KRTAP10-4

Summary

KRTAP10-4 (keratin associated protein 10-4, HGNC:20521) is a protein-coding gene on chromosome 21q22.3, encoding Keratin-associated protein 10-4 (P60372). 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 is an intronless gene located in a cluster of related genes on the q arm of chromosome 21. The proteins encoded by these genes form disulfide bonds with cysteine residues in hair keratins, thereby contributing to the structure and stability of hair fibers.

Source: NCBI Gene 386672 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 97 total
• MANE Select transcript: NM_198687

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20521
Approved symbol	KRTAP10-4
Name	keratin associated protein 10-4
Location	21q22.3
Locus type	gene with protein product
Status	Approved
Aliases	KRTAP18.4, KAP10.4
Ensembl gene	ENSG00000215454
Ensembl biotype	protein_coding
Entrez	386672

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000400374

RefSeq mRNA: 1 — MANE Select: NM_198687 NM_198687

CCDS: CCDS42957

Canonical transcript exons

ENST00000400374 — 1 exons

Exon	Start	End
ENSE00001542630	44573729	44575371

Expression profiles

Bgee: expression breadth broad, 11 present calls, max score 38.29.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bone marrow cell	CL:0002092	38.29	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
sural nerve	UBERON:0015488	36.61	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skin of abdomen	UBERON:0001416	33.88	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
liver	UBERON:0002107	33.25	gold quality
bone marrow	UBERON:0002371	32.83	gold quality
zone of skin	UBERON:0000014	32.70	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
right uterine tube	UBERON:0001302	32.06	gold quality
skin of leg	UBERON:0001511	31.91	gold quality
right lobe of liver	UBERON:0001114	31.14	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
monocyte	CL:0000576	30.75	gold quality
blood	UBERON:0000178	30.62	silver quality
leukocyte	CL:0000738	30.47	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
prefrontal cortex	UBERON:0000451	29.36	gold quality
ectocervix	UBERON:0012249	28.57	gold quality
duodenum	UBERON:0002114	28.14	gold quality
uterine cervix	UBERON:0000002	27.74	gold quality
lymph node	UBERON:0000029	27.57	gold quality
tonsil	UBERON:0002372	27.05	gold quality
islet of Langerhans	UBERON:0000006	26.90	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
gall bladder	UBERON:0002110	25.98	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	0.65

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

22 targeting KRTAP10-4, 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-1184	99.99	68.19	1458
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-922	99.02	67.23	1838
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-1843	98.97	66.07	838
HSA-MIR-4802-5P	98.97	66.26	833
HSA-MIR-6829-5P	98.86	65.12	1480
HSA-MIR-214-3P	98.71	68.12	2128
HSA-MIR-761	98.71	68.07	2051
HSA-MIR-6751-3P	98.44	66.35	835
HSA-MIR-1199-5P	98.44	66.51	829
HSA-MIR-4733-3P	98.35	65.20	994
HSA-MIR-6778-5P	98.19	66.59	1239
HSA-MIR-1233-5P	98.19	66.71	1201
HSA-MIR-9851-5P	97.57	67.49	1067
HSA-MIR-4750-3P	96.65	64.38	512
HSA-MIR-3918	96.13	64.65	1300
HSA-MIR-4471	95.11	66.84	755
HSA-MIR-8059	95.11	66.30	646

Cross-species orthologs

51 orthologs

Organism	Symbol	Gene ID
mus_musculus	Krtap9-3	ENSMUSG00000049809
mus_musculus	Krtap5-2	ENSMUSG00000054759
mus_musculus	Krtap5-20	ENSMUSG00000056885
mus_musculus	Krtap2-22	ENSMUSG00000057674
mus_musculus	Krtap2-21	ENSMUSG00000058725
mus_musculus	Krtap2-4	ENSMUSG00000060756
mus_musculus	Krtap2-20	ENSMUSG00000062278
mus_musculus	Krtap10-4	ENSMUSG00000069582
mus_musculus	Krtap12-1	ENSMUSG00000069583
mus_musculus	Krtap12-23	ENSMUSG00000069584
mus_musculus	Krtap10-31	ENSMUSG00000071195
mus_musculus	Krtap1-4	ENSMUSG00000075567
mus_musculus	Krtap1-3	ENSMUSG00000078131
mus_musculus	Krtap9-5	ENSMUSG00000078255
mus_musculus	Krtap12-22	ENSMUSG00000094012
mus_musculus	Krtap10-21	ENSMUSG00000094120
mus_musculus	Krtap12-21	ENSMUSG00000094146
mus_musculus	Krtap10-27	ENSMUSG00000094913
mus_musculus	Krtap10-26	ENSMUSG00000095593
mus_musculus	Krtap10-25	ENSMUSG00000095721
mus_musculus	Krtap10-22	ENSMUSG00000095817
mus_musculus	Krtap10-33	ENSMUSG00000095970
mus_musculus	Krtap10-29	ENSMUSG00000096131
mus_musculus	Krtap10-34	ENSMUSG00000096380
mus_musculus	Krtap12-20	ENSMUSG00000096421
mus_musculus	Krtap10-23	ENSMUSG00000096481
mus_musculus	Krtap5-26	ENSMUSG00000109859
mus_musculus	Krtap5-24	ENSMUSG00000110324
mus_musculus	Krtap10-24	ENSMUSG00000111915
mus_musculus	Krtap10-28	ENSMUSG00000112170
mus_musculus	Krtap10-10	ENSMUSG00000112223
mus_musculus	Krtap10-30	ENSMUSG00000112380
mus_musculus	Gm49918	ENSMUSG00000112600
mus_musculus	Krtap10-35	ENSMUSG00000112653
mus_musculus	Krtap10-32	ENSMUSG00000112864
rattus_norvegicus	Krtap10-8l1	ENSRNOG00000001218
rattus_norvegicus	Krtap1-1	ENSRNOG00000012955
rattus_norvegicus	Krtap5-8	ENSRNOG00000020131
rattus_norvegicus	Krtap10-10	ENSRNOG00000032530
rattus_norvegicus	Krtap10-9	ENSRNOG00000043302
rattus_norvegicus	Krtap10-1l1	ENSRNOG00000046538
rattus_norvegicus	AABR07006049.1	ENSRNOG00000046649
rattus_norvegicus	Krtap10-1	ENSRNOG00000047532
rattus_norvegicus	Krtap1-3	ENSRNOG00000052388
rattus_norvegicus	LOC120098854	ENSRNOG00000067436
rattus_norvegicus	Krtap10-10l2	ENSRNOG00000069553
rattus_norvegicus		ENSRNOG00000071951
rattus_norvegicus	Krtap2-4	ENSRNOG00000078178
rattus_norvegicus		ENSRNOG00000083452
rattus_norvegicus		ENSRNOG00000088018
rattus_norvegicus		ENSRNOG00000091097

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), KRTAP10-1 (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 10-4 — P60372 (reviewed: P60372)

Alternative names: High sulfur keratin-associated protein 10.4, Keratin-associated protein 10.4, Keratin-associated protein 18-4, Keratin-associated protein 18.4

All UniProt accessions (1): P60372

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. Restricted to hair root, not detected in any other tissues.

Similarity. Belongs to the KRTAP type 10 family.

RefSeq proteins (1): NP_941960* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002494	KAP	Family

Pfam: PF13885

UniProt features (40 total): repeat 35, sequence variant 3, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P60372-F1	35.58	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: 13 (showing top): chr21q22, GOCC_INTERMEDIATE_FILAMENT_CYTOSKELETON, GOCC_KERATIN_FILAMENT, GOCC_SUPRAMOLECULAR_COMPLEX, GOCC_POLYMERIC_CYTOSKELETAL_FIBER, REACTOME_KERATINIZATION, GOCC_SUPRAMOLECULAR_POLYMER, ZNF766_TARGET_GENES, MIR3619_5P, WP_VITAMIN_D_RECEPTOR_PATHWAY, ZAK_PBMC_MRKAD5_HIV_1_GAG_POL_NEF_AGE_20_50YO_CORRELATED_WITH_CD8_T_CELL_RESPONSE_3DY_NEGATIVE, GSE12507_PDC_CELL_LINE_VS_IMMATUE_T_CELL_LINE_DN, GSE11367_CTRL_VS_IL17_TREATED_SMOOTH_MUSCLE_CELL_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

128 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KRTAP10-4	OR1E1	P30953	517
KRTAP10-4	KRTAP2-3	P0C7H8	450
KRTAP10-4	KRT38	O76015	448
KRTAP10-4	WDR90	Q96KV7	445
KRTAP10-4	PRB3	Q04118	420
KRTAP10-4	IGFL1	Q6UW32	418
KRTAP10-4	EFR3A	Q14156	417
KRTAP10-4	NECAB1	Q8N987	417
KRTAP10-4	KRT26	Q7Z3Y9	405
KRTAP10-4	KRTAP1-1	Q07627	395
KRTAP10-4	AGAP3	Q96P47	375
KRTAP10-4	WDR24	Q96S15	358
KRTAP10-4	ART1	P52961	348
KRTAP10-4	SAGE1	Q9NXZ1	337
KRTAP10-4	AGR3	Q8TD06	336

IntAct

33 interactions, top by confidence:

