ZBTB8B

Summary

ZBTB8B (zinc finger and BTB domain containing 8B, HGNC:37057) is a protein-coding gene on chromosome 1p35.1, encoding Zinc finger and BTB domain-containing protein 8B (Q8NAP8). May be involved in transcriptional regulation.

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in cytosol and nucleoplasm.

Source: NCBI Gene 728116 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 70 total
• MANE Select transcript: NM_001145720

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:37057
Approved symbol	ZBTB8B
Name	zinc finger and BTB domain containing 8B
Location	1p35.1
Locus type	gene with protein product
Status	Approved
Aliases	RP1-27O5.1, DKFZp547H154, ZNF916B
Ensembl gene	ENSG00000273274
Ensembl biotype	protein_coding
Entrez	728116

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000609129, ENST00000930949, ENST00000930950, ENST00000930951

RefSeq mRNA: 1 — MANE Select: NM_001145720 NM_001145720

CCDS: CCDS44104

Canonical transcript exons

ENST00000609129 — 4 exons

Exon	Start	End
ENSE00002172003	32465072	32465105
ENSE00003564881	32470584	32471615
ENSE00003625423	32480891	32481069
ENSE00003702530	32485101	32496686

Expression profiles

Bgee: expression breadth broad, 46 present calls, max score 76.54.

FANTOM5 (CAGE): breadth broad, TPM avg 0.5457 / max 54.2742, expressed in 290 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
1990	0.5457	290

Top tissues by expression

224 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	76.54	gold quality
buccal mucosa cell	CL:0002336	68.83	gold quality
ventricular zone	UBERON:0003053	67.42	gold quality
ganglionic eminence	UBERON:0004023	65.22	gold quality
cortical plate	UBERON:0005343	65.21	gold quality
hypothalamus	UBERON:0001898	55.47	gold quality
skin of hip	UBERON:0001554	55.33	silver quality
amygdala	UBERON:0001876	54.05	gold quality
colonic epithelium	UBERON:0000397	53.04	gold quality
prefrontal cortex	UBERON:0000451	52.39	gold quality
anterior cingulate cortex	UBERON:0009835	51.81	gold quality
bone marrow cell	CL:0002092	49.58	gold quality
sural nerve	UBERON:0015488	49.54	gold quality
substantia nigra	UBERON:0002038	49.18	gold quality
neocortex	UBERON:0001950	48.99	gold quality
stromal cell of endometrium	CL:0002255	48.75	gold quality
Brodmann (1909) area 9	UBERON:0013540	48.32	gold quality
temporal lobe	UBERON:0001871	48.14	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	48.08	gold quality
midbrain	UBERON:0001891	48.04	gold quality
frontal cortex	UBERON:0001870	47.93	silver quality
pituitary gland	UBERON:0000007	47.80	gold quality
adenohypophysis	UBERON:0002196	47.79	gold quality
cerebral cortex	UBERON:0000956	47.70	gold quality
islet of Langerhans	UBERON:0000006	47.15	silver quality
forebrain	UBERON:0001890	46.92	gold quality
endometrium	UBERON:0001295	46.75	gold quality
brain	UBERON:0000955	46.66	gold quality
Ammon’s horn	UBERON:0001954	46.56	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	46.21	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.11
E-GEOD-86618	no	41.19
E-MTAB-6678	no	3.68

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
CDKN1A	Unknown
NOTCH1

JASPAR motifs

Motif	Name	Family
MA2579.1	ZBTB8B	Other factors with up to three adjacent zinc fingers

JASPAR matrix evidence (PMIDs): PMID:39605530

miRNA regulators (miRDB)

97 targeting ZBTB8B, 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-4795-3P	100.00	74.62	4024
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-511-3P	99.99	68.85	1467
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-23B-5P	99.98	66.07	587
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-23A-5P	99.94	65.39	468
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-374A-5P	99.90	71.34	2923

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Zbtb8b	ENSMUSG00000048485
rattus_norvegicus	Zbtb8b	ENSRNOG00000026898

Paralogs (5): ZBTB8A (ENSG00000160062), ZBTB10 (ENSG00000205189), ZBTB9 (ENSG00000213588), ZBTB22 (ENSG00000236104), C17orf113 (ENSG00000267221)

Protein

Protein identifiers

Zinc finger and BTB domain-containing protein 8B — Q8NAP8 (reviewed: Q8NAP8)

All UniProt accessions (1): Q8NAP8

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in transcriptional regulation.

