KRTAP2-4

Summary

KRTAP2-4 (keratin associated protein 2-4, HGNC:18891) is a protein-coding gene on chromosome 17q21.2, encoding Keratin-associated protein 2-4 (Q9BYR9). 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 high sulfur KAP family and the gene is localized to a cluster of KAPs at 17q12-q21.

Source: NCBI Gene 85294 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 35 total
• MANE Select transcript: NM_033184

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18891
Approved symbol	KRTAP2-4
Name	keratin associated protein 2-4
Location	17q21.2
Locus type	gene with protein product
Status	Approved
Aliases	KAP2.4
Ensembl gene	ENSG00000213417
Ensembl biotype	protein_coding
Entrez	85294

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000394015

RefSeq mRNA: 1 — MANE Select: NM_033184 NM_033184

CCDS: CCDS32648

Canonical transcript exons

ENST00000394015 — 1 exons

Exon	Start	End
ENSE00001517235	41065116	41065879

Expression profiles

Bgee: expression breadth broad, 38 present calls, max score 41.40.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skin of abdomen	UBERON:0001416	41.40	gold quality
stromal cell of endometrium	CL:0002255	40.73	silver quality
right lung	UBERON:0002167	39.07	gold quality
zone of skin	UBERON:0000014	38.97	gold quality
skin of leg	UBERON:0001511	37.47	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
sural nerve	UBERON:0015488	30.93	gold quality
prefrontal cortex	UBERON:0000451	29.24	gold quality
blood	UBERON:0000178	28.64	gold quality
tonsil	UBERON:0002372	28.64	gold quality
muscle of leg	UBERON:0001383	28.39	gold quality
duodenum	UBERON:0002114	28.14	gold quality
gastrocnemius	UBERON:0001388	27.95	gold quality
lymph node	UBERON:0000029	27.57	gold quality
cortex of kidney	UBERON:0001225	27.00	gold quality
islet of Langerhans	UBERON:0000006	26.55	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
leukocyte	CL:0000738	26.03	gold quality
gall bladder	UBERON:0002110	25.98	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	25.89	gold quality
monocyte	CL:0000576	25.88	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	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

33 targeting KRTAP2-4, 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-6748-5P	100.00	65.81	1057
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
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-488-5P	99.28	68.12	821
HSA-MIR-34B-3P	98.70	67.40	1171
HSA-MIR-6840-3P	98.68	65.95	1923
HSA-MIR-6804-5P	98.39	65.77	1084
HSA-MIR-5691	98.23	67.02	1335
HSA-MIR-6805-3P	98.23	67.02	1334
HSA-MIR-4483	98.09	64.12	1642
HSA-MIR-12116	97.94	68.91	595
HSA-MIR-299-3P	97.73	66.67	773
HSA-MIR-8055	97.62	66.09	1023
HSA-MIR-3622A-3P	97.06	66.43	1000

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), KRTAP4-9 (ENSG00000212722), KRTAP2-3 (ENSG00000212724), KRTAP2-1 (ENSG00000212725), KRTAP10-3 (ENSG00000212935), KRTAP4-12 (ENSG00000213416), 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 2-4 — Q9BYR9 (reviewed: Q9BYR9)

Alternative names: High sulfur keratin-associated protein 2.4, Keratin-associated protein 2.4

All UniProt accessions (1): Q9BYR9

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 specifically in the middle/upper portions of the hair cortex, in the region termed the keratogenous zone.

Similarity. Belongs to the KRTAP type 2 family.

RefSeq proteins (1): NP_149440* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002494	KAP	Family
IPR052154	KRTAP_type_2-like	Family

Pfam: PF01500

UniProt features (2 total): chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BYR9-F1	33.60	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: 74 (showing top): ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, GOCC_INTERMEDIATE_FILAMENT_CYTOSKELETON, GOCC_KERATIN_FILAMENT, GOCC_SUPRAMOLECULAR_COMPLEX, GOCC_POLYMERIC_CYTOSKELETAL_FIBER, ZWANG_CLASS_2_TRANSIENTLY_INDUCED_BY_EGF, REACTOME_KERATINIZATION, GOCC_SUPRAMOLECULAR_POLYMER, LHX9_TARGET_GENES, MAFG_TARGET_GENES, PRMT5_TARGET_GENES, SUPT16H_TARGET_GENES, ZNF175_TARGET_GENES, ZNF197_TARGET_GENES, ZNF589_TARGET_GENES