A	B	Type	Score
E4F1	KRTAP10-4	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-4	ZNF32	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-4	JOSD1	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-4	ZSCAN26	psi-mi:“MI:0915”(physical association)	0.560
RSPO2	KRTAP10-4	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-4	IGSF8	psi-mi:“MI:0915”(physical association)	0.560
ZNF625	KRTAP10-4	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-4	E4F1	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-4	RSPO2	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-4	ZNF625	psi-mi:“MI:0915”(physical association)	0.560
ZNF32	KRTAP10-4	psi-mi:“MI:0915”(physical association)	0.560
JOSD1	KRTAP10-4	psi-mi:“MI:0915”(physical association)	0.560
ZSCAN26	KRTAP10-4	psi-mi:“MI:0915”(physical association)	0.560
HOXA1	KRTAP10-4	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-4	CATSPER1	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-4	WT1	psi-mi:“MI:0915”(physical association)	0.370
KRTAP10-4	ECE1	psi-mi:“MI:0915”(physical association)	0.370
ECE1	KRTAP10-4	psi-mi:“MI:0915”(physical association)	0.370
CATSPER1	KRTAP10-4	psi-mi:“MI:0915”(physical association)	0.000

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: A6QP35, P60371, P60372, P60409, P60410, P60413, P60014, P60331, P60368, P60369, P60370, P60411, P60412

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	80
Likely benign	16
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

435 predictions. Top by Δscore:

Variant	Effect	Δscore
21:44574730:GCCT:G	donor_gain	0.7100
21:44573777:G:GT	donor_gain	0.7000
21:44573754:C:CT	donor_gain	0.6900
21:44573840:C:T	donor_gain	0.6800
21:44573753:TCC:T	donor_gain	0.6500
21:44574758:G:A	acceptor_gain	0.6500
21:44573734:AACCC:A	donor_gain	0.6300
21:44573755:C:CT	donor_gain	0.6300
21:44573806:T:TA	donor_gain	0.6300
21:44574757:T:TA	acceptor_gain	0.6300
21:44573845:G:GA	donor_gain	0.6200
21:44573936:G:GG	donor_gain	0.6200
21:44574734:G:GG	donor_gain	0.6100
21:44575296:T:TA	acceptor_gain	0.6100
21:44573734:AACC:A	donor_gain	0.6000
21:44573785:C:G	donor_gain	0.6000
21:44574854:C:A	acceptor_gain	0.5900
21:44573734:AAC:A	donor_gain	0.5700
21:44573935:A:AG	donor_gain	0.5700
21:44575118:T:TA	acceptor_gain	0.5700
21:44574564:C:T	donor_gain	0.5600
21:44573793:GCCGC:G	donor_gain	0.5500
21:44573738:C:CA	donor_gain	0.5400
21:44574288:GCTGT:G	donor_gain	0.5300
21:44573775:G:C	donor_gain	0.5200
21:44574183:A:AG	donor_gain	0.5200
21:44574184:G:GG	donor_gain	0.5200
21:44574478:GCCT:G	donor_gain	0.5100
21:44574851:T:A	acceptor_gain	0.5000
21:44574186:C:A	donor_gain	0.4900

AlphaMissense

2610 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:44573839:G:C	W27C	0.883
21:44573839:G:T	W27C	0.883
21:44573837:T:A	W27R	0.823
21:44573837:T:C	W27R	0.823
21:44573854:C:G	C32W	0.688
21:44573861:A:C	S35R	0.685
21:44573863:C:A	S35R	0.685
21:44573863:C:G	S35R	0.685
21:44573852:T:C	C32R	0.681
21:44573783:A:C	S9R	0.641
21:44573785:C:A	S9R	0.641
21:44573785:C:G	S9R	0.641
21:44574851:T:C	C365R	0.608
21:44574853:C:G	C365W	0.607
21:44574395:A:C	S213R	0.593
21:44574397:C:A	S213R	0.593
21:44574397:C:G	S213R	0.593
21:44573838:G:T	W27L	0.584
21:44574960:T:A	L401H	0.579
21:44574730:G:C	K324N	0.564
21:44574730:G:T	K324N	0.564

dbSNP variants (sampled 300 via entrez): RS1001026883 (21:44575418 G>A,T), RS1002534710 (21:44575751 T>C), RS1005092569 (21:44575028 T>C,G), RS1005531668 (21:44571860 C>T), RS1007157054 (21:44572119 C>T), RS1008824107 (21:44572877 A>G), RS1011773427 (21:44572270 G>A,C), RS1012560179 (21:44572472 C>T), RS1012756508 (21:44572337 G>A,C), RS1016592413 (21:44572478 A>G), RS1018030046 (21:44572025 T>C), RS1018697818 (21:44575034 C>G,T), RS1019735336 (21:44572538 C>T), RS1026679796 (21:44572668 G>A), RS1027239722 (21:44575521 G>A,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

1 associations (top):

Study	Trait	p-value
GCST009856_44	Leukocyte telomere length	7.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs201441480	Efficacy	3	aspirin;clopidogrel	Acute coronary syndrome;Major Adverse Cardiac Events (MACE)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs201441480	KRTAP10-4, TSPEAR	3	3.50	1	aspirin;clopidogrel

CTD chemical–gene interactions

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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