KRTAP10-3

Summary

KRTAP10-3 (keratin associated protein 10-3, HGNC:22968) is a protein-coding gene on chromosome 21q22.3, encoding Keratin-associated protein 10-3 (P60369). 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 gene encodes 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 gene encodes a member of the high sulfur KAP family. It is localized to a cluster of intronless KAPs at 21q22.3 which are located within the introns of the C21orf29 gene.

Source: NCBI Gene 386682 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 81 total
• MANE Select transcript: NM_198696

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22968
Approved symbol	KRTAP10-3
Name	keratin associated protein 10-3
Location	21q22.3
Locus type	gene with protein product
Status	Approved
Aliases	KAP10.3, KAP18.3
Ensembl gene	ENSG00000212935
Ensembl biotype	protein_coding
Entrez	386682

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000391620

RefSeq mRNA: 1 — MANE Select: NM_198696 NM_198696

CCDS: CCDS42956

Canonical transcript exons

ENST00000391620 — 1 exons

Exon	Start	End
ENSE00001509398	44557790	44558795

Expression profiles

Bgee: expression breadth broad, 13 present calls, max score 42.15.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0171 / max 17.0431, expressed in 2 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
190755	0.0171	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	42.15	gold quality
skin of abdomen	UBERON:0001416	38.28	gold quality
bone marrow cell	CL:0002092	38.27	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
zone of skin	UBERON:0000014	36.89	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
skin of leg	UBERON:0001511	36.18	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
bone marrow	UBERON:0002371	32.82	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
right lung	UBERON:0002167	31.30	silver quality
muscle tissue	UBERON:0002385	31.06	gold quality
right uterine tube	UBERON:0001302	29.90	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
prefrontal cortex	UBERON:0000451	29.39	gold quality
tonsil	UBERON:0002372	28.77	gold quality
monocyte	CL:0000576	28.46	gold quality
leukocyte	CL:0000738	28.39	gold quality
duodenum	UBERON:0002114	28.14	gold quality
muscle of leg	UBERON:0001383	27.76	gold quality
lymph node	UBERON:0000029	27.57	gold quality
gastrocnemius	UBERON:0001388	27.18	gold quality
urinary bladder	UBERON:0001255	26.98	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
placenta	UBERON:0001987	25.81	gold quality
kidney	UBERON:0002113	25.29	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.49

Regulation

Is transcription factor: no

Cross-species orthologs

0 orthologs

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), 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 10-3 — P60369 (reviewed: P60369)

Alternative names: High sulfur keratin-associated protein 10.3, Keratin-associated protein 10.3, Keratin-associated protein 18-3, Keratin-associated protein 18.3

All UniProt accessions (1): P60369

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 a narrow region of the hair fiber cuticle, lying approximately 20 cell layers above the apex of the dermal papilla of the hair root; not detected in any other tissues.

Similarity. Belongs to the KRTAP type 10 family.

RefSeq proteins (1): NP_941969* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002494	KAP	Family

Pfam: PF13885

UniProt features (25 total): repeat 18, sequence conflict 3, sequence variant 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P60369-F1	39.11	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: 12 (showing top): chr21q22, GOCC_INTERMEDIATE_FILAMENT_CYTOSKELETON, GOCC_KERATIN_FILAMENT, CERIBELLI_PROMOTERS_INACTIVE_AND_BOUND_BY_NFY, GOCC_SUPRAMOLECULAR_COMPLEX, GOCC_POLYMERIC_CYTOSKELETAL_FIBER, REACTOME_KERATINIZATION, GOCC_SUPRAMOLECULAR_POLYMER, BPTF_TARGET_GENES, ZAK_PBMC_MRKAD5_HIV_1_GAG_POL_NEF_AGE_20_50YO_CORRELATED_WITH_CD8_T_CELL_RESPONSE_3DY_NEGATIVE, TATAAA_TATA_01, CTGCAGY_UNKNOWN

GO Biological Process (0):

GO Molecular Function (0):

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
cytoplasm	1
cellular anatomical structure	1
intermediate filament	1
intermediate filament cytoskeleton	1
polymeric cytoskeletal fiber	1

Protein interactions and networks

STRING

168 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KRTAP10-3	OR1E1	P30953	525
KRTAP10-3	KRTAP2-3	P0C7H8	474
KRTAP10-3	KRT38	O76015	449
KRTAP10-3	MUCL3	Q3MIW9	447
KRTAP10-3	PRB3	Q04118	432
KRTAP10-3	IGFL1	Q6UW32	419
KRTAP10-3	PERM1	Q5SV97	418
KRTAP10-3	KRT26	Q7Z3Y9	417
KRTAP10-3	KRTAP1-1	Q07627	397
KRTAP10-3	RP1L1	Q8IWN7	355
KRTAP10-3	AGR3	Q8TD06	348
KRTAP10-3	SAGE1	Q9NXZ1	348
KRTAP10-3	FBN3	Q75N90	336
KRTAP10-3	A0A087WZY1	A0A087WZY1	336
KRTAP10-3	PRH1	P02810	322

