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ZBTB25

gene
On this page

Also known as KUP

Summary

ZBTB25 (zinc finger and BTB domain containing 25, HGNC:13112) is a protein-coding gene on chromosome 14q23.3, encoding Zinc finger and BTB domain-containing protein 25 (P24278). 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 nucleoplasm.

Source: NCBI Gene 7597 — RefSeq curated summary.

At a glance

  • GWAS associations: 4
  • Clinical variants (ClinVar): 91 total — 1 pathogenic
  • MANE Select transcript: NM_006977

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:13112
Approved symbolZBTB25
Namezinc finger and BTB domain containing 25
Location14q23.3
Locus typegene with protein product
StatusApproved
AliasesKUP
Ensembl geneENSG00000089775
Ensembl biotypeprotein_coding
OMIM194541
Entrez7597

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 33 protein_coding

ENST00000394715, ENST00000555220, ENST00000555424, ENST00000608382, ENST00000865241, ENST00000865242, ENST00000865243, ENST00000865244, ENST00000865245, ENST00000865246, ENST00000865247, ENST00000865248, ENST00000865249, ENST00000922501, ENST00000922502, ENST00000922503, ENST00000922504, ENST00000922505, ENST00000922506, ENST00000922507, ENST00000922508, ENST00000922509, ENST00000922510, ENST00000922511, ENST00000957083, ENST00000957084, ENST00000957085, ENST00000957086, ENST00000957087, ENST00000957088, ENST00000957089, ENST00000957090, ENST00000957091

RefSeq mRNA: 9 — MANE Select: NM_006977 NM_001304507, NM_001304508, NM_001354682, NM_001354683, NM_001354684, NM_001354685, NM_001354686, NM_001354687, NM_006977

CCDS: CCDS76689, CCDS9765

Canonical transcript exons

ENST00000608382 — 3 exons

ExonStartEnd
ENSE000006584296449036164490540
ENSE000013191586450366164503838
ENSE000037094086447805164488057

Expression profiles

Bgee: expression breadth ubiquitous, 185 present calls, max score 84.76.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.2960 / max 420.6908, expressed in 1810 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter IDTPM avgSamples expressed
1436309.78021735
1436324.89951354
1436253.95001492
1436313.0965847
1436261.3839727
1436281.0151608
1436290.8947545
1436270.8206508
1436350.5153249
1436340.3143136

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
apex of heartUBERON:000209884.76gold quality
gastrocnemiusUBERON:000138882.97gold quality
muscle of legUBERON:000138382.69gold quality
mucosa of stomachUBERON:000119981.61gold quality
calcaneal tendonUBERON:000370181.16gold quality
right atrium auricular regionUBERON:000663180.98gold quality
hindlimb stylopod muscleUBERON:000425280.87gold quality
right uterine tubeUBERON:000130280.80gold quality
heart left ventricleUBERON:000208480.36gold quality
primordial germ cell in gonadCL:0000670 ∩ UBERON:000099180.21gold quality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047379.90gold quality
stromal cell of endometriumCL:000225579.89gold quality
popliteal arteryUBERON:000225079.81gold quality
tibial arteryUBERON:000761079.81gold quality
granulocyteCL:000009479.80gold quality
cardiac ventricleUBERON:000208279.50gold quality
cardiac atriumUBERON:000208179.32gold quality
descending thoracic aortaUBERON:000234578.98gold quality
tibial nerveUBERON:000132378.95gold quality
aortaUBERON:000094778.85gold quality
left ovaryUBERON:000211978.63gold quality
right ovaryUBERON:000211878.59gold quality
muscle layer of sigmoid colonUBERON:003580578.58gold quality
colonic epitheliumUBERON:000039778.54gold quality
left uterine tubeUBERON:000130378.52gold quality
lower esophagus muscularis layerUBERON:003583378.50gold quality
lower esophagusUBERON:001347378.46gold quality
C1 segment of cervical spinal cordUBERON:000646978.44gold quality
heartUBERON:000094878.35gold quality
left coronary arteryUBERON:000162678.34gold quality

Single-cell (SCXA)

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

ExperimentMarker?Max mean expression
E-ANND-3yes7.23
E-CURD-112no2.62

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 4)