Subcellular location. Nucleus.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8NAP8-1	1	yes
Q8NAP8-2	2

RefSeq proteins (1): NP_001139192* (*=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, PF13465

UniProt features (10 total): zinc finger region 2, region of interest 2, compositionally biased region 2, chain 1, domain 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NAP8-F1	58.37	0.07

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 52 (showing top): SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, chr1p35, QI_HYPOXIA, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, LMTK3_TARGET_GENES, ZBTB12_TARGET_GENES, ZNF22_TARGET_GENES, ZSCAN21_TARGET_GENES, MIR4795_3P, MIR4500, MIR4668_3P, LET_7B_5P, LET_7A_5P_LET_7C_5P_LET_7E_5P, LET_7I_5P

GO Biological Process (1): regulation of transcription by RNA polymerase II (GO:0006357)

GO Molecular Function (5): DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA binding (GO:0003677), zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (4): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
chromatin	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
DNA-binding transcription factor activity	1
regulation of transcription by RNA polymerase II	1
nucleic acid binding	1
transition metal ion binding	1
binding	1
cation binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1

Protein interactions and networks

STRING

416 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZBTB8B	GRIFIN	A4D1Z8	527
ZBTB8B	MOCS2	O96007	484
ZBTB8B	MBOAT1	Q6ZNC8	475
ZBTB8B	DHX32	Q7L7V1	470
ZBTB8B	TMEM40	Q8WWA1	434
ZBTB8B	MINDY4B	A8MYZ0	432
ZBTB8B	GPRC5B	Q9NZH0	419
ZBTB8B	NPL	Q9BXD5	418
ZBTB8B	ACSF2	Q96CM8	417
ZBTB8B	TSPAN11	A1L157	404
ZBTB8B	HMGN3	Q15651	404
ZBTB8B	MAB21L1	Q13394	348
ZBTB8B	THAP4	Q8WY91	340
ZBTB8B	SLC22A14	Q9Y267	325
ZBTB8B	SLC35D1	Q9NTN3	323

IntAct

29 interactions, top by confidence:

A	B	Type	Score
MATCAP1	ZBTB8B	psi-mi:“MI:0915”(physical association)	0.560
SGTA	ZBTB8B	psi-mi:“MI:0915”(physical association)	0.560
CDC7	ZBTB8B	psi-mi:“MI:0915”(physical association)	0.560
ZBTB8B	LMO3	psi-mi:“MI:0915”(physical association)	0.560
ZBTB8B	NTAQ1	psi-mi:“MI:0915”(physical association)	0.560
LMO1	ZBTB8B	psi-mi:“MI:0915”(physical association)	0.560
ZBTB8B	SPATC1L	psi-mi:“MI:0915”(physical association)	0.560
ZBTB8B	MORF4L1	psi-mi:“MI:0915”(physical association)	0.560
ZBTB8B	UBQLN1	psi-mi:“MI:0915”(physical association)	0.560
BCAS2	INPPL1	psi-mi:“MI:0914”(association)	0.350
MATCAP1	ZBTB8B	psi-mi:“MI:0915”(physical association)	0.000
SGTA	ZBTB8B	psi-mi:“MI:0915”(physical association)	0.000
CDC7	ZBTB8B	psi-mi:“MI:0915”(physical association)	0.000
LMO3	ZBTB8B	psi-mi:“MI:0915”(physical association)	0.000
NTAQ1	ZBTB8B	psi-mi:“MI:0915”(physical association)	0.000
LMO1	ZBTB8B	psi-mi:“MI:0915”(physical association)	0.000
SPATC1L	ZBTB8B	psi-mi:“MI:0915”(physical association)	0.000
MORF4L1	ZBTB8B	psi-mi:“MI:0915”(physical association)	0.000
UBQLN1	ZBTB8B	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (17): ZBTB8B (Two-hybrid), ZBTB8B (Two-hybrid), ZBTB8B (Two-hybrid), ZBTB8B (Two-hybrid), ZBTB8B (Two-hybrid), ZBTB8B (Two-hybrid), ZBTB8B (Two-hybrid), ZBTB8B (Two-hybrid), ZBTB8B (Two-hybrid), ZBTB8B (Affinity Capture-MS), ZBTB8B (Positive Genetic), ZBTB8B (Co-fractionation), ZBTB8B (Co-fractionation), ZBTB8B (Co-fractionation), ZBTB8B (Co-fractionation)

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: A0JN76, A1L2U9, A1YEX3, A1YPR0, A2AAX3, B1WAZ8, B1WBS3, B1WBU4, B2RXF5, D3ZA50, O14867, O15062, O15156, O15209, O43167, O43298, O43829, O88282, O88939, O93567, O95365, P24278, P41182, P41183, P52739, P97302, P97303, Q08376, Q0IH98, Q0IJ29, Q0P4X6, Q0VCJ6, Q13105, Q14526, Q1H9T6, Q1L8W0, Q2T9Z7, Q3B725, Q3B7N9, Q3SWU4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	66
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1086 predictions. Top by Δscore:

Variant	Effect	Δscore
1:32465103:AAG:A	donor_loss	1.0000
1:32481066:GAGT:G	donor_gain	1.0000
1:32481067:AGTGT:A	donor_loss	1.0000
1:32481068:GT:G	donor_gain	1.0000
1:32481069:TG:T	donor_loss	1.0000
1:32481070:G:C	donor_loss	1.0000
1:32481070:G:GG	donor_gain	1.0000
1:32481071:T:TC	donor_loss	1.0000
1:32485328:GTCGG:G	donor_gain	1.0000
1:32485411:T:G	donor_gain	1.0000
1:32465104:AGGTG:A	donor_loss	0.9900
1:32465105:GGT:G	donor_loss	0.9900
1:32480944:A:AG	acceptor_gain	0.9900
1:32480945:C:G	acceptor_gain	0.9900
1:32481065:TGAGT:T	donor_gain	0.9900
1:32481066:GAGTG:G	donor_gain	0.9900
1:32481067:AGT:A	donor_gain	0.9900
1:32481068:GTG:G	donor_gain	0.9900
1:32481069:TGT:T	donor_gain	0.9900
1:32481072:A:AG	donor_loss	0.9900
1:32485339:A:T	donor_gain	0.9900
1:32485411:T:TG	donor_gain	0.9900
1:32465101:GGAAG:G	donor_gain	0.9800
1:32465102:GAAGG:G	donor_gain	0.9800
1:32465103:A:T	donor_gain	0.9800
1:32466972:G:GG	donor_gain	0.9800
1:32480885:CCCCA:C	acceptor_loss	0.9800
1:32480886:CCCA:C	acceptor_loss	0.9800
1:32480887:CCA:C	acceptor_loss	0.9800
1:32480888:CA:C	acceptor_loss	0.9800

AlphaMissense

3281 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:32480926:T:C	C343R	1.000
1:32480935:T:C	C346R	1.000
1:32480937:C:G	C346W	1.000
1:32481010:T:C	C371R	1.000
1:32481031:T:C	F378L	1.000
1:32481032:T:C	F378S	1.000
1:32481033:C:A	F378L	1.000
1:32481033:C:G	F378L	1.000
1:32485128:T:C	C400R	1.000
1:32480926:T:A	C343S	0.999
1:32480927:G:C	C343S	0.999
1:32480928:T:G	C343W	0.999
1:32480935:T:A	C346S	0.999
1:32480936:G:A	C346Y	0.999
1:32480936:G:C	C346S	0.999
1:32480966:T:C	L356P	0.999
1:32480972:G:C	R358P	0.999
1:32480974:C:G	H359D	0.999
1:32480976:C:A	H359Q	0.999
1:32480976:C:G	H359Q	0.999
1:32480980:C:A	R361S	0.999
1:32480981:G:C	R361P	0.999
1:32480986:C:G	H363D	0.999
1:32480988:C:A	H363Q	0.999
1:32480988:C:G	H363Q	0.999
1:32481010:T:A	C371S	0.999
1:32481011:G:A	C371Y	0.999
1:32481011:G:C	C371S	0.999
1:32481012:T:G	C371W	0.999
1:32481019:T:C	C374R	0.999

dbSNP variants (sampled 300 via entrez): RS1000051325 (1:32467745 A>G), RS1000105842 (1:32496481 G>C), RS1000151458 (1:32467328 C>T), RS1000279917 (1:32489405 G>A), RS1000329824 (1:32482377 A>G), RS1000534010 (1:32490771 A>T), RS1000648552 (1:32490941 G>A), RS1000660689 (1:32486484 G>A), RS1000687857 (1:32480279 G>A), RS1000717889 (1:32483558 T>C), RS1000794463 (1:32476898 C>G), RS1000846909 (1:32476501 A>C), RS1001065906 (1:32483852 C>T), RS1001084279 (1:32463772 A>G), RS1001104916 (1:32466023 C>A,T)

Disease associations

OMIM: gene `` | 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

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
propionaldehyde	increases expression	1
butyraldehyde	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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