IntAct

14 interactions, top by confidence:

A	B	Type	Score
KRTAP10-3	BRME1	psi-mi:“MI:0915”(physical association)	0.370
KRTAP10-3	ACY3	psi-mi:“MI:0915”(physical association)	0.370
KRTAP10-3	WT1	psi-mi:“MI:0915”(physical association)	0.370
KRTAP10-3	LCE1B	psi-mi:“MI:0915”(physical association)	0.370
KRTAP10-3	CHRNG	psi-mi:“MI:0915”(physical association)	0.370
KRTAP10-3	ZNF786	psi-mi:“MI:0915”(physical association)	0.370
KRTAP10-3	ZNF559	psi-mi:“MI:0915”(physical association)	0.370
KRTAP10-3	ECE1	psi-mi:“MI:0915”(physical association)	0.370
ECE1	KRTAP10-3	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (304): KRTAP10-3 (Two-hybrid), KRTAP10-3 (Two-hybrid), KRTAP10-3 (Two-hybrid), KRTAP10-3 (Two-hybrid), KRTAP10-3 (Two-hybrid), KRTAP10-3 (Two-hybrid), KRTAP10-3 (Two-hybrid), KRTAP10-3 (Two-hybrid), KRTAP10-3 (Two-hybrid), KRTAP10-3 (Two-hybrid), KRTAP10-3 (Two-hybrid), KRTAP10-3 (Two-hybrid), KRTAP10-3 (Two-hybrid), KRTAP10-3 (Two-hybrid), KRTAP10-3 (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: P60014, P60331, P60368, P60369, P60370, P60371, P60409, P60411, P60412, P60413, P60372, A6QP35, P60410

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	68
Likely benign	12
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

437 predictions. Top by Δscore:

Variant	Effect	Δscore
21:44558023:CAACT:C	acceptor_gain	0.8600
21:44558567:A:AC	donor_gain	0.8600
21:44558568:C:CC	donor_gain	0.8600
21:44558664:G:A	donor_gain	0.8600
21:44558658:C:CT	donor_gain	0.8100
21:44558636:CAG:C	donor_gain	0.7900
21:44558659:C:CT	donor_gain	0.7900
21:44558026:CT:C	acceptor_gain	0.7800
21:44558657:TCC:T	donor_gain	0.7800
21:44558025:ACTCT:A	acceptor_gain	0.7600
21:44558026:CTCTG:C	acceptor_gain	0.7400
21:44558024:AACTC:A	acceptor_gain	0.7300
21:44558635:A:AC	donor_gain	0.7200
21:44558636:C:CC	donor_gain	0.7200
21:44558024:AACT:A	acceptor_gain	0.6900
21:44558028:C:G	acceptor_gain	0.6800
21:44558028:C:CC	acceptor_gain	0.6700
21:44558656:GTC:G	donor_gain	0.6600
21:44557981:CAGGG:C	acceptor_gain	0.6400
21:44558560:ACAG:A	donor_gain	0.6400
21:44558561:CAGC:C	donor_gain	0.6400
21:44558563:G:GA	donor_gain	0.6300
21:44558578:G:T	donor_gain	0.6300
21:44558562:AG:A	donor_gain	0.6200
21:44558563:G:C	donor_gain	0.6200
21:44557854:C:CT	donor_gain	0.6100
21:44557855:C:CT	donor_gain	0.6100
21:44557952:C:CC	acceptor_gain	0.6100
21:44558027:TC:T	acceptor_loss	0.6100
21:44558655:CGT:C	donor_gain	0.6100

AlphaMissense

1421 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1005911315 (21:44560632 C>G), RS1006899016 (21:44560741 G>A,C), RS1009900643 (21:44559651 A>G), RS1011048826 (21:44557652 G>A), RS1013025697 (21:44557331 A>T), RS1013696773 (21:44558740 G>T), RS1014858954 (21:44560361 T>A,C), RS1017813346 (21:44557427 A>C), RS1019539404 (21:44558346 A>T), RS1021962939 (21:44557654 G>A), RS1022457922 (21:44557821 G>A,T), RS1024070716 (21:44559908 T>A,C,G), RS1024412858 (21:44559701 T>A,C), RS1026355091 (21:44557593 C>T), RS1026526724 (21:44557393 G>A)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:614861, MIM:618180

GenCC curated gene-disease

Mondo (3): autosomal recessive nonsyndromic hearing loss 98 (MONDO:0013929), breast ductal adenocarcinoma (MONDO:0005590), ectodermal dysplasia 14, hair/tooth type with or without hypohidrosis (MONDO:0032584)

Orphanet (2): Rare autosomal recessive non-syndromic sensorineural deafness type DFNB (Orphanet:90636), Hypodontia-scalp hypotrichosis-facial dysmorphism syndrome (Orphanet:685067)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation	1
CGP 52608	affects binding, increases reaction	1
MT19c compound	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Pantothenic Acid	decreases expression	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery