Details for: RNF112

Gene ID: 7732

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: RNF112

Ensembl ID: ENSG00000128482

Description: ring finger protein 112

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • progenitor cell CL0011026
    CSI 11.93
    rCSI 25.36%
    PRS 74.24
  • innate lymphoid cell CL0001065
    CSI 6.7
    rCSI 13.83%
    PRS 76.98
  • VIP GABAergic cortical interneuron CL4023016
    CSI 3.7
    rCSI 4.42%
    PRS 62
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 3.31
    rCSI 5.55%
    PRS 61.87
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 3.18
    rCSI 3.96%
    PRS 59.81
  • astrocyte of the cerebral cortex CL0002605
    CSI 2.94
    rCSI 6.59%
    PRS 62.65
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 2.35
    rCSI 8.87%
    PRS 62.37
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 1.72
    rCSI 3.12%
    PRS 71.37
  • sst GABAergic cortical interneuron CL4023017
    CSI 1.65
    rCSI 2.12%
    PRS 62.99
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.56
    rCSI 2.76%
    PRS 61.19
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.33
    rCSI 2.15%
    PRS 63.53
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.3
    rCSI 3.16%
    PRS 59.89
  • L6b glutamatergic cortical neuron CL4023038
    CSI 1.17
    rCSI 3.65%
    PRS 63.52
  • melanocyte of skin CL1000458
    CSI 0.95
    rCSI 1.3%
    PRS 46.86
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.84
    rCSI 4.92%
    PRS 62.62
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.6
    rCSI 2.16%
    PRS 59.76
  • direct pathway medium spiny neuron CL4023026
    CSI 0.49
    rCSI 11.61%
    PRS 60.22
  • indirect pathway medium spiny neuron CL4023029
    CSI 0.21
    rCSI 4.98%
    PRS 60.78
  • medium spiny neuron CL1001474
    CSI 0.15
    rCSI 1.31%
    PRS 68.13

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.

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  • 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 [RNF112](/details-gene/7732) is a protein-coding gene located on chromosome 17p11.2 that encodes Ring Finger Protein 112, an E3 ubiquitin ligase. Functionally, [RNF112](/details-gene/7732) is implicated in crucial cellular processes including protein ubiquitination, regulation of the cell cycle, and the differentiation of neural cells. Expression data highlights its significant role within the central nervous system, where it is a prominent marker for various neuronal subtypes, glial cells, and their precursors. Notably, it shows the highest significance in [progenitor cell](/details-cell/CL0011026), suggesting a fundamental role in cell fate decisions and development. Research has also linked its activity to tumor suppression in glioblastoma by inducing differentiation and growth arrest ([Link](https://doi.org/10.1038/s41598-017-05305-0)). ## Cellular Roles and Expression Landscape The expression profile of [RNF112](/details-gene/7732) firmly establishes its importance within the nervous system and in developmental contexts. **Overall**, the gene exhibits its highest significance score by a large margin in [progenitor cell](/details-cell/CL0011026) (CSI: 11.93), underscoring a potential primary role in maintaining pluripotency or guiding lineage commitment. Beyond this, [RNF112](/details-gene/7732) is highly active across a diverse landscape of neural cells. It is a significant marker in multiple GABAergic interneuron populations, including [VIP GABAergic cortical interneuron](/details-cell/CL4023016), [lamp5 GABAergic cortical interneuron](/details-cell/CL4023011), and [pvalb GABAergic cortical interneuron](/details-cell/CL4023018). It is also prominent in glutamatergic neurons such as [near-projecting glutamatergic cortical neuron](/details-cell/CL4023012) and glial cell types, including [astrocyte of the cerebral cortex](/details-cell/CL0002605) and [differentiation-committed oligodendrocyte precursor](/details-cell/CL4023059). This broad yet specific expression pattern within the central nervous system suggests a central role in establishing and maintaining the identity and function of multiple neural lineages. Interestingly, [RNF112](/details-gene/7732) also shows high significance in [innate lymphoid cell](/details-cell/CL0001065), indicating a potential, less-characterized function within the immune system that is distinct from its well-defined role in neurobiology. ## Pathways and Molecular Function The functions of [RNF112](/details-gene/7732) are consistent with its expression pattern, centering on development and cell cycle regulation, primarily through its enzymatic activity. As a RING finger protein, its core molecular function is [ubiquitin protein ligase activity](/details-go/GO:0061630), enabling it to tag other proteins for degradation or functional modification. This is further supported by annotations for [protein autoubiquitination](/details-go/GO:0051865) and [protein binding](/details-go/GO:0005515). Its biological roles are heavily enriched in neurodevelopmental processes. Gene Ontology annotations include [embryonic brain development](/details-go/GO:1990403), [neuron differentiation](/details-go/GO:0030182), [positive regulation of neuron differentiation](/details-go/GO:0045666), and [positive regulation of glial cell differentiation](/details-go/GO:0045687). These functions align perfectly with its high expression in progenitor cells and various mature neuronal and glial subtypes. Furthermore, its involvement in the [regulation of cell cycle](/details-go/GO:0051726) and the [g1 to g0 transition involved in cell differentiation](/details-go/GO:0070315) provides a mechanistic link to its role in promoting differentiation and growth arrest, a function observed experimentally in glioblastoma cells ([Link](https://doi.org/10.1038/s41598-017-05305-0)). Cellularly, it is found in both the [cytoplasm](/details-go/GO:0005737) and the [nucleus](/details-go/GO:0005634), with specific localization to neuronal structures like the [neuron projection](/details-go/GO:0043005) and [postsynaptic density](/details-go/GO:0014069). ## Research Directions The available data points to [RNF112](/details-gene/7732) as a key regulator of neural cell fate with potential tumor-suppressive functions. Future research should focus on elucidating the specific mechanisms by which it controls these processes. **Proposed Hypotheses:** 1. Given its peak significance in [progenitor cell](/details-cell/CL0011026) and its established role as a ubiquitin ligase, we hypothesize that [RNF112](/details-gene/7732) acts as a critical switch in neural development by targeting key transcription factors or signaling proteins that maintain pluripotency for ubiquitination, thereby releasing the cell from a progenitor state and permitting terminal differentiation. 2. The high significance of [RNF112](/details-gene/7732) in [innate lymphoid cell](/details-cell/CL0001065) is a notable outlier. We hypothesize that [RNF112](/details-gene/7732) regulates the differentiation or effector function of ILCs by ubiquitinating a substrate that is a shared component of developmental pathways in both the nervous and immune systems. **Experimental Approach:** To test the first hypothesis regarding its role in neural progenitors, a compelling experiment would be to use a human induced pluripotent stem cell (iPSC) model of neural differentiation. CRISPR-Cas9 could be used to generate an [RNF112](/details-gene/7732) knockout iPSC line. Both wild-type and knockout lines would be differentiated into neural progenitor cells (NPCs) and subsequently into mature neurons and astrocytes. The differentiation efficiency and resulting cell populations would be quantified using flow cytometry and immunofluorescence for lineage-specific markers. To identify direct targets, proteomics analysis using proximity-labeling (e.g., BioID) or immunoprecipitation followed by mass spectrometry (IP-MS) could be performed in NPCs to identify proteins that interact with and are ubiquitinated by [RNF112](/details-gene/7732). **Therapeutic Potential:** The demonstrated ability of [RNF112](/details-gene/7732) to induce growth arrest and differentiation in glioblastoma multiforme ([Link](https://doi.org/10.1038/s41598-017-05305-0)) positions it as a tumor suppressor in this context. Therefore, therapeutic strategies should focus on **activation** or restoration of its function rather than inhibition. This could involve developing small-molecule activators that enhance its E3 ligase activity or using gene therapy-based approaches to re-introduce its expression in tumor cells where it has been silenced. Such a strategy could force malignant, undifferentiated cancer cells into a post-mitotic, differentiated state, representing a promising therapeutic avenue for glioblastoma and potentially other neural-derived cancers.

