KRTAP6-2

Summary

KRTAP6-2 (keratin associated protein 6-2, HGNC:18932) is a protein-coding gene on chromosome 21q22.11, encoding Keratin-associated protein 6-2 (Q3LI66). 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….

Enables identical protein binding activity. Predicted to be involved in keratinization. Predicted to be located in cytosol.

Source: NCBI Gene 337967 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 17 total
• MANE Select transcript: NM_181604

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18932
Approved symbol	KRTAP6-2
Name	keratin associated protein 6-2
Location	21q22.11
Locus type	gene with protein product
Status	Approved
Aliases	KAP6.2
Ensembl gene	ENSG00000186930
Ensembl biotype	protein_coding
Entrez	337967

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000334897

RefSeq mRNA: 1 — MANE Select: NM_181604 NM_181604

CCDS: CCDS13600

Canonical transcript exons

ENST00000334897 — 1 exons

Exon	Start	End
ENSE00001337941	30598590	30598902

Expression profiles

Bgee: expression breadth tissue_specific, 8 present calls, max score 91.66.

Top tissues by expression

107 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	91.66	silver 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
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
liver	UBERON:0002107	28.04	gold quality
lymph node	UBERON:0000029	27.57	gold quality
monocyte	CL:0000576	27.54	gold quality
leukocyte	CL:0000738	27.54	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
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
muscle of leg	UBERON:0001383	24.74	gold quality
primary visual cortex	UBERON:0002436	24.61	gold quality
superior frontal gyrus	UBERON:0002661	24.08	gold quality
pancreas	UBERON:0001264	23.89	gold quality
frontal cortex	UBERON:0001870	23.85	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.82

Regulation

Is transcription factor: no

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

Keratin-associated protein 6-2 — Q3LI66 (reviewed: Q3LI66)

All UniProt accessions (1): Q3LI66

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.

Similarity. Belongs to the KRTAP type 6 family.

RefSeq proteins (1): NP_853635* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR040313	KAP6	Family

UniProt features (1 total): chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q3LI66-F1	42.03	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: 21 (showing top): GOBP_EPITHELIUM_DEVELOPMENT, GOBP_EPIDERMAL_CELL_DIFFERENTIATION, GOBP_EPIDERMIS_DEVELOPMENT, GOBP_KERATINIZATION, chr21q22, GOBP_SKIN_DEVELOPMENT, GOCC_INTERMEDIATE_FILAMENT_CYTOSKELETON, GOCC_SUPRAMOLECULAR_COMPLEX, GOCC_POLYMERIC_CYTOSKELETAL_FIBER, REACTOME_KERATINIZATION, GOBP_KERATINOCYTE_DIFFERENTIATION, GOCC_SUPRAMOLECULAR_POLYMER, GOBP_EPITHELIAL_CELL_DIFFERENTIATION, TATA_01, TTANTCA_UNKNOWN

GO Biological Process (1): keratinization (GO:0031424)

GO Molecular Function (2): identical protein binding (GO:0042802), 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
keratinocyte differentiation	1
multicellular organismal process	1
protein binding	1
binding	1
cytoplasm	1
cellular anatomical structure	1
intermediate filament cytoskeleton	1
polymeric cytoskeletal fiber	1

Protein interactions and networks

STRING

118 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KRTAP6-2	KRTAP6-3	Q3LI67	800
KRTAP6-2	KRTAP22-1	Q3MIV0	795
KRTAP6-2	KRTAP24-1	Q3LI83	795
KRTAP6-2	KRTAP6-1	Q3LI64	791
KRTAP6-2	SCYGR1	A0A286YEY9	790
KRTAP6-2	KRTAP20-2	Q3LI61	783
KRTAP6-2	KRTAP26-1	Q6PEX3	774
KRTAP6-2	KRTAP7-1	Q8IUC3	773
KRTAP6-2	KRTAP13-3	Q3SY46	772
KRTAP6-2	KRTAP8-1	Q8IUC2	765
KRTAP6-2	KRTAP20-1	Q3LI63	764
KRTAP6-2	KRTAP15-1	Q3LI76	720
KRTAP6-2	KRTAP11-1	Q8IUC1	716
KRTAP6-2	KRTAP13-1	Q8IUC0	700
KRTAP6-2	KRTAP1-4	P0C5Y4	643

IntAct

648 interactions, top by confidence:

