ZBTB26

Summary

ZBTB26 (zinc finger and BTB domain containing 26, HGNC:23383) is a protein-coding gene on chromosome 9q33.2, encoding Zinc finger and BTB domain-containing protein 26 (Q9HCK0). May be involved in transcriptional regulation.

Enables identical protein binding activity and 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 57684 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 31 total
• MANE Select transcript: NM_020924

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23383
Approved symbol	ZBTB26
Name	zinc finger and BTB domain containing 26
Location	9q33.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000171448
Ensembl biotype	protein_coding
OMIM	620164
Entrez	57684

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000373654, ENST00000373656, ENST00000859132, ENST00000934345, ENST00000934346, ENST00000952348, ENST00000952349

RefSeq mRNA: 3 — MANE Select: NM_020924 NM_001304363, NM_001304364, NM_020924

CCDS: CCDS6847

Canonical transcript exons

ENST00000373656 — 2 exons

Exon	Start	End
ENSE00001291444	122931437	122931512
ENSE00001911340	122915566	122919944

Expression profiles

Bgee: expression breadth ubiquitous, 245 present calls, max score 93.17.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.3965 / max 43.0608, expressed in 1388 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
102400	3.3965	1388

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	93.17	gold quality
epithelial cell of pancreas	CL:0000083	89.83	gold quality
germinal epithelium of ovary	UBERON:0001304	82.40	gold quality
oviduct epithelium	UBERON:0004804	81.80	gold quality
tibia	UBERON:0000979	80.58	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.75	gold quality
secondary oocyte	CL:0000655	79.66	gold quality
pancreatic ductal cell	CL:0002079	79.17	gold quality
ventricular zone	UBERON:0003053	78.66	gold quality
smooth muscle tissue	UBERON:0001135	78.54	gold quality
ganglionic eminence	UBERON:0004023	78.44	gold quality
pigmented layer of retina	UBERON:0001782	78.33	gold quality
cortical plate	UBERON:0005343	77.92	gold quality
muscle layer of sigmoid colon	UBERON:0035805	77.88	gold quality
body of uterus	UBERON:0009853	77.84	gold quality
ovary	UBERON:0000992	77.07	gold quality
left ovary	UBERON:0002119	77.05	gold quality
islet of Langerhans	UBERON:0000006	76.94	gold quality
Brodmann (1909) area 23	UBERON:0013554	76.84	gold quality
lower esophagus	UBERON:0013473	76.79	gold quality
lower esophagus muscularis layer	UBERON:0035833	76.78	gold quality
cauda epididymis	UBERON:0004360	76.76	gold quality
fallopian tube	UBERON:0003889	76.71	gold quality
endometrium	UBERON:0001295	76.64	gold quality
metanephros	UBERON:0000081	76.44	gold quality
monocyte	CL:0000576	76.43	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	76.35	gold quality
seminal vesicle	UBERON:0000998	76.32	gold quality
primary visual cortex	UBERON:0002436	76.25	gold quality
popliteal artery	UBERON:0002250	76.21	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-11	no	182.47
E-ANND-3	no	3.47

Regulation

Is transcription factor: yes

JASPAR motifs

Motif	Name	Family
MA1579.1	ZBTB26	More than 3 adjacent zinc fingers
MA1579.2	ZBTB26	More than 3 adjacent zinc fingers

JASPAR matrix evidence (PMIDs): PMID:28473536

miRNA regulators (miRDB)

59 targeting ZBTB26, 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-3064-3P	100.00	70.09	1254
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-12131	99.48	68.72	1673
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-150-3P	99.43	70.51	920

Literature-anchored findings (GeneRIF, showing 1)

• Identification of ZBTB26 as a Novel Risk Factor for Congenital Hypothyroidism. (PMID:34946811)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	zbtb26	ENSDARG00000028949
mus_musculus	Zbtb26	ENSMUSG00000050714
rattus_norvegicus	Zbtb26	ENSRNOG00000009346

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), ZBTB21 (ENSG00000173276), ZNF683 (ENSG00000176083), ZBTB33 (ENSG00000177485), ZBTB3 (ENSG00000185670), ZBTB6 (ENSG00000186130), ZBTB14 (ENSG00000198081), ZBTB12 (ENSG00000204366), ZNF580 (ENSG00000213015), ZNF280B (ENSG00000275004)

Protein

Protein identifiers

Zinc finger and BTB domain-containing protein 26 — Q9HCK0 (reviewed: Q9HCK0)

Alternative names: Zinc finger protein 481, Zinc finger protein Bioref

All UniProt accessions (1): Q9HCK0

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in transcriptional regulation.

Subcellular location. Nucleus.

Tissue specificity. Ubiquitous.

