KBTBD3

Summary

KBTBD3 (kelch repeat and BTB domain containing 3, HGNC:22934) is a protein-coding gene on chromosome 11q22.3, encoding Kelch repeat and BTB domain-containing protein 3 (Q8NAB2).

Predicted to enable ubiquitin-like ligase-substrate adaptor activity. Predicted to be involved in proteasome-mediated ubiquitin-dependent protein catabolic process. Predicted to be located in nucleus. Predicted to be part of Cul3-RING ubiquitin ligase complex. Predicted to be active in cytoplasm.

Source: NCBI Gene 143879 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 75 total
• MANE Select transcript: NM_198439

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22934
Approved symbol	KBTBD3
Name	kelch repeat and BTB domain containing 3
Location	11q22.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000182359
Ensembl biotype	protein_coding
Entrez	143879

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 14 protein_coding, 2 retained_intron

ENST00000526793, ENST00000526805, ENST00000528483, ENST00000531482, ENST00000531837, ENST00000532662, ENST00000534815, ENST00000883713, ENST00000883714, ENST00000932985, ENST00000932986, ENST00000932987, ENST00000932988, ENST00000932989, ENST00000963660, ENST00000963661

RefSeq mRNA: 3 — MANE Select: NM_198439 NM_001330359, NM_152433, NM_198439

CCDS: CCDS81621, CCDS8334

Canonical transcript exons

ENST00000531837 — 4 exons

Exon	Start	End
ENSE00001303403	106058865	106059109
ENSE00001549048	106076507	106076707
ENSE00002190497	106077312	106077347
ENSE00003564341	106051098	106054455

Expression profiles

Bgee: expression breadth ubiquitous, 181 present calls, max score 86.34.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.6162 / max 114.8289, expressed in 1274 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
122096	2.6545	1122
122098	0.8204	322
122097	0.1414	65

Top tissues by expression

241 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	86.34	gold quality
calcaneal tendon	UBERON:0003701	83.74	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	83.28	gold quality
islet of Langerhans	UBERON:0000006	81.53	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	81.36	gold quality
adrenal tissue	UBERON:0018303	81.03	gold quality
body of pancreas	UBERON:0001150	80.17	gold quality
prefrontal cortex	UBERON:0000451	79.85	gold quality
granulocyte	CL:0000094	79.58	gold quality
spinal cord	UBERON:0002240	79.56	gold quality
pancreas	UBERON:0001264	79.53	gold quality
descending thoracic aorta	UBERON:0002345	77.97	gold quality
mucosa of stomach	UBERON:0001199	77.41	gold quality
ventricular zone	UBERON:0003053	77.08	gold quality
right lung	UBERON:0002167	77.00	gold quality
right testis	UBERON:0004534	76.97	gold quality
hindlimb stylopod muscle	UBERON:0004252	76.85	gold quality
tibial artery	UBERON:0007610	76.84	gold quality
popliteal artery	UBERON:0002250	76.83	gold quality
left testis	UBERON:0004533	76.56	gold quality
tibial nerve	UBERON:0001323	76.53	gold quality
aorta	UBERON:0000947	76.42	gold quality
ascending aorta	UBERON:0001496	76.39	gold quality
thoracic aorta	UBERON:0001515	76.36	gold quality
colonic epithelium	UBERON:0000397	76.35	gold quality
tendon	UBERON:0000043	76.33	gold quality
Brodmann (1909) area 9	UBERON:0013540	76.31	gold quality
leukocyte	CL:0000738	76.04	gold quality
mucosa of transverse colon	UBERON:0004991	75.79	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	75.77	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.91

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

84 targeting KBTBD3, 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-1277-5P	100.00	73.95	5056
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107

Literature-anchored findings (GeneRIF, showing 1)

• Ritonavir (at 100 mg once daily and 100 mg twice daily significantly down-regulated Kelch domain containing 3 in 20 healthy individuals. (PMID:20353815)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	kbtbd3	ENSDARG00000060512
mus_musculus	Kbtbd3	ENSMUSG00000025893
rattus_norvegicus	Kbtbd3	ENSRNOG00000069206

Paralogs (54): KLHL13 (ENSG00000003096), KLHL20 (ENSG00000076321), KEAP1 (ENSG00000079999), KLHL42 (ENSG00000087448), KLHL22 (ENSG00000099910), KLHL4 (ENSG00000102271), KLHL2 (ENSG00000109466), KLHL5 (ENSG00000109790), BACH2 (ENSG00000112182), KLHL18 (ENSG00000114648), KLHL24 (ENSG00000114796), IVNS1ABP (ENSG00000116679), KLHL12 (ENSG00000117153), KLHL29 (ENSG00000119771), KBTBD7 (ENSG00000120696), KLHL7 (ENSG00000122550), KLHL31 (ENSG00000124743), KLHDC7B (ENSG00000130487), KLHL36 (ENSG00000135686), KLHL8 (ENSG00000145332), KLHL3 (ENSG00000146021), KLHL35 (ENSG00000149243), KLHL1 (ENSG00000150361), BACH1 (ENSG00000156273), KLHL40 (ENSG00000157119), KLHL10 (ENSG00000161594), KLHL21 (ENSG00000162413), KLHDC8A (ENSG00000162873), KBTBD8 (ENSG00000163376), KBTBD6 (ENSG00000165572), KLHL26 (ENSG00000167487), KLHL30 (ENSG00000168427), KBTBD2 (ENSG00000170852), KLHL6 (ENSG00000172578), KLHL15 (ENSG00000174010), KLHL38 (ENSG00000175946), KBTBD11 (ENSG00000176595), KLHDC7A (ENSG00000179023), KLHL28 (ENSG00000179454), KLHL33 (ENSG00000185271)

Protein

Protein identifiers

Kelch repeat and BTB domain-containing protein 3 — Q8NAB2 (reviewed: Q8NAB2)

Alternative names: BTB and kelch domain-containing protein 3

All UniProt accessions (4): E9PKJ3, Q8NAB2, G3V161, U3KQF6

UniProt curated annotations — full annotation on UniProt →

RefSeq proteins (3): NP_001317288, NP_689646, NP_940841* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000210	BTB/POZ_dom	Domain
IPR006652	Kelch_1	Repeat
IPR011333	SKP1/BTB/POZ_sf	Homologous_superfamily
IPR011705	BACK	Domain
IPR015915	Kelch-typ_b-propeller	Homologous_superfamily
IPR017096	BTB-kelch_protein	Family
IPR030589	BTB/POZ_KBTBD3	Domain
IPR047062	KBTBD3_BACK	Domain

Pfam: PF00651, PF01344, PF07707

UniProt features (11 total): repeat 5, domain 2, sequence conflict 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NAB2-F1	89.91	0.76

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 73 (showing top): chr11q22, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GGGTGGRR_PAX4_03, GOBP_PROTEASOMAL_PROTEIN_CATABOLIC_PROCESS, GOBP_PROTEIN_CATABOLIC_PROCESS, GOCC_TRANSFERASE_COMPLEX, MARSON_BOUND_BY_FOXP3_STIMULATED, GOBP_PROTEOLYSIS, GOCC_CULLIN_RING_UBIQUITIN_LIGASE_COMPLEX, GOCC_CUL3_RING_UBIQUITIN_LIGASE_COMPLEX, GOCC_UBIQUITIN_LIGASE_COMPLEX, YOSHIMURA_MAPK8_TARGETS_DN, NAB2_TARGET_GENES, PRKDC_TARGET_GENES, ZNF660_TARGET_GENES

GO Biological Process (1): proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161)

GO Molecular Function (5): ubiquitin-like ligase-substrate adaptor activity (GO:1990756), DNA binding (GO:0003677), protein binding (GO:0005515), zinc ion binding (GO:0008270), metal ion binding (GO:0046872)

GO Cellular Component (3): cytoplasm (GO:0005737), Cul3-RING ubiquitin ligase complex (GO:0031463), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
enzyme-substrate adaptor activity	1
nucleic acid binding	1
binding	1
transition metal ion binding	1
cation binding	1
intracellular anatomical structure	1
cellular anatomical structure	1
cullin-RING ubiquitin ligase complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

304 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KBTBD3	TMEM225B	P0DP42	593
KBTBD3	ALKBH8	Q96BT7	576
KBTBD3	ZC3H12C	Q9C0D7	533
KBTBD3	SP110	Q9HB58	526
KBTBD3	SIKE1	Q9BRV8	521
KBTBD3	UQCRB	P14927	493
KBTBD3	SRM	P19623	488
KBTBD3	UQCRQ	O14949	446
KBTBD3	TRIM48	Q8IWZ4	445
KBTBD3	MSANTD4	Q8NCY6	436
KBTBD3	RNF186	Q9NXI6	429
KBTBD3	COPG2	Q9UBF2	420
KBTBD3	ZBTB5	O15062	415
KBTBD3	RNF39	Q9H2S5	410
KBTBD3	CHMP2A	O43633	410

IntAct

3 interactions, top by confidence:

A	B	Type	Score
MME		psi-mi:“MI:0914”(association)	0.350
INSR	BLTP3B	psi-mi:“MI:0914”(association)	0.350

BioGRID (10): KBTBD3 (Affinity Capture-RNA), KBTBD3 (Affinity Capture-MS), KBTBD3 (Affinity Capture-MS), KBTBD3 (Affinity Capture-MS), KBTBD3 (Affinity Capture-MS), KBTBD3 (Affinity Capture-MS), KBTBD3 (Affinity Capture-MS), KBTBD3 (Affinity Capture-MS), KBTBD3 (Affinity Capture-MS), KBTBD3 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B8YAB1, B1H285, B3DIV9, E9QIN8, E9QJ30, F1QEG2, O88879, Q08CL3, Q08CY1, Q0D2A9, Q13939, Q28068, Q3UQV5, Q3ZCT8, Q503R4, Q5F3N5, Q5R4S6, Q5R663, Q5RG82, Q5XHZ6, Q5XI58, Q5ZI33, Q69ZK5, Q6DFF7, Q6DFU2, Q6Q7X9, Q6V595, Q7ZVQ8, Q86V97, Q8BHI4, Q8BUL5, Q8BWA5, Q8CA72, Q8CDE2, Q8CE33, Q8IXQ5, Q8NAB2, Q8NFY9, Q8R179, Q8WVZ9

Diamond homologs: A0A2R8Q1W5, B0WWP2, B3M9V8, B3NDN0, B4GRJ2, B4HIK1, B4J045, B4L0G9, B4LIG6, B4MXW3, B4PD06, B4QLQ2, D3Z8N4, D4A2K4, E0CZ16, E1B932, E7F6F9, E9Q4F2, F1LZ52, F1LZF0, F1MBP6, O14682, O35709, O94889, O95198, P28575, P57790, P59280, Q04652, Q08BL9, Q08DK3, Q08DS0, Q0D2A9, Q0D2K2, Q14145, Q16RL8, Q1ECZ2, Q1LYM6, Q2M0J9, Q2WGJ6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	69
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

475 predictions. Top by Δscore:

Variant	Effect	Δscore
11:106058982:A:AC	donor_gain	1.0000
11:106058983:A:C	donor_gain	1.0000
11:106054451:TAGCC:T	acceptor_gain	0.9900
11:106054452:AGCCC:A	acceptor_loss	0.9900
11:106054453:GCCCT:G	acceptor_loss	0.9900
11:106054454:CC:C	acceptor_gain	0.9900
11:106054455:CC:C	acceptor_gain	0.9900
11:106054455:CCTGC:C	acceptor_loss	0.9900
11:106054456:C:CA	acceptor_loss	0.9900
11:106058977:CA:C	donor_gain	0.9900
11:106059110:C:CC	acceptor_gain	0.9900
11:106077308:CCAC:C	donor_loss	0.9900
11:106077309:CACC:C	donor_loss	0.9900
11:106077311:C:CA	donor_loss	0.9900
11:106054453:GCC:G	acceptor_gain	0.9800
11:106054454:CCC:C	acceptor_gain	0.9800
11:106054456:C:CC	acceptor_gain	0.9800
11:106054457:T:A	acceptor_loss	0.9800
11:106077307:CCCA:C	donor_gain	0.9800
11:106077348:C:CA	donor_gain	0.9800
11:106054464:A:C	acceptor_gain	0.9700
11:106058973:A:AC	donor_gain	0.9700
11:106054464:A:AC	acceptor_gain	0.9600
11:106077310:A:AC	donor_gain	0.9600
11:106077311:C:CC	donor_gain	0.9600
11:106059109:ACT:A	acceptor_gain	0.9400
11:106054452:AGCC:A	acceptor_gain	0.9300
11:106059107:GAAC:G	acceptor_loss	0.9300
11:106059110:C:CG	acceptor_loss	0.9300
11:106059111:T:G	acceptor_loss	0.9300

AlphaMissense

4074 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:106052952:C:A	W579C	1.000
11:106052952:C:G	W579C	1.000
11:106052954:A:G	W579R	1.000
11:106052954:A:T	W579R	1.000
11:106052953:C:G	W579S	0.999
11:106052975:A:C	Y572D	0.999
11:106053019:C:A	G557V	0.999
11:106053019:C:T	G557D	0.999
11:106053020:C:G	G557R	0.999
11:106053029:A:C	Y554D	0.999
11:106053098:A:G	W531R	0.999
11:106053098:A:T	W531R	0.999
11:106053233:A:G	W486R	0.999
11:106053233:A:T	W486R	0.999
11:106053254:A:C	Y479D	0.999
11:106058876:A:C	S74R	0.999
11:106058876:A:T	S74R	0.999
11:106058878:T:G	S74R	0.999
11:106053016:C:A	G558V	0.998
11:106053016:C:T	G558D	0.998
11:106053025:A:T	I555K	0.998
11:106053118:A:G	F524S	0.998
11:106053147:A:C	C514W	0.998
11:106053149:A:G	C514R	0.998
11:106053310:C:T	G460E	0.998
11:106053728:A:G	W321R	0.998
11:106053728:A:T	W321R	0.998
11:106053749:A:C	Y314D	0.998
11:106052980:T:G	Q570P	0.997
11:106053017:C:G	G558R	0.997

dbSNP variants (sampled 300 via entrez): RS1000080423 (11:106071559 A>C), RS1000410722 (11:106066992 C>G), RS1000572140 (11:106051293 A>G,T), RS1000601594 (11:106060196 A>C), RS1000623423 (11:106076359 G>A), RS1000705749 (11:106053545 C>A,G,T), RS1000810212 (11:106066743 A>C), RS1000839066 (11:106072082 T>C), RS1000868551 (11:106063115 G>A), RS1001033009 (11:106070249 T>C), RS1001383431 (11:106056862 C>A,T), RS1001386109 (11:106063482 A>G), RS1001457802 (11:106074945 G>A), RS1001838803 (11:106052373 T>C), RS1001935257 (11:106054873 T>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

2 associations (top):

Study	Trait	p-value
GCST009391_704	Metabolite levels	4.000000e-06
GCST010002_247	Refractive error	4.000000e-39

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010356	lysophosphatidylcholine 14:0 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Nickel	decreases expression	2
Valproic Acid	decreases methylation, increases expression	2
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
cyclic 3’,5’-uridine monophosphate	affects binding	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
Sunitinib	decreases expression	1
Vorinostat	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Carbamazepine	affects expression	1
Estradiol	decreases expression	1
Melphalan	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Quercetin	decreases expression	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	affects expression	1
Urethane	increases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	decreases expression	1
Okadaic Acid	decreases expression	1
Particulate Matter	increases abundance, decreases expression	1

Clinical trials (associated diseases)

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