ZBTB17

Summary

ZBTB17 (zinc finger and BTB domain containing 17, HGNC:12936) is a protein-coding gene on chromosome 1p36.13, encoding Zinc finger and BTB domain-containing protein 17 (Q13105). Transcription factor that can function as an activator or repressor depending on its binding partners, and by targeting negative regulators of cell cycle progression. It is a selective cancer dependency (DepMap: 64.0% of cell lines).

This gene encodes a zinc finger protein involved in the regulation of c-myc. The symbol MIZ1 has also been associated with PIAS2 which is a different gene located on chromosome 18.

Source: NCBI Gene 7709 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 92 total
• Phenotypes (HPO): 1
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 64.0% of screened cell lines
• Transcription factor: yes — 46 downstream targets (CollecTRI)
• MANE Select transcript: NM_003443

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12936
Approved symbol	ZBTB17
Name	zinc finger and BTB domain containing 17
Location	1p36.13
Locus type	gene with protein product
Status	Approved
Aliases	MIZ1, pHZ-67
Ensembl gene	ENSG00000116809
Ensembl biotype	protein_coding
OMIM	604084
Entrez	7709

Gene structure

Transcript identifiers

Ensembl transcripts: 39 — 28 protein_coding, 11 protein_coding_CDS_not_defined

ENST00000375733, ENST00000375743, ENST00000440560, ENST00000444358, ENST00000462525, ENST00000464719, ENST00000471805, ENST00000472658, ENST00000474511, ENST00000479282, ENST00000487785, ENST00000488008, ENST00000490899, ENST00000492834, ENST00000494020, ENST00000537142, ENST00000894622, ENST00000894623, ENST00000894624, ENST00000894625, ENST00000894626, ENST00000894627, ENST00000894628, ENST00000894629, ENST00000894630, ENST00000894631, ENST00000894632, ENST00000894633, ENST00000894634, ENST00000894635, ENST00000894636, ENST00000894637, ENST00000954141, ENST00000954142, ENST00000954143, ENST00000954144, ENST00000954145, ENST00000954146, ENST00000954147

RefSeq mRNA: 6 — MANE Select: NM_003443 NM_001242884, NM_001287603, NM_001287604, NM_001324137, NM_001324138, NM_003443

CCDS: CCDS165, CCDS55576, CCDS72712

Canonical transcript exons

ENST00000375743 — 16 exons

Exon	Start	End
ENSE00000751338	15942529	15942738
ENSE00000751339	15943064	15943194
ENSE00000751340	15943399	15943519
ENSE00001348924	15973039	15973125
ENSE00001684066	15944300	15944600
ENSE00001839520	15975983	15976101
ENSE00002702599	15942331	15942420
ENSE00003461772	15944937	15945202
ENSE00003467258	15943599	15943715
ENSE00003495867	15943808	15943895
ENSE00003499285	15944697	15944839
ENSE00003518767	15945715	15945840
ENSE00003533721	15946935	15947123
ENSE00003552718	15948291	15948497
ENSE00003634264	15941869	15942252
ENSE00003671533	15946154	15946294

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 96.01.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.8924 / max 125.1835, expressed in 1814 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
10484	17.4773	1810
10485	0.8729	559
10481	0.3090	125
10482	0.1394	55
10483	0.0938	54

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	96.01	gold quality
sural nerve	UBERON:0015488	95.90	gold quality
tendon of biceps brachii	UBERON:0008188	94.31	gold quality
granulocyte	CL:0000094	93.76	gold quality
apex of heart	UBERON:0002098	93.60	gold quality
right lobe of thyroid gland	UBERON:0001119	93.31	gold quality
ganglionic eminence	UBERON:0004023	92.96	gold quality
left lobe of thyroid gland	UBERON:0001120	92.90	gold quality
cortical plate	UBERON:0005343	92.59	gold quality
upper lobe of left lung	UBERON:0008952	92.29	gold quality
spleen	UBERON:0002106	92.15	gold quality
ectocervix	UBERON:0012249	92.11	gold quality
left testis	UBERON:0004533	91.92	gold quality
metanephros cortex	UBERON:0010533	91.90	gold quality
right testis	UBERON:0004534	91.77	gold quality
body of uterus	UBERON:0009853	91.47	gold quality
thyroid gland	UBERON:0002046	91.42	gold quality
left ovary	UBERON:0002119	91.40	gold quality
right ovary	UBERON:0002118	91.38	gold quality
left uterine tube	UBERON:0001303	91.34	gold quality
body of stomach	UBERON:0001161	91.29	gold quality
endocervix	UBERON:0000458	91.23	gold quality
small intestine Peyer’s patch	UBERON:0003454	91.18	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	91.13	gold quality
ascending aorta	UBERON:0001496	91.10	gold quality
right lung	UBERON:0002167	91.10	gold quality
ventricular zone	UBERON:0003053	91.06	gold quality
thoracic aorta	UBERON:0001515	90.93	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.93	gold quality
adenohypophysis	UBERON:0002196	90.92	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.94

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

46 targets.

