:0001225	27.20	gold quality
tonsil	UBERON:0002372	27.05	gold quality
muscle of leg	UBERON:0001383	26.63	gold quality
islet of Langerhans	UBERON:0000006	26.55	gold quality
vermiform appendix	UBERON:0001154	26.42	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	0.18

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

59 targeting KRTAP4-11, 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-4533	100.00	69.48	2758
HSA-MIR-6077	99.99	68.04	2299
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-95-5P	99.89	72.17	3973
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-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-4307	99.82	70.45	3374
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-4470	99.66	69.35	1767
HSA-MIR-6849-5P	99.64	66.00	352
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-1252-3P	99.55	67.71	2862

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 68.0% of screened cell lines.

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), KRTAP4-9 (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 4-11 — Q9BYQ6 (reviewed: Q9BYQ6)

Alternative names: Keratin-associated protein 4-14, Keratin-associated protein 4.11, Keratin-associated protein 4.14, Ultrahigh sulfur keratin-associated protein 4.14

All UniProt accessions (1): Q9BYQ6

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_149048* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002494	KAP	Family

Pfam: PF13885

UniProt features (32 total): repeat 27, sequence conflict 2, chain 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BYQ6-F1	36.93	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: 45 (showing top): MARTINEZ_RB1_TARGETS_DN, GOBP_MOLTING_CYCLE, GOCC_INTERMEDIATE_FILAMENT_CYTOSKELETON, GOCC_KERATIN_FILAMENT, GOCC_SUPRAMOLECULAR_COMPLEX, GOCC_POLYMERIC_CYTOSKELETAL_FIBER, REACTOME_KERATINIZATION, GOCC_SUPRAMOLECULAR_POLYMER, MIR3646, MIR4728_5P, MIR6785_5P, MIR3133, MIR338_5P, MIR655_3P, MIR374C_5P

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

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
molting cycle	1
binding	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

292 interactions, top by confidence:

A	B	Type	Score
HOXA1	KRTAP4-11	psi-mi:“MI:0915”(physical association)	0.780
KRTAP4-11	HOXA1	psi-mi:“MI:0915”(physical association)	0.780
KRTAP4-11	NUFIP2	psi-mi:“MI:0915”(physical association)	0.720
GLRX3	KRTAP4-11	psi-mi:“MI:0915”(physical association)	0.720
KRTAP4-11	KRTAP5-9	psi-mi:“MI:0915”(physical association)	0.720
KRTAP4-11	OTX1	psi-mi:“MI:0915”(physical association)	0.720
SMCP	KRTAP4-11	psi-mi:“MI:0915”(physical association)	0.720
KRTAP10-8	KRTAP4-11	psi-mi:“MI:0915”(physical association)	0.720
KRTAP10-9	KRTAP4-11	psi-mi:“MI:0915”(physical association)	0.720
ADAMTSL4	KRTAP4-11	psi-mi:“MI:0915”(physical association)	0.720
KRTAP4-11	CATSPER1	psi-mi:“MI:0915”(physical association)	0.720
KRTAP4-11	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.720
KRTAP4-11	GLRX3	psi-mi:“MI:0915”(physical association)	0.720
OTX1	KRTAP4-11	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (105): KRTAP4-11 (Two-hybrid), KRTAP4-11 (Two-hybrid), KRTAP4-11 (Two-hybrid), KRTAP4-11 (Two-hybrid), KRTAP4-11 (Two-hybrid), KRTAP4-11 (Two-hybrid), KRTAP4-11 (Two-hybrid), KRTAP4-11 (Two-hybrid), KRTAP4-11 (Two-hybrid), KRTAP4-11 (Two-hybrid), KRTAP4-11 (Two-hybrid), KRTAP4-11 (Two-hybrid), KRTAP4-11 (Two-hybrid), KRTAP4-11 (Two-hybrid), KRTAP4-11 (Two-hybrid)

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.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 70 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	29	33.0×	7e-37
Formation of the cornified envelope	14	25.1×	6e-15

