ZBTB43

Summary

ZBTB43 (zinc finger and BTB domain containing 43, HGNC:17908) is a protein-coding gene on chromosome 9q33.3, encoding Zinc finger and BTB domain-containing protein 43 (O43298). May be involved in transcriptional regulation.

Enables RNA polymerase III general transcription initiation factor binding activity and sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in chromatin.

Source: NCBI Gene 23099 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 65 total
• Druggable target: yes
• MANE Select transcript: NM_014007

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17908
Approved symbol	ZBTB43
Name	zinc finger and BTB domain containing 43
Location	9q33.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0414, ZNF-X, FLJ22470, ZBTB22B
Ensembl gene	ENSG00000169155
Ensembl biotype	protein_coding
OMIM	618676
Entrez	23099

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 22 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000373457, ENST00000373464, ENST00000449886, ENST00000450858, ENST00000497064, ENST00000858157, ENST00000858158, ENST00000858159, ENST00000858160, ENST00000858161, ENST00000858162, ENST00000858163, ENST00000858164, ENST00000858165, ENST00000858166, ENST00000858167, ENST00000858168, ENST00000935691, ENST00000961600, ENST00000961601, ENST00000961602, ENST00000961603, ENST00000961604

RefSeq mRNA: 2 — MANE Select: NM_014007 NM_001135776, NM_014007

CCDS: CCDS6867

Canonical transcript exons

ENST00000373464 — 3 exons

Exon	Start	End
ENSE00001259548	126808793	126808915
ENSE00001460633	126832487	126838210
ENSE00001835203	126805040	126805132

Expression profiles

Bgee: expression breadth ubiquitous, 279 present calls, max score 95.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.3655 / max 370.1476, expressed in 1795 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
98569	19.3655	1795

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	95.43	gold quality
nipple	UBERON:0002030	95.43	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	94.39	gold quality
tongue squamous epithelium	UBERON:0006919	93.00	silver quality
secondary oocyte	CL:0000655	92.39	gold quality
body of tongue	UBERON:0011876	91.18	gold quality
pharyngeal mucosa	UBERON:0000355	90.90	gold quality
medial globus pallidus	UBERON:0002477	90.60	gold quality
tongue	UBERON:0001723	90.55	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	90.31	gold quality
globus pallidus	UBERON:0001875	90.03	gold quality
biceps brachii	UBERON:0001507	90.00	gold quality
gastrocnemius	UBERON:0001388	89.97	gold quality
superior surface of tongue	UBERON:0007371	89.94	gold quality
vena cava	UBERON:0004087	89.18	silver quality
muscle of leg	UBERON:0001383	89.14	gold quality
diaphragm	UBERON:0001103	89.10	gold quality
muscle organ	UBERON:0001630	88.88	gold quality
skeletal muscle tissue	UBERON:0001134	88.86	gold quality
cardia of stomach	UBERON:0001162	88.73	silver quality
vastus lateralis	UBERON:0001379	88.36	gold quality
oocyte	CL:0000023	88.32	gold quality
ventral tegmental area	UBERON:0002691	88.17	gold quality
inferior vagus X ganglion	UBERON:0005363	88.15	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.02	gold quality
deltoid	UBERON:0001476	87.83	silver quality
tibialis anterior	UBERON:0001385	87.76	silver quality
hair follicle	UBERON:0002073	87.63	silver quality
pylorus	UBERON:0001166	87.61	gold quality
quadriceps femoris	UBERON:0001377	87.59	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-7052	yes	362.28
E-ANND-3	yes	12.46
E-MTAB-6911	no	569.89
E-GEOD-99795	no	243.90

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

246 targeting ZBTB43, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-1468-3P	99.96	72.74	3797

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	zbtb43	ENSDARG00000045983
mus_musculus	Zbtb43	ENSMUSG00000026788
rattus_norvegicus	Zbtb43	ENSRNOG00000017017
drosophila_melanogaster	klu	FBGN0013469
drosophila_melanogaster	CG4318	FBGN0030455
caenorhabditis_elegans	klu-2	WBGENE00022592

Paralogs (4): ZNF740 (ENSG00000139651), ZNF367 (ENSG00000165244), ZBTB5 (ENSG00000168795), ZBTB7A (ENSG00000178951)

Protein

Protein identifiers

Zinc finger and BTB domain-containing protein 43 — O43298 (reviewed: O43298)

Alternative names: Zinc finger and BTB domain-containing protein 22B, Zinc finger protein 297B, ZnF-x

All UniProt accessions (2): O43298, Q5JU97

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in transcriptional regulation.

Subunit / interactions. Interacts with BDP1.

Subcellular location. Nucleus.

Similarity. Belongs to the krueppel C2H2-type zinc-finger protein family.

