ZBTB5

Summary

ZBTB5 (zinc finger and BTB domain containing 5, HGNC:23836) is a protein-coding gene on chromosome 9p13.2, encoding Zinc finger and BTB domain-containing protein 5 (O15062). May be involved in transcriptional regulation.

Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in nucleus.

Source: NCBI Gene 9925 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 74 total
• MANE Select transcript: NM_014872

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23836
Approved symbol	ZBTB5
Name	zinc finger and BTB domain containing 5
Location	9p13.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0354
Ensembl gene	ENSG00000168795
Ensembl biotype	protein_coding
OMIM	616590
Entrez	9925

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000307750, ENST00000860851, ENST00000933754, ENST00000933755, ENST00000933756, ENST00000953138, ENST00000953139

RefSeq mRNA: 1 — MANE Select: NM_014872 NM_014872

CCDS: CCDS6610

Canonical transcript exons

ENST00000307750 — 2 exons

Exon	Start	End
ENSE00001148633	37465215	37465450
ENSE00001149924	37438102	37442555

Expression profiles

Bgee: expression breadth ubiquitous, 263 present calls, max score 94.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.3230 / max 81.3311, expressed in 1686 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
100729	3.9275	1388
100728	1.9712	1161
100727	0.4243	202

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
esophagus squamous epithelium	UBERON:0006920	94.06	gold quality
epithelium of esophagus	UBERON:0001976	92.81	gold quality
squamous epithelium	UBERON:0006914	91.16	gold quality
secondary oocyte	CL:0000655	89.79	gold quality
cartilage tissue	UBERON:0002418	88.91	gold quality
upper leg skin	UBERON:0004262	88.91	gold quality
lower esophagus mucosa	UBERON:0035834	88.87	gold quality
tongue squamous epithelium	UBERON:0006919	88.60	silver quality
gingival epithelium	UBERON:0001949	88.53	gold quality
gingiva	UBERON:0001828	88.33	gold quality
endometrium epithelium	UBERON:0004811	86.99	gold quality
tibia	UBERON:0000979	86.93	gold quality
oral cavity	UBERON:0000167	86.50	gold quality
ganglionic eminence	UBERON:0004023	86.26	gold quality
pancreatic ductal cell	CL:0002079	86.18	gold quality
ventricular zone	UBERON:0003053	86.00	gold quality
paraflocculus	UBERON:0005351	85.83	silver quality
middle frontal gyrus	UBERON:0002702	85.74	silver quality
cortical plate	UBERON:0005343	85.66	gold quality
esophagus mucosa	UBERON:0002469	84.75	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.37	gold quality
ileal mucosa	UBERON:0000331	84.32	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.16	gold quality
frontal pole	UBERON:0002795	84.04	gold quality
oocyte	CL:0000023	84.03	gold quality
cervix squamous epithelium	UBERON:0006922	83.85	silver quality
cervix epithelium	UBERON:0004801	83.55	silver quality
epithelium of nasopharynx	UBERON:0001951	83.48	silver quality
embryo	UBERON:0000922	82.99	gold quality
cranial nerve II	UBERON:0000941	82.01	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.44

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
CDKN1A	Repression

JASPAR motifs

Motif	Name	Family
MA2509.1	ZBTB5	BTB-POZ

JASPAR matrix evidence (PMIDs): PMID:19491398

miRNA regulators (miRDB)

145 targeting ZBTB5, 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-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4282	99.99	75.36	6408
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-302E	99.96	70.74	2669
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-450B-5P	99.92	71.48	3175

Literature-anchored findings (GeneRIF, showing 2)

• ZBTB5 directly repressed transcription of cell cycle arrest gene p21 by binding to the proximal GC-box 5/6 elements and the two distal p53-responsive elements (bp -2323 to -2299; bp -1416 to -1392) (PMID:19491398)
• Cell fate decisions by c-Myc depend on ZBTB5 and p53. (PMID:33051058)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
mus_musculus	Zbtb5	ENSMUSG00000049657
rattus_norvegicus	Zbtb5	ENSRNOG00000012726
drosophila_melanogaster	klu	FBGN0013469
drosophila_melanogaster	CG4318	FBGN0030455
caenorhabditis_elegans	klu-2	WBGENE00022592

Paralogs (4): ZNF740 (ENSG00000139651), ZNF367 (ENSG00000165244), ZBTB43 (ENSG00000169155), ZBTB7A (ENSG00000178951)

Protein

Protein identifiers

Zinc finger and BTB domain-containing protein 5 — O15062 (reviewed: O15062)

All UniProt accessions (2): O15062, Q5T942

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in transcriptional regulation.

Subcellular location. Nucleus.

