KRTAP21-1

Summary

KRTAP21-1 (keratin associated protein 21-1, HGNC:18945) is a protein-coding gene on chromosome 21q22.11, encoding Keratin-associated protein 21-1 (Q3LI58). 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: 36.0% of cell lines).

Predicted to be located in cytosol.

Source: NCBI Gene 337977 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 17 total
• Cancer dependency (DepMap): dependent in 36.0% of screened cell lines
• MANE Select transcript: NM_181619

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18945
Approved symbol	KRTAP21-1
Name	keratin associated protein 21-1
Location	21q22.11
Locus type	gene with protein product
Status	Approved
Aliases	KAP21.1
Ensembl gene	ENSG00000187005
Ensembl biotype	protein_coding
Entrez	337977

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000335093

RefSeq mRNA: 1 — MANE Select: NM_181619 NM_181619

CCDS: CCDS13606

Canonical transcript exons

ENST00000335093 — 1 exons

Exon	Start	End
ENSE00001339229	30755015	30755428

Expression profiles

Bgee: expression breadth broad, 13 present calls, max score 91.09.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.09	gold quality
sural nerve	UBERON:0015488	38.00	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
stromal cell of endometrium	CL:0002255	29.87	gold quality
prefrontal cortex	UBERON:0000451	29.04	gold quality
duodenum	UBERON:0002114	28.14	gold quality
lymph node	UBERON:0000029	27.57	gold quality
skin of abdomen	UBERON:0001416	27.34	gold quality
tonsil	UBERON:0002372	27.05	gold quality
islet of Langerhans	UBERON:0000006	26.55	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
blood	UBERON:0000178	26.00	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
urinary bladder	UBERON:0001255	25.72	gold quality
leukocyte	CL:0000738	24.80	gold quality
kidney	UBERON:0002113	24.67	gold quality
primary visual cortex	UBERON:0002436	24.61	gold quality
monocyte	CL:0000576	24.52	gold quality
pancreas	UBERON:0001264	24.44	gold quality
cortex of kidney	UBERON:0001225	24.29	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.65

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 36.0% of screened cell lines.

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

Keratin-associated protein 21-1 — Q3LI58 (reviewed: Q3LI58)

All UniProt accessions (1): Q3LI58

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.

RefSeq proteins (1): NP_853650* (*=MANE)

Domains & families (InterPro)

UniProt features (2 total): chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q3LI58-F1	46.33	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: 25 (showing top): chr21q22, GOCC_INTERMEDIATE_FILAMENT_CYTOSKELETON, WGTTNNNNNAAA_UNKNOWN, GOCC_SUPRAMOLECULAR_COMPLEX, GOCC_POLYMERIC_CYTOSKELETAL_FIBER, REACTOME_KERATINIZATION, GSE13522_CTRL_VS_T_CRUZI_G_STRAIN_INF_SKIN_UP, GOCC_SUPRAMOLECULAR_POLYMER, TATA_01, GSE17721_CTRL_VS_LPS_1H_BMDC_UP, GSE17721_CTRL_VS_GARDIQUIMOD_1H_BMDC_UP, GSE17721_POLYIC_VS_PAM3CSK4_16H_BMDC_UP, GSE17721_CPG_VS_GARDIQUIMOD_0.5H_BMDC_DN, GSE17721_LPS_VS_GARDIQUIMOD_1H_BMDC_DN, GSE20366_TREG_VS_TCONV_UP

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (2): cytosol (GO:0005829), 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 cytoskeleton	1
polymeric cytoskeletal fiber	1

Protein interactions and networks

STRING

330 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KRTAP21-1	KRTAP21-2	Q3LI59	772
KRTAP21-1	KRTAP21-3	Q3LHN1	770
KRTAP21-1	KRTAP6-3	Q3LI67	717
KRTAP21-1	KRTAP20-1	Q3LI63	667
KRTAP21-1	KRTAP22-1	Q3MIV0	666
KRTAP21-1	KRTAP20-2	Q3LI61	631
KRTAP21-1	KRTAP4-16	G5E9R7	627
KRTAP21-1	KRTAP26-1	Q6PEX3	624
KRTAP21-1	KRTAP6-1	Q3LI64	599
KRTAP21-1	KRTAP15-1	Q3LI76	599
KRTAP21-1	KRTAP19-6	Q3LI70	593
KRTAP21-1	KRTAP7-1	Q8IUC3	581
KRTAP21-1	KRTAP8-1	Q8IUC2	571
KRTAP21-1	SCYGR1	A0A286YEY9	570
KRTAP21-1	KRTAP6-2	Q3LI66	506