RefSeq proteins (2): NP_001129248, NP_054726* (*=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 (26 total): cross-link 6, strand 5, helix 3, zinc finger region 3, modified residue 2, region of interest 2, compositionally biased region 2, chain 1, domain 1, turn 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
8YMZ	X-RAY DIFFRACTION	2.95
2CSH	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43298-F1	57.24	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 (8): 423, 182, 241, 247, 297, 358, 458, 1

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 210 (showing top): MULLIGHAN_NPM1_SIGNATURE_3_UP, YAGI_AML_WITH_INV_16_TRANSLOCATION, TGCGCANK_UNKNOWN, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, TGACCTY_ERR1_Q2, BROWNE_HCMV_INFECTION_12HR_UP, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLUE_UP, RODWELL_AGING_KIDNEY_NO_BLOOD_DN, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_DN, BACH2_01, TGIF_01, MODULE_123, TGANTCA_AP1_C, HELLER_HDAC_TARGETS_SILENCED_BY_METHYLATION_UP

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

GO Molecular Function (8): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), RNA polymerase III general transcription initiation factor binding (GO:0001025), zinc ion binding (GO:0008270), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (2): chromatin (GO:0000785), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
regulation of transcription by RNA polymerase II	1
general transcription initiation factor binding	1
transition metal ion binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
binding	1
cation binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

664 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZBTB43	MVB12B	Q9H7P6	464
ZBTB43	TP53	P04637	375
ZBTB43	SLC38A8	A6NNN8	346
ZBTB43	TSPAN33	Q86UF1	341
ZBTB43	CDK17	Q00537	337
ZBTB43	MAGEB2	O15479	335
ZBTB43	PLPPR3	Q6T4P5	323
ZBTB43	MSL3	Q8N5Y2	315
ZBTB43	ZCCHC9	Q8N567	298
ZBTB43	L1TD1	Q5T7N2	297
ZBTB43	DMRTB1	Q96MA1	285
ZBTB43	ASCC3	Q8N3C0	282
ZBTB43	MORC1	Q86VD1	278
ZBTB43	PDSS2	Q86YH6	278
ZBTB43	NECAB2	Q7Z6G3	267

IntAct

119 interactions, top by confidence:

A	B	Type	Score
ZBTB43	LMO1	psi-mi:“MI:0915”(physical association)	0.830
LMO1	ZBTB43	psi-mi:“MI:0915”(physical association)	0.830
LMO1	ZBTB43	psi-mi:“MI:0914”(association)	0.830
PSMD3	ZBTB43	psi-mi:“MI:0915”(physical association)	0.780
ZBTB43	PSMD3	psi-mi:“MI:0915”(physical association)	0.780
ARRB1	ZBTB43	psi-mi:“MI:0915”(physical association)	0.740
ZBTB43	LNX1	psi-mi:“MI:0915”(physical association)	0.740
ZBTB43	ARRB1	psi-mi:“MI:0915”(physical association)	0.740
ZBTB43	SYT6	psi-mi:“MI:0915”(physical association)	0.720
ZBTB43	AP1M1	psi-mi:“MI:0915”(physical association)	0.720
SYT6	ZBTB43	psi-mi:“MI:0915”(physical association)	0.720
AP1M1	ZBTB43	psi-mi:“MI:0915”(physical association)	0.720
MORF4L2	ZBTB43	psi-mi:“MI:0915”(physical association)	0.670
ZBTB43	MORF4L2	psi-mi:“MI:0915”(physical association)	0.670
ZBTB43	ZNF417	psi-mi:“MI:0915”(physical association)	0.670

BioGRID (65): ZBTB43 (Two-hybrid), ZBTB43 (Two-hybrid), ZBTB43 (Two-hybrid), ZBTB43 (Two-hybrid), ZBTB43 (Two-hybrid), ZBTB43 (Two-hybrid), ZBTB43 (Two-hybrid), ZBTB43 (Two-hybrid), DIP2A (Two-hybrid), AEN (Two-hybrid), FAM161A (Two-hybrid), SYT6 (Two-hybrid), ZNF417 (Two-hybrid), ZBTB43 (Affinity Capture-MS), ZBTB43 (Two-hybrid)

ESM2 similar proteins: A0JN76, A1L2U9, B1WAZ8, B1WBU4, O15060, O35260, O43298, O93567, P14404, P41182, P41183, Q05516, Q0IH98, Q0IJ29, Q0P4X6, Q0V8G8, Q0VCJ6, Q15916, Q1L8W0, Q3B725, Q3SWU4, Q5TC79, Q5ZM39, Q6NRM8, Q6P882, Q6YND2, Q7TQG0, Q7TSZ8, Q7ZWZ4, Q801P1, Q80X44, Q86UZ6, Q8BID6, Q8CII0, Q8K088, Q8K0L9, Q8N680, Q8NAP8, Q8NCN2, Q8NCP5

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

1 interactions.