RefSeq proteins (1): NP_055687* (*=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: PF00651

UniProt features (28 total): cross-link 10, compositionally biased region 6, region of interest 5, modified residue 2, zinc finger region 2, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
9B9R	ELECTRON MICROSCOPY	3.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15062-F1	50.55	0.09

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 (12): 234, 371, 239, 322, 330, 404, 415, 541, 594, 597, 645, 658

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 176 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, TGGTGCT_MIR29A_MIR29B_MIR29C, CREL_01, WU_APOPTOSIS_BY_CDKN1A_VIA_TP53, TGCGCANK_UNKNOWN, MODULE_255, MODULE_317, BROWNE_HCMV_INFECTION_12HR_UP, GGGTGGRR_PAX4_03, NF1_Q6_01, TGCTGAY_UNKNOWN, chr9p13, HOSHIDA_LIVER_CANCER_LATE_RECURRENCE_DN, BENPORATH_ES_CORE_NINE_CORRELATED, EGR1_01

GO Biological Process (2): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of transcription by RNA polymerase II (GO:0006357)

GO Molecular Function (7): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), zinc ion binding (GO:0008270), 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
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
negative regulation of DNA-templated transcription	1
regulation of DNA-templated transcription	1
transcription cis-regulatory region 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
transition metal ion 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

672 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZBTB5	STPG4	Q8N801	419
ZBTB5	KBTBD3	Q8NAB2	415
ZBTB5	ZNF639	Q9UID6	415
ZBTB5	CCDC198	Q9NVL8	370
ZBTB5	SLC39A6	Q13433	367
ZBTB5	TMEM181	Q9P2C4	358
ZBTB5	MRPS31	Q92665	348
ZBTB5	RIMS3	Q9UJD0	338
ZBTB5	SLC25A1	P53007	334
ZBTB5	MANBAL	Q9NQG1	325
ZBTB5	EID2B	Q96D98	324
ZBTB5	SAAL1	Q96ER3	320
ZBTB5	ALG10B	Q5I7T1	310
ZBTB5	IQSEC1	Q6DN90	310
ZBTB5	RNF39	Q9H2S5	308

IntAct

60 interactions, top by confidence:

A	B	Type	Score
ZBTB5	DCX	psi-mi:“MI:0915”(physical association)	0.670
DCX	ZBTB5	psi-mi:“MI:0915”(physical association)	0.670
DCX	ZBTB5	psi-mi:“MI:0914”(association)	0.670
ZBTB7B	ZBTB5	psi-mi:“MI:0915”(physical association)	0.560
SWAP70	ZBTB5	psi-mi:“MI:0915”(physical association)	0.560
ZBTB5	SWAP70	psi-mi:“MI:0915”(physical association)	0.560
ZBTB5	BAG4	psi-mi:“MI:0915”(physical association)	0.560
ZBTB5	DCX	psi-mi:“MI:0915”(physical association)	0.560
ZBTB5	ZBTB7B	psi-mi:“MI:0915”(physical association)	0.560
ZBTB5	METTL5	psi-mi:“MI:0915”(physical association)	0.560
KLHL40	CBX4	psi-mi:“MI:0914”(association)	0.530
NPRL2	ZBTB5	psi-mi:“MI:0914”(association)	0.530
ZBTB7A	ZBTB5	psi-mi:“MI:0915”(physical association)	0.370
ZBTB5	JADE2	psi-mi:“MI:0915”(physical association)	0.370
PPARG	ZBTB5	psi-mi:“MI:0915”(physical association)	0.370
PTPN5	ZBTB5	psi-mi:“MI:0915”(physical association)	0.370
ZBTB5	CCDC85B	psi-mi:“MI:0915”(physical association)	0.370
ZBTB5	Tamalin	psi-mi:“MI:0915”(physical association)	0.370
Cep170	NEURL4	psi-mi:“MI:0914”(association)	0.350
Herc2	NEURL4	psi-mi:“MI:0914”(association)	0.350
Ankrd26	TBC1D31	psi-mi:“MI:0914”(association)	0.350
KIFC3	CC2D1B	psi-mi:“MI:0914”(association)	0.350
HERC2	ZBTB5	psi-mi:“MI:0914”(association)	0.350

BioGRID (81): ZBTB5 (Two-hybrid), SWAP70 (Two-hybrid), ZBTB7B (Two-hybrid), CCDC85B (Two-hybrid), ZBTB5 (Synthetic Lethality), ZBTB5 (Affinity Capture-MS), ZBTB5 (Affinity Capture-MS), ZBTB5 (Affinity Capture-MS), ZBTB5 (Affinity Capture-MS), ZBTB5 (Affinity Capture-MS), ZBTB5 (Affinity Capture-MS), ZBTB5 (Affinity Capture-MS), ZBTB5 (Affinity Capture-MS), ZBTB5 (Affinity Capture-MS), ZBTB5 (Affinity Capture-MS)

ESM2 similar proteins: A0A1D5NS60, A0JN76, A1L2U9, B1WAZ8, E9Q3T6, O15060, O15062, O35260, O93567, P41182, P41183, Q05516, Q0IH98, Q0IJ29, Q0P4X6, Q0V8G8, Q1L8W0, Q3B725, Q3B7N9, Q3SWU4, Q5EAC5, Q5EXX3, Q5R5N5, Q5SW75, Q5ZM39, Q6DDV0, Q6NRK3, Q6NRM8, Q6ZSB9, Q7TQG0, Q7TS63, Q7TSZ8, Q7ZWZ4, Q801P1, Q80X44, Q86VK4, Q8BKX7, Q8BXX2, Q8CII0, Q8NAP3

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

0 interactions.