IntAct

0 interactions, top by confidence:

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

Diamond homologs: Q3LI58, Q3LI59, Q925H4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	15
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

161 predictions. Top by Δscore:

Variant	Effect	Δscore
21:30755271:ACAG:A	donor_gain	0.8600
21:30755272:CAGC:C	donor_gain	0.8600
21:30755292:G:C	donor_gain	0.8400
21:30755272:CAG:C	donor_gain	0.8300
21:30755280:G:C	donor_gain	0.7800
21:30755271:A:AC	donor_gain	0.7600
21:30755272:C:CC	donor_gain	0.7600
21:30755291:AG:A	donor_gain	0.7400
21:30755322:G:C	donor_gain	0.7400
21:30755321:AG:A	donor_gain	0.6500
21:30755422:T:TA	donor_gain	0.6500
21:30755286:T:A	donor_gain	0.6200
21:30755346:G:C	donor_gain	0.6000
21:30755093:TCAG:T	donor_gain	0.5800
21:30755144:A:T	acceptor_gain	0.5800
21:30755279:AG:A	donor_gain	0.5700
21:30755358:G:A	donor_gain	0.5700
21:30755268:CCCA:C	donor_gain	0.5600
21:30755139:T:C	acceptor_gain	0.5500
21:30755158:CTT:C	acceptor_gain	0.5400
21:30755178:G:GT	acceptor_gain	0.5400
21:30755179:T:TT	acceptor_gain	0.5400
21:30755263:CCATA:C	donor_loss	0.5400
21:30755264:CATA:C	donor_loss	0.5400
21:30755265:ATAC:A	donor_loss	0.5400
21:30755266:TACCC:T	donor_loss	0.5400
21:30755267:A:C	donor_loss	0.5400
21:30755268:C:CG	donor_loss	0.5400
21:30755162:T:TG	acceptor_gain	0.5300
21:30755267:A:AC	donor_gain	0.5300

AlphaMissense

491 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:30755163:A:C	F72L	0.712
21:30755163:A:T	F72L	0.712
21:30755165:A:G	F72L	0.712
21:30755253:A:C	F42L	0.677
21:30755253:A:T	F42L	0.677
21:30755255:A:G	F42L	0.677
21:30755227:C:T	G51E	0.664
21:30755144:A:G	C79R	0.644
21:30755287:C:T	G31E	0.626
21:30755142:G:C	C79W	0.594
21:30755209:C:T	G57E	0.593
21:30755169:A:C	F70L	0.575
21:30755169:A:T	F70L	0.575
21:30755171:A:G	F70L	0.575

dbSNP variants (sampled 300 via entrez): RS1000342267 (21:30754777 A>G), RS1001331366 (21:30757417 G>A), RS1003829725 (21:30755714 A>C,G,T), RS1003873403 (21:30755661 G>A), RS1005494223 (21:30756778 A>T), RS1008404220 (21:30755015 G>A,C), RS1010729262 (21:30755760 CT>C,CTT), RS1010786635 (21:30756088 C>G,T), RS1014932360 (21:30756771 G>A,C), RS1017162634 (21:30756788 T>C), RS1019388224 (21:30756117 A>T), RS1019390557 (21:30755030 G>A,C), RS1019714628 (21:30754732 G>C), RS1020455534 (21:30754685 CATT>C), RS1021739084 (21:30755765 T>C,G)

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

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

Chemical	Actions (top 5)	PubMed papers
Bortezomib	increases expression, increases response to substance	1
Benzo(a)pyrene	decreases methylation	1
Endosulfan	decreases reaction, increases expression	1
Tetrachlorodibenzodioxin	decreases reaction, increases expression	1

Clinical trials (associated diseases)

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