Target	Regulation
AQP1
BCL2
BGLAP
BIN1
CAMK2N1
CCR4
CD44	Activation
CDKN1A	Repression
CDKN1C	Activation
CDKN2B	Unknown
CEBPD	Activation
EBP
EFNB2	Activation
ESR1	Repression
EYA1
FOXG1
GABRA6
HCFC1
IL7R
LDLR	Unknown
LEP
LRRN3	Unknown
MAPK1
MXD4	Activation
NDRG2	Unknown
NGF
NGFR
NOTCH1
NTRK1
ODC1

JASPAR motifs

Motif	Name	Family
MA2102.1	ZBTB17	Factors with multiple dispersed zinc fingers

JASPAR matrix evidence (PMIDs): PMID:24983942

Upstream regulators (CollecTRI, top): ZBTB17

miRNA regulators (miRDB)

5 targeting ZBTB17, 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-6873-3P	100.00	71.42	2626
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-3059-3P	96.71	67.08	606

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 64.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• repression of p21 promoter/reporters as well as the endogenous p21 gene by Myc depends on interaction with Miz-1. Expression of Miz-1 increases during hematopoietic differentiation and Miz-1 activates the p21 promoter under conditions of low Myc levels (PMID:12545156)
• Miz-1 has a role in inducing apoptosis along with MAGE-A4 (PMID:14739298)
• replicative senescence-specific factors may block c-Myc inhibition of Miz-1 activation of hMad4 expression, and the continual presence of hMad4 protein may transcriptionally repress selected c-Myc target genes (PMID:16167342)
• Miz-1 targeting is essential for Myc-mediated apoptosis (PMID:16352593)
• Miz-1 transcription factor was identified as an interactor of the SB transposase (PMID:16537485)
• NDRG2 expression is repressed by Myc via Miz-1-dependent interaction with the NDRG2 core promoter (PMID:17050536)
• repression of BCL2 transcription is the single essential consequence of targeting the MIZ-1 pathway during apoptosis induction, which explains a copperative interaction between c-MYC and BCL2 (PMID:17082179)
• The crystal structure of the Miz-1 POZ domain show that the beta-sheet interface directs the tetramerisation of the Miz-1 POZ domain in solution. (PMID:17880999)
• MIZ-1 is a new favorable neuroblastoma gene, which may directly or indirectly regulate the expression of other favorable neuroblastoma genes (PMID:17947461)
• Miz1 and Myc affect the activity of the Atr checkpoint through their effect on TopBP1 chromatin association and stability. (PMID:18923429)
• The ribosomal protein L23 is a negative regulator of Miz1-dependent transactivation. (PMID:19160485)
• Gfi-1 does not directly bind to CDKN2B, but interacts with Miz-1 and, via Miz-1, is recruited to the core promoter of CDKN2B (PMID:19164764)
• These results identify an important function for BCL6 in facilitating apoptosis of germinal center B cells via suppression of BCL2, and suggest that blocking this pathway is critical for lymphomagenesis. (PMID:19549844)
• transcription factor Myc-interacting zinc-finger protein 1 (Miz1) selectively suppresses TNF-alpha-induced JNK1 activation and cell death independently. (PMID:19815509)
• Miz-1 acts as a p53 suppressor by interfering with p53 DNA-binding ability (PMID:19901969)
• Binding of Arf disrupts the interaction of Miz1 with its coactivator, nucleophosmin, induces the sumoylation of Miz1, and facilitates the assembly of a heterochromatic complex that contains Myc and trimethylated H3K9 in addition to Miz1. (PMID:20308430)
• Miz1 BTB domain resembles a typical swapped BTB dimer, although it has a shorter N-terminus that is not able to form the interchain sheet (PMID:20493880)
• Although the transient repression mediated by Miz-1/c-Myc is independent of de novo methylation, the stable repression by this complex is associated with CpG island methylation of the critical -295 to -95-bp region of the WIF-1 promoter (PMID:20697356)
• NLRR3 is a direct target of MYCN, which associates with Miz-1 and negatively regulates NLRR3 expression. (PMID:21908575)
• study demonstrate that HPV-16 E7 forms a complex with Miz-1; These findings suggest that HPV-16 E7 protein can repress Miz-1-induced p21(Cip1) gene expression (PMID:22099967)
• The repression of TNF-alpha-induced JNK activation by Miz1 is de-repressed by its own site-specific ubiquitination and degradation. (PMID:22184250)
• The ZBTB17 polymorphism rs10927875 appears to play a role in the susceptibility of the Han Chinese population to dilated cardiomyopathy . (PMID:23570452)
• The functional interaction of both proteins becomes apparent at oncogenic expression levels of MYC and association with MIZ-1 mediates both oncogenic functions of MYC as well as tumor-suppressive responses to oncogenic levels of MYC. (PMID:24296348)
• We demonstrate that Arnt is an interaction partner for Miz-1, and that Arnt has a functional role in the regulation of CDKN2B (PMID:24618291)
• results indicate that Miz-1 may be directed in vivo to the novel motif sequences we have identified, where it can recruit its specific binding partners to control gene expression and ultimately regulate cell fate (PMID:24983942)
• strategy for the purification of tethered POZ domains that form forced heterodimers is described, and crystal structures of the heterodimeric POZ domains of Miz1/BCL6 and of Miz1/NAC1 are reported (PMID:25484205)
• MIZ-1 can promote the proliferation of breast cancer cells through Wnt signaling. (PMID:25558878)
• This study presents the structure of the synthetic Miz-1 Zinc Finger 13 determined by 2D (1)H-(1)H NMR. (PMID:26972249)
• the silencing of Miz-1 expression inhibited cell proliferation and promoted apoptosis in vitro and reduced the migration ability in esophageal carcinoma cells. (PMID:27109891)
• These data suggest that MYC acts as a master coordinator that inversely modulates the impact of cell cycle and circadian clock on gene expression via its interaction with MIZ1. (PMID:27339797)
• Miz1 is a newly identified ING4-induced target gene which can drive prostate luminal epithelial cell differentiation. (PMID:27527891)
• The mechanism of inhibition of c-Myc transcriptional activity by Miz-1 that binds c-Myc while competing for binding with Max has been described. (PMID:27859590)
• This study used NMR to deduce the role of Miz-1 Zinc Fingers 1-4 in detecting the Miz-1 consensus sequence and preventing nonspecific DNA binding. (PMID:28035002)
• Because RPL23 is encoded by a target gene of c-Myc, the RPL23/Miz-1/c-Myc regulatory circuit provides a feedback loop that links efficient RPL23 expression with c-Myc’s function to suppress Miz-1-induced Cdk inhibitors and thereby leads to apoptotic resistance in higher-risk myelodysplastic syndrome patients (PMID:28539603)
• This study firstly associates ZBTB17 loss-of-function mutation with enhanced susceptibility to DCM in humans, which provides novel insight into the molecular mechanism underpinning DCM, implying potential implications for genetic counseling and personalized management of DCM (PMID:29445930)
• Identification of the transcription factor Miz1 as an essential regulator of diphthamide biosynthesis using a CRISPR-mediated genome-wide screen. (PMID:33057331)
• MXD/MIZ1 transcription regulatory complexes activate the expression of MYC-repressed genes. (PMID:33914337)
• MYC- and MIZ1-Dependent Vesicular Transport of Double-Strand RNA Controls Immune Evasion in Pancreatic Ductal Adenocarcinoma. (PMID:34145038)
• Identification of the SARS-CoV-2 Entry Receptor ACE2 as a Direct Target for Transcriptional Repression by Miz1. (PMID:34305888)
• Miz1 promotes KRAS-driven lung tumorigenesis by repressing the protocadherin Pcdh10. (PMID:36538983)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	zbtb17	ENSDARG00000074548
mus_musculus	Zbtb17	ENSMUSG00000006215
rattus_norvegicus	Zbtb17	ENSRNOG00000010436

