Details for: ZNF76

Gene ID: 7629

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: ZNF76

Ensembl ID: ENSG00000065029

Description: zinc finger protein 76

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

  • Central nervous system development
    (GO:0007417)
  • Dna-binding transcription activator activity, rna polymerase ii-specific
    (GO:0001228)
  • Dna-binding transcription factor activity, rna polymerase ii-specific
    (GO:0000981)
  • Metal ion binding
    (GO:0046872)
  • Nucleus
    (GO:0005634)
  • Positive regulation of transcription by rna polymerase ii
    (GO:0045944)
  • Protein binding
    (GO:0005515)
  • Regulation of transcription by rna polymerase ii
    (GO:0006357)
  • Regulation of transcription by rna polymerase iii
    (GO:0006359)
  • Rna polymerase ii cis-regulatory region sequence-specific dna binding
    (GO:0000978)
  • Sequence-specific dna binding
    (GO:0043565)
  • Sequence-specific double-stranded dna binding
    (GO:1990837)

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • mature B cell CL0000785
    CSI 10.27
    rCSI 8.93%
    PRS 81.07
  • intestinal tuft cell CL0019032
    CSI 6.93
    rCSI 10.59%
    PRS 75.02
  • neural progenitor cell CL0011020
    CSI 5.72
    rCSI 25.15%
    PRS 59.65
  • glial cell CL0000125
    CSI 4.64
    rCSI 17.67%
    PRS 61.03
  • effector CD8-positive, alpha-beta T cell CL0001050
    CSI 3.6
    rCSI 2.74%
    PRS 83.33
  • retinal rod cell CL0000604
    CSI 3.21
    rCSI 5.67%
    PRS 66.67
  • midzonal region hepatocyte CL0019028
    CSI 3.16
    rCSI 7.42%
    PRS 73.19
  • immature B cell CL0000816
    CSI 3.08
    rCSI 2.28%
    PRS 83
  • naive T cell CL0000898
    CSI 3.01
    rCSI 2.1%
    PRS 85.11
  • plasmablast CL0000980
    CSI 2.86
    rCSI 2.25%
    PRS 77.14
  • early lymphoid progenitor CL0000936
    CSI 2.78
    rCSI 2.44%
    PRS 75.96
  • alpha-beta T cell CL0000789
    CSI 2.71
    rCSI 3.17%
    PRS 85.56
  • melanocyte CL0000148
    CSI 2.66
    rCSI 1.97%
    PRS 63.37
  • kidney connecting tubule epithelial cell CL1000768
    CSI 2.62
    rCSI 6.65%
    PRS 60.14
  • epithelial cell of lower respiratory tract CL0002632
    CSI 2.58
    rCSI 2%
    PRS 73.79
  • secretory cell CL0000151
    CSI 2.56
    rCSI 2.67%
    PRS 70.56
  • choroid plexus epithelial cell CL0000706
    CSI 2.5
    rCSI 4.09%
    PRS 59.59
  • cardiac muscle cell CL0000746
    CSI 2.44
    rCSI 3.51%
    PRS 60.04
  • epithelial cell of lung CL0000082
    CSI 2.36
    rCSI 1.96%
    PRS 70.61
  • renal alpha-intercalated cell CL0005011
    CSI 2.32
    rCSI 3.11%
    PRS 78.64
  • lung neuroendocrine cell CL1000223
    CSI 2.26
    rCSI 3.34%
    PRS 75.45
  • Mueller cell CL0000636
    CSI 2.24
    rCSI 5.11%
    PRS 61.9
  • interneuron CL0000099
    CSI 2.2
    rCSI 4.42%
    PRS 59.78
  • sst GABAergic cortical interneuron CL4023017
    CSI 2.2
    rCSI 2.84%
    PRS 53.12
  • neural crest cell CL0011012
    CSI 2.19
    rCSI 1.73%
    PRS 57.78
  • lung ciliated cell CL1000271
    CSI 2.18
    rCSI 2.52%
    PRS 61.55
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 2.14
    rCSI 3.03%
    PRS 66.73
  • cardiac endothelial cell CL0010008
    CSI 2.13
    rCSI 8.59%
    PRS 69.94
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 2.1
    rCSI 3.81%
    PRS 61.9
  • CD16-positive, CD56-dim natural killer cell, human CL0000939
    CSI 1.9
    rCSI 1.26%
    PRS 86.51