  • ZBTB25 functions as a negative regulator of nuclear factor of activated T cells (NF-AT) activation, such that RNA interference mediated knockdown resulted in enhanced activation of target genes. (PMID:20410506)
  • study demonstrates that ZBTB25 regulates IAV (Influenza A virus) RNA transcription and replication and serves as a promising antiviral target for IAV treatment. (PMID:28768860)
  • Transcription Repressor Protein ZBTB25 Associates with HDAC1-Sin3a Complex in Mycobacterium tuberculosis-Infected Macrophages, and Its Inhibition Clears Pathogen by Autophagy. (PMID:33627504)
  • E3 ubiquitin ligase ZBTB25 suppresses beta coronavirus infection through ubiquitination of the main viral protease MPro. (PMID:37890782)

Cross-species orthologs

3 orthologs

OrganismSymbolGene ID
danio_reriozbtb25ENSDARG00000042383
mus_musculusZbtb25ENSMUSG00000056459
rattus_norvegicusZbtb25ENSRNOG00000006441

Paralogs (28): ZNF280C (ENSG00000056277), 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), ZBTB6 (ENSG00000186130), ZBTB14 (ENSG00000198081), ZBTB12 (ENSG00000204366), ZNF580 (ENSG00000213015), ZNF280B (ENSG00000275004)

Protein

Protein identifiers

Zinc finger and BTB domain-containing protein 25 — P24278 (reviewed: P24278)

Alternative names: Zinc finger protein 46, Zinc finger protein KUP

All UniProt accessions (3): P24278, G3V2K3, G3V351

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in transcriptional regulation.

Subcellular location. Nucleus.

Tissue specificity. Expressed mainly in hematopoietic cells and testis.

RefSeq proteins (9): NP_001291436, NP_001291437, NP_001341611, NP_001341612, NP_001341613, NP_001341614, NP_001341615, NP_001341616, NP_008908* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR000210BTB/POZ_domDomain
IPR011333SKP1/BTB/POZ_sfHomologous_superfamily
IPR013087Znf_C2H2_typeDomain
IPR036236Znf_C2H2_sfHomologous_superfamily

Pfam: PF00096, PF00651

UniProt features (13 total): cross-link 7, sequence conflict 2, zinc finger region 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-P24278-F159.170.21

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): 405, 142, 148, 198, 204, 303, 330

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 199 (showing top): BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, MYOGENIN_Q6, E2F4DP1_01, LFA1_Q6, GCANCTGNY_MYOD_Q6, MENSE_HYPOXIA_UP, RACCACAR_AML_Q6, CAGCTG_AP4_Q5, MORF_ZNF10, E2F_Q3, AML_Q6, GOBP_CYTOKINE_PRODUCTION, chr14q23, MODULE_98, AML1_01

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 (7): 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 transcription factor activity (GO:0003700), zinc ion binding (GO:0008270), 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:

CategoryTerms
RNA polymerase II transcription regulatory region sequence-specific DNA binding2
regulation of transcription by RNA polymerase II1
transcription by RNA polymerase II1
negative regulation of DNA-templated transcription1
cytokine production1
regulation of gene expression1
regulation of multicellular organismal process1
immune system process1
regulation of biological process1
cis-regulatory region sequence-specific DNA binding1
negative regulation of transcription by RNA polymerase II1
DNA-binding transcription factor activity, RNA polymerase II-specific1
DNA-binding transcription repressor activity1
transcription cis-regulatory region binding1
regulation of DNA-templated transcription1
transcription regulator activity1
transition metal ion binding1
nucleic acid binding1
binding1
cation binding1
nuclear lumen1
cellular anatomical structure1
intracellular membrane-bounded organelle1

Protein interactions and networks

STRING

882 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
ZBTB25WNK1P54963581
ZBTB25USHBP1Q8N6Y0487
ZBTB25CPA1P15085448
ZBTB25AK1P00568447
ZBTB25PIP4P1Q86T03445
ZBTB25PPP3R2Q96LZ3433
ZBTB25PPA1Q15181419
ZBTB25ZNF639Q9UID6415
ZBTB25GMCL1Q96IK5407
ZBTB25SLC9B1Q4ZJI4398
ZBTB25CHP1Q99653398
ZBTB25H3BQ15H3BQ15394
ZBTB25AMDHD2Q9Y303393
ZBTB25KPNA1P52294382
ZBTB25ZNF16P17020374

IntAct

135 interactions, top by confidence:

ABTypeScore
ZBTB25SEPHS1psi-mi:“MI:0915”(physical association)0.780
ZBTB25TNIP1psi-mi:“MI:0915”(physical association)0.720
TNIP1ZBTB25psi-mi:“MI:0915”(physical association)0.720
ZBTB25TRAF2psi-mi:“MI:0915”(physical association)0.670
ZBTB25PNMA5psi-mi:“MI:0915”(physical association)0.670
TRAF2ZBTB25psi-mi:“MI:0915”(physical association)0.670
ZBTB25ZBTB1psi-mi:“MI:0915”(physical association)0.670
ZBTB25ZBTB2psi-mi:“MI:0915”(physical association)0.670
ZBTB2ZBTB25psi-mi:“MI:0914”(association)0.670
CARNMT1NUP42psi-mi:“MI:0914”(association)0.640
DDIT3ZBTB25psi-mi:“MI:0915”(physical association)0.560
ZBTB25KCTD1psi-mi:“MI:0915”(physical association)0.560
ZBTB25APIPpsi-mi:“MI:0915”(physical association)0.560
LZTS2ZBTB25psi-mi:“MI:0915”(physical association)0.560
TSSK3ZBTB25psi-mi:“MI:0915”(physical association)0.560

BioGRID (67): ZBTB25 (Two-hybrid), ZBTB25 (Two-hybrid), ZBTB25 (Two-hybrid), TNIP1 (Two-hybrid), SEPHS1 (Two-hybrid), APIP (Two-hybrid), TSSK3 (Two-hybrid), LZTS2 (Two-hybrid), PNMA5 (Two-hybrid), KCTD1 (Two-hybrid), ZBTB25 (Reconstituted Complex), ZBTB25 (Affinity Capture-MS), ZBTB25 (Affinity Capture-MS), ZBTB25 (Two-hybrid), ZBTB25 (Two-hybrid)

ESM2 similar proteins: A0A5K7RLP0, A1YEX3, A7YWH3, B1WBU4, O15151, O35618, O43298, O88850, P24278, P97303, Q01954, Q0V8G8, Q15916, Q17RG1, Q562E2, Q5RC05, Q5RDQ6, Q5SXH7, Q5TC79, Q5VYS8, Q5W0Q7, Q5XIN1, Q6ZPY5, Q6ZSB9, Q6ZU67, Q7ZUW7, Q7ZYI3, Q8BLK9, Q8BSV3, Q8IW35, Q8K088, Q8N680, Q8N7W2, Q8TCN5, Q8VHI4, Q8WW38, Q90W33, Q96BR9, Q96S38, Q99ME3

Diamond homologs: A0JMG1, A1YEX3, B0WWP2, B3DIV9, B3M9V8, B3NDN0, B4GRJ2, B4HIK1, B4J045, B4L0G9, B4LIG6, B4MXW3, B4PD06, B4QLQ2, B7U179, D3Z8N4, D4A2K4, E0CZ16, E7F6F9, F1LZF0, F1MBP6, O14682, O22286, O35709, O43791, O81432, O95198, P0DMR5, P0DMR6, P24278, P28575, P34568, P58544, P58545, Q08DK3, Q08DS0, Q0D2A9, Q0IHH9, Q0VCW1, Q16RL8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic1
Likely pathogenic0
Uncertain significance71
Likely benign12
Benign4

Top pathogenic / likely-pathogenic (1)

Variant IDHGVSClassification
2738637NM_005956.4(MTHFD1):c.2555del (p.Tyr852fs)Pathogenic

SpliceAI

1905 predictions. Top by Δscore:

VariantEffectΔscore
14:64449442:TAG:Tacceptor_loss1.0000
14:64449443:A:AGacceptor_gain1.0000
14:64449443:A:Gacceptor_loss1.0000
14:64449443:AG:Aacceptor_gain1.0000
14:64449443:AGGAC:Aacceptor_gain1.0000
14:64449444:G:GAacceptor_gain1.0000
14:64449444:G:GCacceptor_loss1.0000
14:64449444:GG:Gacceptor_gain1.0000
14:64449444:GGAC:Gacceptor_gain1.0000
14:64449444:GGACG:Gacceptor_gain1.0000
14:64449619:CAAGG:Cdonor_loss1.0000
14:64449620:AAG:Adonor_loss1.0000
14:64449623:G:Cdonor_loss1.0000
14:64449624:T:Adonor_loss1.0000
14:64453752:A:AGacceptor_gain1.0000
14:64453753:G:GGacceptor_gain1.0000
14:64465609:CCTAC:Cdonor_gain1.0000
14:64465610:CTAC:Cdonor_gain1.0000
14:64465611:TAC:Tdonor_gain1.0000
14:64465611:TACG:Tdonor_loss1.0000
14:64465612:AC:Adonor_gain1.0000
14:64465614:G:GGdonor_gain1.0000
14:64465615:T:TCdonor_loss1.0000
14:64465618:G:GGdonor_gain1.0000
14:64490359:A:ACdonor_gain1.0000
14:64490359:AC:Adonor_gain1.0000
14:64490359:ACC:Adonor_loss1.0000
14:64490360:C:CCdonor_gain1.0000
14:64490360:CC:Cdonor_gain1.0000
14:64490536:TGGTT:Tacceptor_gain1.0000