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	72
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

497 predictions. Top by Δscore:

Variant	Effect	Δscore
9:37442551:TGATC:T	acceptor_gain	1.0000
9:37442552:GATC:G	acceptor_gain	1.0000
9:37442554:TC:T	acceptor_gain	1.0000
9:37442554:TCC:T	acceptor_loss	1.0000
9:37442555:CC:C	acceptor_gain	1.0000
9:37442556:C:CC	acceptor_gain	1.0000
9:37442556:C:CG	acceptor_loss	1.0000
9:37442557:T:C	acceptor_loss	1.0000
9:37442553:ATC:A	acceptor_gain	0.9900
9:37442559:C:CT	acceptor_gain	0.9900
9:37442560:A:T	acceptor_gain	0.9900
9:37442567:C:CT	acceptor_gain	0.9900
9:37463986:C:CT	acceptor_gain	0.9900
9:37463986:C:T	acceptor_gain	0.9900
9:37463987:A:C	acceptor_gain	0.9900
9:37463994:T:TC	acceptor_gain	0.9900
9:37465210:CTCA:C	donor_loss	0.9900
9:37465212:CAC:C	donor_loss	0.9900
9:37465213:A:AG	donor_loss	0.9900
9:37465214:C:T	donor_loss	0.9900
9:37442568:A:T	acceptor_gain	0.9800
9:37454796:C:CT	donor_gain	0.9800
9:37454797:T:TC	donor_gain	0.9800
9:37463994:T:C	acceptor_gain	0.9800
9:37442556:C:T	acceptor_gain	0.9700
9:37454794:TAC:T	donor_gain	0.9700
9:37463985:CCA:C	acceptor_gain	0.9700
9:37464111:C:T	acceptor_gain	0.9700
9:37463987:A:T	acceptor_gain	0.9600
9:37464111:C:CT	acceptor_gain	0.9600

AlphaMissense

4521 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:37440575:G:C	H659Q	1.000
9:37440575:G:T	H659Q	1.000
9:37440577:G:C	H659D	1.000
9:37440585:A:G	L656P	1.000
9:37440602:A:C	F650L	1.000
9:37440602:A:T	F650L	1.000
9:37440603:A:C	F650C	1.000
9:37440603:A:G	F650S	1.000
9:37440604:A:G	F650L	1.000
9:37440608:C:A	K648N	1.000
9:37440608:C:G	K648N	1.000
9:37440612:C:A	G647V	1.000
9:37440615:C:G	C646S	1.000
9:37440616:A:G	C646R	1.000
9:37440616:A:T	C646S	1.000
9:37440623:G:C	C643W	1.000
9:37440625:A:G	C643R	1.000
9:37440631:A:C	Y641D	1.000
9:37440647:G:C	H635Q	1.000
9:37440647:G:T	H635Q	1.000
9:37440649:G:C	H635D	1.000
9:37440654:C:G	R633P	1.000
9:37440655:G:T	R633S	1.000
9:37440659:G:C	H631Q	1.000
9:37440659:G:T	H631Q	1.000
9:37440660:T:C	H631R	1.000
9:37440661:G:C	H631D	1.000
9:37440686:A:C	F622L	1.000
9:37440686:A:T	F622L	1.000
9:37440687:A:G	F622S	1.000

dbSNP variants (sampled 300 via entrez): RS1000117495 (9:37465104 G>A), RS1000183440 (9:37439548 T>C), RS1000253941 (9:37447482 G>A,T), RS1000295192 (9:37454352 T>C), RS1000370890 (9:37447013 T>C), RS1000378182 (9:37453417 G>A), RS1000433706 (9:37454063 C>T), RS1000435179 (9:37453708 A>C), RS1000607074 (9:37459980 G>A,C), RS1000661618 (9:37465763 T>A), RS1000722403 (9:37447348 A>C), RS1000840431 (9:37459267 T>C), RS1001120373 (9:37465014 C>T), RS1001187385 (9:37441324 A>G), RS1001384071 (9:37455128 C>T)

Disease associations

OMIM: gene MIM:616590 | 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
GCST008103_35	Bipolar disorder	8.000000e-08
GCST011494_45	Daytime nap	1.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007828	daytime rest measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation, affects methylation, decreases expression	3
Estradiol	affects expression, affects binding, increases expression	2
Valproic Acid	affects expression, increases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	increases expression	1
TAK-243	increases sumoylation	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases methylation	1
dimethylselenide	decreases expression, increases expression, increases oxidation	1
sodium arsenite	decreases expression, increases abundance	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	decreases methylation	1
cupric chloride	decreases expression	1
cupric oxide	increases expression	1
ICG 001	decreases expression	1
abrine	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Air Pollutants, Occupational	increases expression	1
Arsenic	decreases expression, increases abundance	1
Cisplatin	increases expression	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Methapyrilene	increases methylation	1
Methyl Methanesulfonate	increases expression	1
Nickel	increases expression	1
Ozone	affects expression, increases abundance	1
Phthalic Acids	increases methylation	1

Clinical trials (associated diseases)

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