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 1.89
    rCSI 4.89%
    PRS 65.45
  • vascular leptomeningeal cell CL4023051
    CSI 1.89
    rCSI 3.31%
    PRS 63.02
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 1.81
    rCSI 2.09%
    PRS 62.9
  • ciliated epithelial cell CL0000067
    CSI 1.76
    rCSI 1.55%
    PRS 58.52
  • chondrocyte CL0000138
    CSI 1.75
    rCSI 2.79%
    PRS 63.22
  • retina horizontal cell CL0000745
    CSI 1.75
    rCSI 2.67%
    PRS 66.82
  • respiratory suprabasal cell CL4033048
    CSI 1.73
    rCSI 2.22%
    PRS 74.75
  • VIP GABAergic cortical interneuron CL4023016
    CSI 1.7
    rCSI 2.03%
    PRS 51.58
  • type B pancreatic cell CL0000169
    CSI 1.68
    rCSI 3.72%
    PRS 69.19
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 1.6
    rCSI 1.99%
    PRS 49.82
  • regular atrial cardiac myocyte CL0002129
    CSI 1.46
    rCSI 4.7%
    PRS 68.23
  • astrocyte of the cerebral cortex CL0002605
    CSI 1.44
    rCSI 3.22%
    PRS 52.36
  • ionocyte CL0005006
    CSI 1.43
    rCSI 1.54%
    PRS 71
  • extravillous trophoblast CL0008036
    CSI 1.43
    rCSI 1.77%
    PRS 67.61
  • glycinergic amacrine cell CL4030028
    CSI 1.41
    rCSI 3.67%
    PRS 66.64
  • pancreatic A cell CL0000171
    CSI 1.4
    rCSI 1.47%
    PRS 74.08
  • cerebral cortex endothelial cell CL1001602
    CSI 1.37
    rCSI 2.38%
    PRS 60.99
  • retinal cone cell CL0000573
    CSI 1.24
    rCSI 1.99%
    PRS 59.93
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 1.22
    rCSI 0.94%
    PRS 72.4
  • cardiac neuron CL0010022
    CSI 1.17
    rCSI 3.76%
    PRS 67.59
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.09
    rCSI 1.76%
    PRS 53.62
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.07
    rCSI 1.89%
    PRS 50.83
  • retinal bipolar neuron CL0000748
    CSI 1.06
    rCSI 1.98%
    PRS 58.24
  • effector memory CD8-positive, alpha-beta T cell, terminally differentiated CL0001062
    CSI 1.06
    rCSI 5.31%
    PRS 82.97
  • indirect pathway medium spiny neuron CL4023029
    CSI 1
    rCSI 24.14%
    PRS 51.32
  • direct pathway medium spiny neuron CL4023026
    CSI 0.99
    rCSI 23.77%
    PRS 50.71
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 0.92
    rCSI 1.55%
    PRS 51.73
  • retinal ganglion cell CL0000740
    CSI 0.88
    rCSI 1.95%
    PRS 56.39
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 0.81
    rCSI 1.98%
    PRS 50.14
  • dopaminergic neuron CL0000700
    CSI 0.76
    rCSI 4.31%
    PRS 55.84
  • blood vessel smooth muscle cell CL0019018
    CSI 0.76
    rCSI 6.17%
    PRS 64.07
  • amacrine cell CL0000561
    CSI 0.66
    rCSI 1.92%
    PRS 59.66
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 0.66
    rCSI 2.07%
    PRS 56
  • podocyte CL0000653
    CSI 0.61
    rCSI 2.72%
    PRS 70.8
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.61
    rCSI 1.9%
    PRS 53.55
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 0.6
    rCSI 2.28%
    PRS 52.3
  • regular ventricular cardiac myocyte CL0002131
    CSI 0.59
    rCSI 3.65%
    PRS 61.94
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.57
    rCSI 3.37%
    PRS 52.83
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.51
    rCSI 1.82%
    PRS 49.9
  • ON parasol ganglion cell CL4033052
    CSI 0.31
    rCSI 4.45%
    PRS 61.53
  • OFF midget ganglion cell CL4033047
    CSI 0.27
    rCSI 5.46%
    PRS 62.25

