ZBTB21

gene
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Also known as KIAA1227

Summary

ZBTB21 (zinc finger and BTB domain containing 21, HGNC:13083) is a protein-coding gene on chromosome 21q22.3, encoding Zinc finger and BTB domain-containing protein 21 (Q9ULJ3). Acts as a transcription repressor.

Enables several functions, including DNA-binding transcription repressor activity, RNA polymerase II-specific; POZ domain binding activity; and methyl-CpG binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in cytosol and nucleoplasm.

Source: NCBI Gene 49854 — RefSeq curated summary.

At a glance

  • GWAS associations: 1
  • Clinical variants (ClinVar): 170 total
  • Druggable target: yes
  • MANE Select transcript: NM_001098402

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:13083
Approved symbolZBTB21
Namezinc finger and BTB domain containing 21
Location21q22.3
Locus typegene with protein product
StatusApproved
AliasesKIAA1227
Ensembl geneENSG00000173276
Ensembl biotypeprotein_coding
OMIM616485
Entrez49854

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 9 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000310826, ENST00000398497, ENST00000398499, ENST00000398505, ENST00000398511, ENST00000425521, ENST00000449949, ENST00000465968, ENST00000881815, ENST00000932835

RefSeq mRNA: 5 — MANE Select: NM_001098402 NM_001098402, NM_001098403, NM_001320729, NM_001320731, NM_020727

CCDS: CCDS13678, CCDS42934

Canonical transcript exons

ENST00000310826 — 3 exons

ExonStartEnd
ENSE000014851324200289742002961
ENSE000015472654198683141994108
ENSE000038495284201025242010360

Expression profiles

Bgee: expression breadth ubiquitous, 257 present calls, max score 97.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.3239 / max 179.2426, expressed in 1802 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter IDTPM avgSamples expressed
19057813.92461768
1905772.98741266
1905760.2800116
1905750.132049

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
cauda epididymisUBERON:000436097.06gold quality
endothelial cellCL:000011595.76gold quality
epithelial cell of pancreasCL:000008394.06gold quality
corpus epididymisUBERON:000435993.98gold quality
secondary oocyteCL:000065593.55gold quality
caput epididymisUBERON:000435893.51gold quality
Brodmann (1909) area 23UBERON:001355491.89gold quality
cartilage tissueUBERON:000241891.84gold quality
mucosa of paranasal sinusUBERON:000503089.88gold quality
calcaneal tendonUBERON:000370189.30gold quality
lower lobe of lungUBERON:000894988.59gold quality
visceral pleuraUBERON:000240188.28gold quality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047387.40gold quality
parietal pleuraUBERON:000240086.89gold quality
bone marrow cellCL:000209286.88gold quality
superficial temporal arteryUBERON:000161486.66gold quality
oocyteCL:000002386.36gold quality
kidney epitheliumUBERON:000481986.18gold quality
pancreatic ductal cellCL:000207985.99gold quality
palpebral conjunctivaUBERON:000181285.92gold quality
bone marrowUBERON:000237185.81gold quality
mammary ductUBERON:000176585.75gold quality
epithelium of mammary glandUBERON:000324485.71gold quality
placentaUBERON:000198785.69gold quality
mammalian vulvaUBERON:000099785.44gold quality
adrenal tissueUBERON:001830385.13gold quality
primary visual cortexUBERON:000243685.09gold quality
middle temporal gyrusUBERON:000277185.09gold quality
islet of LangerhansUBERON:000000685.05gold quality
eyeUBERON:000097085.03gold quality

Single-cell (SCXA)

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

ExperimentMarker?Max mean expression
E-ANND-3yes7.38

Regulation

Is transcription factor: yes

JASPAR motifs

MotifNameFamily
MA2487.1ZBTB21Factors with multiple dispersed zinc fingers

JASPAR matrix evidence (PMIDs): PMID:38959316

miRNA regulators (miRDB)

200 targeting ZBTB21, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-4795-3P100.0074.624024
HSA-MIR-340-5P100.0072.504437
HSA-MIR-3163100.0077.238605
HSA-MIR-3646100.0073.565283
HSA-MIR-3613-3P100.0076.367965
HSA-MIR-548C-3P99.9974.017587
HSA-MIR-428299.9975.366408
HSA-MIR-366299.9973.825684
HSA-MIR-513B-5P99.9969.962150
HSA-MIR-186-5P99.9970.833707
HSA-MIR-485-3P99.9870.681585
HSA-MIR-539-3P99.9870.741616
HSA-MIR-548P99.9872.253784
HSA-MIR-548N99.9871.944170
HSA-MIR-1213699.9872.815713
HSA-MIR-3688-3P99.9772.022834
HSA-MIR-314899.9775.066478
HSA-MIR-302C-5P99.9772.563642
HSA-MIR-6778-3P99.9667.292693
HSA-MIR-548AA99.9670.643753
HSA-MIR-548AP-3P99.9670.643753
HSA-MIR-548T-3P99.9670.643753
HSA-MIR-365899.9673.874379
HSA-MIR-551B-5P99.9671.283493
HSA-MIR-548AT-5P99.9670.832666
HSA-MIR-590-3P99.9674.346478
HSA-MIR-1468-3P99.9672.743797
HSA-MIR-1250-3P99.9670.044038
HSA-MIR-55999.9572.283609
HSA-MIR-548AB99.9571.313488