A	B	Type	Score
KRTAP6-2	VAC14	psi-mi:“MI:0915”(physical association)	0.000
KRTAP6-2	TNIP1	psi-mi:“MI:0915”(physical association)	0.000
KRTAP6-2	DAZAP2	psi-mi:“MI:0915”(physical association)	0.000
KRTAP6-2	CAMK2B	psi-mi:“MI:0915”(physical association)	0.000
KRTAP6-2	ATN1	psi-mi:“MI:0915”(physical association)	0.000
KRTAP6-2	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000
KRTAP6-2	KRTAP12-2	psi-mi:“MI:0915”(physical association)	0.000
KRTAP6-2	CAMK2A	psi-mi:“MI:0915”(physical association)	0.000
KRTAP6-2	TRIP13	psi-mi:“MI:0915”(physical association)	0.000
ESR2	KRTAP6-2	psi-mi:“MI:0915”(physical association)	0.000
FRS3	KRTAP6-2	psi-mi:“MI:0915”(physical association)	0.000
NAF1	KRTAP6-2	psi-mi:“MI:0915”(physical association)	0.000
CATSPER1	KRTAP6-2	psi-mi:“MI:0915”(physical association)	0.000
PLEKHN1	KRTAP6-2	psi-mi:“MI:0915”(physical association)	0.000
LASP1	KRTAP6-2	psi-mi:“MI:0915”(physical association)	0.000
CYSRT1	KRTAP6-2	psi-mi:“MI:0915”(physical association)	0.000
CELF5	KRTAP6-2	psi-mi:“MI:0915”(physical association)	0.000
LRRC41	KRTAP6-2	psi-mi:“MI:0915”(physical association)	0.000
HAPLN2	KRTAP6-2	psi-mi:“MI:0915”(physical association)	0.000
NR1D2	KRTAP6-2	psi-mi:“MI:0915”(physical association)	0.000
PITX1	KRTAP6-2	psi-mi:“MI:0915”(physical association)	0.000
LRFN4	KRTAP6-2	psi-mi:“MI:0915”(physical association)	0.000
RHOXF2	KRTAP6-2	psi-mi:“MI:0915”(physical association)	0.000
TCF7L2	KRTAP6-2	psi-mi:“MI:0915”(physical association)	0.000
SMN1	KRTAP6-2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (187): KRTAP6-2 (Two-hybrid), KRTAP6-2 (Two-hybrid), KRTAP6-2 (Two-hybrid), KRTAP6-2 (Two-hybrid), KRTAP6-2 (Two-hybrid), KRTAP6-2 (Two-hybrid), KRTAP6-2 (Two-hybrid), KRTAP6-2 (Two-hybrid), KRTAP6-2 (Two-hybrid), KRTAP6-2 (Two-hybrid), KRTAP6-2 (Two-hybrid), KRTAP6-2 (Two-hybrid), KRTAP6-2 (Two-hybrid), KRTAP6-2 (Two-hybrid), KRTAP6-2 (Two-hybrid)

ESM2 similar proteins: H2A0M6, O08632, O08633, O08640, P02448, P04459, P05685, P08826, P25692, P82170, P83358, Q02957, Q02958, Q28580, Q3LHN2, Q3LI54, Q3LI58, Q3LI59, Q3LI60, Q3LI61, Q3LI63, Q3LI64, Q3LI66, Q3LI67, Q3LI68, Q3LI70, Q3LI72, Q3LI73, Q3LI77, Q3MIV0, Q3SYF9, Q4W7G7, Q4W7G8, Q4W7G9, Q4W7H0, Q4W7H1, Q6F4C6, Q6R645, Q7Z4W3, Q8C1I6

Diamond homologs: Q3LI64, Q3LI66, Q3LI67, Q925H3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 152 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	14	10.8×	9e-09

GO biological processes:

GO term	Partners	Fold	FDR
keratinization	6	10.8×	3e-03
anterior/posterior pattern specification	6	8.4×	8e-03
anatomical structure morphogenesis	7	7.5×	5e-03

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	16
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

71 predictions. Top by Δscore:

Variant	Effect	Δscore
21:30598807:AGG:A	donor_gain	0.8200
21:30598830:ATAG:A	donor_gain	0.8200
21:30598791:T:TA	donor_gain	0.8000
21:30598854:T:TA	donor_gain	0.8000
21:30598822:CA:C	donor_gain	0.7900
21:30598802:AG:A	donor_gain	0.7500
21:30598823:A:AC	donor_gain	0.7500
21:30598863:G:C	donor_gain	0.7400
21:30598796:AG:A	donor_gain	0.7100
21:30598818:T:C	donor_gain	0.6900
21:30598832:AG:A	donor_gain	0.6900
21:30598833:G:C	donor_gain	0.6800
21:30598817:AT:A	donor_gain	0.6400
21:30598745:AG:A	donor_gain	0.6300
21:30598803:G:C	donor_gain	0.6300
21:30598750:TG:T	donor_gain	0.6100
21:30598746:G:C	donor_gain	0.6000
21:30598828:C:CT	donor_gain	0.5800
21:30598873:A:C	donor_gain	0.5800
21:30598751:G:T	donor_gain	0.5700
21:30598797:G:C	donor_gain	0.5700
21:30598724:C:CT	acceptor_gain	0.5600
21:30598683:T:TA	donor_gain	0.5300
21:30598749:A:AC	donor_gain	0.5100
21:30598850:AGTTT:A	donor_gain	0.5000
21:30598874:T:TA	donor_gain	0.5000
21:30598674:C:CA	donor_gain	0.4900
21:30598792:C:A	donor_gain	0.4900
21:30598830:ATAGC:A	donor_gain	0.4900
21:30598825:C:T	donor_gain	0.4800

AlphaMissense

388 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000111536 (21:30598958 A>G), RS1000270364 (21:30599228 A>C,G), RS1001937248 (21:30600540 C>T), RS1002154218 (21:30599353 T>C), RS1005241273 (21:30598678 C>A,T), RS1005506079 (21:30598441 G>A,C), RS1005735454 (21:30600017 A>G), RS1006098587 (21:30598281 C>T), RS1006181093 (21:30599722 A>G), RS1006775426 (21:30600893 A>G), RS1006916663 (21:30599979 C>T), RS1008849905 (21:30600846 C>G), RS1009351478 (21:30599064 G>A), RS1009690309 (21:30599429 A>T), RS1012097545 (21:30598920 G>C)

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
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Silicon Dioxide	decreases expression	1
Valproic Acid	decreases methylation	1
Cyclosporine	increases methylation	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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