KRTAP4-12

Summary

KRTAP4-12 (keratin associated protein 4-12, HGNC:16776) is a protein-coding gene on chromosome 17q21.2, encoding Keratin-associated protein 4-12 (Q9BQ66). 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: 60.0% 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 83755 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 51 total
• Cancer dependency (DepMap): dependent in 60.0% of screened cell lines
• MANE Select transcript: NM_031854

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16776
Approved symbol	KRTAP4-12
Name	keratin associated protein 4-12
Location	17q21.2
Locus type	gene with protein product
Status	Approved
Aliases	KAP4.12
Ensembl gene	ENSG00000213416
Ensembl biotype	protein_coding
Entrez	83755

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000394014

RefSeq mRNA: 1 — MANE Select: NM_031854 NM_031854

CCDS: CCDS32649

Canonical transcript exons

ENST00000394014 — 1 exons

Exon	Start	End
ENSE00001615097	41123091	41124182

Expression profiles

Bgee: expression breadth broad, 28 present calls, max score 43.89.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1037 / max 29.0365, expressed in 43 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165875	0.1037	43

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	43.89	gold quality
skin of abdomen	UBERON:0001416	40.60	gold quality
stromal cell of endometrium	CL:0002255	39.88	gold quality
zone of skin	UBERON:0000014	38.13	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
granulocyte	CL:0000094	37.18	gold quality
skin of leg	UBERON:0001511	36.62	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
right lung	UBERON:0002167	35.02	gold quality
blood	UBERON:0000178	33.58	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
islet of Langerhans	UBERON:0000006	32.11	silver quality
bone marrow	UBERON:0002371	31.74	gold quality
lymph node	UBERON:0000029	31.62	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
liver	UBERON:0002107	30.64	gold quality
prefrontal cortex	UBERON:0000451	29.04	gold quality
muscle of leg	UBERON:0001383	28.51	gold quality
right lobe of liver	UBERON:0001114	28.48	gold quality
duodenum	UBERON:0002114	28.14	gold quality
gastrocnemius	UBERON:0001388	27.94	gold quality
leukocyte	CL:0000738	27.56	gold quality
tonsil	UBERON:0002372	27.05	gold quality
monocyte	CL:0000576	26.93	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
kidney	UBERON:0002113	26.07	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.10

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

44 targeting KRTAP4-12, 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-4533	100.00	69.48	2758
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-219A-5P	99.91	73.36	735
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-4782-3P	99.88	73.31	735
HSA-MIR-6766-3P	99.88	73.38	732
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-7161-5P	99.68	68.92	1592
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-548U	99.65	67.78	1463
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-150-3P	99.43	70.51	920
HSA-MIR-20B-3P	99.29	67.05	784
HSA-MIR-8065	99.19	70.38	1289
HSA-MIR-4263	99.18	69.25	2236
HSA-MIR-4520-2-3P	99.14	69.28	1009
HSA-MIR-452-3P	99.01	66.25	1241
HSA-MIR-6894-5P	98.70	63.78	809
HSA-MIR-624-3P	98.37	67.06	1067

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 60.0% of screened cell lines.

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
mus_musculus	Krtap4-7	ENSMUSG00000045109
mus_musculus	Krtap4-24	ENSMUSG00000078130
rattus_norvegicus	Krtap9-7	ENSRNOG00000026803
rattus_norvegicus		ENSRNOG00000077385
rattus_norvegicus		ENSRNOG00000080465

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), 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 4-12 — Q9BQ66 (reviewed: Q9BQ66)

Alternative names: Keratin-associated protein 4.12, Ultrahigh sulfur keratin-associated protein 4.12

All UniProt accessions (1): Q9BQ66

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_114060* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002494	KAP	Family

Pfam: PF13885

UniProt features (33 total): repeat 30, chain 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BQ66-F1	35.58	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 37 (showing top): GOBP_MOLTING_CYCLE, GOCC_INTERMEDIATE_FILAMENT_CYTOSKELETON, GOCC_KERATIN_FILAMENT, GOCC_SUPRAMOLECULAR_COMPLEX, GOCC_POLYMERIC_CYTOSKELETAL_FIBER, GOCC_SUPRAMOLECULAR_POLYMER, MIR4802_3P, MIR4443, MIR4520_2_3P, MIR3612, MIR650, MIR7154_3P, GSE13485_CTRL_VS_DAY1_YF17D_VACCINE_PBMC_DN, GSE13485_DAY1_VS_DAY3_YF17D_VACCINE_PBMC_UP, GSE13485_DAY1_VS_DAY7_YF17D_VACCINE_PBMC_UP

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)

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

467 interactions, top by confidence:

A	B	Type	Score
KRTAP4-12	SMCP	psi-mi:“MI:0915”(physical association)	0.790
SMCP	KRTAP4-12	psi-mi:“MI:0915”(physical association)	0.790
KRTAP4-12	GLRX3	psi-mi:“MI:0915”(physical association)	0.780
KRTAP4-12	HOXA1	psi-mi:“MI:0915”(physical association)	0.780
KRTAP4-12	LCE1B	psi-mi:“MI:0915”(physical association)	0.780
CATSPER1	KRTAP4-12	psi-mi:“MI:0915”(physical association)	0.780
KRTAP4-12	OTX1	psi-mi:“MI:0915”(physical association)	0.780
CRCT1	KRTAP4-12	psi-mi:“MI:0915”(physical association)	0.780
GLRX3	KRTAP4-12	psi-mi:“MI:0915”(physical association)	0.780
HOXA1	KRTAP4-12	psi-mi:“MI:0915”(physical association)	0.780
OTX1	KRTAP4-12	psi-mi:“MI:0915”(physical association)	0.780
KRTAP4-12	CRCT1	psi-mi:“MI:0915”(physical association)	0.780
LCE1B	KRTAP4-12	psi-mi:“MI:0915”(physical association)	0.780
NUFIP2	KRTAP4-12	psi-mi:“MI:0915”(physical association)	0.720
KRTAP4-12	MAPKBP1	psi-mi:“MI:0915”(physical association)	0.720
KRTAP4-12	KRTAP5-9	psi-mi:“MI:0915”(physical association)	0.720
KRTAP4-12	CREB5	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (199): KRTAP4-12 (Two-hybrid), KRTAP4-12 (Two-hybrid), KRTAP4-12 (Two-hybrid), KRTAP4-12 (Two-hybrid), KRTAP4-12 (Two-hybrid), KRTAP4-12 (Two-hybrid), KRTAP4-12 (Two-hybrid), KRTAP4-12 (Two-hybrid), KRTAP4-12 (Two-hybrid), KRTAP4-12 (Two-hybrid), KRTAP4-12 (Two-hybrid), KRTAP4-12 (Two-hybrid), KRTAP4-12 (Two-hybrid), KRTAP4-12 (Two-hybrid), KRTAP4-12 (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 64 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	25	31.6×	6e-31
Formation of the cornified envelope	14	27.9×	9e-16

GO biological processes:

GO term	Partners	Fold	FDR
keratinization	13	66.2×	1e-18

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	42
Likely benign	9
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

276 predictions. Top by Δscore:

Variant	Effect	Δscore
17:41123786:T:TA	donor_gain	0.7100
17:41123726:A:AC	donor_gain	0.6900
17:41123727:C:CC	donor_gain	0.6900
17:41123723:CAGA:C	donor_gain	0.6700
17:41123846:A:AC	donor_gain	0.6700
17:41123847:C:CC	donor_gain	0.6700
17:41123735:A:AC	donor_gain	0.5900
17:41123736:C:CC	donor_gain	0.5900
17:41123843:CAGA:C	donor_gain	0.5900
17:41123183:CTGGA:C	donor_gain	0.5800
17:41124026:T:TA	donor_gain	0.5800
17:41123966:A:AC	donor_gain	0.5700
17:41123967:C:CC	donor_gain	0.5700
17:41123758:A:T	donor_gain	0.5500
17:41123345:T:G	acceptor_gain	0.5400
17:41123182:A:AC	donor_gain	0.5300
17:41123183:C:CC	donor_gain	0.5300
17:41123766:G:C	donor_gain	0.5300
17:41123341:T:TA	donor_gain	0.5200
17:41123520:G:C	donor_gain	0.5200
17:41123763:G:C	donor_gain	0.5200
17:41123878:A:T	donor_gain	0.5200
17:41123470:C:CC	acceptor_gain	0.5100
17:41123751:G:C	donor_gain	0.5000
17:41123180:TC:T	donor_gain	0.4800
17:41123906:T:TA	donor_gain	0.4700
17:41123673:G:C	donor_gain	0.4600
17:41123725:G:T	donor_gain	0.4600
17:41123101:CAA:C	acceptor_gain	0.4500
17:41123190:T:TA	donor_gain	0.4500

AlphaMissense

1325 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:41123871:G:C	S84R	0.864
17:41123871:G:T	S84R	0.864
17:41123873:T:G	S84R	0.864
17:41123991:G:C	S44R	0.831
17:41123991:G:T	S44R	0.831
17:41123993:T:G	S44R	0.831
17:41123570:A:G	C185R	0.828
17:41123585:A:G	C180R	0.816
17:41123563:A:G	I187T	0.812
17:41123568:A:C	C185W	0.804
17:41124005:A:G	C40R	0.800
17:41124032:A:G	C31R	0.787
17:41123751:G:C	S124R	0.784
17:41123751:G:T	S124R	0.784
17:41123753:T:G	S124R	0.784
17:41123990:A:G	C45R	0.784
17:41123597:A:G	C176R	0.779
17:41124035:A:G	C30R	0.779
17:41123583:G:C	C180W	0.777
17:41124020:A:G	C35R	0.765
17:41123975:A:G	C50R	0.763
17:41123900:A:G	C75R	0.761
17:41124003:G:C	C40W	0.759
17:41123555:A:G	C190R	0.755
17:41123960:A:G	C55R	0.754
17:41123563:A:T	I187N	0.751
17:41123569:C:T	C185Y	0.748
17:41124030:G:C	C31W	0.743
17:41123870:A:G	C85R	0.742
17:41123930:A:G	C65R	0.740

dbSNP variants (sampled 300 via entrez): RS1001453766 (17:41123397 A>G), RS1001795255 (17:41123104 T>A,C), RS1003068274 (17:41124460 C>T), RS1003393985 (17:41125319 G>T), RS1003528680 (17:41124666 G>C,T), RS1006087501 (17:41125283 C>G), RS1010040470 (17:41123417 G>A,C), RS1010092731 (17:41123617 G>A), RS1011717838 (17:41124697 G>A), RS1011775897 (17:41124945 C>G,T), RS1012463508 (17:41125978 A>T), RS1014225320 (17:41123351 G>A), RS1015483459 (17:41125718 A>T), RS1017926707 (17:41123475 G>A), RS1018114648 (17:41122732 C>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

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
hydroxyhydroquinone	increases expression	1
CGP 52608	increases reaction, affects binding	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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