KRTAP4-2

Summary

KRTAP4-2 (keratin associated protein 4-2, HGNC:18900) is a protein-coding gene on chromosome 17q21.2, encoding Keratin-associated protein 4-2 (Q9BYR5). 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 common-essential gene (DepMap: required in 93.4% of cancer 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 85291 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 31 total
• Cancer dependency (DepMap): dependent in 93.4% of screened cell lines (common-essential)
• MANE Select transcript: NM_033062

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18900
Approved symbol	KRTAP4-2
Name	keratin associated protein 4-2
Location	17q21.2
Locus type	gene with protein product
Status	Approved
Aliases	KAP4.2
Ensembl gene	ENSG00000244537
Ensembl biotype	protein_coding
Entrez	85291

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000377726

RefSeq mRNA: 1 — MANE Select: NM_033062 NM_033062

CCDS: CCDS11384

Canonical transcript exons

ENST00000377726 — 1 exons

Exon	Start	End
ENSE00001508571	41177446	41178221

Expression profiles

Bgee: expression breadth broad, 25 present calls, max score 85.20.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0160 / max 13.5704, expressed in 2 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165880	0.0160	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibialis anterior	UBERON:0001385	85.20	silver quality
ileal mucosa	UBERON:0000331	82.83	silver quality
pancreatic ductal cell	CL:0002079	82.17	silver quality
upper arm skin	UBERON:0004263	81.03	silver quality
kidney epithelium	UBERON:0004819	68.78	gold quality
deltoid	UBERON:0001476	65.61	silver quality
epithelium of nasopharynx	UBERON:0001951	60.54	gold quality
quadriceps femoris	UBERON:0001377	59.41	gold quality
cardia of stomach	UBERON:0001162	59.01	gold quality
vastus lateralis	UBERON:0001379	57.23	gold quality
skin of hip	UBERON:0001554	56.55	silver quality
left ventricle myocardium	UBERON:0006566	56.46	gold quality
cardiac muscle of right atrium	UBERON:0003379	56.14	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	55.89	silver quality
tendon of biceps brachii	UBERON:0008188	54.72	gold quality
nasal cavity epithelium	UBERON:0005384	54.47	gold quality
myocardium	UBERON:0002349	51.25	gold quality
upper leg skin	UBERON:0004262	47.53	silver quality
bone marrow	UBERON:0002371	46.34	gold quality
layer of synovial tissue	UBERON:0007616	45.49	gold quality
lower lobe of lung	UBERON:0008949	45.45	silver quality
lateral globus pallidus	UBERON:0002476	44.92	gold quality
ventral tegmental area	UBERON:0002691	44.42	gold quality
superior vestibular nucleus	UBERON:0007227	44.11	gold quality
medulla oblongata	UBERON:0001896	44.06	gold quality
subthalamic nucleus	UBERON:0001906	43.42	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
trachea	UBERON:0003126	43.15	gold quality
germinal epithelium of ovary	UBERON:0001304	42.68	gold quality
secondary oocyte	CL:0000655	42.57	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.81

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

35 targeting KRTAP4-2, 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-4282	99.99	75.36	6408
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-133A-5P	99.28	69.13	941
HSA-MIR-664A-3P	99.22	71.08	2696
HSA-MIR-3125	99.14	68.49	2269
HSA-MIR-3916	98.99	68.04	2155
HSA-MIR-6859-5P	98.99	68.07	2049
HSA-MIR-4451	98.82	68.17	1455
HSA-MIR-3149	98.77	67.13	1639
HSA-MIR-138-5P	98.43	70.49	1292
HSA-MIR-3689A-5P	98.35	70.12	1049
HSA-MIR-3689B-5P	98.35	70.12	1049
HSA-MIR-3689E	98.35	70.12	1049
HSA-MIR-10395-3P	98.10	66.70	1726
HSA-MIR-4443	98.02	66.25	1928
HSA-MIR-4736	97.96	65.89	1287
HSA-MIR-3127-5P	97.52	65.24	786
HSA-MIR-379-5P	97.52	67.81	485
HSA-MIR-7855-5P	97.39	67.18	925
HSA-MIR-6131	97.22	66.72	960

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 93.4% of screened cell lines, common-essential.

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
mus_musculus	Krtap4-16	ENSMUSG00000046474
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	Krtap4-3	ENSRNOG00000034110
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), 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 4-2 — Q9BYR5 (reviewed: Q9BYR5)

Alternative names: Keratin-associated protein 4.2, Ultrahigh sulfur keratin-associated protein 4.2

All UniProt accessions (1): Q9BYR5

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 4 family.

RefSeq proteins (1): NP_149051* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002494	KAP	Family

Pfam: PF13885

UniProt features (23 total): repeat 20, chain 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BYR5-F1	39.28	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, GOCC_INTERMEDIATE_FILAMENT_CYTOSKELETON, GOCC_KERATIN_FILAMENT, GOCC_SUPRAMOLECULAR_COMPLEX, GOCC_POLYMERIC_CYTOSKELETAL_FIBER, REACTOME_KERATINIZATION, GOCC_SUPRAMOLECULAR_POLYMER, MIR579_3P, MIR664B_3P, MIR205_3P, MIR4451, MIR10395_3P, MIR12128, TATA_01, MIR4662A_3P

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

GO Molecular Function (2): identical protein binding (GO:0042802), 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
protein binding	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

495 interactions, top by confidence:

A	B	Type	Score
LCE1B	KRTAP4-2	psi-mi:“MI:0915”(physical association)	0.780
NR1D2	KRTAP4-2	psi-mi:“MI:0915”(physical association)	0.780
LNX1	KRTAP4-2	psi-mi:“MI:0915”(physical association)	0.780
KRTAP4-2	CRCT1	psi-mi:“MI:0915”(physical association)	0.780
KRTAP4-2	NR1D2	psi-mi:“MI:0915”(physical association)	0.780
CRCT1	KRTAP4-2	psi-mi:“MI:0915”(physical association)	0.780
KRTAP4-2	LCE1B	psi-mi:“MI:0915”(physical association)	0.780
KRTAP4-2	KRTAP5-9	psi-mi:“MI:0915”(physical association)	0.720
KRTAP4-2	AQP1	psi-mi:“MI:0915”(physical association)	0.720
HOXA1	KRTAP4-2	psi-mi:“MI:0915”(physical association)	0.720
KRTAP4-2	KRTAP10-5	psi-mi:“MI:0915”(physical association)	0.720
KRTAP10-8	KRTAP4-2	psi-mi:“MI:0915”(physical association)	0.720
KRTAP4-2	CREB5	psi-mi:“MI:0915”(physical association)	0.720
KRTAP4-2	LCE3C	psi-mi:“MI:0915”(physical association)	0.720
LCE3E	KRTAP4-2	psi-mi:“MI:0915”(physical association)	0.720
LCE4A	KRTAP4-2	psi-mi:“MI:0915”(physical association)	0.720
KRTAP4-2	LCE2A	psi-mi:“MI:0915”(physical association)	0.720
KRTAP5-6	KRTAP4-2	psi-mi:“MI:0915”(physical association)	0.720
KRTAP9-2	KRTAP4-2	psi-mi:“MI:0915”(physical association)	0.720
KRTAP4-2	NUFIP2	psi-mi:“MI:0915”(physical association)	0.720
RGS20	KRTAP4-2	psi-mi:“MI:0915”(physical association)	0.720
KRTAP10-5	KRTAP4-2	psi-mi:“MI:0915”(physical association)	0.720
KRTAP4-2	KRTAP26-1	psi-mi:“MI:0915”(physical association)	0.720
KRTAP4-2	ADAMTSL4	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (161): KRTAP4-2 (Two-hybrid), KRTAP4-2 (Two-hybrid), KRTAP4-2 (Two-hybrid), KRTAP4-2 (Two-hybrid), KRTAP4-2 (Two-hybrid), KRTAP4-2 (Two-hybrid), KRTAP4-2 (Two-hybrid), KRTAP4-2 (Two-hybrid), KRTAP4-2 (Two-hybrid), KRTAP4-2 (Two-hybrid), KRTAP4-2 (Two-hybrid), KRTAP4-2 (Two-hybrid), KRTAP4-2 (Two-hybrid), KRTAP4-2 (Two-hybrid), KRTAP4-2 (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 67 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	15	18.2×	2e-13
Formation of the cornified envelope	5	9.6×	1e-02

GO biological processes:

GO term	Partners	Fold	FDR
keratinization	5	22.1×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	28
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

132 predictions. Top by Δscore:

Variant	Effect	Δscore
17:41177913:G:C	donor_gain	0.8000
17:41177888:A:AC	donor_gain	0.7900
17:41177889:C:CC	donor_gain	0.7900
17:41178068:T:TA	donor_gain	0.7600
17:41177928:G:C	donor_gain	0.7400
17:41178008:A:AC	donor_gain	0.7300
17:41178009:C:CC	donor_gain	0.7300
17:41178040:A:T	donor_gain	0.7200
17:41177948:T:TA	donor_gain	0.7000
17:41178005:CAGA:C	donor_gain	0.7000
17:41177803:CAG:C	donor_gain	0.6900
17:41177925:G:C	donor_gain	0.6600
17:41177808:G:C	donor_gain	0.6400
17:41177802:A:AC	donor_gain	0.6300
17:41177803:C:CC	donor_gain	0.6300
17:41177805:G:C	donor_gain	0.6300
17:41177828:T:TA	donor_gain	0.6300
17:41177887:G:T	donor_gain	0.6300
17:41177879:A:AC	donor_gain	0.6200
17:41177897:A:AC	donor_gain	0.6100
17:41177898:C:CC	donor_gain	0.6100
17:41177915:TGGA:T	donor_gain	0.6000
17:41177853:G:C	donor_gain	0.5900
17:41177920:A:T	donor_gain	0.5900
17:41177639:AAT:A	donor_gain	0.5700
17:41177800:A:T	donor_gain	0.5600
17:41177923:CAG:C	donor_gain	0.5600
17:41178017:A:AC	donor_gain	0.5400
17:41178018:C:CC	donor_gain	0.5400
17:41178045:G:C	donor_gain	0.5400

AlphaMissense

898 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:41178033:G:C	S44R	0.728
17:41178033:G:T	S44R	0.728
17:41178035:T:G	S44R	0.728
17:41178047:A:G	C40R	0.636
17:41177913:G:C	S84R	0.611
17:41177913:G:T	S84R	0.611
17:41177915:T:G	S84R	0.611
17:41178032:A:G	C45R	0.600
17:41178077:A:G	C30R	0.590
17:41177907:G:C	F86L	0.589
17:41177907:G:T	F86L	0.589
17:41177909:A:G	F86L	0.589
17:41178045:G:C	C40W	0.581
17:41178062:A:G	C35R	0.570

dbSNP variants (sampled 300 via entrez): RS1002426151 (17:41178363 T>C), RS1002694344 (17:41179228 G>C), RS1003218733 (17:41179468 G>T), RS1003643750 (17:41179253 C>T), RS1004080052 (17:41178936 A>AT), RS1004181924 (17:41179149 T>A), RS1004434377 (17:41178150 A>G), RS1004821749 (17:41178860 T>G), RS1005176287 (17:41179192 C>T), RS1007103767 (17:41177135 C>A,G,T), RS1007210469 (17:41177425 A>G,T), RS1008057329 (17:41178648 C>T), RS1009000832 (17:41178636 G>C), RS1009298117 (17:41178400 T>G), RS1011009558 (17:41178608 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

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	1
CGP 52608	affects binding, increases reaction	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
Cadmium Chloride	increases expression	1

Clinical trials (associated diseases)

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