ZBTB45

Summary

ZBTB45 (zinc finger and BTB domain containing 45, HGNC:23715) is a protein-coding gene on chromosome 19q13.43, encoding Zinc finger and BTB domain-containing protein 45 (Q96K62). May be involved in transcriptional regulation.

Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II; regulation of cytokine production; and regulation of immune system process. Predicted to be located in nucleus. Predicted to be active in nucleoplasm.

Source: NCBI Gene 84878 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 86 total
• MANE Select transcript: NM_001316979

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23715
Approved symbol	ZBTB45
Name	zinc finger and BTB domain containing 45
Location	19q13.43
Locus type	gene with protein product
Status	Approved
Aliases	FLJ14486
Ensembl gene	ENSG00000119574
Ensembl biotype	protein_coding
OMIM	621256
Entrez	84878

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 12 protein_coding

ENST00000354590, ENST00000594051, ENST00000596739, ENST00000600130, ENST00000600990, ENST00000869554, ENST00000869555, ENST00000869556, ENST00000869557, ENST00000869558, ENST00000927208, ENST00000927209

RefSeq mRNA: 5 — MANE Select: NM_001316979 NM_001316978, NM_001316979, NM_001316981, NM_001316982, NM_032792

CCDS: CCDS12984

Canonical transcript exons

ENST00000594051 — 3 exons

Exon	Start	End
ENSE00001005546	58516395	58517673
ENSE00001199356	58513530	58514310
ENSE00003028970	58519742	58519810

Expression profiles

Bgee: expression breadth ubiquitous, 205 present calls, max score 89.51.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.0969 / max 55.1527, expressed in 1793 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
182965	11.8597	1792
182964	0.2371	86

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	89.51	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.49	silver quality
parotid gland	UBERON:0001831	85.81	silver quality
apex of heart	UBERON:0002098	83.45	gold quality
right frontal lobe	UBERON:0002810	83.12	gold quality
anterior cingulate cortex	UBERON:0009835	82.19	gold quality
prefrontal cortex	UBERON:0000451	82.06	gold quality
popliteal artery	UBERON:0002250	82.06	gold quality
tibial artery	UBERON:0007610	82.03	gold quality
stromal cell of endometrium	CL:0002255	81.92	gold quality
hindlimb stylopod muscle	UBERON:0004252	81.75	gold quality
skin of leg	UBERON:0001511	81.63	gold quality
aorta	UBERON:0000947	81.54	gold quality
right coronary artery	UBERON:0001625	81.45	gold quality
granulocyte	CL:0000094	81.38	gold quality
gastrocnemius	UBERON:0001388	81.37	gold quality
Brodmann (1909) area 9	UBERON:0013540	81.33	gold quality
mucosa of transverse colon	UBERON:0004991	81.28	gold quality
descending thoracic aorta	UBERON:0002345	81.25	gold quality
lower esophagus muscularis layer	UBERON:0035833	81.19	gold quality
lower esophagus	UBERON:0013473	81.18	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	81.12	gold quality
muscle layer of sigmoid colon	UBERON:0035805	81.10	gold quality
thoracic aorta	UBERON:0001515	81.08	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.05	gold quality
skin of abdomen	UBERON:0001416	81.05	gold quality
ascending aorta	UBERON:0001496	80.98	gold quality
cortical plate	UBERON:0005343	80.87	gold quality
left coronary artery	UBERON:0001626	80.85	gold quality
neocortex	UBERON:0001950	80.79	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.10

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

22 targeting ZBTB45, 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-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-1843	98.97	66.07	838
HSA-MIR-4802-5P	98.97	66.26	833
HSA-MIR-589-5P	98.72	66.96	927
HSA-MIR-6787-5P	97.54	63.85	457
HSA-MIR-1910-5P	97.42	66.36	844
HSA-MIR-3943	95.87	64.57	523
HSA-MIR-1229-5P	94.57	65.78	487

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:dkeyp-84f3.5	ENSDARG00000042989
mus_musculus	Zbtb45	ENSMUSG00000049600
rattus_norvegicus	Zbtb45	ENSRNOG00000027459

Paralogs (36): ZBTB32 (ENSG00000011590), SNAI2 (ENSG00000019549), PRDM1 (ENSG00000057657), PRDM6 (ENSG00000061455), ZNF76 (ENSG00000065029), PATZ1 (ENSG00000100105), MAZ (ENSG00000103495), ZBTB16 (ENSG00000109906), ZNF451 (ENSG00000112200), 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 45 — Q96K62 (reviewed: Q96K62)

Alternative names: Zinc finger protein 499

All UniProt accessions (3): Q96K62, M0QZ57, M0R1I4

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in transcriptional regulation. In the central nervous system, may play a role in glial cell differentiation.

Subcellular location. Nucleus.