A	Effect	B	Mechanism
ZBTB43	unknown	BDP1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	58
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

839 predictions. Top by Δscore:

Variant	Effect	Δscore
9:126832482:TGTA:T	acceptor_loss	1.0000
9:126832483:GTAGC:G	acceptor_loss	1.0000
9:126832484:TA:T	acceptor_loss	1.0000
9:126832485:A:AG	acceptor_gain	1.0000
9:126832486:G:GA	acceptor_gain	1.0000
9:126832486:GC:G	acceptor_gain	1.0000
9:126832486:GCA:G	acceptor_gain	1.0000
9:126832486:GCAC:G	acceptor_gain	1.0000
9:126832486:GCACC:G	acceptor_gain	1.0000
9:126805092:G:GT	donor_gain	0.9900
9:126805130:C:T	donor_gain	0.9900
9:126805567:T:G	donor_gain	0.9900
9:126805567:T:TG	donor_gain	0.9900
9:126808792:GAA:G	acceptor_gain	0.9900
9:126805130:CAGGT:C	donor_loss	0.9800
9:126805131:AGGTA:A	donor_loss	0.9800
9:126805133:G:T	donor_loss	0.9800
9:126805565:GTT:G	donor_gain	0.9800
9:126805566:TTT:T	donor_gain	0.9800
9:126805571:G:GG	donor_gain	0.9800
9:126807531:A:AG	donor_gain	0.9800
9:126808791:A:AG	acceptor_gain	0.9800
9:126808792:G:GG	acceptor_gain	0.9800
9:126808855:T:G	acceptor_gain	0.9800
9:126832484:TAG:T	acceptor_gain	0.9800
9:126806210:GC:G	donor_gain	0.9700
9:126808195:T:A	donor_gain	0.9700
9:126832482:T:TA	acceptor_gain	0.9700
9:126832482:TGTAG:T	acceptor_gain	0.9700
9:126832485:AGCA:A	acceptor_gain	0.9700

AlphaMissense

3148 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:126833632:T:C	C375R	1.000
9:126833650:T:C	F381L	1.000
9:126833651:T:C	F381S	1.000
9:126833652:C:A	F381L	1.000
9:126833652:C:G	F381L	1.000
9:126833675:G:C	R389P	1.000
9:126833713:T:C	C402R	1.000
9:126833723:G:A	C405Y	1.000
9:126833734:T:C	F409L	1.000
9:126833735:T:C	F409S	1.000
9:126833736:C:A	F409L	1.000
9:126833736:C:G	F409L	1.000
9:126833753:T:C	L415P	1.000
9:126833797:T:C	C430R	1.000
9:126833806:T:C	C433R	1.000
9:126833808:T:G	C433W	1.000
9:126833818:T:C	F437L	1.000
9:126833819:T:C	F437S	1.000
9:126833820:T:A	F437L	1.000
9:126833820:T:G	F437L	1.000
9:126833632:T:A	C375S	0.999
9:126833633:G:A	C375Y	0.999
9:126833633:G:C	C375S	0.999
9:126833634:T:G	C375W	0.999
9:126833638:T:A	C377S	0.999
9:126833638:T:C	C377R	0.999
9:126833639:G:C	C377S	0.999
9:126833640:T:G	C377W	0.999
9:126833651:T:G	F381C	0.999
9:126833677:C:G	H390D	0.999

dbSNP variants (sampled 300 via entrez): RS1000017432 (9:126824595 C>T), RS1000236593 (9:126810182 GTTTGTTTA>G), RS1000284693 (9:126815848 A>G), RS1000287706 (9:126818396 C>G,T), RS1000324115 (9:126813245 G>A), RS1000476844 (9:126818523 G>A), RS1000531265 (9:126831252 G>T), RS1000548573 (9:126838355 A>G), RS1000579793 (9:126837937 G>C), RS1000602342 (9:126808974 C>G), RS1000658778 (9:126814559 C>T), RS1000851477 (9:126826313 A>C,T), RS1001045072 (9:126831873 G>A), RS1001126765 (9:126803100 G>A), RS1001140899 (9:126824095 C>T)

Disease associations

OMIM: gene MIM:618676 | 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
GCST003476_10	Eyebrow thickness	3.000000e-06
GCST004495_84	BMI (adjusted for smoking behaviour)	9.000000e-06
GCST004497_62	Body mass index (joint analysis main effects and smoking interaction)	5.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004318	smoking behavior
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5069369 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

59 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression	2
Copper	increases expression, affects binding, decreases expression	2
Tobacco Smoke Pollution	increases expression	2
Zinc	affects cotreatment, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression, increases expression	2
Cyclosporine	increases expression	2
Cadmium Chloride	increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	increases expression	1
TAK-243	decreases sumoylation	1
methylmercuric chloride	decreases expression	1
alpha-pinene	affects cotreatment, decreases expression, increases oxidation, increases abundance	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
ferrous chloride	increases expression	1
cupric oxide	increases expression	1
methacrylaldehyde	affects cotreatment, decreases expression, increases oxidation, increases abundance	1
celastrol	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
pentabromodiphenyl ether	increases expression	1
gedunin	decreases expression	1
2-palmitoylglycerol	increases expression	1
K 7174	increases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
ICG 001	increases expression	1
abrine	increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
NSC 689534	increases expression, affects binding	1
PCI 5002	affects cotreatment, increases expression	1
Acetaminophen	increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5059502	Binding	Proteomics fold change data (SUDHL4 cells, 1h)	Data for DCP probe CCT369260

Clinical trials (associated diseases)

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