RefSeq proteins (3): NP_001291292, NP_001291293, NP_065975* (*=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): zinc finger region 4, cross-link 3, region of interest 2, chain 1, domain 1, sequence variant 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HCK0-F1	54.28	0.00

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 (3): 255, 329, 184

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 88 (showing top): RRAGTTGT_UNKNOWN, CMYB_01, GTCTACC_MIR379, GOBP_CYTOKINE_PRODUCTION, WTGAAAT_UNKNOWN, MYB_Q3, NRF2_01, MYB_Q5_01, SENESE_HDAC3_TARGETS_DN, MZF1_02, ZHAN_MULTIPLE_MYELOMA_MS_DN, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, GOBP_NEGATIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II, GOBP_NEGATIVE_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOMF_DNA_BINDING_TRANSCRIPTION_REPRESSOR_ACTIVITY

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 (8): 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), identical protein binding (GO:0042802), 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
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
protein 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

822 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZBTB26	ELF2	Q15723	482
ZBTB26	ETV2	O00321	435
ZBTB26	TGIF2LX	Q8IUE1	428
ZBTB26	POU2F3	Q9UKI9	425
ZBTB26	EGR4	Q05215	401
ZBTB26	IRF5	Q13568	394
ZBTB26	ZNF740	Q8NDX6	381
ZBTB26	ZFHX2	Q9C0A1	353
ZBTB26	ZSWIM3	Q96MP5	346
ZBTB26	HOXA6	P31267	344
ZBTB26	PHTF2	Q8N3S3	330
ZBTB26	ZNF821	O75541	327
ZBTB26	PHYHIPL	Q96FC7	326
ZBTB26	RASGEF1C	Q8N431	322
ZBTB26	ZNF518B	Q9C0D4	304

IntAct

138 interactions, top by confidence:

A	B	Type	Score
SUMO1	ZBTB26	psi-mi:“MI:0915”(physical association)	0.720
ZBTB6	ZBTB26	psi-mi:“MI:0915”(physical association)	0.720
ZBTB26	SUMO1	psi-mi:“MI:0915”(physical association)	0.720
ZBTB26	ZBTB26	psi-mi:“MI:0915”(physical association)	0.700
SUMO1P1	ZBTB26	psi-mi:“MI:0915”(physical association)	0.560
ZBTB26	UBE2I	psi-mi:“MI:0915”(physical association)	0.560
ZBTB26	GIPC2	psi-mi:“MI:0915”(physical association)	0.560
ZBTB26	HEL164	psi-mi:“MI:0915”(physical association)	0.560
ZBTB26	SUMO1P1	psi-mi:“MI:0915”(physical association)	0.560
GIPC2	ZBTB26	psi-mi:“MI:0915”(physical association)	0.560
UBE2I	ZBTB26	psi-mi:“MI:0915”(physical association)	0.560
ZBTB26	TAE1	psi-mi:“MI:0915”(physical association)	0.560
PSH1	ZBTB26	psi-mi:“MI:0915”(physical association)	0.560
ZBTB26		psi-mi:“MI:0915”(physical association)	0.560
SMT3	ZBTB26	psi-mi:“MI:0915”(physical association)	0.560
	ZBTB26	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (45): ZBTB26 (Two-hybrid), ZBTB26 (Two-hybrid), ZBTB26 (Two-hybrid), ZBTB26 (Two-hybrid), ZBTB26 (Two-hybrid), ZBTB26 (Two-hybrid), SUMO1P1 (Two-hybrid), ZBTB26 (Two-hybrid), ZBTB26 (Two-hybrid), ZBTB26 (Two-hybrid), ZBTB26 (Two-hybrid), ZBTB26 (Two-hybrid), ZBTB26 (Affinity Capture-MS), ZBTB26 (Two-hybrid), ZBTB26 (Two-hybrid)

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: A0JPB4, A4IFJ6, H2L008, Q03267, Q5R9W9, Q5ZLR2, Q6NRM0, Q6XDT6, Q8BU00, Q90ZS6, Q925H1, Q9BLC4, Q9H5V7, Q9HCK0, Q9UHF7, A0JN76, A1L2U9, A1YPR0, B1WAZ8, B1WBS3, B1WBU4, B2RXF5, E9Q4F2, G5E8B9, O14867, O15062, O15156, O15209, O35260, O43298, O43829, O88282, O88939, O93567, O94889, O95365, O95625, P28575, P41182, P41183

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 41 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
regulation of apoptotic process	5	12.3×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	31
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

489 predictions. Top by Δscore:

Variant	Effect	Δscore
9:122931435:A:AC	donor_gain	1.0000
9:122931436:C:CC	donor_gain	1.0000
9:122931436:CAGA:C	donor_gain	1.0000
9:122916494:A:T	acceptor_gain	0.9800
9:122931431:A:AC	donor_gain	0.9700
9:122931432:C:CC	donor_gain	0.9700
9:122931436:CAG:C	donor_gain	0.9600
9:122929429:C:CC	acceptor_gain	0.9500
9:122931430:CACT:C	donor_loss	0.9500
9:122931431:ACTT:A	donor_loss	0.9500
9:122931432:CT:C	donor_loss	0.9500
9:122931433:TT:T	donor_loss	0.9500
9:122931435:ACA:A	donor_loss	0.9500
9:122922654:T:C	donor_gain	0.9400
9:122930911:T:C	donor_gain	0.9200
9:122929006:TGGTG:T	donor_gain	0.9100
9:122931436:CA:C	donor_gain	0.9100
9:122930910:A:AC	donor_gain	0.8900
9:122919942:GACCT:G	acceptor_loss	0.8800
9:122919943:AC:A	acceptor_loss	0.8800
9:122919944:CCT:C	acceptor_loss	0.8800
9:122919946:T:G	acceptor_loss	0.8800
9:122931433:T:C	donor_gain	0.8800
9:122931062:A:AC	donor_gain	0.8700
9:122931063:C:CC	donor_gain	0.8700
9:122929323:CTTA:C	donor_loss	0.8600
9:122929324:TTAC:T	donor_loss	0.8600
9:122929325:TA:T	donor_loss	0.8600
9:122919958:A:C	acceptor_loss	0.8500
9:122929322:ACTT:A	donor_loss	0.8500

AlphaMissense

2974 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:122918817:A:G	L373P	1.000
9:122918821:G:C	H372D	1.000
9:122918846:A:C	F363L	1.000
9:122918846:A:T	F363L	1.000
9:122918847:A:G	F363S	1.000
9:122918848:A:G	F363L	1.000
9:122918858:A:C	C359W	1.000
9:122918859:C:T	C359Y	1.000
9:122918860:A:G	C359R	1.000
9:122918867:A:C	C356W	1.000
9:122918868:C:G	C356S	1.000
9:122918869:A:G	C356R	1.000
9:122918869:A:T	C356S	1.000
9:122918891:G:C	H348Q	1.000
9:122918891:G:T	H348Q	1.000
9:122918893:G:C	H348D	1.000
9:122918901:A:G	L345P	1.000
9:122918903:A:C	H344Q	1.000
9:122918903:A:T	H344Q	1.000
9:122918904:T:G	H344P	1.000
9:122918905:G:C	H344D	1.000
9:122918905:G:T	H344N	1.000
9:122918913:A:G	L341S	1.000
9:122918930:A:C	F335L	1.000
9:122918930:A:T	F335L	1.000
9:122918931:A:G	F335S	1.000
9:122918932:A:G	F335L	1.000
9:122918943:C:T	C331Y	1.000
9:122918944:A:G	C331R	1.000
9:122918951:A:C	C328W	1.000

dbSNP variants (sampled 300 via entrez): RS1000114377 (9:122920027 C>A,T), RS1000224103 (9:122922589 T>C), RS1000362056 (9:122923512 C>T), RS1000375108 (9:122923077 G>A,T), RS1000474320 (9:122928581 A>G), RS1001106202 (9:122921944 C>A,T), RS1001133925 (9:122929044 G>A), RS1001196708 (9:122931525 C>A,G), RS1001301089 (9:122926170 C>A,T), RS1001365700 (9:122925099 C>G), RS1001649612 (9:122931309 C>G,T), RS1001964386 (9:122920271 C>A), RS1002226353 (9:122917294 C>A,T), RS1002312379 (9:122920723 T>TA), RS1002355841 (9:122927245 T>C)

Disease associations

OMIM: gene MIM:620164 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST005951_64	Body mass index	2.000000e-10
GCST010703_296	Brain morphology (MOSTest)	2.000000e-14
GCST90000025_427	Appendicular lean mass	5.000000e-20

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004346	neuroimaging measurement
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, decreases methylation, affects cotreatment	8
trichostatin A	affects cotreatment, decreases expression	3
Cyclosporine	increases expression	3
entinostat	decreases expression, affects cotreatment	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	increases phosphorylation	1
TAK-243	increases sumoylation	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
pentanal	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases expression, decreases reaction	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Air Pollutants	affects expression, increases abundance	1
Vehicle Emissions	decreases expression, decreases reaction	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	affects cotreatment, increases expression	1
Coumestrol	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Endosulfan	decreases expression	1
Formaldehyde	decreases expression	1
Ozone	affects expression, increases abundance	1
Smoke	decreases expression	1
Sodium Dodecyl Sulfate	decreases expression	1
Dihydrotestosterone	increases 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_XV90	HEK293 eGFP-ZBTB26	Transformed cell line	Female

Clinical trials (associated diseases)

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