Literature-anchored findings (GeneRIF, showing 2)

  • ZNF295 may be involved in the bi-directional control of gene expression in concert with ZFP161 (PMID:15629158)
  • Genotyping was accomplished on Infinium Human610-QUAD version 1. In the ilSIRENTE population, genetic variants in ZNF295 and C2CD2 (rs928874 and rs1788355) on chromosome 21q22.3, were significantly associated with the 4-meter gait speed (PMID:29158487)

Cross-species orthologs

3 orthologs

OrganismSymbolGene ID
danio_reriozbtb21ENSDARG00000043285
mus_musculusZbtb21ENSMUSG00000046962
rattus_norvegicusZbtb21ENSRNOG00000001623

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), 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 21Q9ULJ3 (reviewed: Q9ULJ3)

Alternative names: Zinc finger protein 295

All UniProt accessions (3): Q9ULJ3, E7EVF9, Q5KS07

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a transcription repressor.

Subunit / interactions. Homodimer. Interacts with ZBTB14.

Subcellular location. Nucleus.

Tissue specificity. Ubiquitous in fetal and adult tissues.

Isoforms (2)

UniProt IDNamesCanonical?
Q9ULJ3-11, ZNF295Lyes
Q9ULJ3-22, ZNF295S

RefSeq proteins (5): NP_001091872, NP_001091873, NP_001307658, NP_001307660, NP_065778 (=MANE)

Domains & families (InterPro)

IDNameType
IPR000210BTB/POZ_domDomain
IPR011333SKP1/BTB/POZ_sfHomologous_superfamily
IPR013087Znf_C2H2_typeDomain
IPR036236Znf_C2H2_sfHomologous_superfamily
IPR041011Znf_C2H2_6Domain

Pfam: PF00096, PF00651, PF18450

UniProt features (68 total): cross-link 21, modified residue 11, region of interest 8, zinc finger region 8, compositionally biased region 6, helix 5, sequence variant 2, turn 2, chain 1, domain 1, splice variant 1, sequence conflict 1, strand 1

Structure

Experimental structures (PDB)

1 structures.

PDBMethodResolution (Å)
1WJPSOLUTION NMR

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q9ULJ3-F154.060.06

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 (32): 345, 381, 411, 422, 431, 434, 435, 438, 605, 714, 1003, 40, 40, 255, 266, 273, 312, 337, 383, 430 …

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 162 (showing top): TGCGCANK_UNKNOWN, CREBP1_Q2, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLUE_UP, CREB_Q4, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM5, E4F1_Q6, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, PYEON_CANCER_HEAD_AND_NECK_VS_CERVICAL_UP, CREBP1_01, chr21q22, P53_DECAMER_Q2, ATF_01, CREB_01, LEE_RECENT_THYMIC_EMIGRANT, SANSOM_APC_MYC_TARGETS

GO Biological Process (3): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of transcription by RNA polymerase II (GO:0006357), negative regulation of DNA-templated transcription (GO:0045892)

GO Molecular Function (9): DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), zinc ion binding (GO:0008270), methyl-CpG binding (GO:0008327), POZ domain binding (GO:0031208), identical protein binding (GO:0042802), DNA binding (GO:0003677), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
regulation of transcription by RNA polymerase II2
transcription by RNA polymerase II2
regulation of DNA-templated transcription2
RNA polymerase II transcription regulatory region sequence-specific DNA binding2
cellular anatomical structure2
negative regulation of DNA-templated transcription1
DNA-templated transcription1
negative regulation of RNA biosynthetic process1
chromatin1
DNA-binding transcription factor activity1
negative regulation of transcription by RNA polymerase II1
DNA-binding transcription factor activity, RNA polymerase II-specific1
DNA-binding transcription repressor activity1
transition metal ion binding1
nucleotide binding1
sequence-specific DNA binding1
protein domain specific binding1
protein binding1
nucleic acid binding1
binding1
cation binding1
intracellular membrane-bounded organelle1
nuclear lumen1
cytoplasm1

