ZBTB8A

Summary

ZBTB8A (zinc finger and BTB domain containing 8A, HGNC:24172) is a protein-coding gene on chromosome 1p35.1, encoding Zinc finger and BTB domain-containing protein 8A (Q96BR9). May be involved in transcriptional regulation.

Enables several functions, including DNA-binding transcription repressor activity, RNA polymerase II-specific; RNA polymerase II-specific DNA-binding transcription factor binding activity; and transcription coactivator binding activity. Involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus.

Source: NCBI Gene 653121 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 50 total
• MANE Select transcript: NM_001040441

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24172
Approved symbol	ZBTB8A
Name	zinc finger and BTB domain containing 8A
Location	1p35.1
Locus type	gene with protein product
Status	Approved
Aliases	BOZF1, FLJ90065, ZNF916A
Ensembl gene	ENSG00000160062
Ensembl biotype	protein_coding
OMIM	618742
Entrez	653121

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 20 protein_coding

ENST00000316459, ENST00000373510, ENST00000854540, ENST00000854541, ENST00000854542, ENST00000854543, ENST00000926868, ENST00000926869, ENST00000952738, ENST00000952739, ENST00000952740, ENST00000952741, ENST00000952742, ENST00000952743, ENST00000952744, ENST00000952745, ENST00000952746, ENST00000952747, ENST00000952748, ENST00000952749

RefSeq mRNA: 2 — MANE Select: NM_001040441 NM_001040441, NM_001291496

CCDS: CCDS30664, CCDS76133

Canonical transcript exons

ENST00000373510 — 5 exons

Exon	Start	End
ENSE00001846132	32539427	32539572
ENSE00001854787	32600087	32605941
ENSE00003520329	32553459	32553540
ENSE00003561058	32592931	32593754
ENSE00003563561	32595054	32595223

Expression profiles

Bgee: expression breadth ubiquitous, 129 present calls, max score 86.20.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.0624 / max 90.1110, expressed in 1545 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
1994	5.7166	1505
1992	1.5558	821
1993	0.7900	453

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.20	gold quality
cortical plate	UBERON:0005343	85.36	gold quality
ganglionic eminence	UBERON:0004023	83.45	gold quality
calcaneal tendon	UBERON:0003701	83.17	gold quality
endometrium	UBERON:0001295	82.60	gold quality
ventricular zone	UBERON:0003053	79.61	gold quality
stromal cell of endometrium	CL:0002255	78.59	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.29	gold quality
colonic epithelium	UBERON:0000397	77.07	gold quality
smooth muscle tissue	UBERON:0001135	76.41	gold quality
islet of Langerhans	UBERON:0000006	75.37	gold quality
muscle tissue	UBERON:0002385	74.29	gold quality
myometrium	UBERON:0001296	73.72	gold quality
skeletal muscle tissue	UBERON:0001134	73.67	gold quality
body of uterus	UBERON:0009853	73.18	gold quality
urinary bladder	UBERON:0001255	72.98	gold quality
hindlimb stylopod muscle	UBERON:0004252	72.88	gold quality
right lung	UBERON:0002167	72.68	gold quality
popliteal artery	UBERON:0002250	72.53	gold quality
tibial artery	UBERON:0007610	72.51	gold quality
descending thoracic aorta	UBERON:0002345	71.87	gold quality
uterine cervix	UBERON:0000002	71.71	gold quality
rectum	UBERON:0001052	71.43	gold quality
endocervix	UBERON:0000458	71.28	gold quality
corpus callosum	UBERON:0002336	71.19	gold quality
adrenal tissue	UBERON:0018303	71.16	gold quality
subcutaneous adipose tissue	UBERON:0002190	71.15	gold quality
pancreas	UBERON:0001264	70.98	gold quality
muscle of leg	UBERON:0001383	70.97	gold quality
left coronary artery	UBERON:0001626	70.92	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.90
E-GEOD-99795	no	40.14