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

RefSeq proteins (5): NP_001303907, NP_001303908, NP_001303910, NP_001303911, NP_116181 (=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 (13 total): compositionally biased region 4, zinc finger region 4, region of interest 2, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96K62-F1	63.51	0.08

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 142 (showing top): ROVERSI_GLIOMA_COPY_NUMBER_UP, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM5, GOBP_CYTOKINE_PRODUCTION, HNF4_DR1_Q3, LEF1_Q6, RAY_TUMORIGENESIS_BY_ERBB2_CDC25A_UP, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, MODULE_49, MARTENS_TRETINOIN_RESPONSE_DN, FIGUEROA_AML_METHYLATION_CLUSTER_3_UP, GOBP_NEGATIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II, PILON_KLF1_TARGETS_UP, GOBP_NEGATIVE_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_METABOLIC_PROCESS, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, GOMF_DNA_BINDING_TRANSCRIPTION_REPRESSOR_ACTIVITY

GO Biological Process (4): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of cytokine production (GO:0001817), regulation of immune system process (GO:0002682), nervous system development (GO:0007399)

GO Molecular Function (7): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), 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): nucleoplasm (GO:0005654), 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 transcription by RNA polymerase II	1
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
system development	1
cis-regulatory region sequence-specific DNA binding	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
transition metal ion binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
binding	1
cation binding	1
nuclear lumen	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

746 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZBTB45	FAM185A	Q8N0U4	518
ZBTB45	SLC35G4	P0C7Q5	479
ZBTB45	BTBD9	Q96Q07	451
ZBTB45	ZNF487	B1APH4	447
ZBTB45	INAFM1	C9JVW0	432
ZBTB45	C19orf47	Q8N9M1	419
ZBTB45	FAM76B	Q5HYJ3	399
ZBTB45	TMEM134	Q9H6X4	383
ZBTB45	ZHX2	Q9Y6X8	381
ZBTB45	UBALD1	Q8TB05	366
ZBTB45	FAM124A	Q86V42	358
ZBTB45	HHIPL2	Q6UWX4	354
ZBTB45	XRRA1	Q6P2D8	348
ZBTB45	EML3	Q32P44	340
ZBTB45	TMEM209	Q96SK2	333

IntAct

10 interactions, top by confidence:

A	B	Type	Score
BAG4	ZBTB45	psi-mi:“MI:0915”(physical association)	0.560
ZBTB7A	ZBTB45	psi-mi:“MI:0915”(physical association)	0.370
NOTCH2	ZNF320	psi-mi:“MI:0914”(association)	0.350
BACH2	ENC1	psi-mi:“MI:0914”(association)	0.350
ORF33	ATN1	psi-mi:“MI:0914”(association)	0.350
ZBTB45	BAG4	psi-mi:“MI:0915”(physical association)	0.000
ftsP	ZBTB45	psi-mi:“MI:0915”(physical association)	0.000
ZBTB45	MED31	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (7): ZBTB45 (Affinity Capture-MS), MED31 (Two-hybrid), BAG4 (Two-hybrid), ZBTB45 (Affinity Capture-MS), ZBTB45 (Affinity Capture-MS), ZBTB45 (Negative Genetic), ZBTB45 (Affinity Capture-MS)

ESM2 similar proteins: A4IHR5, A6H7J1, A6NKL6, A6NL88, A7UKY7, A7YY54, B8ZZ34, C9J069, C9JLR9, E9Q1P8, O15209, O35615, O35779, P04198, P15066, P17535, P39881, P52909, Q01101, Q0PHV7, Q14526, Q14934, Q15742, Q32KV8, Q4VA45, Q52KG4, Q5TJE2, Q61976, Q63ZV0, Q6NUJ5, Q6P0F9, Q7T3H2, Q7Z5L9, Q7Z6J2, Q8C3Q5, Q8IX07, Q8R4T5, Q8TF61, Q8VCG9, Q96B18

Diamond homologs: A0A0A6YY25, B2RXH4, E0CZ16, E1B932, E7F6F9, F1LZ52, F1LZF0, F1MBP6, O88282, O93567, O95198, P10074, P17789, P42282, P42283, P42284, Q01295, Q1H9T6, Q24174, Q24206, Q3B7M1, Q52KG4, Q53G59, Q53HC5, Q5R633, Q5REP9, Q5U374, Q66HD2, Q6NRH0, Q7KQZ4, Q7KRI2, Q867Z4, Q86B87, Q8BGY4, Q8BZM0, Q8CA72, Q8IN81, Q8JZP3, Q8K0L9, Q8N143

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	77
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

670 predictions. Top by Δscore:

Variant	Effect	Δscore
19:58514306:CTCCC:C	acceptor_gain	1.0000
19:58514308:CCC:C	acceptor_gain	1.0000
19:58514309:CC:C	acceptor_gain	1.0000
19:58514309:CCC:C	acceptor_gain	1.0000
19:58514310:CC:C	acceptor_gain	1.0000
19:58514311:C:CC	acceptor_gain	1.0000
19:58516390:CTCA:C	donor_loss	1.0000
19:58516391:TCACC:T	donor_loss	1.0000
19:58516392:CACCC:C	donor_loss	1.0000
19:58516393:AC:A	donor_gain	1.0000
19:58516393:ACCC:A	donor_loss	1.0000
19:58516394:CC:C	donor_gain	1.0000
19:58517669:GCCAT:G	acceptor_gain	1.0000
19:58517670:CCAT:C	acceptor_gain	1.0000
19:58517670:CCATC:C	acceptor_gain	1.0000
19:58517671:CAT:C	acceptor_gain	1.0000
19:58517671:CATC:C	acceptor_gain	1.0000
19:58517672:ATCT:A	acceptor_loss	1.0000
19:58517673:TC:T	acceptor_loss	1.0000
19:58517674:C:CC	acceptor_gain	1.0000
19:58517675:T:A	acceptor_loss	1.0000
19:58519340:T:A	donor_gain	1.0000
19:58519373:T:TA	donor_gain	1.0000
19:58519454:T:TA	donor_gain	1.0000
19:58519455:C:A	donor_gain	1.0000
19:58514307:TCCC:T	acceptor_gain	0.9900
19:58514308:CCCC:C	acceptor_gain	0.9900
19:58514311:C:T	acceptor_gain	0.9900
19:58514314:C:CT	acceptor_gain	0.9900
19:58514315:G:T	acceptor_gain	0.9900

AlphaMissense

3257 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:58514159:G:C	H477Q	1.000
19:58514159:G:T	H477Q	1.000
19:58514161:G:C	H477D	1.000
19:58514161:G:T	H477N	1.000
19:58514169:A:G	L474P	1.000
19:58514186:G:C	F468L	1.000
19:58514186:G:T	F468L	1.000
19:58514187:A:G	F468S	1.000
19:58514188:A:G	F468L	1.000
19:58514188:A:T	F468I	1.000
19:58514200:A:G	C464R	1.000
19:58514207:G:C	C461W	1.000
19:58514209:A:G	C461R	1.000
19:58514213:G:C	F459L	1.000
19:58514213:G:T	F459L	1.000
19:58514215:A:G	F459L	1.000
19:58514231:G:C	H453Q	1.000
19:58514231:G:T	H453Q	1.000
19:58514233:G:C	H453D	1.000
19:58514243:G:C	H449Q	1.000
19:58514243:G:T	H449Q	1.000
19:58514245:G:C	H449D	1.000
19:58514245:G:T	H449N	1.000
19:58514253:A:G	L446P	1.000
19:58514270:G:C	F440L	1.000
19:58514270:G:T	F440L	1.000
19:58514271:A:G	F440S	1.000
19:58514272:A:G	F440L	1.000
19:58514282:G:C	C436W	1.000
19:58514283:C:T	C436Y	1.000

dbSNP variants (sampled 300 via entrez): RS1000009784 (19:58527218 C>G), RS1000017709 (19:58544053 C>T), RS1000064811 (19:58526962 G>C), RS1000091034 (19:58513695 C>G), RS1000121357 (19:58531596 T>C), RS1000130008 (19:58521018 C>G,T), RS1000136372 (19:58520816 G>A), RS1000243302 (19:58532554 CT>C,CTT), RS1000441607 (19:58513878 G>A,T), RS1000466163 (19:58532923 C>T), RS1000618511 (19:58543087 T>C,G), RS1000644493 (19:58521374 AAAAAAAAAAAG>A), RS1000857965 (19:58520518 G>A,T), RS1001006526 (19:58538188 C>T), RS1001022050 (19:58527142 T>C)

Disease associations

OMIM: gene MIM:621256 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	3
Arsenic	affects methylation, increases abundance, increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
TAK-243	decreases sumoylation	1
dicrotophos	increases expression	1
di-n-butylphosphoric acid	affects expression	1
clothianidin	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	decreases expression	1
Bucladesine	increases expression, affects cotreatment	1
Doxorubicin	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Hydrogen Peroxide	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Theophylline	affects cotreatment, decreases expression	1
Thiram	decreases expression	1
Medroxyprogesterone Acetate	affects cotreatment, increases expression	1
Cadmium Chloride	decreases 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_A8A8	SEES3-1V human ZBTB45, clone1	Embryonic stem cell	Male
CVCL_A8A9	SEES3-1V human ZBTB45, clone2	Embryonic stem cell	Male
CVCL_A8B0	SEES3-1V human ZBTB45, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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