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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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ZNF76
zinc finger protein 76
Chromosome 6 · 6p21.31
NCBI Gene: 7629Ensembl: ENSG00000065029.16HGNC: HGNC:13149UniProt: P36508
28PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
DNA-binding transcription repressor activity, RNA polymerase II-specificchromatinpositive regulation of transcription by RNA polymerase IIDNA-binding transcription activator activity, RNA polymerase II-specificosteoarthritis, hiptype 2 diabetes mellitusosteoarthritis, kneetotal joint arthroplasty
✦AI Summary

ZNF76 is a sequence-specific DNA-binding transcription factor that regulates genes transcribed by both RNA polymerase II and III 1. It recognizes the Staf-binding site (SBS) motif and activates expression of small nuclear RNAs (snRNAs) and mRNAs 1. ZNF76 also functions as a transcriptional repressor by inhibiting TATA-binding protein (TBP) activity, with this repression regulated by acetylation, sumoylation, and alternative splicing 2. Clinically, reduced ZNF76 expression associates with platinum chemotherapy resistance and poor survival in ovarian cancer patients, suggesting prognostic value as a biomarker 3. Additionally, the ZNF76 rs10947540 polymorphism is a genetic susceptibility factor for systemic lupus erythematosus (SLE), with the C allele increasing SLE risk and correlating with elevated serum creatinine levels 4. Recent evidence indicates ZNF76 functions as a transcription factor for DRP1, where succinylation-mediated activation of ZNF76 by high glucose promotes mitophagy and accelerates T cell aging in rheumatoid arthritis 5. Together, these findings establish ZNF76 as a multifunctional transcriptional regulator with significant roles in cancer chemoresistance and autoimmune disease pathogenesis.

Sources cited
1
ZNF76 recognizes Staf-binding sites and activates transcription of snRNAs and mRNAs via RNA polymerases II and III
PMID: 9705341
2
ZNF76 is a TBP-targeting transcriptional repressor regulated by acetylation, sumoylation, and alternative splicing
PMID: 16337145
3
Low ZNF76 expression predicts platinum chemotherapy resistance and poor prognosis in ovarian cancer
PMID: 34793589
4
ZNF76 rs10947540 polymorphism is associated with SLE susceptibility, with the C allele increasing disease risk
PMID: 33664275
5
Succinate-mediated ZNF76 succinylation activates DRP1 transcription, promoting mitophagy and T cell aging in rheumatoid arthritis
PMID: 41261244
Disease Associationsⓘ20
osteoarthritis, hipOpen Targets
0.33Weak
type 2 diabetes mellitusOpen Targets
0.29Weak
osteoarthritis, kneeOpen Targets
0.29Weak
total hip arthroplastyOpen Targets
0.26Weak
total joint arthroplastyOpen Targets
0.26Weak
systemic lupus erythematosusOpen Targets
0.23Weak
type 1 diabetes mellitusOpen Targets
0.23Weak
neurodegenerative diseaseOpen Targets
0.19Weak
celiac diseaseOpen Targets
0.19Weak
sweat gland diseaseOpen Targets
0.18Weak
respiratory system diseaseOpen Targets
0.09Suggestive
asthmaOpen Targets
0.08Suggestive
HypercholesterolemiaOpen Targets
0.07Suggestive
colorectal cancerOpen Targets
0.07Suggestive
psoriasis vulgarisOpen Targets
0.07Suggestive
iridocyclitisOpen Targets
0.06Suggestive
childhood onset asthmaOpen Targets
0.06Suggestive
inflammatory spondylopathyOpen Targets
0.04Suggestive
ACPA-positive rheumatoid arthritisOpen Targets
0.03Suggestive
neoplasmOpen Targets
0.03Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
TCP11Protein interaction98%ZNF143Shared pathway38%ZNF345Shared pathway33%BRF2Shared pathway20%POLR3FShared pathway17%POLR3CShared pathway14%
Tissue Expression6 tissues
Ovary
100%
Heart
78%
Liver
70%
Lung
56%
Bone Marrow
43%
Brain
26%
Gene Interaction Network
Click a node to explore
ZNF76TCP11ZNF143ZNF345BRF2POLR3FPOLR3C
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt P36508
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.20LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.97 [0.80–1.20]
RankingsWhere ZNF76 stands among ~20K protein-coding genes
  • #12,493of 20,598
    Most Researched28
  • #12,577of 17,882
    Most Constrained (LOEUF)1.20
Genes detectedZNF76
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
ZNF76 predicts prognosis and response to platinum chemotherapy in human ovarian cancer.
PMID: 34793589
Biosci Rep · 2021
1.00
2
ZNF76 and ZNF143 are two human homologs of the transcriptional activator Staf.
PMID: 9705341
J Biol Chem · 1998
0.90
3
A testis-expressed Zn finger gene (ZNF76) in human 6p21.3 centromeric to the MHC is closely linked to the human homolog of the t-complex gene tcp-11.
PMID: 1427894
Genomics · 1992
0.80
4
The ZNF76 rs10947540 polymorphism associated with systemic lupus erythematosus risk in Chinese populations.
PMID: 33664275
Sci Rep · 2021
0.70
5
Acetylation and alternative splicing regulate ZNF76-mediated transcription.
PMID: 16337145
Biochem Biophys Res Commun · 2006
0.60