ZBTB6

Summary

ZBTB6 (zinc finger and BTB domain containing 6, HGNC:16764) is a protein-coding gene on chromosome 9q33.2, encoding Zinc finger and BTB domain-containing protein 6 (Q15916). May be involved in transcriptional regulation.

Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific 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. Located in mitochondrion and nucleoplasm.

Source: NCBI Gene 10773 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 35 total
• MANE Select transcript: NM_006626

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16764
Approved symbol	ZBTB6
Name	zinc finger and BTB domain containing 6
Location	9q33.2
Locus type	gene with protein product
Status	Approved
Aliases	ZID
Ensembl gene	ENSG00000186130
Ensembl biotype	protein_coding
OMIM	605976
Entrez	10773

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000373659, ENST00000899189, ENST00000899190, ENST00000915652

RefSeq mRNA: 1 — MANE Select: NM_006626 NM_006626

CCDS: CCDS6846

Canonical transcript exons

ENST00000373659 — 2 exons

Exon	Start	End
ENSE00001377956	122913251	122913323
ENSE00001461163	122908056	122912081

Expression profiles

Bgee: expression breadth ubiquitous, 182 present calls, max score 88.34.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.0690 / max 227.7270, expressed in 1715 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
102399	12.0690	1715

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	88.34	gold quality
calcaneal tendon	UBERON:0003701	86.66	gold quality
ganglionic eminence	UBERON:0004023	81.59	gold quality
islet of Langerhans	UBERON:0000006	80.66	gold quality
ventricular zone	UBERON:0003053	78.27	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.75	silver quality
stromal cell of endometrium	CL:0002255	77.72	gold quality
adrenal tissue	UBERON:0018303	77.57	gold quality
muscle of leg	UBERON:0001383	76.63	gold quality
gastrocnemius	UBERON:0001388	76.23	gold quality
rectum	UBERON:0001052	76.07	gold quality
hindlimb stylopod muscle	UBERON:0004252	75.42	gold quality
granulocyte	CL:0000094	75.03	gold quality
lymph node	UBERON:0000029	75.03	gold quality
leukocyte	CL:0000738	74.76	gold quality
monocyte	CL:0000576	74.56	gold quality
descending thoracic aorta	UBERON:0002345	74.16	gold quality
mononuclear cell	CL:0000842	74.11	gold quality
gall bladder	UBERON:0002110	73.93	gold quality
pancreas	UBERON:0001264	73.43	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	73.35	gold quality
right adrenal gland cortex	UBERON:0035827	73.23	gold quality
smooth muscle tissue	UBERON:0001135	73.04	gold quality
vermiform appendix	UBERON:0001154	72.95	gold quality
right adrenal gland	UBERON:0001233	72.62	gold quality
left adrenal gland	UBERON:0001234	72.60	gold quality
lower esophagus mucosa	UBERON:0035834	72.25	gold quality
prefrontal cortex	UBERON:0000451	72.21	gold quality
body of pancreas	UBERON:0001150	72.20	gold quality
small intestine Peyer’s patch	UBERON:0003454	72.03	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-6058	no	134.36
E-ANND-3	no	2.30

Regulation

Is transcription factor: yes

JASPAR motifs

Motif	Name	Family
MA1581.1	ZBTB6	More than 3 adjacent zinc fingers
MA1581.2	ZBTB6	More than 3 adjacent zinc fingers

JASPAR matrix evidence (PMIDs): PMID:16381825

miRNA regulators (miRDB)

178 targeting ZBTB6, 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-5692A	100.00	74.40	6850
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AN	99.97	70.91	2817

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Zbtb6	ENSMUSG00000066798
rattus_norvegicus	Zbtb6	ENSRNOG00000009340

Paralogs (28): ZNF280C (ENSG00000056277), ZBTB25 (ENSG00000089775), PRDM13 (ENSG00000112238), BCL6 (ENSG00000113916), FEZF1 (ENSG00000128610), ZBTB46 (ENSG00000130584), PRDM12 (ENSG00000130711), ZNF280D (ENSG00000137871), NACC2 (ENSG00000148411), FEZF2 (ENSG00000153266), ZBTB7B (ENSG00000160685), NACC1 (ENSG00000160877), BCL6B (ENSG00000161940), GFI1 (ENSG00000162676), GFI1B (ENSG00000165702), ZBTB49 (ENSG00000168826), ZNF280A (ENSG00000169548), ZNF581 (ENSG00000171425), ZNF524 (ENSG00000171443), ZBTB26 (ENSG00000171448), ZBTB21 (ENSG00000173276), ZNF683 (ENSG00000176083), ZBTB33 (ENSG00000177485), ZBTB3 (ENSG00000185670), ZBTB14 (ENSG00000198081), ZBTB12 (ENSG00000204366), ZNF580 (ENSG00000213015), ZNF280B (ENSG00000275004)

Protein

Protein identifiers

Zinc finger and BTB domain-containing protein 6 — Q15916 (reviewed: Q15916)

Alternative names: Zinc finger protein 482, Zinc finger protein with interaction domain

All UniProt accessions (1): Q15916

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in transcriptional regulation.

Subcellular location. Nucleus.

Tissue specificity. Widely expressed with highest levels in brain.

RefSeq proteins (1): NP_006617* (*=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 (9 total): zinc finger region 4, chain 1, domain 1, region of interest 1, compositionally biased region 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15916-F1	59.18	0.10

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 (1): 202

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 123 (showing top): TTTGTAG_MIR520D, BROWNE_HCMV_INFECTION_16HR_UP, GTGCCTT_MIR506, MODULE_285, GOBP_CYTOKINE_PRODUCTION, ACATTCC_MIR1_MIR206, DEBIASI_APOPTOSIS_BY_REOVIRUS_INFECTION_UP, CTTTGTA_MIR524, AACATTC_MIR4093P, KRIGE_RESPONSE_TO_TOSEDOSTAT_24HR_UP, GEORGES_TARGETS_OF_MIR192_AND_MIR215, GCACTTT_MIR175P_MIR20A_MIR106A_MIR106B_MIR20B_MIR519D, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, MARTENS_TRETINOIN_RESPONSE_DN, GOBP_NEGATIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II

GO Biological Process (3): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of cytokine production (GO:0001817), regulation of immune system process (GO:0002682)

GO Molecular Function (6): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), DNA binding (GO:0003677), zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), mitochondrion (GO:0005739)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
intracellular membrane-bounded organelle	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
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
nucleic acid binding	1
transition metal ion binding	1
binding	1
cation binding	1
nuclear lumen	1
cellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

686 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZBTB6	ACTA1	P02568	762
ZBTB6	ANP32E	Q9BTT0	509
ZBTB6	KLHL18	O94889	403
ZBTB6	HDAC2	Q92769	388
ZBTB6	ZSCAN1	Q8NBB4	377
ZBTB6	KCTD2	Q14681	351
ZBTB6	BTBD7	Q9P203	347
ZBTB6	TMEM106A	Q96A25	334
ZBTB6	C11orf71	Q6IPW1	324
ZBTB6	FAM110B	Q8TC76	324
ZBTB6	UBAC1	Q9BSL1	318
ZBTB6	TRMT2B	Q96GJ1	292
ZBTB6	FERRY3	Q9NQ89	290
ZBTB6	ANKFY1	Q9P2R3	288
ZBTB6	L3MBTL3	Q96JM7	278

IntAct

40 interactions, top by confidence:

A	B	Type	Score
ZBTB6	ZBTB26	psi-mi:“MI:0915”(physical association)	0.720
SUMO1P1	ZBTB6	psi-mi:“MI:0915”(physical association)	0.560
ZBTB6	SUMO1	psi-mi:“MI:0915”(physical association)	0.560
ZBTB6	SUMO1P1	psi-mi:“MI:0915”(physical association)	0.560
SUMO1	ZBTB6	psi-mi:“MI:0915”(physical association)	0.560
ZBTB6	PLEKHF2	psi-mi:“MI:0915”(physical association)	0.560
ZNF250	ZBTB6	psi-mi:“MI:0915”(physical association)	0.560
ZBTB6	FAM9A	psi-mi:“MI:0915”(physical association)	0.560
ZBTB48	ZBTB6	psi-mi:“MI:0915”(physical association)	0.560
RNF4	ZBTB6	psi-mi:“MI:0915”(physical association)	0.560
PRKN	ZBTB6	psi-mi:“MI:0915”(physical association)	0.560
VHL	ZBTB6	psi-mi:“MI:0915”(physical association)	0.560
ZBTB6	ZBTB6	psi-mi:“MI:0915”(physical association)	0.370
SKIL	ZBTB6	psi-mi:“MI:0915”(physical association)	0.370
ATF7IP	ZBTB6	psi-mi:“MI:0915”(physical association)	0.370
ZBTB6	ZBTB26	psi-mi:“MI:0915”(physical association)	0.000
PLEKHF2	ZBTB6	psi-mi:“MI:0915”(physical association)	0.000
ZNF250	ZBTB6	psi-mi:“MI:0915”(physical association)	0.000
ZBTB6	FAM9A	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (15): ZBTB6 (Two-hybrid), ZBTB26 (Two-hybrid), SUMO1P1 (Two-hybrid), SAR1B (Affinity Capture-MS), ZBTB6 (Two-hybrid), ZBTB6 (Two-hybrid), ZBTB6 (Two-hybrid), ZBTB6 (Two-hybrid), ZNF250 (Two-hybrid), ZBTB48 (Two-hybrid), ZBTB6 (Two-hybrid), ZBTB6 (Two-hybrid), ZBTB6 (Two-hybrid), ZBTB6 (Affinity Capture-Western), ZBTB6 (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: A0JMG1, A1YPR0, B0WWP2, B1WBS3, B2RXF5, B3M9V8, B3NDN0, B4GRJ2, B4HIK1, B4J045, B4L0G9, B4LIG6, B4MXW3, B4PD06, B4QLQ2, D3Z8N4, E0CZ16, E1B932, E7F6F9, E9Q4F2, F1LZ52, F1LZF0, F1MBP6, O14682, O15060, O35709, O43791, O88939, O93567, O94889, O95198, O95365, P0DMR5, P34568, P41182, P41183, Q04652, Q08DK3, Q0D2A9, Q0IHH9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	32
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

194 predictions. Top by Δscore:

Variant	Effect	Δscore
9:122912078:CAAT:C	acceptor_gain	0.9900
9:122913250:CCGA:C	donor_gain	0.9900
9:122913244:CACT:C	donor_loss	0.9800
9:122913245:A:AC	donor_gain	0.9800
9:122913246:C:CC	donor_gain	0.9800
9:122913247:T:TA	donor_loss	0.9800
9:122913248:C:CC	donor_loss	0.9800
9:122913249:A:AC	donor_gain	0.9800
9:122913250:C:CC	donor_gain	0.9800
9:122913246:CTCA:C	donor_gain	0.9700
9:122913245:AC:A	donor_loss	0.9500
9:122913246:CT:C	donor_gain	0.9400
9:122912082:C:CC	acceptor_gain	0.9300
9:122912079:AATCT:A	acceptor_loss	0.9200
9:122912080:ATCT:A	acceptor_loss	0.9200
9:122912081:TCTA:T	acceptor_loss	0.9200
9:122912082:C:CG	acceptor_loss	0.9200
9:122912083:T:A	acceptor_loss	0.9200
9:122913248:CACCG:C	donor_gain	0.9100
9:122913249:ACCGA:A	donor_gain	0.9100
9:122913250:CCGAC:C	donor_gain	0.9100
9:122912929:TC:T	donor_gain	0.9000
9:122912930:CC:C	donor_gain	0.9000
9:122912936:C:A	donor_gain	0.9000
9:122912097:C:CT	acceptor_loss	0.8900
9:122911435:TTAAA:T	donor_gain	0.8700
9:122913243:TCAC:T	donor_loss	0.8700
9:122912935:T:TA	donor_gain	0.8600
9:122913250:CCG:C	donor_gain	0.8600
9:122912084:A:C	acceptor_loss	0.8400

