KRTAP10-1

Summary

KRTAP10-1 (keratin associated protein 10-1, HGNC:22966) is a protein-coding gene on chromosome 21q22.3, encoding Keratin-associated protein 10-1 (P60331). 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: 13.3% of cell lines).

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 386677 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 83 total
• Cancer dependency (DepMap): dependent in 13.3% of screened cell lines
• MANE Select transcript: NM_198691

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22966
Approved symbol	KRTAP10-1
Name	keratin associated protein 10-1
Location	21q22.3
Locus type	gene with protein product
Status	Approved
Aliases	KAP10.1, KAP18.1
Ensembl gene	ENSG00000215455
Ensembl biotype	protein_coding
Entrez	386677

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000400375

RefSeq mRNA: 1 — MANE Select: NM_198691 NM_198691

CCDS: CCDS42954

Canonical transcript exons

ENST00000400375 — 1 exons

Exon	Start	End
ENSE00001542634	44538981	44540195

Expression profiles

Bgee: expression breadth tissue_specific, 7 present calls, max score 37.20.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	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
sural nerve	UBERON:0015488	35.34	gold quality
skeletal muscle tissue	UBERON:0001134	35.13	gold quality
skin of abdomen	UBERON:0001416	33.83	gold quality
zone of skin	UBERON:0000014	32.82	gold quality
muscle tissue	UBERON:0002385	32.34	gold quality
skin of leg	UBERON:0001511	32.29	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
right uterine tube	UBERON:0001302	31.26	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
liver	UBERON:0002107	29.56	gold quality
prefrontal cortex	UBERON:0000451	29.39	gold quality
duodenum	UBERON:0002114	28.14	gold quality
monocyte	CL:0000576	27.63	gold quality
leukocyte	CL:0000738	27.63	gold quality
lymph node	UBERON:0000029	27.57	gold quality
primary visual cortex	UBERON:0002436	27.55	gold quality
tonsil	UBERON:0002372	27.05	gold quality
urinary bladder	UBERON:0001255	26.73	gold quality
islet of Langerhans	UBERON:0000006	26.55	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
right lung	UBERON:0002167	26.21	gold quality
muscle of leg	UBERON:0001383	26.09	gold quality
uterine cervix	UBERON:0000002	26.08	gold quality
gall bladder	UBERON:0002110	25.98	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.33

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

5 targeting KRTAP10-1, 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-4291	99.20	68.88	2969
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-1207-3P	98.99	66.22	1532
HSA-MIR-873-5P	98.84	66.90	1348
HSA-MIR-1247-5P	85.92	61.07	65

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 13.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• hair shaft cuticle-specific KRTAP10-1 protein displays characteristics similar to the hair shaft cortex-specific KRTAP2 proteins (PMID:23702583)

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), KRTAP10-3 (ENSG00000212935), KRTAP4-12 (ENSG00000213416), KRTAP2-4 (ENSG00000213417), KRTAP2-2 (ENSG00000214518), KRTAP10-4 (ENSG00000215454), 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 10-1 — P60331 (reviewed: P60331)

Alternative names: High sulfur keratin-associated protein 10.1, Keratin-associated protein 10.1, Keratin-associated protein 18-1, Keratin-associated protein 18.1

All UniProt accessions (1): P60331

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_941964* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002494	KAP	Family

Pfam: PF13885

UniProt features (32 total): repeat 24, sequence variant 4, sequence conflict 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P60331-F1	35.72	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: 10 (showing top): chr21q22, GOCC_INTERMEDIATE_FILAMENT_CYTOSKELETON, GOCC_KERATIN_FILAMENT, GOCC_SUPRAMOLECULAR_COMPLEX, GOCC_POLYMERIC_CYTOSKELETAL_FIBER, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, REACTOME_KERATINIZATION, GOCC_SUPRAMOLECULAR_POLYMER, MYOCD_TARGET_GENES, ZAK_PBMC_MRKAD5_HIV_1_GAG_POL_NEF_AGE_20_50YO_CORRELATED_WITH_CD8_T_CELL_RESPONSE_3DY_NEGATIVE

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

268 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KRTAP10-1	KRTAP5-1	Q6L8H4	657
KRTAP10-1	FRG2B	Q96QU4	523
KRTAP10-1	CCDC89	Q8N998	507
KRTAP10-1	TSPEAR	Q8WU66	507
KRTAP10-1	OR5L2	Q8NGL0	506
KRTAP10-1	AKAP3	O75969	450
KRTAP10-1	KIAA1671	Q9BY89	433
KRTAP10-1	XKR3	Q5GH77	431
KRTAP10-1	GARNL3	Q5VVW2	419
KRTAP10-1	ZNF595	Q8IYB9	397
KRTAP10-1	PRR16	Q569H4	395
KRTAP10-1	GPATCH4	Q5T3I0	393
KRTAP10-1	IQCF2	Q8IXL9	380
KRTAP10-1	IQCF5	A8MTL0	369
KRTAP10-1	GXYLT1	Q4G148	356

