ZBTB3

Summary

ZBTB3 (zinc finger and BTB domain containing 3, HGNC:22918) is a protein-coding gene on chromosome 11q12.3, encoding Zinc finger and BTB domain-containing protein 3 (Q9H5J0). May be involved in transcriptional regulation.

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus.

Source: NCBI Gene 79842 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 74 total
• MANE Select transcript: NM_001370809

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22918
Approved symbol	ZBTB3
Name	zinc finger and BTB domain containing 3
Location	11q12.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ23392
Ensembl gene	ENSG00000185670
Ensembl biotype	protein_coding
OMIM	621294
Entrez	79842

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 11 protein_coding, 1 nonsense_mediated_decay

ENST00000394807, ENST00000527994, ENST00000530112, ENST00000673933, ENST00000906475, ENST00000913752, ENST00000913753, ENST00000913754, ENST00000913755, ENST00000913756, ENST00000913757, ENST00000969506

RefSeq mRNA: 3 — MANE Select: NM_001370809 NM_001363108, NM_001363109, NM_001370809

CCDS: CCDS8034

Canonical transcript exons

ENST00000394807 — 2 exons

Exon	Start	End
ENSE00001310941	62753964	62754160
ENSE00001519645	62750963	62753715

Expression profiles

Bgee: expression breadth ubiquitous, 214 present calls, max score 83.79.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.1396 / max 28.6356, expressed in 1621 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
120231	4.1396	1621

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	83.79	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.99	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.82	gold quality
monocyte	CL:0000576	77.22	gold quality
leukocyte	CL:0000738	77.10	gold quality
stromal cell of endometrium	CL:0002255	77.02	gold quality
mononuclear cell	CL:0000842	76.97	gold quality
apex of heart	UBERON:0002098	76.58	gold quality
granulocyte	CL:0000094	75.18	gold quality
sural nerve	UBERON:0015488	75.09	gold quality
right uterine tube	UBERON:0001302	74.74	gold quality
parotid gland	UBERON:0001831	74.13	silver quality
cortical plate	UBERON:0005343	74.01	gold quality
lower esophagus mucosa	UBERON:0035834	73.96	gold quality
ganglionic eminence	UBERON:0004023	73.76	gold quality
tendon of biceps brachii	UBERON:0008188	73.76	silver quality
mucosa of transverse colon	UBERON:0004991	72.96	gold quality
ventricular zone	UBERON:0003053	72.46	gold quality
blood	UBERON:0000178	72.23	gold quality
body of stomach	UBERON:0001161	72.14	gold quality
body of pancreas	UBERON:0001150	72.05	gold quality
right lobe of liver	UBERON:0001114	72.03	gold quality
palpebral conjunctiva	UBERON:0001812	71.88	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	71.35	gold quality
pancreas	UBERON:0001264	71.20	gold quality
islet of Langerhans	UBERON:0000006	71.17	gold quality
skin of leg	UBERON:0001511	71.14	gold quality
right adrenal gland	UBERON:0001233	71.06	gold quality
skin of abdomen	UBERON:0001416	71.06	gold quality
stomach	UBERON:0000945	70.98	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.54

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

59 targeting ZBTB3, 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-3613-3P	100.00	76.36	7965
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-4753-5P	99.54	68.51	1356
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-372-5P	99.41	69.11	2299
HSA-MIR-508-5P	99.41	64.25	1248
HSA-MIR-888-5P	99.30	70.15	1855
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-3064-5P	99.26	66.13	1497
HSA-MIR-3085-3P	99.26	66.16	1490
HSA-MIR-6504-5P	99.26	65.95	1487
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-5190	99.15	67.76	1234
HSA-MIR-6799-5P	99.14	65.72	2093
HSA-MIR-485-5P	99.10	64.78	1889
HSA-MIR-6884-5P	99.10	64.50	1987
HSA-MIR-371A-5P	99.08	66.51	1914

Literature-anchored findings (GeneRIF, showing 2)

• Suppression of ZBTB3 activates a caspase cascade, including caspase-9, -3, and PARP leading to cellular apoptosis, resulting from failed ROS detoxification. (PMID:24856827)
• An autoimmune pleiotropic SNP modulates IRF5 alternative promoter usage through ZBTB3-mediated chromatin looping. (PMID:36869052)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	zbtb3	ENSDARG00000036235
mus_musculus	Zbtb3	ENSMUSG00000071661
rattus_norvegicus	Zbtb3	ENSRNOG00000019461

Paralogs (28): ZNF280C (ENSG00000056277), ZBTB25 (ENSG00000089775), PRDM13 (ENSG00000112238), BCL6 (ENSG00000113916), FEZF1 (ENSG00000128610), ZBTB46 (ENSG00000130584), PRDM12 (ENSG00000130711), ZNF280D (ENSG00000137871), NACC2 (ENSG00000148411), FEZF2 (ENSG00000153266), ZBTB7B (ENSG00000160685), NACC1 (ENSG00000160877), BCL6B (ENSG00000161940), GFI1 (ENSG00000162676), GFI1B (ENSG00000165702), ZBTB49 (ENSG00000168826), ZNF280A (ENSG00000169548), ZNF581 (ENSG00000171425), ZNF524 (ENSG00000171443), ZBTB26 (ENSG00000171448), ZBTB21 (ENSG00000173276), ZNF683 (ENSG00000176083), ZBTB33 (ENSG00000177485), ZBTB6 (ENSG00000186130), ZBTB14 (ENSG00000198081), ZBTB12 (ENSG00000204366), ZNF580 (ENSG00000213015), ZNF280B (ENSG00000275004)

Protein

Protein identifiers

Zinc finger and BTB domain-containing protein 3 — Q9H5J0 (reviewed: Q9H5J0)

All UniProt accessions (3): A0A6E1W9L1, E9PPE9, Q9H5J0

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in transcriptional regulation.

Subcellular location. Nucleus.

RefSeq proteins (3): NP_001350037, NP_001350038, NP_001357738* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000210	BTB/POZ_dom	Domain
IPR011333	SKP1/BTB/POZ_sf	Homologous_superfamily
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR050457	ZnFinger_BTB_dom_contain	Family

Pfam: PF00096, PF00651

UniProt features (19 total): region of interest 4, compositionally biased region 3, cross-link 3, sequence variant 3, modified residue 2, zinc finger region 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H5J0-F1	54.86	0.12

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (5): 362, 549, 181, 182, 532

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 78 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_UP, MODULE_511, TANAKA_METHYLATED_IN_ESOPHAGEAL_CARCINOMA, AACTTT_UNKNOWN, NOUZOVA_TRETINOIN_AND_H4_ACETYLATION, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_DN, SPZ1_01, SCGGAAGY_ELK1_02, GSE13762_CTRL_VS_125_VITAMIND_DAY5_DC_DN, MARTENS_BOUND_BY_PML_RARA_FUSION, MARTENS_TRETINOIN_RESPONSE_DN, WAKABAYASHI_ADIPOGENESIS_PPARG_BOUND_8D, ZWANG_DOWN_BY_2ND_EGF_PULSE, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, ASH1L_TARGET_GENES

GO Biological Process (1): regulation of transcription by RNA polymerase II (GO:0006357)

GO Molecular Function (5): DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA binding (GO:0003677), zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
chromatin	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
DNA-binding transcription factor activity	1
regulation of transcription by RNA polymerase II	1
nucleic acid binding	1
transition metal ion binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

686 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZBTB3	AP5S1	Q9NUS5	490
ZBTB3	ZNF367	Q7RTV3	445
ZBTB3	NR2C2AP	Q86WQ0	413
ZBTB3	ARFGAP2	Q8N6H7	408
ZBTB3	MAZ	P56270	404
ZBTB3	KLF7	O75840	398
ZBTB3	SRCAP	Q6ZRS2	378
ZBTB3	OR2I1	Q8NGU4	364
ZBTB3	ZNF585A	Q6P3V2	361
ZBTB3	ZNF8	P17098	354
ZBTB3	ZNF565	Q8N9K5	348
ZBTB3	ZNF182	P17025	346
ZBTB3	BTBD7	Q9P203	334
ZBTB3	HRCT1	Q6UXD1	324
ZBTB3	NOXRED1	Q6NXP6	322

IntAct

44 interactions, top by confidence:

A	B	Type	Score
MYO15B	ZBTB3	psi-mi:“MI:0915”(physical association)	0.560
SMYD1	ZBTB3	psi-mi:“MI:0915”(physical association)	0.560
AP1M1	ZBTB3	psi-mi:“MI:0915”(physical association)	0.560
ZBTB3	LMNB2	psi-mi:“MI:0915”(physical association)	0.400
	ZBTB3	psi-mi:“MI:0915”(physical association)	0.370
SSX3	ZBTB3	psi-mi:“MI:0915”(physical association)	0.370
GTF2A1L	ZBTB3	psi-mi:“MI:0915”(physical association)	0.370
FOXM1	ZBTB3	psi-mi:“MI:0915”(physical association)	0.370
JADE2	ZBTB3	psi-mi:“MI:0915”(physical association)	0.370
GATA4	ZBTB3	psi-mi:“MI:0915”(physical association)	0.370
ANKRD2	ZBTB3	psi-mi:“MI:0915”(physical association)	0.370
BIN1	ZBTB3	psi-mi:“MI:0915”(physical association)	0.370
NR3C1	ZBTB3	psi-mi:“MI:0915”(physical association)	0.370
IRF6	ZBTB3	psi-mi:“MI:0915”(physical association)	0.370
SMAD3	ZBTB3	psi-mi:“MI:0915”(physical association)	0.370
LEF1	ZBTB3	psi-mi:“MI:0915”(physical association)	0.370
PKNOX1	ZBTB3	psi-mi:“MI:0915”(physical association)	0.370
PPARG	ZBTB3	psi-mi:“MI:0915”(physical association)	0.370
PROX1	ZBTB3	psi-mi:“MI:0915”(physical association)	0.370
SUPT5H	ZBTB3	psi-mi:“MI:0915”(physical association)	0.370
THRA	ZBTB3	psi-mi:“MI:0915”(physical association)	0.370
ZMYM2	ZBTB3	psi-mi:“MI:0915”(physical association)	0.370
IKBKG	ZBTB3	psi-mi:“MI:0915”(physical association)	0.370
EIF5B	ZBTB3	psi-mi:“MI:0915”(physical association)	0.370
ZBTB3	ZNF556	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (63): ZBTB3 (Affinity Capture-MS), ZBTB3 (Affinity Capture-MS), ZBTB3 (Two-hybrid), ZBTB3 (Two-hybrid), MYO15B (Two-hybrid), ZBTB3 (Affinity Capture-MS), SPOP (Affinity Capture-Western), ZBTB3 (Affinity Capture-Western), ZBTB3 (Proximity Label-MS), ZBTB3 (Affinity Capture-RNA), SNX1 (Affinity Capture-MS), SNX5 (Affinity Capture-MS), SNX6 (Affinity Capture-MS), ZBTB3 (Affinity Capture-MS), NHLRC2 (Affinity Capture-MS)

ESM2 similar proteins: A1YGK1, A2T7E6, A4D1S0, A9YTQ3, B1WBS3, I7HJS4, O43593, O43918, O60304, O75593, O95201, P0C6A0, P0C7X2, P97609, Q2MHN3, Q3B7M4, Q3SY56, Q3U133, Q58DK7, Q5JPB2, Q5SXI5, Q5T619, Q61645, Q6KAU7, Q6NUN9, Q6ZMS7, Q76NI1, Q7Z6P3, Q8BZ34, Q8BZW2, Q8CGW9, Q8IWN7, Q8IXT2, Q8IZ20, Q8NBB4, Q8NDX1, Q8NHY3, Q91X45, Q96PX9, Q99558

Diamond homologs: A0JN76, A1L2U9, A1YEX3, A1YPR0, A2AAX3, B1WAZ8, B1WBS3, B1WBU4, B2RXF5, D3ZA50, O14867, O15062, O15156, O15209, O43167, O43298, O43829, O88282, O88939, O93567, O95365, P24278, P41182, P41183, P52739, P97302, P97303, Q08376, Q0IH98, Q0IJ29, Q0P4X6, Q0VCJ6, Q13105, Q14526, Q1H9T6, Q1L8W0, Q2T9Z7, Q3B725, Q3B7N9, Q3SWU4

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 33 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.

GO biological processes:

GO term	Partners	Fold	FDR
transcription by RNA polymerase II	5	11.4×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	65
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

184 predictions. Top by Δscore:

Variant	Effect	Δscore
11:62753950:T:TA	donor_gain	1.0000
11:62753712:CTCC:C	acceptor_gain	0.9900
11:62753714:CC:C	acceptor_gain	0.9900
11:62753715:CC:C	acceptor_gain	0.9900
11:62753716:C:CC	acceptor_gain	0.9900
11:62753716:CTGA:C	acceptor_loss	0.9900
11:62753717:T:C	acceptor_loss	0.9900
11:62753713:TCC:T	acceptor_gain	0.9700
11:62753714:CCC:C	acceptor_gain	0.9700
11:62753716:C:T	acceptor_gain	0.9700
11:62753951:C:A	donor_gain	0.9700
11:62753959:CCCA:C	donor_loss	0.9700
11:62753960:CCACC:C	donor_loss	0.9700
11:62753963:C:CG	donor_loss	0.9700
11:62753711:GCTCC:G	acceptor_gain	0.9600
11:62753712:CTCCC:C	acceptor_gain	0.9600
11:62753713:TCCCT:T	acceptor_gain	0.9600
11:62753958:GCCCA:G	donor_loss	0.9600
11:62753962:AC:A	donor_gain	0.9400
11:62753963:CC:C	donor_gain	0.9400
11:62753973:T:TA	donor_gain	0.9300
11:62753931:C:A	donor_gain	0.9100
11:62753935:TAGCC:T	donor_gain	0.9100
11:62753936:AGCCA:A	donor_gain	0.9100
11:62753962:A:AC	donor_gain	0.9100
11:62753963:C:CC	donor_gain	0.9100
11:62754091:C:CT	donor_gain	0.9100
11:62754092:T:TT	donor_gain	0.9100
11:62753938:C:CT	donor_gain	0.8900
11:62753941:C:CA	donor_gain	0.8500

AlphaMissense

3661 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:62752311:A:G	C502R	1.000
11:62752372:G:C	F481L	1.000
11:62752372:G:T	F481L	1.000
11:62752373:A:C	F481C	1.000
11:62752373:A:G	F481S	1.000
11:62752374:A:G	F481L	1.000
11:62752393:G:C	C474W	1.000
11:62752395:A:G	C474R	1.000
11:62752261:G:C	H518Q	0.999
11:62752261:G:T	H518Q	0.999
11:62752262:T:G	H518P	0.999
11:62752263:G:C	H518D	0.999
11:62752265:C:G	R517P	0.999
11:62752271:A:G	L515P	0.999
11:62752274:T:C	D514G	0.999
11:62752277:C:T	G513E	0.999
11:62752302:A:G	C505R	0.999
11:62752309:G:C	C502W	0.999
11:62752310:C:G	C502S	0.999
11:62752311:A:T	C502S	0.999
11:62752333:G:C	H494Q	0.999
11:62752333:G:T	H494Q	0.999
11:62752335:G:C	H494D	0.999
11:62752345:A:C	H490Q	0.999
11:62752345:A:T	H490Q	0.999
11:62752347:G:C	H490D	0.999
11:62752349:C:G	R489P	0.999
11:62752355:A:G	L487P	0.999
11:62752374:A:T	F481I	0.999
11:62752378:C:A	K479N	0.999

dbSNP variants (sampled 300 via entrez): RS1000289029 (11:62752162 T>C), RS1000681755 (11:62752487 G>A,C), RS1000932774 (11:62750633 G>A), RS1001521685 (11:62756154 A>G), RS1001574134 (11:62755881 C>G), RS1001919529 (11:62751416 A>G), RS1002804379 (11:62751082 G>A), RS1003182681 (11:62750847 T>C), RS1003546663 (11:62750611 G>A,T), RS1003569103 (11:62755509 C>A), RS1003941590 (11:62754725 G>A,C,T), RS1004817162 (11:62754485 G>A,T), RS1005415038 (11:62755995 C>T), RS1005882222 (11:62751114 T>A), RS1006076665 (11:62751373 G>A)

Disease associations

OMIM: gene MIM:621294 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST005956_2	Waist-to-hip ratio adjusted for BMI	1.000000e-08
GCST005962_37	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	5.000000e-07
GCST005962_51	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	1.000000e-07

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	5
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	increases phosphorylation	1
TAK-243	increases sumoylation	1
methylmercuric chloride	decreases expression	1
coumarin	increases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
abrine	decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
jinfukang	increases expression	1
Bortezomib	increases expression	1
Vorinostat	decreases expression	1
Atrazine	decreases expression	1
Formaldehyde	decreases expression	1
Hydrogen Peroxide	affects expression	1
Urethane	decreases expression, increases expression	1
Copper Sulfate	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A7Z9	SEES3-1V human ZBTB3, clone1	Embryonic stem cell	Male
CVCL_A8A0	SEES3-1V human ZBTB3, clone2	Embryonic stem cell	Male
CVCL_A8A1	SEES3-1V human ZBTB3, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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