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

0 interactions, top by confidence (×1000):

IntAct

271 interactions, top by confidence:

A	B	Type	Score
SDC3	KRTAP2-4	psi-mi:“MI:0915”(physical association)	0.720
ZDHHC1	KRTAP2-4	psi-mi:“MI:0915”(physical association)	0.560
VASN	KRTAP2-4	psi-mi:“MI:0915”(physical association)	0.560
CREB5	KRTAP2-4	psi-mi:“MI:0915”(physical association)	0.560
KRTAP2-4	HAPLN2	psi-mi:“MI:0915”(physical association)	0.560
TNP2	KRTAP2-4	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	KRTAP2-4	psi-mi:“MI:0915”(physical association)	0.560
NOTCH2NLC	KRTAP2-4	psi-mi:“MI:0915”(physical association)	0.560
RHBDL1	KRTAP2-4	psi-mi:“MI:0915”(physical association)	0.560
BAHD1	KRTAP2-4	psi-mi:“MI:0915”(physical association)	0.560
HOXB9	KRTAP2-4	psi-mi:“MI:0915”(physical association)	0.560
LCE1E	KRTAP2-4	psi-mi:“MI:0915”(physical association)	0.560
P2RY6	KRTAP2-4	psi-mi:“MI:0915”(physical association)	0.560
LCE2C	KRTAP2-4	psi-mi:“MI:0915”(physical association)	0.560
ZNF764	KRTAP2-4	psi-mi:“MI:0915”(physical association)	0.560
C11orf87	KRTAP2-4	psi-mi:“MI:0915”(physical association)	0.560
KRTAP9-3	KRTAP2-4	psi-mi:“MI:0915”(physical association)	0.560
IGSF8	KRTAP2-4	psi-mi:“MI:0915”(physical association)	0.560
JOSD1	KRTAP2-4	psi-mi:“MI:0915”(physical association)	0.560
LCE1B	KRTAP2-4	psi-mi:“MI:0915”(physical association)	0.560
CXCL16	KRTAP2-4	psi-mi:“MI:0915”(physical association)	0.560
ZNF524	KRTAP2-4	psi-mi:“MI:0915”(physical association)	0.560
ZNF672	KRTAP2-4	psi-mi:“MI:0915”(physical association)	0.560
SPATA3	KRTAP2-4	psi-mi:“MI:0915”(physical association)	0.560
ADAMTSL3	KRTAP2-4	psi-mi:“MI:0915”(physical association)	0.560
KRTAP12-4	KRTAP2-4	psi-mi:“MI:0915”(physical association)	0.560
KRTAP4-12	KRTAP2-4	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (199): KRTAP2-4 (Two-hybrid), KRTAP2-4 (Two-hybrid), KRTAP2-4 (Two-hybrid), KRTAP2-4 (Two-hybrid), KRTAP2-4 (Two-hybrid), KRTAP2-4 (Two-hybrid), PTPMT1 (Two-hybrid), TMEM190 (Two-hybrid), KRTAP10-1 (Two-hybrid), KRTAP10-5 (Two-hybrid), KRTAP2-4 (Two-hybrid), KRTAP2-3 (Two-hybrid), KRTAP2-4 (Two-hybrid), KRTAP2-3 (Two-hybrid), KRTAP2-4 (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: P02441, P02442, P02443, P0C7H8, Q9BYR9, Q9BYT5, Q9BYU5

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 87 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	21	22.5×	1e-21
Formation of the cornified envelope	11	18.6×	6e-10

GO biological processes:

GO term	Partners	Fold	FDR
keratinization	11	34.3×	4e-12

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	34
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

197 predictions. Top by Δscore:

Variant	Effect	Δscore
17:41065804:G:C	donor_gain	0.8600
17:41065796:C:A	donor_gain	0.7800
17:41065797:C:A	donor_gain	0.7600
17:41065634:T:A	donor_gain	0.7400
17:41065157:T:TC	acceptor_gain	0.6200
17:41065795:T:TA	donor_gain	0.6000
17:41065584:C:CT	donor_gain	0.5900
17:41065153:CACAT:C	acceptor_gain	0.5800
17:41065339:C:CT	acceptor_gain	0.5800
17:41065808:A:AC	donor_gain	0.5700
17:41065119:C:CT	acceptor_gain	0.5600
17:41065635:C:A	donor_gain	0.5600
17:41065725:A:T	donor_gain	0.5600
17:41065155:CAT:C	acceptor_gain	0.5500
17:41065394:A:C	donor_gain	0.5500
17:41065659:A:T	donor_gain	0.5500
17:41065660:C:T	donor_gain	0.5400
17:41065664:G:T	donor_gain	0.5400
17:41065323:TAC:T	donor_gain	0.5300
17:41065324:ACA:A	donor_gain	0.5300
17:41065325:CAC:C	donor_gain	0.5300
17:41065366:T:C	acceptor_gain	0.5300
17:41065663:C:CT	donor_gain	0.5200
17:41065325:CA:C	donor_gain	0.5100
17:41065422:AGG:A	donor_gain	0.5100
17:41065630:G:GA	donor_gain	0.5100
17:41065157:T:C	acceptor_gain	0.5000
17:41065250:T:C	donor_gain	0.4900
17:41065462:G:C	donor_gain	0.4800
17:41065696:G:A	donor_gain	0.4800

AlphaMissense

812 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:41065564:C:A	W94C	0.938
17:41065564:C:G	W94C	0.938
17:41065581:A:G	C89R	0.937
17:41065579:G:C	C89W	0.917
17:41065611:A:G	C79R	0.897
17:41065616:A:G	I77T	0.892
17:41065580:C:T	C89Y	0.889
17:41065580:C:G	C89S	0.873
17:41065581:A:T	C89S	0.873
17:41065616:A:T	I77N	0.873
17:41065609:G:C	C79W	0.872
17:41065616:A:C	I77S	0.871
17:41065566:A:G	W94R	0.870
17:41065566:A:T	W94R	0.870
17:41065596:A:G	C84R	0.852
17:41065606:G:C	C80W	0.841
17:41065632:C:G	G72R	0.839
17:41065569:A:G	C93R	0.838
17:41065567:G:C	C93W	0.835
17:41065570:G:C	C92W	0.834
17:41065626:A:G	C74R	0.826
17:41065577:C:A	R90M	0.824
17:41065574:G:T	P91H	0.821
17:41065610:C:T	C79Y	0.821
17:41065594:G:C	C84W	0.818
17:41065733:G:A	T38I	0.811
17:41065624:G:C	C74W	0.810
17:41065576:C:A	R90S	0.809
17:41065576:C:G	R90S	0.809
17:41065629:A:G	C73R	0.809

dbSNP variants (sampled 300 via entrez): RS1000739351 (17:41066406 G>A), RS1000803836 (17:41065297 G>A,C,T), RS1002643276 (17:41066851 A>C), RS1004194978 (17:41065209 A>C), RS1004535847 (17:41066658 C>T), RS1004585476 (17:41066811 T>A,C), RS1007435089 (17:41066077 C>A,T), RS1008340730 (17:41064864 G>A), RS1008453605 (17:41064641 A>T), RS1008665871 (17:41066244 T>C), RS1009437357 (17:41066870 A>C), RS1011831935 (17:41065233 G>A), RS1011904265 (17:41065496 G>A,T), RS1012413117 (17:41066893 A>G), RS1013509052 (17:41066365 T>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

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Formaldehyde	decreases expression, increases expression	2
2-methyl-4-isothiazolin-3-one	increases expression	1
CGP 52608	affects binding, increases reaction	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation	1
Cadmium	decreases expression, increases abundance	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	increases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	decreases expression, increases abundance	1
Copper Sulfate	increases expression	1
Genistein	decreases expression	1

Clinical trials (associated diseases)

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