IntAct

13 interactions, top by confidence:

A	B	Type	Score
KRTAP10-1	LCE1B	psi-mi:“MI:0915”(physical association)	0.550
KRTAP10-1	ZNF559	psi-mi:“MI:0915”(physical association)	0.550
KRTAP10-1	DKK1	psi-mi:“MI:0915”(physical association)	0.370
KRTAP10-1	ZNF264	psi-mi:“MI:0915”(physical association)	0.370
KRTAP10-1	SPRY1	psi-mi:“MI:0915”(physical association)	0.370
KRTAP10-1	WT1	psi-mi:“MI:0915”(physical association)	0.370
KRTAP10-1	ECE1	psi-mi:“MI:0915”(physical association)	0.370
ECE1	KRTAP10-1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (176): KRTAP10-1 (Two-hybrid), KRTAP10-1 (Two-hybrid), KRTAP10-1 (Two-hybrid), KRTAP10-1 (Two-hybrid), KRTAP10-1 (Two-hybrid), KRTAP10-1 (Two-hybrid), KRTAP10-1 (Two-hybrid), KRTAP10-1 (Two-hybrid), KRTAP10-1 (Two-hybrid), KRTAP10-1 (Two-hybrid), KRTAP10-1 (Two-hybrid), KRTAP10-1 (Two-hybrid), KRTAP10-1 (Two-hybrid), KRTAP10-1 (Two-hybrid), KRTAP10-1 (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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	69
Likely benign	10
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

434 predictions. Top by Δscore:

Variant	Effect	Δscore
21:44540002:A:AC	donor_gain	0.8900
21:44540003:C:CC	donor_gain	0.8900
21:44539966:CAGG:C	donor_gain	0.8300
21:44539737:CTGG:C	acceptor_gain	0.8200
21:44539972:G:GA	donor_gain	0.7800
21:44539741:C:CC	acceptor_gain	0.7500
21:44540099:G:A	donor_gain	0.7400
21:44539801:T:TA	donor_gain	0.7100
21:44539436:CAGGG:C	donor_gain	0.6700
21:44540071:CAG:C	donor_gain	0.6700
21:44540093:C:CT	donor_gain	0.6600
21:44539739:GGC:G	acceptor_gain	0.6500
21:44540092:TCC:T	donor_gain	0.6400
21:44540094:C:CT	donor_gain	0.6400
21:44539941:G:GA	donor_gain	0.6300
21:44540004:T:C	donor_gain	0.6300
21:44539738:TGG:T	acceptor_gain	0.6200
21:44539739:GG:G	acceptor_gain	0.6200
21:44540013:G:T	donor_gain	0.6200
21:44540070:A:AC	donor_gain	0.6200
21:44540071:C:CC	donor_gain	0.6200
21:44539653:CTG:C	acceptor_gain	0.6000
21:44539779:CTG:C	acceptor_gain	0.6000
21:44539998:G:A	donor_gain	0.6000
21:44539224:A:C	donor_gain	0.5800
21:44539995:ACGG:A	donor_gain	0.5800
21:44539996:CGGC:C	donor_gain	0.5800
21:44540017:A:T	donor_gain	0.5800
21:44539223:AAC:A	donor_gain	0.5700
21:44539698:G:C	donor_gain	0.5700

AlphaMissense

1824 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000677637 (21:44540986 T>A), RS1001617642 (21:44541989 A>G), RS1004606964 (21:44540962 C>G), RS1006661140 (21:44542003 G>A), RS1010323213 (21:44541322 T>C,G), RS1014461953 (21:44540580 G>A), RS1015151541 (21:44541771 C>T), RS1018577018 (21:44540823 T>G), RS1018841043 (21:44540651 G>A), RS1022333240 (21:44540216 G>A,C,T), RS1022747294 (21:44540431 G>C), RS1027342838 (21:44540463 C>T), RS1027700383 (21:44540599 G>A), RS1029207450 (21:44540842 G>A), RS1030451619 (21:44542095 A>T)

Disease associations

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

GenCC curated gene-disease

Mondo (2): autosomal recessive nonsyndromic hearing loss 98 (MONDO:0013929), 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):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	affects binding, increases reaction	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	decreases methylation, 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.