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [ZNF76](/details-gene/7629) is a protein-coding gene located on chromosome 6 that encodes Zinc Finger Protein 76. As its name suggests, it is a member of the zinc finger protein family, which typically function as DNA-binding transcription factors. Functional annotations confirm its localization to the [nucleus](/details-cell/GO:0005634) and its role in the [positive regulation of transcription by rna polymerase ii](/details-cell/GO:0045944). **Overall**, [ZNF76](/details-gene/7629) exhibits its most significant expression signature in immune cells, particularly [mature B cell](/details-cell/CL0000785)s, but also shows notable significance in diverse non-immune cell types such as [intestinal tuft cell](/details-cell/CL0019032)s and [neural progenitor cell](/details-cell/CL0011020)s. This expression pattern suggests a role not only in lymphocyte biology but also in the development and function of specialized cells in other tissues. It has a clinical association with an OMIM entry ([194549](https://omim.org/entry/194549)). ## Cellular Roles and Expression Landscape The expression profile of [ZNF76](/details-gene/7629) highlights its prominent role within the adaptive immune system. It demonstrates the highest significance in [mature B cell](/details-cell/CL0000785) (CSI: 10.27), with substantial signatures also observed across the B-cell lineage, including in [immature B cell](/details-cell/CL0000816)s and [plasmablast](/details-cell/CL0000980)s. This suggests a continuous requirement for [ZNF76](/details-gene/7629) throughout B-cell maturation and differentiation. Similarly, it is significantly expressed in the T-cell lineage, including [effector CD8-positive, alpha-beta T cell](/details-cell/CL0001050)s and [naive T cell](/details-cell/CL0000898)s, indicating a broad function in lymphocyte biology. Beyond the immune system, [ZNF76](/details-gene/7629) shows a surprisingly specific and significant expression pattern in several other cell types. It is a key marker for [intestinal tuft cell](/details-cell/CL0019032)s (CSI: 6.93), specialized chemosensory cells in the gut epithelium. Furthermore, its high significance in [neural progenitor cell](/details-cell/CL0011020)s and [glial cell](/details-cell/CL0000125)s is consistent with its annotated role in [central nervous system development](/details-cell/GO:0007417). This diverse expression landscape suggests that [ZNF76](/details-gene/7629) may regulate fundamental transcriptional programs related to cell differentiation and specialized function across multiple, distinct lineages. ## Pathways and Molecular Function [ZNF76](/details-gene/7629) primarily functions as a transcriptional regulator. Its molecular functions are dominated by activities related to [sequence-specific dna binding](/details-cell/GO:0043565) and acting as a [dna-binding transcription activator activity, rna polymerase ii-specific](/details-cell/GO:0001228). These roles are physically supported by its composition as a zinc finger protein, which involves [metal ion binding](/details-cell/GO:0046872) to maintain structural integrity for DNA interaction, and its localization within the [nucleus](/details-cell/GO:0005634). The gene is implicated in several core biological processes, most notably the [regulation of transcription by rna polymerase ii](/details-cell/GO:0006357) and [central nervous system development](/details-cell/GO:0007417). The former is a general function consistent with its high expression in metabolically active and differentiating cells like lymphocytes, while the latter directly explains its significance in neural cell types. Additionally, its annotation for [protein binding](/details-cell/GO:0005515) suggests it may act as part of larger transcriptional complexes. This is supported by research identifying it as a target for post-translational modification by SUMOylation, a process that can modulate protein-protein interactions and transcriptional activity [Link](https://doi.org/10.1038/nsmb.3366). ## Research Directions The widespread yet specific expression of [ZNF76](/details-gene/7629) across both immune and non-immune lineages presents several avenues for future investigation. ### Proposed Hypotheses: 1. Given its consistently high significance across B-cell development from [immature B cell](/details-cell/CL0000816) to [plasmablast](/details-cell/CL0000980), [ZNF76](/details-gene/7629) may be a master regulator required for orchestrating the transcriptional changes that drive B-cell maturation, class-switch recombination, and terminal differentiation into antibody-secreting cells. 2. The shared high expression in disparate cell types like [neural progenitor cell](/details-cell/CL0011020)s and [early lymphoid progenitor](/details-cell/CL0000936)s suggests that [ZNF76](/details-gene/7629) may regulate a common set of genes involved in cell fate determination and lineage commitment, potentially by controlling cellular plasticity or differentiation pathways. ### Key Experiments: To test the first hypothesis regarding its role in B-cell differentiation, a B-cell-specific conditional knockout of [ZNF76](/details-gene/7629) (e.g., using a CD19-Cre driver mouse model) would be highly informative. Following immunization with a T-dependent antigen, analyses of germinal center formation, B-cell population dynamics via flow cytometry, and antigen-specific antibody titers via ELISA would reveal defects in the humoral immune response. Concurrently, RNA-sequencing and ATAC-sequencing of B cells at different developmental stages from both knockout and wild-type mice could identify the direct transcriptional targets of [ZNF76](/details-gene/7629) and the gene regulatory networks it controls. ### Therapeutic Potential: As an intracellular transcription factor, [ZNF76](/details-gene/7629) is a challenging direct drug target. However, its crucial role in the B-cell lineage suggests it could be a potential therapeutic node for B-cell-mediated pathologies. In B-cell malignancies (e.g., lymphomas) or autoimmune diseases characterized by hyperactive B-cells, strategies aimed at disrupting the function of [ZNF76](/details-gene/7629) could be beneficial. Rather than direct inhibition of its DNA-binding domain, a more viable approach may be to develop small molecules that disrupt its essential protein-protein interactions, thereby destabilizing the transcriptional complexes it requires for function. Therefore, inhibition of its activity, rather than activation, would likely be the therapeutic goal.

