KRTAP3-3

Summary

KRTAP3-3 (keratin associated protein 3-3, HGNC:18890) is a protein-coding gene on chromosome 17q21.2, encoding Keratin-associated protein 3-3 (Q9BYR6). 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….

This protein is a member of the keratin-associated protein (KAP) family. The KAP proteins form a matrix of keratin intermediate filaments which contribute to the structure of hair fibers. KAP family members appear to have unique, family-specific amino- and carboxyl-terminal regions and are subdivided into three multi-gene families according to amino acid composition: the high sulfur, the ultrahigh sulfur, and the high tyrosine/glycine KAPs. This protein is a member of the high sulfur KAP family and the gene is localized to a cluster of KAPs at 17q12-q21.

Source: NCBI Gene 85293 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 12 total
• MANE Select transcript: NM_033185

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18890
Approved symbol	KRTAP3-3
Name	keratin associated protein 3-3
Location	17q21.2
Locus type	gene with protein product
Status	Approved
Aliases	KAP3.3
Ensembl gene	ENSG00000212899
Ensembl biotype	protein_coding
Entrez	85293

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000391586

RefSeq mRNA: 1 — MANE Select: NM_033185 NM_033185

CCDS: CCDS32643

Canonical transcript exons

ENST00000391586 — 1 exons

Exon	Start	End
ENSE00001509365	40993430	40994164

Expression profiles

Bgee: expression breadth broad, 73 present calls, max score 52.90.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4011 / max 436.9944, expressed in 12 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165861	0.3893	12
165860	0.0118	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skin of abdomen	UBERON:0001416	52.90	gold quality
right lung	UBERON:0002167	51.66	gold quality
zone of skin	UBERON:0000014	50.50	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	50.14	silver quality
skin of leg	UBERON:0001511	49.07	gold quality
sural nerve	UBERON:0015488	41.42	gold quality
granulocyte	CL:0000094	39.47	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
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
tonsil	UBERON:0002372	32.57	gold quality
gastrocnemius	UBERON:0001388	32.53	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
muscle of leg	UBERON:0001383	32.14	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
blood	UBERON:0000178	30.95	gold quality
islet of Langerhans	UBERON:0000006	30.45	gold quality
prostate gland	UBERON:0002367	30.12	silver quality
saliva-secreting gland	UBERON:0001044	30.00	silver quality
pancreas	UBERON:0001264	29.94	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
minor salivary gland	UBERON:0001830	29.68	silver quality
prefrontal cortex	UBERON:0000451	29.48	gold quality
gall bladder	UBERON:0002110	29.38	gold quality
body of pancreas	UBERON:0001150	28.98	silver quality
leukocyte	CL:0000738	28.77	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

32 targeting KRTAP3-3, 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-1252-5P	100.00	69.80	2774
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-651-5P	99.64	68.49	1104
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-6848-3P	99.64	66.49	885
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-130A-5P	99.33	70.26	2623
HSA-MIR-6843-3P	99.26	66.42	915
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-181A-2-3P	98.91	67.60	1168
HSA-MIR-8060	98.61	66.93	1187
HSA-MIR-4536-5P	98.47	64.39	657
HSA-MIR-6509-3P	98.32	67.33	1343
HSA-MIR-509-3-5P	97.21	67.74	1517
HSA-MIR-509-5P	97.21	67.90	1512
HSA-MIR-4418	97.04	67.16	1372
HSA-MIR-4790-3P	96.63	67.08	806

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Krtap3-2	ENSMUSG00000069721
mus_musculus	Krtap3-3	ENSMUSG00000069722
rattus_norvegicus	Krtap3-2	ENSRNOG00000083895
rattus_norvegicus	Krtap3-3	ENSRNOG00000084880

Paralogs (3): KRTAP24-1 (ENSG00000188694), KRTAP3-2 (ENSG00000212900), KRTAP3-1 (ENSG00000212901)

Protein

Protein identifiers

Keratin-associated protein 3-3 — Q9BYR6 (reviewed: Q9BYR6)

Alternative names: High sulfur keratin-associated protein 3.3, Keratin-associated protein 3.3

All UniProt accessions (1): Q9BYR6

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.

Tissue specificity. Localized to the upper cortex of the hair shaft.

Similarity. Belongs to the KRTAP type 3 family.

RefSeq proteins (1): NP_149441* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007659	Keratin_matx	Family

Pfam: PF04579

UniProt features (6 total): repeat 3, chain 1, region of interest 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BYR6-F1	43.47	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: 33 (showing top): GOCC_INTERMEDIATE_FILAMENT_CYTOSKELETON, GOCC_KERATIN_FILAMENT, ZHOU_INFLAMMATORY_RESPONSE_LIVE_UP, GSE13522_WT_VS_IFNG_KO_SKIN_DN, GOMF_STRUCTURAL_MOLECULE_ACTIVITY, GOCC_SUPRAMOLECULAR_COMPLEX, GOCC_POLYMERIC_CYTOSKELETAL_FIBER, REACTOME_KERATINIZATION, GOCC_SUPRAMOLECULAR_POLYMER, LHX9_TARGET_GENES, MIR130A_5P, GSE11924_TH1_VS_TH17_CD4_TCELL_DN, MIR31_3P, GSE17721_CTRL_VS_LPS_8H_BMDC_DN, MEBARKI_HCC_PROGENITOR_FZD8CRD_DN

