KRTAP6-1

Summary

KRTAP6-1 (keratin associated protein 6-1, HGNC:18931) is a protein-coding gene on chromosome 21q22.11, encoding Keratin-associated protein 6-1 (Q3LI64). 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 involved in keratinization. Located in cytosol.

Source: NCBI Gene 337966 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 15 total
• MANE Select transcript: NM_181602

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18931
Approved symbol	KRTAP6-1
Name	keratin associated protein 6-1
Location	21q22.11
Locus type	gene with protein product
Status	Approved
Aliases	KAP6.1, C21orf103
Ensembl gene	ENSG00000184724
Ensembl biotype	protein_coding
Entrez	337966

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000329122

RefSeq mRNA: 1 — MANE Select: NM_181602 NM_181602

CCDS: CCDS13602

Canonical transcript exons

ENST00000329122 — 1 exons

Exon	Start	End
ENSE00001540538	30613431	30613930

Expression profiles

Bgee: expression breadth broad, 12 present calls, max score 37.47.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	37.47	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
skeletal muscle tissue	UBERON:0001134	35.73	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
muscle tissue	UBERON:0002385	32.79	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
prefrontal cortex	UBERON:0000451	29.50	silver quality
primary visual cortex	UBERON:0002436	29.16	silver quality
duodenum	UBERON:0002114	28.14	gold quality
liver	UBERON:0002107	28.04	gold quality
lymph node	UBERON:0000029	27.57	gold quality
skin of abdomen	UBERON:0001416	27.16	gold quality
tonsil	UBERON:0002372	27.05	gold quality
leukocyte	CL:0000738	26.85	gold quality
monocyte	CL:0000576	26.78	gold quality
islet of Langerhans	UBERON:0000006	26.55	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
blood	UBERON:0000178	26.10	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
zone of skin	UBERON:0000014	25.59	gold quality
muscle of leg	UBERON:0001383	25.02	gold quality
skin of leg	UBERON:0001511	24.31	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.98

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• Expressed and purified are a high sulfur KAP (KAP11.1) and a high glycine-tyrosine KAP (KAP6.1). (PMID:29391282)

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

Keratin-associated protein 6-1 — Q3LI64 (reviewed: Q3LI64)

All UniProt accessions (1): Q3LI64

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_853633* (*=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-Q3LI64-F1	43.85	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: 38 (showing top): GOBP_EPITHELIUM_DEVELOPMENT, DARWICHE_SKIN_TUMOR_PROMOTER_DN, DARWICHE_PAPILLOMA_RISK_LOW_UP, DARWICHE_PAPILLOMA_RISK_HIGH_DN, DARWICHE_SQUAMOUS_CELL_CARCINOMA_DN, DARWICHE_PAPILLOMA_PROGRESSION_RISK, GGGTGGRR_PAX4_03, GOBP_EPIDERMAL_CELL_DIFFERENTIATION, HOWLIN_PUBERTAL_MAMMARY_GLAND, MARTINEZ_RB1_TARGETS_DN, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM6, GOBP_EPIDERMIS_DEVELOPMENT, POU3F2_02, GOBP_KERATINIZATION, chr21q22

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

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
keratinocyte differentiation	1
multicellular organismal process	1
binding	1
cytoplasm	1
cellular anatomical structure	1
intermediate filament cytoskeleton	1
polymeric cytoskeletal fiber	1

Protein interactions and networks

STRING

186 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KRTAP6-1	KRTAP22-1	Q3MIV0	877
KRTAP6-1	KRTAP6-3	Q3LI67	870
KRTAP6-1	KRTAP20-1	Q3LI63	791
KRTAP6-1	KRTAP6-2	Q3LI66	791
KRTAP6-1	KRTAP20-2	Q3LI61	782
KRTAP6-1	KRTAP26-1	Q6PEX3	769
KRTAP6-1	KRTAP8-1	Q8IUC2	767
KRTAP6-1	KRTAP24-1	Q3LI83	723
KRTAP6-1	SCYGR1	A0A286YEY9	720
KRTAP6-1	KRTAP15-1	Q3LI76	720
KRTAP6-1	KRTAP7-1	Q8IUC3	701
KRTAP6-1	KRTAP13-3	Q3SY46	690
KRTAP6-1	A8MUN0	A8MUN0	669
KRTAP6-1	KRTAP11-1	Q8IUC1	659
KRTAP6-1	KRTAP1-1	Q07627	626

IntAct

293 interactions, top by confidence:

A	B	Type	Score
TRIP13	KRTAP6-1	psi-mi:“MI:0915”(physical association)	0.600
GLIS3	KRTAP6-1	psi-mi:“MI:0915”(physical association)	0.560
VENTX	KRTAP6-1	psi-mi:“MI:0915”(physical association)	0.560
HOXC8	KRTAP6-1	psi-mi:“MI:0915”(physical association)	0.560
NOTO	KRTAP6-1	psi-mi:“MI:0915”(physical association)	0.560
MAGED1	KRTAP6-1	psi-mi:“MI:0915”(physical association)	0.560
CCDC24	KRTAP6-1	psi-mi:“MI:0915”(physical association)	0.560
MED25	KRTAP6-1	psi-mi:“MI:0915”(physical association)	0.560
TENT5B	KRTAP6-1	psi-mi:“MI:0915”(physical association)	0.560
CATSPER1	KRTAP6-1	psi-mi:“MI:0915”(physical association)	0.560
KRTAP6-1	KRTAP12-3	psi-mi:“MI:0915”(physical association)	0.560
KPRP	KRTAP6-1	psi-mi:“MI:0915”(physical association)	0.560
GPS2	KRTAP6-1	psi-mi:“MI:0915”(physical association)	0.560
MAPK1IP1L	KRTAP6-1	psi-mi:“MI:0915”(physical association)	0.560
CRYAB	KRTAP6-1	psi-mi:“MI:0915”(physical association)	0.560
CAMK2G	KRTAP6-1	psi-mi:“MI:0915”(physical association)	0.560
KRTAP6-1	CAMK2A	psi-mi:“MI:0915”(physical association)	0.560
TNIP1	KRTAP6-1	psi-mi:“MI:0915”(physical association)	0.560
VAC14	KRTAP6-1	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	KRTAP6-1	psi-mi:“MI:0915”(physical association)	0.560
DAZAP2	KRTAP6-1	psi-mi:“MI:0915”(physical association)	0.560
KRTAP6-1	ITIH6	psi-mi:“MI:0915”(physical association)	0.560
KRTAP6-1	GLIS2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (103): KRTAP6-1 (Two-hybrid), KRTAP6-1 (Two-hybrid), KRTAP6-1 (Two-hybrid), KRTAP6-1 (Two-hybrid), KRTAP6-1 (Two-hybrid), KRTAP6-1 (Two-hybrid), KRTAP6-1 (Two-hybrid), KRTAP6-1 (Two-hybrid), KRTAP6-1 (Two-hybrid), KRTAP6-1 (Two-hybrid), KRTAP6-1 (Two-hybrid), KRTAP6-1 (Two-hybrid), KRTAP6-1 (Two-hybrid), KRTAP6-1 (Two-hybrid), KRTAP6-1 (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 87 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	8	9.5×	4e-04

GO biological processes:

GO term	Partners	Fold	FDR
anterior/posterior pattern specification	6	14.5×	5e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

170 predictions. Top by Δscore:

Variant	Effect	Δscore
21:30613884:T:A	donor_gain	0.8000
21:30613860:ATAG:A	donor_gain	0.7900
21:30613903:A:C	donor_gain	0.7900
21:30613880:AGTTT:A	donor_gain	0.7800
21:30613893:G:C	donor_gain	0.7800
21:30613895:TGCCA:T	donor_gain	0.7600
21:30613878:G:C	donor_gain	0.7500
21:30613863:G:C	donor_gain	0.7100
21:30613897:C:CT	donor_gain	0.7000
21:30613862:AG:A	donor_gain	0.6900
21:30613877:A:AC	donor_gain	0.6900
21:30613755:G:C	donor_gain	0.6700
21:30613872:G:A	donor_gain	0.6700
21:30613724:AG:A	donor_gain	0.6600
21:30613855:A:T	donor_gain	0.6600
21:30613899:A:T	donor_gain	0.6600
21:30613581:T:TA	donor_gain	0.6500
21:30613837:AGG:A	donor_gain	0.6500
21:30613895:TGC:T	donor_gain	0.6500
21:30613686:T:TA	donor_gain	0.6400
21:30613853:A:AC	donor_gain	0.6400
21:30613858:C:CT	donor_gain	0.6400
21:30613754:AG:A	donor_gain	0.6300
21:30613821:T:TA	donor_gain	0.6300
21:30613826:AG:A	donor_gain	0.6100
21:30613925:T:TA	donor_gain	0.6100
21:30613842:T:TA	donor_gain	0.6000
21:30613827:G:C	donor_gain	0.5900
21:30613847:AG:A	donor_gain	0.5900
21:30613852:CA:C	donor_gain	0.5800

AlphaMissense

430 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:30613779:G:C	F42L	0.857
21:30613779:G:T	F42L	0.857
21:30613781:A:G	F42L	0.857
21:30613769:C:G	G46R	0.664
21:30613763:C:G	G48R	0.603
21:30613893:G:C	S4R	0.602
21:30613893:G:T	S4R	0.602
21:30613895:T:G	S4R	0.602
21:30613901:A:G	C2R	0.602
21:30613899:A:C	C2W	0.592
21:30613756:C:T	G50D	0.566
21:30613762:C:T	G48D	0.565

dbSNP variants (sampled 300 via entrez): RS1001092125 (21:30615888 A>T), RS1002741151 (21:30615841 G>A), RS1002874265 (21:30613998 G>A,T), RS1003494580 (21:30613011 T>C), RS1004373699 (21:30613921 G>A), RS1006093814 (21:30615170 G>A), RS1006454122 (21:30615430 G>A,C), RS1008436894 (21:30615321 G>A), RS1009015718 (21:30615593 C>T), RS1010535796 (21:30613384 C>T), RS1011048021 (21:30614755 A>G), RS1011639356 (21:30613147 T>A,G), RS1013293883 (21:30614881 T>C), RS1017415412 (21:30615190 A>G), RS1018494598 (21:30613506 C>T)

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

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

Chemical	Actions (top 5)	PubMed papers
CGP 52608	affects binding, increases reaction	1
Resveratrol	affects cotreatment, decreases expression	1
Atrazine	increases expression	1
Phthalic Acids	increases methylation	1
Plant Extracts	decreases expression, affects cotreatment	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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