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
CDKN1A	Unknown

JASPAR motifs

Motif	Name	Family
MA2578.1	ZBTB8A	Other factors with up to three adjacent zinc fingers

JASPAR matrix evidence (PMIDs): PMID:39605530

Literature-anchored findings (GeneRIF, showing 1)

• Data indicate BOZF1 represses transcription of CDKN1A by inhibition of p53 acetylation and Sp1 binding. (PMID:23329847)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	zbtb8a	ENSDARG00000059226
mus_musculus	Zbtb8a	ENSMUSG00000028807
rattus_norvegicus	Zbtb8a	ENSRNOG00000008300

Paralogs (5): ZBTB10 (ENSG00000205189), ZBTB9 (ENSG00000213588), ZBTB22 (ENSG00000236104), C17orf113 (ENSG00000267221), ZBTB8B (ENSG00000273274)

Protein

Protein identifiers

Zinc finger and BTB domain-containing protein 8A — Q96BR9 (reviewed: Q96BR9)

Alternative names: BTB/POZ and zinc-finger domain-containing factor, BTB/POZ and zinc-finger domains factor on chromosome 1

All UniProt accessions (2): Q96BR9, D3DPQ1

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in transcriptional regulation.

Subcellular location. Nucleus.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96BR9-1	1	yes
Q96BR9-2	2

RefSeq proteins (2): NP_001035531, NP_001278425 (=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 (19 total): cross-link 5, compositionally biased region 4, modified residue 2, zinc finger region 2, chain 1, domain 1, splice variant 1, sequence variant 1, sequence conflict 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96BR9-F1	61.58	0.21

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 (7): 167, 178, 182, 191, 199, 437, 161

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 145 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, AHRARNT_01, RRAGTTGT_UNKNOWN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, RACCACAR_AML_Q6, AATGGAG_MIR136, FOSTER_TOLERANT_MACROPHAGE_UP, PYEON_CANCER_HEAD_AND_NECK_VS_CERVICAL_UP, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, JAATINEN_HEMATOPOIETIC_STEM_CELL_UP, AML1_01, AGTCAGC_MIR345, CUI_TCF21_TARGETS_2_DN, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN

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 (10): transcription cis-regulatory region binding (GO:0000976), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), transcription coactivator binding (GO:0001223), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), zinc ion binding (GO:0008270), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), DNA binding (GO:0003677), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (1): 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	3
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
negative regulation of DNA-templated transcription	1
regulation of DNA-templated transcription	1
transcription regulatory region nucleic acid binding	1
sequence-specific double-stranded DNA binding	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
transcription coregulator 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
DNA-binding transcription factor binding	1
nucleic acid binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

464 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZBTB8A	KAT5	Q92993	502
ZBTB8A	MID1IP1	Q9NPA3	479
ZBTB8A	CCDC28B	Q9BUN5	400
ZBTB8A	ZNF524	Q96C55	375
ZBTB8A	ZNF513	Q8N8E2	373
ZBTB8A	ZFHX2	Q9C0A1	372
ZBTB8A	ZNF785	A8K8V0	348
ZBTB8A	RNF186	Q9NXI6	343
ZBTB8A	NAIP	Q13075	338
ZBTB8A	RNF39	Q9H2S5	325
ZBTB8A	TRIM48	Q8IWZ4	325
ZBTB8A	BTBD8	Q5XKL5	323
ZBTB8A	TMEM54	Q969K7	321
ZBTB8A	SLC22A14	Q9Y267	319
ZBTB8A	RASL10A	Q92737	313

IntAct

338 interactions, top by confidence:

A	B	Type	Score
ZBTB8A	ZBTB48	psi-mi:“MI:0915”(physical association)	0.780
ZBTB8A	ZNF276	psi-mi:“MI:0915”(physical association)	0.780
AP1M1	ZBTB8A	psi-mi:“MI:0915”(physical association)	0.780
ZBTB48	ZBTB8A	psi-mi:“MI:0915”(physical association)	0.780
ZBTB8A	AP1M1	psi-mi:“MI:0915”(physical association)	0.780
ZNF276	ZBTB8A	psi-mi:“MI:0915”(physical association)	0.780
SDCBP	ZBTB8A	psi-mi:“MI:0915”(physical association)	0.720
ZBTB8A	ZBTB24	psi-mi:“MI:0915”(physical association)	0.720
YES1	ZBTB8A	psi-mi:“MI:0915”(physical association)	0.720
DDX6	ZBTB8A	psi-mi:“MI:0915”(physical association)	0.720
RPL9	ZBTB8A	psi-mi:“MI:0915”(physical association)	0.720
RAD23A	ZBTB8A	psi-mi:“MI:0915”(physical association)	0.720
ZBTB8A	BYSL	psi-mi:“MI:0915”(physical association)	0.720
ZBTB49	ZBTB8A	psi-mi:“MI:0915”(physical association)	0.720
ZBTB8A	FAM161A	psi-mi:“MI:0915”(physical association)	0.720
ZBTB8A	CDKL3	psi-mi:“MI:0915”(physical association)	0.720
ZBTB8A	EIF1AD	psi-mi:“MI:0915”(physical association)	0.720
ZBTB8A	ZNF417	psi-mi:“MI:0915”(physical association)	0.720
ZBTB8A	ZNF587	psi-mi:“MI:0915”(physical association)	0.720
ARMCX1	ZBTB8A	psi-mi:“MI:0915”(physical association)	0.720
ZBTB8A	RPL9	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (137): ZBTB8A (Two-hybrid), ZBTB8A (Two-hybrid), ZBTB8A (Two-hybrid), ZBTB8A (Two-hybrid), ZBTB8A (Two-hybrid), ZBTB8A (Two-hybrid), ZBTB8A (Two-hybrid), ZBTB8A (Two-hybrid), ZBTB8A (Two-hybrid), ZBTB8A (Two-hybrid), ZBTB8A (Two-hybrid), ZBTB8A (Two-hybrid), ZBTB8A (Two-hybrid), ZBTB8A (Two-hybrid), ZBTB8A (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: A0A1V6NWD3, A0A2H1A5W4, A1L2U9, B0XS89, B1WAZ8, B1WBU4, P53243, P56270, P56670, P56671, P78871, Q00453, Q0IH98, Q0VCJ6, Q12132, Q4WXK4, Q6P882, Q96BR9, Q99PV8, Q9C0K0, Q9CWH1, Q9H165, Q9QYE3, Q9UPG8, Q9US36, Q9UTS5, A0JN76, A1YEX3, A1YPR0, A2AAX3, B1WBS3, B2RXF5, D3ZA50, O14867, O15062, O15156, O15209, O43167, O43298, O43829

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
LNX1	“down-regulates quantity by destabilization”	ZBTB8A	polyubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	44
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1447 predictions. Top by Δscore:

Variant	Effect	Δscore
1:32539570:GCG:G	donor_gain	1.0000
1:32539571:CGGTA:C	donor_loss	1.0000
1:32539572:GGTA:G	donor_loss	1.0000
1:32539573:G:GG	donor_gain	1.0000
1:32539573:G:T	donor_loss	1.0000
1:32539574:T:G	donor_loss	1.0000
1:32553453:CTACA:C	acceptor_loss	1.0000
1:32553454:TACAG:T	acceptor_loss	1.0000
1:32553455:ACAGG:A	acceptor_loss	1.0000
1:32553456:CA:C	acceptor_loss	1.0000
1:32553456:CAGGA:C	acceptor_loss	1.0000
1:32553457:A:AC	acceptor_loss	1.0000
1:32553457:A:AG	acceptor_gain	1.0000
1:32553457:AGGAC:A	acceptor_loss	1.0000
1:32553458:G:GC	acceptor_loss	1.0000
1:32553458:G:GG	acceptor_gain	1.0000
1:32553458:GGAC:G	acceptor_gain	1.0000
1:32553458:GGACA:G	acceptor_gain	1.0000
1:32593714:G:GG	donor_gain	1.0000
1:32593720:TC:T	donor_gain	1.0000
1:32593766:GAGCA:G	donor_gain	1.0000
1:32595203:C:G	donor_gain	1.0000
1:32595219:GAACA:G	donor_gain	1.0000
1:32595224:G:GG	donor_gain	1.0000
1:32539568:CCGCG:C	donor_gain	0.9900
1:32539569:CGCG:C	donor_gain	0.9900
1:32539570:GCGG:G	donor_gain	0.9900
1:32539571:CG:C	donor_gain	0.9900
1:32539572:GG:G	donor_gain	0.9900
1:32553457:AG:A	acceptor_gain	0.9900