Paralogs (51): WIZ (ENSG00000011451), ZNF416 (ENSG00000083817), MYNN (ENSG00000085274), PRDM4 (ENSG00000110851), PRDM2 (ENSG00000116731), ZNF644 (ENSG00000122482), GZF1 (ENSG00000125812), ZNF426 (ENSG00000130818), ZNF287 (ENSG00000141040), ZNF697 (ENSG00000143067), ZNF687 (ENSG00000143373), ZNF214 (ENSG00000149050), ZNF547 (ENSG00000152433), ZNF776 (ENSG00000152443), ZNF230 (ENSG00000159882), ZNF222 (ENSG00000159885), ZNF233 (ENSG00000159915), ZNF333 (ENSG00000160961), ZNF319 (ENSG00000166188), ZNF592 (ENSG00000166716), ZNF646 (ENSG00000167395), ZNF507 (ENSG00000168813), ZNF768 (ENSG00000169957), ZNF417 (ENSG00000173480), ZNF408 (ENSG00000175213), ZBTB41 (ENSG00000177888), ZNF223 (ENSG00000178386), ZNF852 (ENSG00000178917), ZNF784 (ENSG00000179922), ZNF572 (ENSG00000180938), ZNF707 (ENSG00000181135), ZNF746 (ENSG00000181220), ZNF467 (ENSG00000181444), ZNF530 (ENSG00000183647), ZNF17 (ENSG00000186272), ZNF527 (ENSG00000189164), ZKSCAN7 (ENSG00000196345), ZNF34 (ENSG00000196378), ZNF774 (ENSG00000196391), ZNF777 (ENSG00000196453)

Protein

Protein identifiers

Zinc finger and BTB domain-containing protein 17 — Q13105 (reviewed: Q13105)

Alternative names: Myc-interacting zinc finger protein 1, Zinc finger protein 151, Zinc finger protein 60

All UniProt accessions (3): Q13105, H0Y6X2, H7C1K8

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor that can function as an activator or repressor depending on its binding partners, and by targeting negative regulators of cell cycle progression. Plays a critical role in early lymphocyte development, where it is essential to prevent apoptosis in lymphoid precursors, allowing them to survive in response to IL7 and undergo proper lineage commitment. Has been shown to bind to the promoters of adenovirus major late protein and cyclin D1 and activate transcription. Required for early embryonic development during gastrulation. Represses RB1 transcription; this repression can be blocked by interaction with ZBTB49 isoform 3/ZNF509S1.

Subunit / interactions. Homooligomerizes (via the BTB/POZ domain), multimerization is required for DNA binding. Interacts (via the C-terminal zinc fingers) with GIF1; the interaction results in the recruitment of MYB to the CDKN1A/p21 and CDKN1B promoters and repression of transcription. Interacts with TRAF2, interfering with the binding of UBC13 to TRAF2, and inhibiting TRAF2 E3 ligase activity. Interacts with MYC (via the C-terminal helix-loop-helix motif); the interaction inhibits ZBTB17 transactivation and growth arrest activities and renders it insoluble in the nucleus. Also interacts with HCFC1, MAGEA4 and TMPRSS11A. Interacts with BCL6; the interaction inhibits ZBTB17 transactivation activity on target genes involved in cell cycle arrest. Interacts with ZBTB49 isoform 3/ZNF509S1; this interaction blocks ZBTB17-mediated repression of RB1.

Subcellular location. Nucleus.

Tissue specificity. Expressed in germinal center B-cells.

Post-translational modifications. Undergoes ‘Lys-48’-linked polyubiquitination at Lys-397 and Lys-481 and subsequent proteasomal degradation in a TRAF2-dependent manner.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q13105-1	1	yes
Q13105-2	2
Q13105-3	3

RefSeq proteins (6): NP_001229813, NP_001274532, NP_001274533, NP_001311066, NP_001311067, NP_003434* (*=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, PF13894

UniProt features (83 total): helix 21, strand 16, turn 14, zinc finger region 13, region of interest 5, compositionally biased region 5, cross-link 2, splice variant 2, sequence conflict 2, chain 1, domain 1, modified residue 1

Structure

Experimental structures (PDB)

19 structures.

PDB	Method	Resolution (Å)
7T58	X-RAY DIFFRACTION	2.05
2Q81	X-RAY DIFFRACTION	2.1
7AZW	X-RAY DIFFRACTION	2.1
4U2M	X-RAY DIFFRACTION	2.23
7AZX	X-RAY DIFFRACTION	2.25
4U2N	X-RAY DIFFRACTION	2.3
3M52	X-RAY DIFFRACTION	2.59
2LVR	SOLUTION NMR
2LVT	SOLUTION NMR
2LVU	SOLUTION NMR
2M0D	SOLUTION NMR
2M0E	SOLUTION NMR
2M0F	SOLUTION NMR
2N25	SOLUTION NMR
2N26	SOLUTION NMR
5ION	SOLUTION NMR
7MC1	SOLUTION NMR
7MC2	SOLUTION NMR
7MC3	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13105-F1	65.03	0.02

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 (3): 120, 397, 481

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-381038	XBP1(S) activates chaperone genes

MSigDB gene sets: 0 (showing top):

GO Biological Process (10): negative regulation of transcription by RNA polymerase II (GO:0000122), gastrulation with mouth forming second (GO:0001702), regulation of cytokine production (GO:0001817), regulation of immune system process (GO:0002682), ectoderm development (GO:0007398), negative regulation of cell population proliferation (GO:0008285), negative regulation of cell cycle (GO:0045786), positive regulation of transcription by RNA polymerase II (GO:0045944), G1 to G0 transition (GO:0070314), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (11): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), core promoter sequence-specific DNA binding (GO:0001046), transcription coactivator binding (GO:0001223), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA-binding transcription factor activity (GO:0003700), zinc ion binding (GO:0008270), DNA-binding transcription factor binding (GO:0140297), DNA binding (GO:0003677), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (4): nucleoplasm (GO:0005654), protein-containing complex (GO:0032991), protein-DNA complex (GO:0032993), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
IRE1alpha activates chaperones	1

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
transcription by RNA polymerase II	2
negative regulation of cellular process	2
regulation of DNA-templated transcription	2
transcription cis-regulatory region binding	2
DNA-binding transcription factor activity, RNA polymerase II-specific	2
negative regulation of DNA-templated transcription	1
gastrulation	1
cytokine production	1
regulation of gene expression	1
regulation of multicellular organismal process	1
immune system process	1
regulation of biological process	1
tissue development	1
cell population proliferation	1
regulation of cell population proliferation	1
cell cycle	1
regulation of cell cycle	1
positive regulation of DNA-templated transcription	1
cell cycle process	1
DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1
transcription coregulator binding	1
negative regulation of transcription by RNA polymerase II	1
DNA-binding transcription repressor activity	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
transcription regulator activity	1
transition metal ion binding	1
transcription factor binding	1
nucleic acid binding	1
binding	1
cation binding	1
nuclear lumen	1
cellular anatomical structure	1
cellular_component	1
protein-containing complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1254 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZBTB17	MYC	P01106	976
ZBTB17	ZBTB4	Q9P1Z0	773
ZBTB17	BCL6	P41182	764
ZBTB17	TOPBP1	Q92547	617
ZBTB17	EP300	Q09472	617
ZBTB17	GFI1	Q99684	611
ZBTB17	CDKN2B	P42772	593
ZBTB17	CRBN	Q96SW2	580
ZBTB17	CDKN1A	P38936	557
ZBTB17	MYCN	P04198	551
ZBTB17	METAP2	P50579	494
ZBTB17	DNMT3A	Q9Y6K1	472
ZBTB17	RTL10	Q7L3V2	470
ZBTB17	DDX18	Q9NVP1	468
ZBTB17	NACC1	Q96RE7	446

IntAct

57 interactions, top by confidence:

A	B	Type	Score
MYC	ZBTB17	psi-mi:“MI:0915”(physical association)	0.780
ZBTB17	MYC	psi-mi:“MI:0915”(physical association)	0.780
ZBTB17	MYC	psi-mi:“MI:0407”(direct interaction)	0.780
MYCN	ZBTB17	psi-mi:“MI:0915”(physical association)	0.600
ZBTB17	MYCN	psi-mi:“MI:0407”(direct interaction)	0.600
HCFC1	ZBTB17	psi-mi:“MI:0915”(physical association)	0.580
ZBTB17	HCFC1	psi-mi:“MI:0915”(physical association)	0.580
ZBTB17	ZBTB8A	psi-mi:“MI:0915”(physical association)	0.560
ZBTB17	APBB2	psi-mi:“MI:0915”(physical association)	0.560
ZBTB17		psi-mi:“MI:0915”(physical association)	0.560
ZBTB17	MAGEA4	psi-mi:“MI:0915”(physical association)	0.540

BioGRID (112): ZBTB17 (FRET), ZBTB17 (Co-localization), ZBTB17 (Affinity Capture-Western), ZBTB49 (Affinity Capture-Western), ZBTB17 (Two-hybrid), ZBTB17 (Affinity Capture-Western), ZBTB4 (Affinity Capture-Western), ZBTB17 (Affinity Capture-Western), GFI1 (Reconstituted Complex), GFI1 (Affinity Capture-Western), MYCN (Affinity Capture-Western), ZBTB17 (Reconstituted Complex), TOPBP1 (Affinity Capture-Western), ZBTB17 (Two-hybrid), MYC (Affinity Capture-Western)

ESM2 similar proteins: A1L1J6, A2A5K6, A2APF3, D3ZUU2, E9Q8T2, G3V893, G5E8B9, O43167, O70237, O95625, P10074, P22227, P52739, P57071, P98169, Q05516, Q13105, Q1H9T6, Q3B725, Q3B7N9, Q3U288, Q3UH06, Q4VBD9, Q5DU09, Q5EAC5, Q5R633, Q5VTD9, Q60821, Q6DDV0, Q6GL52, Q6NS86, Q6YND2, Q6ZSB9, Q7TS63, Q80X44, Q8BKX7, Q8BXX2, Q8C8V1, Q8CCE9, Q8N1W2

Diamond homologs: A0A1B8YAB1, A1YPR0, B0WWP2, B1H285, B3M9V8, B3NDN0, B4GRJ2, B4HIK1, B4J045, B4L0G9, B4LIG6, B4MXW3, B4PD06, B4QLQ2, C9JR72, D3Z8N4, E0CZ16, G3X9X1, O15062, O88939, O93567, O95365, P28575, P41182, P41183, Q08CL3, Q08DK3, Q13105, Q16RL8, Q2M0J9, Q3UQV5, Q52KB5, Q5EXX3, Q5R7B8, Q5RDY3, Q5TC79, Q5ZI33, Q5ZKD9, Q5ZM39, Q60821

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
HUWE1	“down-regulates quantity by destabilization”	ZBTB17	ubiquitination
HCFC1	“down-regulates activity”	ZBTB17	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 23 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
negative regulation of apoptotic process	6	10.4×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	61
Likely benign	9
Benign	11

Top pathogenic / likely-pathogenic (0)

SpliceAI

2782 predictions. Top by Δscore:

Variant	Effect	Δscore
1:15942253:C:CC	acceptor_gain	1.0000
1:15942327:TCA:T	donor_loss	1.0000
1:15942329:ACCT:A	donor_loss	1.0000
1:15942330:C:CA	donor_loss	1.0000
1:15942330:CCTT:C	donor_gain	1.0000
1:15942333:T:A	donor_gain	1.0000
1:15942336:T:TA	donor_gain	1.0000
1:15942416:CACCA:C	acceptor_gain	1.0000
1:15942417:ACCA:A	acceptor_gain	1.0000
1:15942418:CCA:C	acceptor_gain	1.0000
1:15942418:CCAC:C	acceptor_gain	1.0000
1:15942419:CA:C	acceptor_gain	1.0000
1:15942419:CAC:C	acceptor_gain	1.0000
1:15942421:C:CC	acceptor_gain	1.0000
1:15942421:C:CG	acceptor_loss	1.0000
1:15942422:T:A	acceptor_loss	1.0000
1:15942523:CCGCA:C	donor_loss	1.0000
1:15942524:CGCAC:C	donor_loss	1.0000
1:15942525:GCACC:G	donor_loss	1.0000
1:15942526:CA:C	donor_loss	1.0000
1:15942527:AC:A	donor_loss	1.0000
1:15942528:CCTG:C	donor_loss	1.0000
1:15943060:TCACC:T	donor_loss	1.0000
1:15943062:A:AC	donor_gain	1.0000
1:15943062:AC:A	donor_gain	1.0000
1:15943063:C:CC	donor_gain	1.0000
1:15943063:C:CT	donor_loss	1.0000
1:15943063:CC:C	donor_gain	1.0000
1:15943063:CCA:C	donor_gain	1.0000
1:15943063:CCAG:C	donor_gain	1.0000

AlphaMissense

5308 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:15942203:A:C	F726L	1.000
1:15942203:A:T	F726L	1.000
1:15942204:A:G	F726S	1.000
1:15942205:A:G	F726L	1.000
1:15942216:C:T	C722Y	1.000
1:15942226:A:G	C719R	1.000
1:15942671:G:C	H632Q	1.000
1:15942671:G:T	H632Q	1.000
1:15942673:G:C	H632D	1.000
1:15942673:G:T	H632N	1.000
1:15942681:A:G	L629P	1.000
1:15942693:C:G	R625P	1.000
1:15942698:G:C	F623L	1.000
1:15942698:G:T	F623L	1.000
1:15942699:A:G	F623S	1.000
1:15942700:A:C	F623V	1.000
1:15942700:A:G	F623L	1.000
1:15942700:A:T	F623I	1.000
1:15942711:C:G	C619S	1.000
1:15942712:A:G	C619R	1.000
1:15942712:A:T	C619S	1.000
1:15942719:A:C	C616W	1.000
1:15942720:C:G	C616S	1.000
1:15942720:C:T	C616Y	1.000
1:15942721:A:G	C616R	1.000
1:15942721:A:T	C616S	1.000
1:15943068:G:C	H608Q	1.000
1:15943068:G:T	H608Q	1.000
1:15943070:G:C	H608D	1.000
1:15943080:G:C	H604Q	1.000