Protein interactions and networks

STRING

962 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
ZBTB21C2CD2Q9Y426610
ZBTB21RRP1BQ14684586
ZBTB21LIPIQ6XZB0553
ZBTB21PDXKO00764530
ZBTB21CXorf58Q96LI9512
ZBTB21LRRC42Q9Y546453
ZBTB21RIPK4P57078448
ZBTB21TRARG1Q8IXB3448
ZBTB21CRELD1Q96HD1428
ZBTB21DYRK1AQ13627420
ZBTB21HUNKP57058412
ZBTB21ZNF697Q5TEC3412
ZBTB21PRDM15P57071405
ZBTB21PPP1R14DQ9NXH3405
ZBTB21VPS26CO14972394
ZBTB21UMODL1Q5DID0394

IntAct

180 interactions, top by confidence:

ABTypeScore
ZBTB21YWHAGpsi-mi:“MI:0915”(physical association)0.900
YWHAQWDR62psi-mi:“MI:0914”(association)0.830
KBTBD7METTL15psi-mi:“MI:0914”(association)0.730
PPP2R2DYEATS4psi-mi:“MI:0914”(association)0.730
FBXL17BACH1psi-mi:“MI:0914”(association)0.730
PPP2R2BMYO9Apsi-mi:“MI:0914”(association)0.640
CETN1SFI1psi-mi:“MI:0914”(association)0.640
CHCHD4SSNA1psi-mi:“MI:0914”(association)0.640
KPNA1TCERG1psi-mi:“MI:0914”(association)0.640
ABTB1ZBTB21psi-mi:“MI:0915”(physical association)0.620
YWHAHPLEKHG3psi-mi:“MI:0914”(association)0.610
POLE2CYP4F12psi-mi:“MI:0914”(association)0.560
YWHAGSHTN1psi-mi:“MI:0914”(association)0.560
GSTA1GSTA4psi-mi:“MI:0914”(association)0.530
PRICKLE3SIAH2psi-mi:“MI:0914”(association)0.530
NAP1L5RPS2psi-mi:“MI:0914”(association)0.530
ABTB1VARS1psi-mi:“MI:0914”(association)0.530
YWHAQIGLC7psi-mi:“MI:0914”(association)0.530
YWHABSHTN1psi-mi:“MI:0914”(association)0.530
YWHAZBLTP3Bpsi-mi:“MI:0914”(association)0.530
CASQ2PES1psi-mi:“MI:0914”(association)0.530
CLEC11AVWA8psi-mi:“MI:0914”(association)0.530
PRICKLE3TUBG1psi-mi:“MI:0914”(association)0.530

BioGRID (198): ZBTB21 (Affinity Capture-MS), ZBTB21 (Affinity Capture-MS), ZBTB21 (Affinity Capture-MS), ZBTB21 (Affinity Capture-MS), ZBTB21 (Affinity Capture-MS), ZBTB21 (Affinity Capture-MS), ZBTB21 (Proximity Label-MS), ZBTB21 (Affinity Capture-MS), ZBTB21 (Affinity Capture-MS), ZBTB21 (Affinity Capture-MS), ZBTB21 (Affinity Capture-MS), ZBTB21 (Affinity Capture-MS), ZBTB21 (Affinity Capture-MS), ZBTB21 (Affinity Capture-MS), ZBTB21 (Affinity Capture-MS)

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: A0A1B8YAB1, A1YPR0, B0WWP2, B1H285, B3M9V8, B3NDN0, B4GRJ2, B4HIK1, B4J045, B4L0G9, B4LIG6, B4MXW3, B4PD06, B4QLQ2, C9JR72, D3Z8N4, E0CZ16, G3X9X1, O15062, O88939, O93567, O95365, P28575, P41182, P41183, Q08CL3, Q08DK3, Q13105, Q16RL8, Q2M0J9, Q3UQV5, Q52KB5, Q5EXX3, Q5R7B8, Q5RDY3, Q5TC79, Q5ZI33, Q5ZKD9, Q5ZM39, Q60821

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 194 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.

