ZBTB32

Summary

ZBTB32 (zinc finger and BTB domain containing 32, HGNC:16763) is a protein-coding gene on chromosome 19q13.12, encoding Zinc finger and BTB domain-containing protein 32 (Q9Y2Y4). DNA-binding protein that binds to the to a 5’-TGTACAGTGT-3’ core sequence.

Enables DNA-binding transcription repressor activity, RNA polymerase II-specific; identical protein binding activity; and sequence-specific double-stranded DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in nucleus.

Source: NCBI Gene 27033 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 77 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_014383

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16763
Approved symbol	ZBTB32
Name	zinc finger and BTB domain containing 32
Location	19q13.12
Locus type	gene with protein product
Status	Approved
Aliases	TZFP, FAZF, FAXF, Rog, ZNF538, mynn
Ensembl gene	ENSG00000011590
Ensembl biotype	protein_coding
OMIM	605859
Entrez	27033

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000262630, ENST00000392197, ENST00000426659, ENST00000442282, ENST00000451726, ENST00000481182, ENST00000890380, ENST00000890381

RefSeq mRNA: 3 — MANE Select: NM_014383 NM_001316902, NM_001316903, NM_014383

CCDS: CCDS12471

Canonical transcript exons

ENST00000392197 — 7 exons

Exon	Start	End
ENSE00000699876	35715757	35715830
ENSE00001773740	35704558	35704623
ENSE00001774840	35712917	35713033
ENSE00002178086	35714523	35715507
ENSE00003501677	35715939	35716007
ENSE00003597855	35716133	35716297
ENSE00003609801	35716478	35717038

Expression profiles

Bgee: expression breadth ubiquitous, 161 present calls, max score 99.66.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 2.3737 / max 480.8403, expressed in 126 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
175372	2.0625	122
175369	0.1579	3
175373	0.0892	15
175368	0.0348	3
175370	0.0250	3
175371	0.0042	1

Top tissues by expression

288 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	99.66	gold quality
left testis	UBERON:0004533	95.58	gold quality
right testis	UBERON:0004534	95.08	gold quality
testis	UBERON:0000473	92.02	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.46	gold quality
pancreatic ductal cell	CL:0002079	76.38	silver quality
spleen	UBERON:0002106	73.75	gold quality
lymph node	UBERON:0000029	72.16	gold quality
right uterine tube	UBERON:0001302	71.68	gold quality
sural nerve	UBERON:0015488	68.90	gold quality
vermiform appendix	UBERON:0001154	68.68	gold quality
granulocyte	CL:0000094	67.01	gold quality
mucosa of stomach	UBERON:0001199	66.30	gold quality
small intestine Peyer’s patch	UBERON:0003454	65.78	gold quality
lower esophagus mucosa	UBERON:0035834	65.59	gold quality
sperm	CL:0000019	64.85	gold quality
male germ cell	CL:0000015	64.78	gold quality
adult organism	UBERON:0007023	64.59	gold quality
caecum	UBERON:0001153	64.16	gold quality
blood	UBERON:0000178	63.34	gold quality
small intestine	UBERON:0002108	63.14	gold quality
gluteal muscle	UBERON:0002000	62.86	gold quality
calcaneal tendon	UBERON:0003701	62.74	gold quality
parotid gland	UBERON:0001831	62.62	gold quality
tonsil	UBERON:0002372	62.41	gold quality
triceps brachii	UBERON:0001509	62.31	gold quality
left uterine tube	UBERON:0001303	62.18	gold quality
left ovary	UBERON:0002119	62.13	gold quality
right ovary	UBERON:0002118	61.71	gold quality
right coronary artery	UBERON:0001625	61.58	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.32

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

6 targets.

Target	Regulation
AURKC
BGLAP	Activation
MYC	Repression
RUNX2	Activation
TRIB3
ZDHHC2

JASPAR motifs

Motif	Name	Family
MA1580.1	ZBTB32	Other factors with up to three adjacent zinc fingers

JASPAR matrix evidence (PMIDs): PMID:23794217

miRNA regulators (miRDB)

6 targeting ZBTB32, 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-8064	99.45	66.92	875
HSA-MIR-3196	98.96	63.91	326
HSA-MIR-3180	98.46	64.68	348
HSA-MIR-3180-3P	98.46	64.68	348
HSA-MIR-6816-5P	98.46	64.35	364
HSA-MIR-4529-3P	96.40	66.46	582

Literature-anchored findings (GeneRIF, showing 6)