GO Biological Process (0):

GO Molecular Function (2): structural molecule activity (GO:0005198), protein binding (GO:0005515)

GO Cellular Component (3): cytosol (GO:0005829), keratin filament (GO:0045095), 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
molecular_function	1
binding	1
cytoplasm	1
cellular anatomical structure	1
intermediate filament	1
intermediate filament cytoskeleton	1
polymeric cytoskeletal fiber	1

Protein interactions and networks

STRING

346 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KRTAP3-3	KRTAP11-1	Q8IUC1	585
KRTAP3-3	KRTAP4-1	Q9BYQ7	571
KRTAP3-3	KRTAP9-1	A8MXZ3	564
KRTAP3-3	KRT73	Q86Y46	511
KRTAP3-3	KRTAP4-3	Q9BYR4	480
KRTAP3-3	S100A3	P33764	473
KRTAP3-3	KRTAP8-1	Q8IUC2	467
KRTAP3-3	KRTAP9-3	Q9BYQ3	467
KRTAP3-3	KRT34	O76011	464
KRTAP3-3	CCHCR1	Q8TD31	457
KRTAP3-3	KRTAP13-1	Q8IUC0	453
KRTAP3-3	KRTAP16-1	A8MUX0	447
KRTAP3-3	KRTAP9-8	Q9BYQ0	436
KRTAP3-3	KRT33B	Q14525	434
KRTAP3-3	KRTAP9-4	Q9BYQ2	434
KRTAP3-3	KRTAP1-4	P0C5Y4	434

IntAct

242 interactions, top by confidence:

A	B	Type	Score
OTX1	KRTAP3-3	psi-mi:“MI:0915”(physical association)	0.720
KRTAP3-3	OTX1	psi-mi:“MI:0915”(physical association)	0.720
KRT83	KRTAP3-3	psi-mi:“MI:0915”(physical association)	0.630
KRTAP3-3	NUFIP2	psi-mi:“MI:0915”(physical association)	0.560
LCE3C	KRTAP3-3	psi-mi:“MI:0915”(physical association)	0.560
NUFIP2	KRTAP3-3	psi-mi:“MI:0915”(physical association)	0.560
HOXA1	KRTAP3-3	psi-mi:“MI:0915”(physical association)	0.560
MXD3	KRTAP3-3	psi-mi:“MI:0915”(physical association)	0.560
ALDH3B1	KRTAP3-3	psi-mi:“MI:0915”(physical association)	0.560
VENTX	KRTAP3-3	psi-mi:“MI:0915”(physical association)	0.560
LCE3A	KRTAP3-3	psi-mi:“MI:0915”(physical association)	0.560
KRTAP15-1	KRTAP3-3	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	KRTAP3-3	psi-mi:“MI:0915”(physical association)	0.560
KRTAP3-3	GNE	psi-mi:“MI:0915”(physical association)	0.560
FADS6	KRTAP3-3	psi-mi:“MI:0915”(physical association)	0.560
KRTAP3-3	PATZ1	psi-mi:“MI:0915”(physical association)	0.560
	KRTAP3-3	psi-mi:“MI:0915”(physical association)	0.560
KRTAP4-2	KRTAP3-3	psi-mi:“MI:0915”(physical association)	0.560
FOXH1	KRTAP3-3	psi-mi:“MI:0915”(physical association)	0.560
LCE1F	KRTAP3-3	psi-mi:“MI:0915”(physical association)	0.560
SMARCC1	KRTAP3-3	psi-mi:“MI:0915”(physical association)	0.560
MRPL23	KRTAP3-3	psi-mi:“MI:0915”(physical association)	0.560
CERCAM	KRTAP3-3	psi-mi:“MI:0915”(physical association)	0.560
GSTP1	KRTAP3-3	psi-mi:“MI:0915”(physical association)	0.560
NTAQ1	KRTAP3-3	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (84): KRTAP3-3 (Two-hybrid), KRTAP3-3 (Two-hybrid), LCE3C (Two-hybrid), KRTAP3-3 (Affinity Capture-MS), KRTAP3-3 (Two-hybrid), KRTAP3-3 (Two-hybrid), KRTAP3-3 (Two-hybrid), KRTAP3-3 (Two-hybrid), KRTAP3-3 (Two-hybrid), KRTAP3-3 (Two-hybrid), KRTAP3-3 (Two-hybrid), KRTAP3-3 (Two-hybrid), KRTAP3-3 (Two-hybrid), KRTAP3-3 (Two-hybrid), KRTAP3-3 (Two-hybrid)

ESM2 similar proteins: A1A580, A2A591, A2A5X4, A2A5X5, A8MUX0, A8MX34, B2RUR4, O13152, O93499, O93500, P02444, P02445, P02446, P02447, P02449, P02450, P02451, P04458, P07521, P08335, P0DV60, P20307, P20308, P25692, P60329, Q24JX8, Q24JX9, Q3LI81, Q3LI83, Q4KL71, Q5T749, Q5T750, Q5TA77, Q6PEX3, Q6R648, Q6S343, Q7TQM5, Q8IUC1, Q92012, Q98U05

Diamond homologs: A2A591, P02444, P02445, P02446, P02447, Q24JX8, Q24JX9, Q6S343, Q9BYR6, Q9BYR7, Q9BYR8, Q9D638, Q9D7P0, A2A5X5, A6QP35, A8MUX0, Q3LI83, Q4W7G7, Q4W7G8, Q4W7G9, Q6R648, Q8IUC1

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 73 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	20	24.8×	2e-21
Formation of the cornified envelope	8	15.6×	2e-06

GO biological processes:

GO term	Partners	Fold	FDR
keratinization	9	34.5×	2e-09

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	11
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

240 predictions. Top by Δscore:

Variant	Effect	Δscore
17:40993979:A:C	donor_gain	0.7700
17:40994012:C:CA	donor_gain	0.7500
17:40993701:C:CC	acceptor_gain	0.7300
17:40994011:TC:T	donor_gain	0.7100
17:40994012:CC:C	donor_gain	0.7100
17:40993698:TTT:T	acceptor_gain	0.6800
17:40993548:A:AC	donor_gain	0.6500
17:40993549:C:CC	donor_gain	0.6500
17:40993797:T:TA	donor_gain	0.6400
17:40993868:AGG:A	donor_gain	0.6400
17:40993980:C:CC	donor_gain	0.6200
17:40993479:T:TA	donor_gain	0.6000
17:40993698:TTTC:T	acceptor_loss	0.6000
17:40993699:TT:T	acceptor_gain	0.6000
17:40993700:TC:T	acceptor_loss	0.6000
17:40993701:CTAAA:C	acceptor_loss	0.6000
17:40993870:G:A	donor_gain	0.6000
17:40993702:T:G	acceptor_loss	0.5900
17:40993530:C:CT	donor_gain	0.5800
17:40993547:CA:C	donor_gain	0.5800
17:40993707:CAGAG:C	acceptor_loss	0.5800
17:40993928:A:AC	acceptor_gain	0.5700
17:40993971:G:C	donor_gain	0.5700
17:40993916:CAGGG:C	acceptor_gain	0.5500
17:40993500:C:CT	donor_gain	0.5400
17:40993531:C:CT	donor_gain	0.5400
17:40993554:A:C	donor_gain	0.5400
17:40993703:A:C	acceptor_loss	0.5400
17:40993828:A:AC	donor_gain	0.5300
17:40993829:C:CC	donor_gain	0.5300

AlphaMissense

627 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:40993900:G:C	F66L	0.984
17:40993900:G:T	F66L	0.984
17:40993902:A:G	F66L	0.984
17:40993996:G:C	S34R	0.960
17:40993996:G:T	S34R	0.960
17:40993998:T:G	S34R	0.960
17:40993992:A:G	C36R	0.954
17:40993901:A:G	F66S	0.953
17:40993901:A:C	F66C	0.949
17:40993990:G:C	C36W	0.938
17:40994007:A:G	C31R	0.921
17:40994005:G:C	C31W	0.914
17:40994000:G:T	P33H	0.911
17:40993895:A:T	L68H	0.909
17:40993905:A:G	C65R	0.902
17:40993898:A:G	L67P	0.901
17:40993984:G:C	H38Q	0.899
17:40993984:G:T	H38Q	0.899
17:40994040:A:G	C20R	0.899
17:40994038:G:C	C20W	0.895
17:40993991:C:T	C36Y	0.894
17:40993902:A:C	F66V	0.893
17:40993997:C:A	S34I	0.893
17:40994003:A:G	L32P	0.893
17:40993902:A:T	F66I	0.889
17:40993895:A:G	L68P	0.883
17:40994022:A:G	C26R	0.883
17:40993898:A:T	L67Q	0.881
17:40994001:G:T	P33T	0.881
17:40993991:C:G	C36S	0.878

dbSNP variants (sampled 300 via entrez): RS1000168772 (17:40993669 T>A,C,G), RS1000507061 (17:40994982 G>A), RS1001562207 (17:40993384 C>T), RS1002159185 (17:40994685 T>C,G), RS1002227078 (17:40993619 T>C,G), RS1002510141 (17:40994479 G>A), RS1003781200 (17:40995742 A>G), RS1004236562 (17:40995944 G>A), RS1004740340 (17:40995823 C>T), RS1005641314 (17:40995721 G>C,T), RS1006926240 (17:40993061 T>C), RS1007205577 (17:40995725 G>A), RS1008681975 (17:40995142 C>G), RS1008942750 (17:40995337 T>G), RS1009253375 (17:40995513 TC>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

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

Chemical	Actions (top 5)	PubMed papers
beta-lapachone	decreases expression	1
sodium arsenite	decreases expression	1
CGP 52608	affects binding, increases reaction	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression, increases abundance	1
Cadmium Chloride	decreases expression, increases abundance	1
beta-Naphthoflavone	increases expression	1

Clinical trials (associated diseases)

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