Reactome pathways:

PathwayPartnersFoldFDR
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex946.5×4e-11
Activation of BAD and translocation to mitochondria741.0×2e-08
SARS-CoV-1 targets host intracellular signalling and regulatory pathways736.2×4e-08
Activation of BH3-only proteins726.7×3e-07
RHO GTPases activate PKNs922.0×2e-08
Intrinsic Pathway for Apoptosis715.8×1e-05
SARS-CoV-1-host interactions1013.5×2e-07
FOXO-mediated transcription512.9×6e-04

GO biological processes:

GO termPartnersFoldFDR
protein targeting612.5×4e-03
negative regulation of translation77.8×1e-02
intracellular protein localization106.0×4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance154
Likely benign8
Benign0

Top pathogenic / likely-pathogenic (0)

SpliceAI

786 predictions. Top by Δscore:

VariantEffectΔscore
21:42010246:ACTC:Adonor_loss1.0000
21:42010248:TCACC:Tdonor_loss1.0000
21:42010249:CA:Cdonor_loss1.0000
21:42010250:A:ACdonor_gain1.0000
21:42010250:A:Tdonor_loss1.0000
21:42010251:C:CCdonor_gain1.0000
21:42010251:CCGG:Cdonor_gain1.0000
21:42010251:CCGGT:Cdonor_gain1.0000
21:42009445:C:CAdonor_gain0.9900
21:42010245:TAC:Tdonor_loss0.9900
21:42010246:A:ACdonor_gain0.9900
21:42010247:C:CCdonor_gain0.9900
21:42010250:AC:Adonor_gain0.9900
21:42010251:CC:Cdonor_gain0.9900
21:42010251:CCG:Cdonor_gain0.9900
21:41994104:TTTAT:Tacceptor_gain0.9800
21:41994106:TAT:Tacceptor_gain0.9800
21:41994109:C:CCacceptor_gain0.9800
21:42010244:TTAC:Tdonor_loss0.9800
21:41993904:ATTTT:Adonor_gain0.9700
21:41994105:TTAT:Tacceptor_gain0.9700
21:41994106:TATC:Tacceptor_loss0.9700
21:41994108:TCTA:Tacceptor_loss0.9700
21:41994109:CTA:Cacceptor_loss0.9700
21:41994117:CAAAA:Cacceptor_loss0.9700
21:42002896:CCA:Cdonor_gain0.9700
21:42010049:TGGGA:Tdonor_gain0.9700
21:42008650:T:Cdonor_gain0.9600
21:42002959:CTT:Cacceptor_gain0.9500
21:42008188:T:TAdonor_gain0.9500

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000112195 (21:42009807 C>G), RS1000169708 (21:42009012 G>C), RS1000536399 (21:42009660 G>A), RS1000635288 (21:42005579 G>A,C), RS1000656183 (21:42010469 A>C,G,T), RS1001005770 (21:42006796 C>A,G,T), RS1001026992 (21:41987976 C>A), RS1001103996 (21:42000636 G>C), RS1001351871 (21:42006442 AAAT>A), RS1001531586 (21:42005112 A>T), RS1001591320 (21:42011533 A>G), RS1001644965 (21:42011356 C>G), RS1002002943 (21:41998708 G>T), RS1002082126 (21:41994773 G>A), RS1002285464 (21:42001225 G>C)

Disease associations

OMIM: gene MIM:616485 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

StudyTraitp-value
GCST002770_1Hand grip strength6.000000e-07

EFO canonical traits (1, from GWAS)

EFO IDTrait name
EFO:0006941grip strength measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5069368 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
Valproic Aciddecreases expression, increases expression, affects cotreatment5
trichostatin Aaffects cotreatment, decreases expression3
sodium arsenitedecreases expression, increases expression3
Cyclosporineincreases expression3
Cadmium Chloridedecreases expression, increases abundance, increases expression3
Air Pollutantsdecreases expression, increases abundance, increases expression2
Tetrachlorodibenzodioxinaffects expression, increases expression2
Tobacco Smoke Pollutionincreases expression2
Particulate Matterincreases abundance, increases expression, decreases expression2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamidedecreases expression1
FR900359affects phosphorylation1
TAK-243decreases sumoylation1
triphenyl phosphateaffects expression1
bisphenol Aincreases expression1
deoxynivalenolincreases expression1
beta-lapachoneincreases expression1
tris(1,3-dichloro-2-propyl)phosphateincreases expression1
coumarindecreases phosphorylation1
15-acetyldeoxynivalenolincreases expression1
diethyl malateincreases expression1
di-n-butylphosphoric acidaffects expression1
pentabromodiphenyl etherincreases expression1
CGP 52608affects binding, increases reaction1
2-palmitoylglycerolincreases expression1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamideaffects cotreatment, decreases expression1
torcetrapibincreases expression1
abrineincreases expression1
2,2’,4,4’-tetrabromodiphenyl etherincreases expression1
dorsomorphinaffects cotreatment, decreases expression1
eprenetapoptaffects expression, affects reaction1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL5059501BindingProteomics fold change data (SUDHL4 cells, 1h)Data for DCP probe CCT369260

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

CellosaurusNameCategorySex
CVCL_XV89HEK293 eGFP-ZBTB21Transformed cell lineFemale

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.