• can interact with GATA-2 and can modify GATA-2 transactivation capacity (PMID:11964310)
• results suggest an essential role for FAZF during the proliferative stages of primitive hematopoietic progenitors, possibly acting in concert with (a subset of) the Fanconi anemia proteins (PMID:11986317)
• TZFP is identified as a novel BMP2-induced transcription factor during osteoblastic differentiation. (PMID:17171645)
• Here, it was shown that human endogenous retrovirus Rec can form a trimeric complex with TZFP and AR, and can relieve the TZFP-mediated repression of AR-induced transactivation. (PMID:20147518)
• confirmed that the promyelocytic leukemia zinc finger (PLZF) BTB dimer is strand exchanged in solution, while the FAZF BTB dimer is not (PMID:20493880)
• ZBTB32 is a novel negative regulator of antibody recall responses. (PMID:27357154)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	mynn	ENSDARG00000007271
mus_musculus	Zbtb32	ENSMUSG00000006310
rattus_norvegicus	Zbtb32	ENSRNOG00000042465

Paralogs (36): SNAI2 (ENSG00000019549), PRDM1 (ENSG00000057657), PRDM6 (ENSG00000061455), ZNF76 (ENSG00000065029), PATZ1 (ENSG00000100105), MAZ (ENSG00000103495), ZBTB16 (ENSG00000109906), ZNF451 (ENSG00000112200), ZBTB45 (ENSG00000119574), ZNF410 (ENSG00000119725), SNAI1 (ENSG00000124216), ZNF384 (ENSG00000126746), ZBTB1 (ENSG00000126804), VEZF1 (ENSG00000136451), PRDM14 (ENSG00000147596), ZNF276 (ENSG00000158805), ZNF362 (ENSG00000160094), ZNF653 (ENSG00000161914), ZNF281 (ENSG00000162702), ZNF148 (ENSG00000163848), ZNF143 (ENSG00000166478), HIC2 (ENSG00000169635), PRDM10 (ENSG00000170325), ZNF296 (ENSG00000170684), ZNF692 (ENSG00000171163), ZNF575 (ENSG00000176472), HIC1 (ENSG00000177374), ZBTB18 (ENSG00000179456), ZBTB42 (ENSG00000179627), ZBTB20 (ENSG00000181722), ZBTB7C (ENSG00000184828), SNAI3 (ENSG00000185669), ZFP91 (ENSG00000186660), MTF1 (ENSG00000188786), SCRT2 (ENSG00000215397), SCRT1 (ENSG00000261678)

Protein

Protein identifiers

Zinc finger and BTB domain-containing protein 32 — Q9Y2Y4 (reviewed: Q9Y2Y4)

Alternative names: FANCC-interacting protein, Fanconi anemia zinc finger protein, Testis zinc finger protein, Zinc finger protein 538

All UniProt accessions (3): Q9Y2Y4, A0A0C4DGF1, K7EMJ1

UniProt curated annotations — full annotation on UniProt →

Function. DNA-binding protein that binds to the to a 5’-TGTACAGTGT-3’ core sequence. May function as a transcriptional transactivator and transcriptional repressor. Probably exerts its repressor effect by preventing GATA3 from binding to DNA. May play a role in regulating the differentiation and activation of helper T-cells.

Subunit / interactions. Homodimer (via PTB domain). Interacts with the N-terminal of FANCC. Interacts with ZBTB16. Interacts with GATA3.

Subcellular location. Nucleus.

Tissue specificity. Predominantly expressed in testis. Some isoforms are ubiquitously expressed.

Domain organisation. The C-terminal zinc finger domain functions as a transcriptional transactivator. The BTB (POZ) domain possesses repressor activity.

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

RefSeq proteins (3): NP_001303831, NP_001303832, NP_055198* (*=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

Pfam: PF00096, PF00651, PF12874

UniProt features (26 total): helix 7, strand 5, compositionally biased region 3, zinc finger region 3, region of interest 3, turn 2, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3M5B	X-RAY DIFFRACTION	2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y2Y4-F1	56.89	0.16

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 284 (showing top): RNGTGGGC_UNKNOWN, GOBP_RESPONSE_TO_PEPTIDE, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GGGTGGRR_PAX4_03, chr3q26, SHIRAISHI_PLZF_TARGETS_UP, YY1_Q6, FOSTER_TOLERANT_MACROPHAGE_UP, YY1_02, GOBP_CYTOKINE_PRODUCTION, TGANTCA_AP1_C, TGACATY_UNKNOWN, IRF_Q6

GO Biological Process (5): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of cytokine production (GO:0001817), regulation of immune system process (GO:0002682), regulation of gene expression (GO:0010468), negative regulation of DNA-templated transcription (GO:0045892)

GO Molecular Function (9): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), DNA binding (GO:0003677), zinc ion binding (GO:0008270), sequence-specific double-stranded DNA binding (GO:1990837), protein binding (GO:0005515), identical protein binding (GO:0042802), metal ion binding (GO:0046872)