AlphaMissense

2833 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:122910875:G:C	H400D	1.000
9:122910883:A:G	L397P	1.000
9:122910900:G:C	F391L	1.000
9:122910900:G:T	F391L	1.000
9:122910901:A:G	F391S	1.000
9:122910902:A:G	F391L	1.000
9:122910923:A:G	C384R	1.000
9:122910945:G:C	H376Q	1.000
9:122910945:G:T	H376Q	1.000
9:122910957:G:C	H372Q	1.000
9:122910957:G:T	H372Q	1.000
9:122910959:G:C	H372D	1.000
9:122910959:G:T	H372N	1.000
9:122910967:A:G	L369P	1.000
9:122910984:A:C	F363L	1.000
9:122910984:A:T	F363L	1.000
9:122910985:A:G	F363S	1.000
9:122910986:A:G	F363L	1.000
9:122910996:G:C	C359W	1.000
9:122910998:A:G	C359R	1.000
9:122911005:A:C	C356W	1.000
9:122911007:A:G	C356R	1.000
9:122911011:A:C	F354L	1.000
9:122911011:A:T	F354L	1.000
9:122911013:A:G	F354L	1.000
9:122911041:G:C	H344Q	1.000
9:122911041:G:T	H344Q	1.000
9:122911043:G:C	H344D	1.000
9:122911045:C:G	R343P	1.000
9:122911051:A:G	L341P	1.000

dbSNP variants (sampled 300 via entrez): RS1000074128 (9:122908471 A>C,G), RS1000862254 (9:122914531 GTAA>G), RS1002385562 (9:122910118 G>A), RS1002414909 (9:122909853 A>G), RS1002810229 (9:122909670 A>G), RS1003057670 (9:122913490 G>C), RS1003088887 (9:122913299 C>G), RS1003390406 (9:122912143 A>C,G), RS1003756288 (9:122911808 A>G), RS1004023820 (9:122915260 T>C,G), RS1004257620 (9:122915019 T>TC), RS1004435384 (9:122908541 A>G), RS1004714336 (9:122914814 CTCAG>C), RS1004940010 (9:122908344 T>C), RS1005971152 (9:122909535 A>G)

Disease associations

OMIM: gene MIM:605976 | 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
GCST005951_64	Body mass index	2.000000e-10
GCST010703_296	Brain morphology (MOSTest)	2.000000e-14

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression	3
sodium arsenite	decreases expression, increases abundance, increases expression	2
Air Pollutants	affects expression, increases abundance, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	increases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
TAK-243	increases sumoylation	1
TL8-506	affects cotreatment, increases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	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
jinfukang	decreases expression	1
Leflunomide	increases expression	1
Arsenic	increases abundance, increases expression	1
Cadmium	increases abundance, increases expression	1
Caffeine	decreases phosphorylation	1
Doxorubicin	decreases expression	1
Endosulfan	decreases expression	1
Formaldehyde	decreases expression	1
Ozone	affects expression, increases abundance	1
Silicon Dioxide	increases expression	1
Urethane	increases expression	1
Cyclosporine	decreases expression	1
Aflatoxin M1	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_XV93	HEK293 eGFP-ZBTB6	Transformed cell line	Female

Clinical trials (associated diseases)

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