AlphaMissense

2941 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:32593271:T:C	C114R	1.000
1:32595080:T:C	C284R	1.000
1:32595089:T:C	C287R	1.000
1:32595090:G:A	C287Y	1.000
1:32595091:C:G	C287W	1.000
1:32595120:T:C	L297P	1.000
1:32595125:C:A	R299S	1.000
1:32595126:G:C	R299P	1.000
1:32595128:C:G	H300D	1.000
1:32595130:C:A	H300Q	1.000
1:32595130:C:G	H300Q	1.000
1:32595140:C:G	H304D	1.000
1:32595142:T:A	H304Q	1.000
1:32595142:T:G	H304Q	1.000
1:32595164:T:C	C312R	1.000
1:32595166:T:G	C312W	1.000
1:32595173:T:C	C315R	1.000
1:32595185:T:C	F319L	1.000
1:32595186:T:C	F319S	1.000
1:32595187:T:A	F319L	1.000
1:32595187:T:G	F319L	1.000
1:32595204:T:C	L325P	1.000
1:32595212:C:G	H328D	1.000
1:32595214:T:A	H328Q	1.000
1:32595214:T:G	H328Q	1.000
1:32600111:T:C	C340R	1.000
1:32600113:C:G	C340W	1.000
1:32592972:T:C	L14P	0.999
1:32593233:C:A	A101D	0.999
1:32593236:C:A	A102D	0.999

dbSNP variants (sampled 300 via entrez): RS1000012179 (1:32567960 T>A), RS1000051793 (1:32553674 G>T), RS1000084799 (1:32545010 A>G), RS1000148468 (1:32580891 G>T), RS1000149330 (1:32540164 A>G), RS1000195855 (1:32581006 T>C), RS1000313684 (1:32547204 G>A), RS1000416505 (1:32569111 T>C), RS1000501148 (1:32601270 T>C,G), RS1000563842 (1:32578392 T>C), RS1000725281 (1:32563923 G>A,T), RS1000806448 (1:32570342 C>T), RS1000807311 (1:32540204 A>G), RS1000811145 (1:32570664 C>T), RS1000815002 (1:32583355 T>C)

Disease associations

OMIM: gene MIM:618742 | 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

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	5
Cyclosporine	increases expression	3
Arsenic	affects methylation, increases methylation	2
aristolochic acid I	decreases expression	1
TAK-243	increases sumoylation	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	increases expression	1
CGP 52608	increases reaction, affects binding	1
ICG 001	increases expression	1
bisphenol S	affects cotreatment, decreases methylation	1
(+)-JQ1 compound	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Air Pollutants	increases abundance, decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Methyl Methanesulfonate	increases expression	1
Tretinoin	decreases expression	1
Urethane	decreases expression	1
Oxyquinoline	decreases expression	1
Aflatoxin B1	increases methylation	1
Asbestos, Crocidolite	affects methylation	1
Antirheumatic Agents	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_HD02	HEK293 eGFP-ZBTB8A	Transformed cell line	Female

Clinical trials (associated diseases)

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