dbSNP variants (sampled 300 via entrez): RS1000014596 (1:15973304 T>C), RS1000034969 (1:15944717 C>A), RS1000063228 (1:15951672 C>T), RS1000200450 (1:15946088 C>T), RS1000342333 (1:15957388 T>C), RS1000382554 (1:15950699 A>G), RS1000686554 (1:15971405 T>G), RS1000730091 (1:15964767 A>T), RS1000842447 (1:15957041 A>G,T), RS1000930117 (1:15977599 G>A), RS1001212027 (1:15965299 G>A,C), RS1001310186 (1:15945464 G>A,T), RS1001398204 (1:15957906 G>C), RS1001524726 (1:15958271 A>C), RS1001536207 (1:15945496 G>A)

Disease associations

OMIM: gene MIM:604084 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): dilated cardiomyopathy (MONDO:0005021)

Orphanet (1): Dilated cardiomyopathy (Orphanet:217604)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0001644	Dilated cardiomyopathy

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001023_2	Idiopathic dilated cardiomyopathy	1.000000e-09
GCST005984_23	Glomerular filtration rate	1.000000e-12
GCST006956_22	Erectile dysfunction	3.000000e-06
GCST006979_855	Heel bone mineral density	5.000000e-24
GCST011202_1	Dilated cardiomyopathy (MTAG)	8.000000e-25
GCST011210_1	Dilated cardiomyopathy	6.000000e-18

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D002311	Cardiomyopathy, Dilated	C14.280.195.160; C14.280.238.070; C16.320.488.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5069374 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
bisphenol F	affects cotreatment, increases methylation	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	decreases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	increases expression	1
nickel sulfate	decreases expression	1
coumarin	increases phosphorylation	1
cylindrospermopsin	increases expression	1
K 7174	increases expression	1
T 113242	increases expression, increases reaction	1
ICG 001	decreases expression	1
abrine	increases expression	1
5-(4-ethylbenzylidene)-2-thioxothiazolidin-4-one	affects binding, decreases expression, increases reaction	1
Fulvestrant	affects cotreatment, increases methylation	1
Air Pollutants	affects expression, increases abundance	1
Vehicle Emissions	decreases methylation	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Carmustine	decreases expression	1
Chelating Agents	affects binding, increases expression	1
Copper	affects binding, increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Dinitrochlorobenzene	decreases expression	1
Eugenol	decreases expression	1
Ozone	affects expression, increases abundance	1
Phenobarbital	affects expression	1
Smoke	decreases expression	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5059507	Binding	Proteomics fold change data (SUDHL4 cells, 1h)	Data for DCP probe CCT369260

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_XV87	HEK293 eGFP-ZBTB17	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00374465	PHASE4	UNKNOWN	Therapy With Verapamil or Carvedilol in Chronic Heart Failure
NCT01293903	PHASE4	COMPLETED	Study of Qiliqiangxin Capsule to Treat Dilated Cardiomyopathy
NCT01557140	PHASE4	COMPLETED	A Randomized Trial of Carvedilol in Chronic Chagas Cardiomyopathy
NCT01917149	PHASE4	COMPLETED	Supramaximal Titrated Inhibition of RAAS in Dilated Cardiomyopathy
NCT02115581	PHASE4	COMPLETED	Coenzyme Q10 Supplementation in Children With Idiopathic Dilated Cardiomyopathy
NCT06236022	PHASE4	RECRUITING	The Effects of Sirolimus in Patients With Dilated Cardiomyopathy Infected With Kaposi Sarcoma-associated Virus
NCT00333827	PHASE3	COMPLETED	Cell Therapy In Dilated Cardiomyopathy
NCT00505154	PHASE3	COMPLETED	Effect of Rosuvastatin on Left Ventricular Remodeling
NCT01223703	PHASE3	COMPLETED	PUFAs and Left Ventricular Function in Heart Failure
NCT01583114	PHASE3	TERMINATED	PREclinical Mutation CARriers From Families With DIlated Cardiomyopathy and ACE Inhibitors
NCT01914081	PHASE3	UNKNOWN	Resveratrol: A Potential Anti- Remodeling Agent in Heart Failure, From Bench to Bedside
NCT02989181	PHASE3	UNKNOWN	Continues Positive Airway Pressure Treatment for Patients With Dilated Cardiomyopathy and Obstructive Sleep Apnea
NCT03439514	PHASE3	TERMINATED	A Study of ARRY-371797 (PF-07265803) in Patients With Symptomatic Dilated Cardiomyopathy Due to a Lamin A/C Gene Mutation
NCT05237323	PHASE3	COMPLETED	Micophenolate Mofetil Versus Azathioprine in Myocarditis
NCT05849766	PHASE3	COMPLETED	Effect of Dapagliflozin on Cardiac Structure, Function and Secondary Mitral Regurgitation in Patients with Left Ventricle Dysfunction
NCT06250257	PHASE3	RECRUITING	Bromocriptine in Dilated Cardiomyopathy Among Women of Reproductive Age
NCT00629018	PHASE2	COMPLETED	Safety and Efficacy Study of Stem Cell Transplantation to Treat Dilated Cardiomyopathy
NCT00629096	PHASE2	COMPLETED	Intracoronary Infusion of Autologous Bone Marrow Cells for Treatment of Idiopathic Dilated Cardiomyopathy
NCT00765518	PHASE2	COMPLETED	Use of Ixmyelocel-T (Formerly Cardiac Repair Cell [CRC] Treatment) in Patients With Heart Failure Due to Dilated Cardiomyopathy (IMPACT-DCM)
NCT00847964	PHASE2	COMPLETED	Safety and Feasibility of Algisyl-LVR™ as a Method of Left Ventricular Restoration in Patients With DCM Undergoing Open-heart Surgery
NCT01020968	PHASE2	COMPLETED	Use of Ixmyelocel-T (Formerly Catheter-based Cardiac Repair Cell [CRC]) Treatment in Patients With Heart Failure Due to Dilated Cardiomyopathy
NCT01302171	PHASE2	COMPLETED	Bone Marrow Derived Adult Stem Cells for Dilated Cardiomyopathy
NCT01350310	PHASE2	COMPLETED	Safety and Efficacy Study of Intramyocardial Stem Cell Therapy in Patients With Dilated Cardiomyopathy
NCT02133911	PHASE2	COMPLETED	A Pilot Trial of Ranolazine to Treat Patients With Dilated Cardiomyopathy
NCT03071653	PHASE2	SUSPENDED	Left Cardiac Sympathetic Denervation for Cardiomyopathy Feasibility Pilot Study
NCT03572660	PHASE2	ACTIVE_NOT_RECRUITING	Use of Bone Marrow Derived Stem Cell and G-CSF With Circulatory Assistance in the Treatment of DCM
NCT03775070	PHASE2	COMPLETED	Simvastatin Therapy in Patients With Dilated Cardiomyopathy.
NCT04405804	PHASE2	UNKNOWN	Early Administration of Ivabradine in Children With Heart Failure
NCT05410873	PHASE2	COMPLETED	Examining the Effects of Mitochondrial Oxidative Stress in DCM
NCT06632834	PHASE2	RECRUITING	Outcome-targeted Therapy: Principle and Outcome Evaluation: Clinical Study and Phenotype-genotype Correlation
NCT00585546	PHASE1	TERMINATED	Harefield Recovery Protocol Study for Patients With Refractory Chronic Heart Failure
NCT02293603	PHASE1	UNKNOWN	Dilated cardiomYopathy iNtervention With Allogeneic MyocardIally-regenerative Cells (DYNAMIC)
NCT03062956	PHASE1	COMPLETED	A Single Ascending Dose Study Assessing the Safety, Tolerability, PK and PD of MYK-491
NCT03129568	PHASE1	COMPLETED	Transcoronary Infusion of Cardiac Progenitor Cells in Pediatric Dilated Cardiomyopathy
NCT04982081	PHASE1	UNKNOWN	Treating Congestive HF With hiPSC-CMs Through Endocardial Injection
NCT06381466	PHASE1	TERMINATED	A Study to Investigate Safety, Tolerability, and Pharmacokinetics of Oral AZD0233 Compared With Placebo in Healthy Adult Participants.
NCT06464588	PHASE1	RECRUITING	A Phase 1 Open-Label Study of the Safety of Intravenous Allogeneic Neonatal Mesenchymal Cells (nMSCs) in Young Adult (1A) and Pediatric (1B) Patients With Dilated Cardiomyopathy (DCM)
NCT06902896	PHASE1	COMPLETED	Safety and Efficacy of FAP iCDC in End-stage Dilated Cardiomyopathy
NCT07137338	PHASE1	RECRUITING	A Phase 1 AAV Gene Therapy Trial Evaluating Safety and Preliminary Efficacy of RP-A701 in Subjects With BAG3 Dilated Cardiomyopathy
NCT07241104	PHASE1	RECRUITING	A Study of AZD4063 in PLN R14del Dilated Cardiomyopathy