AlphaMissense

2892 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
14:64487926:A:GL102P1.000
14:64487990:A:GY81H1.000
14:64488001:A:GL77S1.000
14:64488013:A:GF73S1.000
14:64490375:A:CF53L1.000
14:64490375:A:TF53L1.000
14:64490377:A:GF53L1.000
14:64490387:G:CF49L1.000
14:64490387:G:TF49L1.000
14:64490388:A:GF49S1.000
14:64490389:A:GF49L1.000
14:64490397:G:AS46F1.000
14:64490397:G:TS46Y1.000
14:64490398:A:GS46P1.000
14:64490399:A:CF45L1.000
14:64490399:A:TF45L1.000
14:64490401:A:GF45L1.000
14:64490403:G:TA44D1.000
14:64490406:G:TA43D1.000
14:64490409:A:CL42R1.000
14:64490409:A:GL42P1.000
14:64490409:A:TL42H1.000
14:64490420:G:CH38Q1.000
14:64490420:G:TH38Q1.000
14:64490422:G:CH38D1.000
14:64490424:G:TA37D1.000
14:64490429:G:CF35L1.000
14:64490429:G:TF35L1.000
14:64490430:A:GF35S1.000
14:64490431:A:GF35L1.000

dbSNP variants (sampled 300 via entrez): RS1000036268 (14:64472171 A>T), RS1000133290 (14:64493147 A>G,T), RS1000163932 (14:64478551 T>C,G), RS1000169706 (14:64477938 T>C), RS1000283333 (14:64486506 A>C,G), RS1000302372 (14:64505835 C>A,G), RS1000323786 (14:64504310 G>A,T), RS1000335895 (14:64486809 A>G), RS1000339816 (14:64458107 T>A), RS1000398635 (14:64480391 C>A,G), RS1000507083 (14:64474792 T>A), RS1000535342 (14:64491115 C>T), RS1000558731 (14:64475196 T>C), RS1000585302 (14:64493484 C>T), RS1000765354 (14:64467431 T>C)

Disease associations

OMIM: gene MIM:194541 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

StudyTraitp-value
GCST004627_154Lymphocyte count2.000000e-12
GCST004632_40Lymphocyte percentage of white cells2.000000e-09
GCST006979_1005Heel bone mineral density2.000000e-11
GCST90002389_486Lymphocyte percentage of white cells2.000000e-26

EFO canonical traits (3, from GWAS)

EFO IDTrait name
EFO:0004587lymphocyte count
EFO:0007993lymphocyte percentage of leukocytes
EFO:0009270heel bone mineral density

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — E3 ubiquitin ligase components

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

ChemicalActions (top 5)PubMed papers
Arsenicaffects methylation, affects cotreatment, decreases expression, increases abundance, affects expression3
bisphenol Aaffects expression, affects cotreatment, decreases methylation2
sodium arsenitedecreases expression, affects cotreatment, increases abundance2
Valproic Acidaffects expression, increases methylation2
TAK-243increases sumoylation1
cobaltous chloridedecreases expression1
manganese chlorideaffects cotreatment, decreases expression, increases abundance1
CGP 52608affects binding, increases reaction1
abrineincreases expression1
Resveratrolaffects cotreatment, increases expression1
Sunitinibincreases expression1
Fulvestrantaffects cotreatment, decreases methylation1
Leflunomideincreases expression1
Acetaminophenincreases expression1
Air Pollutants, Occupationalaffects expression1
Doxorubicindecreases expression1
Hydrogen Peroxideaffects cotreatment, decreases expression1
Manganeseaffects cotreatment, decreases expression, increases abundance1
Phthalic Acidsincreases methylation1
Plant Extractsaffects cotreatment, increases expression1
Theophyllineaffects cotreatment, decreases expression1
Tobacco Smoke Pollutiondecreases expression1
Cyclosporineincreases expression1
Cadmium Chloridedecreases expression1
Okadaic Aciddecreases expression1
Acrylamidedecreases expression1

Clinical trials (associated diseases)

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

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.4
BioBTree
v2.0.2

Sources 75

This page pulls from 75 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgtopdb_interactiongwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomerefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot