KRTAP21-2

Summary

KRTAP21-2 (keratin associated protein 21-2, HGNC:18946) is a protein-coding gene on chromosome 21q22.11, encoding Keratin-associated protein 21-2 (Q3LI59). 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….

Predicted to be located in cytosol.

Source: NCBI Gene 337978 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 9 total
• MANE Select transcript: NM_181617

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18946
Approved symbol	KRTAP21-2
Name	keratin associated protein 21-2
Location	21q22.11
Locus type	gene with protein product
Status	Approved
Aliases	KAP21.2
Ensembl gene	ENSG00000187026
Ensembl biotype	protein_coding
Entrez	337978

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000333892

RefSeq mRNA: 1 — MANE Select: NM_181617 NM_181617

CCDS: CCDS13605

Canonical transcript exons

ENST00000333892 — 1 exons

Exon	Start	End
ENSE00001339702	30746794	30747259

Expression profiles

Bgee: expression breadth broad, 23 present calls, max score 98.89.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0760 / max 16.7770, expressed in 18 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
190128	0.0760	18

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	98.89	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	95.69	gold quality
left testis	UBERON:0004533	56.12	gold quality
testis	UBERON:0000473	55.29	gold quality
right testis	UBERON:0004534	55.00	gold quality
skin of abdomen	UBERON:0001416	42.39	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
zone of skin	UBERON:0000014	37.16	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
right uterine tube	UBERON:0001302	35.16	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
skin of leg	UBERON:0001511	33.14	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
islet of Langerhans	UBERON:0000006	31.43	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
sural nerve	UBERON:0015488	30.93	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
tonsil	UBERON:0002372	27.05	gold quality
uterine cervix	UBERON:0000002	26.76	gold quality
leukocyte	CL:0000738	26.63	gold quality
pancreas	UBERON:0001264	26.55	gold quality
monocyte	CL:0000576	26.54	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.48

Regulation

Is transcription factor: no

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

Keratin-associated protein 21-2 — Q3LI59 (reviewed: Q3LI59)

All UniProt accessions (1): Q3LI59

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_853648* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR021743	KRTAP_type8/19/20/21/22	Family

Pfam: PF11759

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

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q3LI59-F1	35.38	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: 9 (showing top): chr21q22, TGGAAA_NFAT_Q4_01, GOCC_INTERMEDIATE_FILAMENT_CYTOSKELETON, GOCC_SUPRAMOLECULAR_COMPLEX, GOCC_POLYMERIC_CYTOSKELETAL_FIBER, REACTOME_KERATINIZATION, GOCC_SUPRAMOLECULAR_POLYMER, PAX3_TARGET_GENES, TATAAA_TATA_01

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

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

Protein interactions and networks

STRING

294 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KRTAP21-2	KRTAP21-3	Q3LHN1	785
KRTAP21-2	KRTAP21-1	Q3LI58	772
KRTAP21-2	KRTAP6-3	Q3LI67	696
KRTAP21-2	KRTAP7-1	Q8IUC3	623
KRTAP21-2	KRTAP6-1	Q3LI64	621
KRTAP21-2	SCYGR1	A0A286YEY9	621
KRTAP21-2	KRTAP19-6	Q3LI70	621
KRTAP21-2	KRTAP15-1	Q3LI76	621
KRTAP21-2	KRTAP20-1	Q3LI63	608
KRTAP21-2	KRTAP22-1	Q3MIV0	606
KRTAP21-2	KRTAP20-2	Q3LI61	592
KRTAP21-2	LCA5L	O95447	585
KRTAP21-2	KRTAP8-1	Q8IUC2	583
KRTAP21-2	KRTAP24-1	Q3LI83	583
KRTAP21-2	KRTAP6-2	Q3LI66	581

IntAct

88 interactions, top by confidence:

A	B	Type	Score
FOXD2	KRTAP21-2	psi-mi:“MI:0915”(physical association)	0.560
KRTAP21-2	RNF38	psi-mi:“MI:0915”(physical association)	0.560
KRTAP21-2	ADAMTSL4	psi-mi:“MI:0915”(physical association)	0.560
GATA2	KRTAP21-2	psi-mi:“MI:0915”(physical association)	0.560
KRTAP21-2	PLSCR4	psi-mi:“MI:0915”(physical association)	0.560
SMN1	KRTAP21-2	psi-mi:“MI:0915”(physical association)	0.560
CLCNKA	KRTAP21-2	psi-mi:“MI:0915”(physical association)	0.560
	KRTAP21-2	psi-mi:“MI:0915”(physical association)	0.560
ZIC1	KRTAP21-2	psi-mi:“MI:0915”(physical association)	0.560
VENTX	KRTAP21-2	psi-mi:“MI:0915”(physical association)	0.560
KRTAP12-2	KRTAP21-2	psi-mi:“MI:0915”(physical association)	0.560
KRTAP21-2	RNF44	psi-mi:“MI:0915”(physical association)	0.560
KRTAP21-2	PRR13	psi-mi:“MI:0915”(physical association)	0.560
KRTAP21-2	NTN4	psi-mi:“MI:0915”(physical association)	0.560
FAM221A	KRTAP21-2	psi-mi:“MI:0915”(physical association)	0.560
SNRPC	KRTAP21-2	psi-mi:“MI:0915”(physical association)	0.560
EFEMP1	KRTAP21-2	psi-mi:“MI:0915”(physical association)	0.560
KRTAP21-2	SMARCC1	psi-mi:“MI:0915”(physical association)	0.560
POU4F2	KRTAP21-2	psi-mi:“MI:0915”(physical association)	0.560
KRTAP21-2	LCE5A	psi-mi:“MI:0915”(physical association)	0.560
KRTAP21-2	BEX2	psi-mi:“MI:0915”(physical association)	0.560
KRTAP21-2	TCF7L2	psi-mi:“MI:0915”(physical association)	0.560
KRTAP21-2	LCE1A	psi-mi:“MI:0915”(physical association)	0.560
KRTAP21-2	LCE2A	psi-mi:“MI:0915”(physical association)	0.560
KRTAP21-2	SPAG8	psi-mi:“MI:0915”(physical association)	0.560
MKRN3	KRTAP21-2	psi-mi:“MI:0915”(physical association)	0.560
KRTAP21-2	DMRTB1	psi-mi:“MI:0915”(physical association)	0.560
KRTAP21-2	KRTAP26-1	psi-mi:“MI:0915”(physical association)	0.560
ATXN1L	KRTAP21-2	psi-mi:“MI:0915”(physical association)	0.560
	KRTAP21-2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (30): KRTAP21-2 (Two-hybrid), KRTAP21-2 (Two-hybrid), KRTAP21-2 (Two-hybrid), KRTAP21-2 (Two-hybrid), KRTAP21-2 (Two-hybrid), KRTAP21-2 (Two-hybrid), KRTAP21-2 (Two-hybrid), KRTAP21-2 (Two-hybrid), KRTAP21-2 (Two-hybrid), KRTAP21-2 (Two-hybrid), KRTAP21-2 (Two-hybrid), KRTAP21-2 (Two-hybrid), KRTAP21-2 (Two-hybrid), KRTAP21-2 (Two-hybrid), KRTAP21-2 (Two-hybrid)

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.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 28 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	5	16.4×	4e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	9
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

92 predictions. Top by Δscore:

Variant	Effect	Δscore
21:30747124:A:AT	donor_gain	0.8100
21:30747089:T:C	donor_gain	0.8000
21:30747123:C:CT	donor_gain	0.7500
21:30746972:T:C	donor_gain	0.7200
21:30747071:T:TA	donor_gain	0.6500
21:30747076:AG:A	donor_gain	0.5500
21:30746981:G:C	donor_gain	0.5200
21:30747130:AT:A	donor_gain	0.5200
21:30747146:C:CA	donor_gain	0.5200
21:30746972:T:TA	donor_gain	0.5000
21:30746996:G:C	donor_gain	0.5000
21:30747107:T:C	donor_gain	0.5000
21:30747131:T:C	donor_gain	0.4900
21:30746933:GATGA:G	donor_loss	0.4700
21:30746938:C:A	donor_loss	0.4700
21:30746939:C:G	donor_loss	0.4700
21:30747090:C:CT	donor_gain	0.4700
21:30747091:T:TT	donor_gain	0.4700
21:30747106:AT:A	donor_gain	0.4700
21:30746920:T:TC	acceptor_gain	0.4600
21:30746940:T:C	donor_loss	0.4600
21:30747077:G:C	donor_gain	0.4600
21:30747047:T:C	donor_gain	0.4400
21:30746861:T:C	acceptor_gain	0.4100
21:30747122:A:AC	donor_gain	0.4100
21:30746864:G:C	donor_gain	0.4000
21:30747119:G:C	donor_gain	0.4000
21:30747161:T:C	donor_gain	0.4000
21:30746859:A:AC	donor_gain	0.3900
21:30747118:AG:A	donor_gain	0.3900

AlphaMissense

512 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000243330 (21:30748641 T>A,C), RS1003188637 (21:30748635 C>G), RS1004172493 (21:30747944 A>C), RS1004971152 (21:30747098 A>G), RS1005369352 (21:30746907 C>T), RS1006807028 (21:30746468 A>G), RS1006817061 (21:30746817 CTT>C), RS1008064705 (21:30747303 T>C), RS1009017056 (21:30747637 T>C), RS1009874733 (21:30746398 G>A), RS1011850395 (21:30747466 C>T), RS1012022664 (21:30747814 C>A), RS1012872339 (21:30746946 G>C), RS1013154840 (21:30747190 A>C,G,T), RS1013875635 (21:30748237 G>A)

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

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
2-methyl-4-isothiazolin-3-one	increases expression	1
Thiram	increases expression	1
Tunicamycin	increases expression	1
Asbestos, Serpentine	affects expression	1
Asbestos, Crocidolite	affects expression	1
Cadmium Chloride	decreases expression	1
Thapsigargin	increases expression	1

Clinical trials (associated diseases)

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