Genular Protein ID: 3475042558

Symbol: ZNF76_HUMAN

Name: Zinc finger protein 76

UniProtKB Accession Codes:

P36508 Q9BQB2

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 4 Ensembl 2 ExpressionAtlas 1 GO 11 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIR 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 RefSeq 4 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 1427894

Title: 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.

PubMed ID: 1427894

DOI: 10.1016/s0888-7543(05)80167-3

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 28112733

Title: Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation.

PubMed ID: 28112733

DOI: 10.1038/nsmb.3366

Sequence Information:

  • Length: 570
  • Mass: 61831
  • Checksum: 333C99E0E79D86C2
  • Sequence:
    • MESLGLHTVT LSDGTTAYVQ QAVKGEKLLE GQVIQLEDGT TAYIHQVTVQ KEALSFEDGQ 
PVQLEDGSMA YIHRTPREGY DPSTLEAVQL EDGSTAYIHH PVAVPSESTI LAVQTEVGLE 
DLAAEDDEGF SADAVVALEQ YASKVLHDSQ IPRNGKGQQV GDRAFRCGYK GCGRLYTTAH 
HLKVHERAHT GDRPYRCDFP SCGKAFATGY GLKSHVRTHT GEKPYKCPEE LCSKAFKTSG 
DLQKHVRTHT GERPFQCPFE GCGRSFTTSN IRKVHVRTHT GERPYTCPEP HCGRGFTSAT 
NYKNHVRIHT GEKPYVCTVP GCGKRFTEYS SLYKHHVVHT HCKPYTCSTC GKTYRQTSTL 
AMHKRSAHGE LEATEESEQA LYEQQQLEAA SAAEESPPPK RPRIAYLSEV KEERDDIPAQ 
VAMVTEEDGA PQVALITQDG AQQVSLSPED LQALGSAISM VTQHGSTTLT IPSPDADLAT 
SGTHTVTMVS ADGTQTQPVT IITSGAVVAE DSSVASLRHQ QVALLATANG THIAVQLEEQ 
QTLEEAINVA TAAMQQGAVT LETTVSESGC