GO biological processes:

GO term	Partners	Fold	FDR
keratinization	14	65.5×	6e-20

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	62
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

274 predictions. Top by Δscore:

Variant	Effect	Δscore
17:41117518:C:CC	acceptor_gain	0.6900
17:41118147:A:AC	donor_gain	0.6800
17:41118148:C:CC	donor_gain	0.6800
17:41118097:G:C	donor_gain	0.6600
17:41117515:TGA:T	acceptor_gain	0.6400
17:41117937:A:AC	donor_gain	0.6400
17:41117938:C:CC	donor_gain	0.6400
17:41117479:G:C	donor_gain	0.6200
17:41118222:T:TA	donor_gain	0.6200
17:41117887:G:C	donor_gain	0.6100
17:41117934:CAGA:C	donor_gain	0.6100
17:41118207:T:TA	donor_gain	0.6000
17:41118074:A:T	donor_gain	0.5900
17:41117992:G:C	donor_gain	0.5800
17:41118079:G:C	donor_gain	0.5700
17:41117513:CATGA:C	acceptor_gain	0.5600
17:41117863:T:C	donor_gain	0.5600
17:41118144:CAGA:C	donor_gain	0.5600
17:41117406:A:AC	donor_gain	0.5400
17:41117407:C:CC	donor_gain	0.5400
17:41117857:G:C	donor_gain	0.5400
17:41117969:A:T	donor_gain	0.5400
17:41117572:CAGA:C	donor_gain	0.5200
17:41117571:A:AC	donor_gain	0.5100
17:41117572:C:CC	donor_gain	0.5100
17:41117946:A:AC	donor_gain	0.5100
17:41117947:C:CC	donor_gain	0.5100
17:41117731:G:C	donor_gain	0.5000
17:41117767:G:C	donor_gain	0.5000
17:41117974:G:C	donor_gain	0.5000

AlphaMissense

1290 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:41118097:G:C	S73R	0.715
17:41118097:G:T	S73R	0.715
17:41118099:T:G	S73R	0.715
17:41117779:A:C	C179W	0.655
17:41118067:G:C	S83R	0.655
17:41118067:G:T	S83R	0.655
17:41118069:T:G	S83R	0.655
17:41117887:G:C	S143R	0.652
17:41117887:G:T	S143R	0.652
17:41117889:T:G	S143R	0.652
17:41117962:G:C	S118R	0.638
17:41117962:G:T	S118R	0.638
17:41117964:T:G	S118R	0.638
17:41117794:G:C	C174W	0.626
17:41117781:A:G	C179R	0.622
17:41117992:G:C	S108R	0.620
17:41117992:G:T	S108R	0.620
17:41117994:T:G	S108R	0.620
17:41117774:A:G	I181T	0.614
17:41118172:G:C	S48R	0.601
17:41118172:G:T	S48R	0.601
17:41118174:T:G	S48R	0.601
17:41117806:G:C	C170W	0.575
17:41117808:A:G	C170R	0.570
17:41117793:A:C	Y175D	0.569

dbSNP variants (sampled 300 via entrez): RS1001501837 (17:41118698 A>T), RS1001837358 (17:41119708 C>T), RS1004406838 (17:41119625 A>G), RS1006035523 (17:41120311 G>A,C), RS1006125945 (17:41117005 A>C,G), RS1006175295 (17:41117132 G>A), RS1010272111 (17:41117549 T>C,G), RS1010490794 (17:41119912 T>C), RS1010586638 (17:41120130 T>C), RS1010660015 (17:41119118 C>T), RS1012648485 (17:41117188 A>G), RS1013121527 (17:41117360 G>T), RS1016082076 (17:41116845 T>A,C), RS1016132757 (17:41117022 G>A), RS1017763232 (17:41117595 G>C)

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

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Resveratrol	affects cotreatment, decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Polystyrenes	increases expression	1
Asbestos, Serpentine	increases methylation	1
Asbestos, Crocidolite	increases methylation	1

Clinical trials (associated diseases)

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