GO Cellular Component (3): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of transcription by RNA polymerase II	2
cellular anatomical structure	2
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
cytokine production	1
regulation of gene expression	1
regulation of multicellular organismal process	1
immune system process	1
regulation of biological process	1
gene expression	1
regulation of macromolecule biosynthetic process	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
negative regulation of transcription by RNA polymerase II	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription repressor activity	1
nucleic acid binding	1
transition metal ion binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
binding	1
protein binding	1
cation binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1

Protein interactions and networks

STRING

914 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZBTB32	GATA3	P23771	808
ZBTB32	FUT7	Q11130	727
ZBTB32	FANCC	Q00597	675
ZBTB32	TBX21	Q9UL17	660
ZBTB32	BACH2	Q9BYV9	580
ZBTB32	EOMES	O95936	564
ZBTB32	HDAC5	Q9UQL6	551
ZBTB32	HDAC3	O15379	551
ZBTB32	BCL6	P41182	517
ZBTB32	IL9R	Q01113	516
ZBTB32	ITK	Q08881	512
ZBTB32	STAT4	Q14765	511
ZBTB32	TXK	P42681	497
ZBTB32	ZBTB7A	O95365	468
ZBTB32	S1PR1	P21453	459

IntAct

13 interactions, top by confidence:

A	B	Type	Score
KBTBD8	KBTBD7	psi-mi:“MI:0914”(association)	0.740
RHOXF2	ZBTB32	psi-mi:“MI:0915”(physical association)	0.670
ZBTB32	RHOXF2	psi-mi:“MI:0915”(physical association)	0.670
Hoxa1	ZBTB32	psi-mi:“MI:0915”(physical association)	0.570
ZBTB32	Hoxa1	psi-mi:“MI:0915”(physical association)	0.570
ELF2	ZBTB32	psi-mi:“MI:0915”(physical association)	0.370
GATA2	ZBTB32	psi-mi:“MI:0915”(physical association)	0.370
HOXD4	ZBTB32	psi-mi:“MI:0915”(physical association)	0.370
ZBTB32	ZNF490	psi-mi:“MI:0915”(physical association)	0.370
CFAP206	ZBTB32	psi-mi:“MI:0915”(physical association)	0.370
ZBTB32	ATXN1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (87): ZBTB32 (Two-hybrid), ZBTB32 (Two-hybrid), ZBTB32 (Two-hybrid), RHOXF2 (Two-hybrid), RHOXF2 (Two-hybrid), Hoxa1 (Affinity Capture-Western), PRDM1 (Affinity Capture-Western), ZBTB32 (Two-hybrid), ZBTB32 (Two-hybrid), ZBTB32 (Two-hybrid), ZBTB32 (Two-hybrid), ZBTB32 (Two-hybrid), ZBTB32 (Two-hybrid), ZBTB32 (Two-hybrid), ZBTB32 (PCA)

ESM2 similar proteins: A0A5F9ZHS7, A1YGK1, A2T7E6, A8MZG2, O08574, O43593, O60393, O75593, O88621, O95231, P0C1T1, P0CG20, P20428, P97609, Q04667, Q17QR5, Q2KIS6, Q2M1V0, Q2T9Q7, Q32LE6, Q497V6, Q5JUK2, Q5M844, Q5RJB0, Q5TGS1, Q61645, Q61657, Q6ZMY3, Q6ZN32, Q6ZNG2, Q7RTU1, Q8BZW2, Q8CGW9, Q8IWN7, Q8IXT2, Q8IZ20, Q8N1L9, Q8N7G0, Q8N944, Q8N9Y4

Diamond homologs: A1YGK1, A2T7E6, E1B932, Q05516, Q53G59, Q5U374, Q6NRH0, Q802Y8, Q8BZM0, Q8R2H4, Q9JKD9, Q9Y2Y4, Q8NCN2, Q9ULJ3, P18718, P18725, P18731, P24399, A0A1B8YAB1, A1L2U9, A1YPR0, B1WAZ8, D3ZUU2, G5E8B9, O14867, O15060, O15062, O15156, O15209, O35260, O43298, O43829, O88939, O93567, O95365, O95625, P97303, Q04652, Q08376, Q0IH98

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ZBTB32	“form complex”	ZBTB16/ZBTB32	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	66
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
146619	GRCh38/hg38 19q12-13.13(chr19:29661858-38114723)x1	Pathogenic

SpliceAI

798 predictions. Top by Δscore:

Variant	Effect	Δscore
19:35716127:CCACA:C	acceptor_loss	0.9900
19:35716128:CACA:C	acceptor_loss	0.9900
19:35716130:CAG:C	acceptor_loss	0.9900
19:35716131:A:AG	acceptor_gain	0.9900
19:35716131:AG:A	acceptor_gain	0.9900
19:35716131:AGGC:A	acceptor_gain	0.9900
19:35716132:G:GA	acceptor_gain	0.9900
19:35716132:GG:G	acceptor_gain	0.9900
19:35716132:GGC:G	acceptor_gain	0.9900
19:35716132:GGCG:G	acceptor_gain	0.9900
19:35716132:GGCGC:G	acceptor_gain	0.9900
19:35704624:G:GG	donor_gain	0.9800
19:35714604:T:G	donor_gain	0.9800
19:35716005:CAGG:C	donor_loss	0.9800
19:35716006:AGGT:A	donor_loss	0.9800
19:35716008:GT:G	donor_loss	0.9800
19:35716009:T:G	donor_loss	0.9800
19:35716122:T:A	acceptor_gain	0.9800
19:35716129:A:AG	acceptor_gain	0.9800
19:35704619:GGCCG:G	donor_gain	0.9700
19:35704620:GCCG:G	donor_gain	0.9700
19:35704620:GCCGG:G	donor_gain	0.9700
19:35704624:G:GA	donor_loss	0.9700
19:35704625:T:G	donor_loss	0.9700
19:35704626:GAGT:G	donor_loss	0.9700
19:35710425:G:GT	acceptor_gain	0.9700
19:35710431:G:GT	acceptor_gain	0.9700
19:35716010:GA:G	donor_loss	0.9700
19:35716129:ACAG:A	acceptor_gain	0.9700
19:35716293:CACAG:C	donor_loss	0.9700

AlphaMissense

3115 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:35716252:T:C	F382L	1.000
19:35716254:T:A	F382L	1.000
19:35716254:T:G	F382L	1.000
19:35716253:T:C	F382S	0.999
19:35716281:C:A	H391Q	0.999
19:35716281:C:G	H391Q	0.999
19:35716293:C:A	H395Q	0.999
19:35716293:C:G	H395Q	0.999
19:35716489:T:C	F401L	0.999
19:35716491:C:A	F401L	0.999
19:35716491:C:G	F401L	0.999
19:35716545:C:A	H419Q	0.999
19:35716545:C:G	H419Q	0.999
19:35716231:T:C	C375R	0.998
19:35716240:T:C	C378R	0.998
19:35716241:G:A	C378Y	0.998
19:35716253:T:G	F382C	0.998
19:35716279:C:G	H391D	0.998
19:35716291:C:G	H395D	0.998
19:35716504:T:C	C406R	0.998
19:35716543:C:G	H419D	0.998
19:35716233:C:G	C375W	0.997
19:35716240:T:A	C378S	0.997
19:35716241:G:C	C378S	0.997
19:35716242:T:G	C378W	0.997
19:35716252:T:A	F382I	0.997
19:35716279:C:A	H391N	0.997
19:35716495:T:C	C403R	0.997
19:35716506:T:G	C406W	0.997
19:35716523:A:T	D412V	0.997

dbSNP variants (sampled 300 via entrez): RS1000031603 (19:35711762 C>A,G,T), RS1000101691 (19:35711332 G>A), RS1000379143 (19:35704923 G>A), RS1000937637 (19:35713317 G>A), RS1000982762 (19:35703557 C>T), RS1000989801 (19:35713124 G>C), RS1001106306 (19:35710013 C>A,T), RS1001115514 (19:35707245 TGAG>T,TGAGGAG), RS1001287686 (19:35703259 G>A), RS1001531993 (19:35706952 T>C), RS1002074481 (19:35708894 C>A,G), RS1002107459 (19:35708480 G>A), RS1002453660 (19:35712989 C>T), RS1002592825 (19:35713521 C>T), RS1003105368 (19:35707054 G>C)

Disease associations

OMIM: gene MIM:605859 | 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
GCST010002_54	Refractive error	1.000000e-10
GCST010703_277	Brain morphology (MOSTest)	2.000000e-15

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5291542 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation	2
TL8-506	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
terbufos	increases methylation	1
arsenite	affects expression	1
benzo(e)pyrene	decreases methylation	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
jinfukang	affects cotreatment, increases expression	1
Air Pollutants	increases abundance, increases expression	1
Allergens	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Fonofos	increases methylation	1
Ethyl Methanesulfonate	decreases expression	1
Lipopolysaccharides	decreases reaction, increases expression	1
Methapyrilene	decreases methylation	1
Methyl Methanesulfonate	decreases expression	1
Parathion	increases methylation	1
Poly I-C	increases expression, affects cotreatment	1
Toluene	decreases methylation, increases expression	1
Zinc	increases expression	1
8-Bromo Cyclic Adenosine Monophosphate	decreases expression	1
Aflatoxin B1	decreases methylation	1
Particulate Matter	increases expression, increases abundance	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
CHEMBL5226235	Binding	Binding affinity to FAZF (unknown origin) assessed as fold change	Discovery of OICR12694: A Novel, Potent, Selective, and Orally Bioavailable BCL6 BTB Inhibitor. — ACS Med Chem Lett

Clinical trials (associated diseases)

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