KRTAP6-3

Summary

KRTAP6-3 (keratin associated protein 6-3, HGNC:18933) is a protein-coding gene on chromosome 21q22.11, encoding Keratin-associated protein 6-3 (Q3LI67). 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. Predicted to be located in cytosol.

Source: NCBI Gene 337968 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 17 total
• MANE Select transcript: NM_001433434

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18933
Approved symbol	KRTAP6-3
Name	keratin associated protein 6-3
Location	21q22.11
Locus type	gene with protein product
Status	Approved
Aliases	KAP6.3
Ensembl gene	ENSG00000212938
Ensembl biotype	protein_coding
Entrez	337968

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000391624

RefSeq mRNA: 1 — MANE Select: NM_001433434 NM_001433434

Canonical transcript exons

ENST00000391624 — 1 exons

Exon	Start	End
ENSE00001509402	30592440	30593055

Expression profiles

Bgee: expression breadth tissue_specific, 1 present calls, max score 54.11.

Top tissues by expression

120 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	54.11	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
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
liver	UBERON:0002107	28.70	gold quality
duodenum	UBERON:0002114	28.14	gold quality
lymph node	UBERON:0000029	27.57	gold quality
tonsil	UBERON:0002372	27.05	gold quality
islet of Langerhans	UBERON:0000006	26.55	gold quality
leukocyte	CL:0000738	26.42	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
monocyte	CL:0000576	26.30	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
blood	UBERON:0000178	25.75	gold quality
urinary bladder	UBERON:0001255	25.72	gold quality
muscle of leg	UBERON:0001383	24.82	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

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.15

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

25 targeting KRTAP6-3, 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-513A-5P	100.00	69.77	2465
HSA-MIR-10395-5P	99.86	67.35	676
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-106A-3P	99.53	67.58	995
HSA-MIR-324-3P	99.26	66.31	1034
HSA-MIR-412-3P	98.86	66.89	712
HSA-MIR-1288-5P	98.85	67.01	734
HSA-MIR-6804-5P	98.39	65.77	1084
HSA-MIR-6509-3P	98.32	67.33	1343
HSA-MIR-4518	98.12	66.82	1030
HSA-MIR-1266-5P	97.71	66.92	1052
HSA-MIR-5196-3P	97.57	65.98	979
HSA-MIR-219B-3P	97.31	66.96	672
HSA-MIR-5694	97.06	67.70	682
HSA-MIR-4793-5P	96.88	65.90	872
HSA-MIR-4296	96.35	63.55	1233
HSA-MIR-4265	96.18	64.68	557
HSA-MIR-4322	96.18	64.85	539
HSA-MIR-136-3P	93.27	66.31	131
HSA-MIR-503-3P	92.89	66.09	537

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

Keratin-associated protein 6-3 — Q3LI67 (reviewed: Q3LI67)

All UniProt accessions (1): Q3LI67

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_001420363* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR040313	KAP6	Family

UniProt features (4 total): sequence variant 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q3LI67-F1	40.40	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): GOBP_EPITHELIUM_DEVELOPMENT, RACCACAR_AML_Q6, GOBP_EPIDERMAL_CELL_DIFFERENTIATION, GOBP_EPIDERMIS_DEVELOPMENT, GOBP_KERATINIZATION, chr21q22, GOBP_SKIN_DEVELOPMENT, GOCC_INTERMEDIATE_FILAMENT_CYTOSKELETON, GOCC_SUPRAMOLECULAR_COMPLEX, GOCC_POLYMERIC_CYTOSKELETAL_FIBER, GCNP_SHH_UP_EARLY.V1_UP, GCNP_SHH_UP_LATE.V1_UP, REACTOME_KERATINIZATION, GSE13522_CTRL_VS_T_CRUZI_Y_STRAIN_INF_SKIN_BALBC_MOUSE_UP, GOBP_KERATINOCYTE_DIFFERENTIATION

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

100 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KRTAP6-3	KRTAP22-1	Q3MIV0	881
KRTAP6-3	KRTAP6-1	Q3LI64	870
KRTAP6-3	KRTAP20-1	Q3LI63	870
KRTAP6-3	KRTAP6-2	Q3LI66	800
KRTAP6-3	KRTAP20-2	Q3LI61	791
KRTAP6-3	KRTAP26-1	Q6PEX3	789
KRTAP6-3	SCYGR1	A0A286YEY9	772
KRTAP6-3	KRTAP24-1	Q3LI83	763
KRTAP6-3	KRTAP15-1	Q3LI76	761
KRTAP6-3	KRTAP8-1	Q8IUC2	724
KRTAP6-3	KRTAP13-3	Q3SY46	720
KRTAP6-3	A8MUN0	A8MUN0	719
KRTAP6-3	KRTAP21-1	Q3LI58	717
KRTAP6-3	KRTAP21-2	Q3LI59	696
KRTAP6-3	KRTAP7-1	Q8IUC3	662

IntAct

492 interactions, top by confidence:

A	B	Type	Score
KRTAP6-3	NR4A3	psi-mi:“MI:0915”(physical association)	0.000
BSCL2	KRTAP6-3	psi-mi:“MI:0915”(physical association)	0.000
ATPAF2	KRTAP6-3	psi-mi:“MI:0915”(physical association)	0.000
FOXD2	KRTAP6-3	psi-mi:“MI:0915”(physical association)	0.000
CHRD	KRTAP6-3	psi-mi:“MI:0915”(physical association)	0.000
KRTAP6-3	LCE1E	psi-mi:“MI:0915”(physical association)	0.000
SAMD7	KRTAP6-3	psi-mi:“MI:0915”(physical association)	0.000
VASN	KRTAP6-3	psi-mi:“MI:0915”(physical association)	0.000
SNRPC	KRTAP6-3	psi-mi:“MI:0915”(physical association)	0.000
PPP1R37	KRTAP6-3	psi-mi:“MI:0915”(physical association)	0.000
CCDC24	KRTAP6-3	psi-mi:“MI:0915”(physical association)	0.000
ARMC7	KRTAP6-3	psi-mi:“MI:0915”(physical association)	0.000
TYK2	KRTAP6-3	psi-mi:“MI:0915”(physical association)	0.000
OTX1	KRTAP6-3	psi-mi:“MI:0915”(physical association)	0.000
TEKT4	KRTAP6-3	psi-mi:“MI:0915”(physical association)	0.000
ZNF414	KRTAP6-3	psi-mi:“MI:0915”(physical association)	0.000
DHRS1	KRTAP6-3	psi-mi:“MI:0915”(physical association)	0.000
SMARCE1	KRTAP6-3	psi-mi:“MI:0915”(physical association)	0.000
RUNX1T1	KRTAP6-3	psi-mi:“MI:0915”(physical association)	0.000
DMRT3	KRTAP6-3	psi-mi:“MI:0915”(physical association)	0.000
COL8A1	KRTAP6-3	psi-mi:“MI:0915”(physical association)	0.000
INPP5D	KRTAP6-3	psi-mi:“MI:0915”(physical association)	0.000
CNNM3	KRTAP6-3	psi-mi:“MI:0915”(physical association)	0.000
MAPK1IP1L	KRTAP6-3	psi-mi:“MI:0915”(physical association)	0.000
ATOSB	KRTAP6-3	psi-mi:“MI:0915”(physical association)	0.000
PVR	KRTAP6-3	psi-mi:“MI:0915”(physical association)	0.000
CCER1	KRTAP6-3	psi-mi:“MI:0915”(physical association)	0.000
LCE2B	KRTAP6-3	psi-mi:“MI:0915”(physical association)	0.000
POU4F3	KRTAP6-3	psi-mi:“MI:0915”(physical association)	0.000

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 129 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
Formation of the cornified envelope	11	14.2×	4e-08
Keratinization	13	10.7×	4e-08

GO biological processes:

GO term	Partners	Fold	FDR
keratinization	10	20.4×	4e-08

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	14
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

290 predictions. Top by Δscore:

Variant	Effect	Δscore
21:30592478:C:G	donor_gain	0.8900
21:30592507:GCTA:G	donor_gain	0.8400
21:30592508:C:G	donor_gain	0.8300
21:30592522:GC:G	donor_gain	0.8300
21:30592531:GCC:G	donor_gain	0.8300
21:30592528:G:GT	donor_gain	0.8200
21:30592546:A:AG	donor_gain	0.8200
21:30592885:G:GT	donor_gain	0.8000
21:30592600:G:GT	donor_gain	0.7800
21:30592468:T:G	donor_gain	0.7700
21:30592471:GTGGC:G	donor_gain	0.7700
21:30592517:C:CG	donor_gain	0.7700
21:30592579:G:GT	donor_gain	0.7600
21:30592512:G:GA	donor_gain	0.7500
21:30592473:G:GA	donor_gain	0.7400
21:30592523:C:G	donor_gain	0.7400
21:30592542:G:GA	donor_gain	0.7400
21:30592574:C:G	donor_gain	0.7400
21:30592621:G:GT	donor_gain	0.7300
21:30592445:G:GT	donor_gain	0.7200
21:30592616:C:G	donor_gain	0.7200
21:30592500:G:GA	donor_gain	0.7100
21:30592499:T:TA	donor_gain	0.7000
21:30592502:C:G	donor_gain	0.7000
21:30592637:C:G	donor_gain	0.6900
21:30592700:C:G	donor_gain	0.6900
21:30592506:GGCTA:G	donor_gain	0.6800
21:30592543:GT:G	donor_gain	0.6700
21:30592544:T:G	donor_gain	0.6700
21:30592544:TT:T	donor_gain	0.6700

AlphaMissense

689 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000996787 (21:30591383 T>C), RS1001292211 (21:30590687 G>A), RS1002849561 (21:30591770 T>C), RS1002962558 (21:30592062 CTAAT>C), RS1004299521 (21:30592303 G>A), RS1004551143 (21:30590948 T>C), RS1006296614 (21:30591664 AT>A), RS1006720106 (21:30591394 T>C), RS1008034151 (21:30590738 T>G), RS1008566601 (21:30591120 A>G), RS1009431070 (21:30593185 A>G), RS1009460754 (21:30592885 G>C), RS1011898286 (21:30590713 T>A), RS1012023853 (21:30591039 T>C), RS1012156897 (21:30593459 T>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

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

Chemical	Actions (top 5)	PubMed papers
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Cadmium	increases abundance, decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Cadmium Chloride	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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