Genular Protein ID: 2418574417

Symbol: RN112_HUMAN

Name: RING finger protein 112

UniProtKB Accession Codes:

Q9ULX5 O60633 Q7Z5V9

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEBI 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EC 1 EMBL 4 Ensembl 1 ExpressionAtlas 1 GO 25 Gene3D 2 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MANE-Select 1 MIM 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 2 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 RefSeq 1 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 UCSC 1 UniPathway 1 VEuPathDB 1 eggNOG 2 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 10574464

Title: cDNA cloning of a human brain finger protein, BFP/ZNF179, a member of the RING finger protein family.

PubMed ID: 10574464

DOI: 10.1093/dnares/6.5.353

PubMed ID: 16625196

Title: DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage.

PubMed ID: 16625196

DOI: 10.1038/nature04689

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: 8660987

Title: Chromosome mapping of human (ZNF179), mouse, and rat genes for brain finger protein (bfp), a member of the RING finger family.

PubMed ID: 8660987

DOI: 10.1006/geno.1996.0203

PubMed ID: 28684796

Title: Znf179 induces differentiation and growth arrest of human primary glioblastoma multiforme in a p53-dependent cell cycle pathway.

PubMed ID: 28684796

DOI: 10.1038/s41598-017-05305-0

Sequence Information:

  • Length: 631
  • Mass: 68298
  • Checksum: 770C4F33B1395954
  • Sequence:
    • MPRPALSVTS FCHRLGKRER KQSFMGNSGN SWSHTPFPKL ELGLGPQPMA PRELPTCSIC 
LERLRDPISL DCGHDFCIRC FSTHRLPGCE PPCCPECRKI CKQKRGLRSL GEKMKLLPQR 
PLPPALQETC PVRAEPLLLV RINASGGLIL RMGAINRCLK HPLARDTPVC LLAVLGEQHS 
GKSFLLNHLL QGLPGLESGE GGRPRGGEAS LQGCRWGANG LARGIWMWSH PFLLGKEGKK 
VAVFLVDTGD AMSPELSRET RIKLCALTTM LSSYQILSTS QELKDTDLDY LEMFVHVAEV 
MGKHYGMVPI QHLDLLVRDS SHPNKAGQGH VGNIFQRLSG RYPKVQELLQ GKRARCCLLP 
APGRRRMNQG HASPGDTDDD FRHLLGAYVS DVLSAAPQHA KSRCQGYWNE GRAVARGDRR 
LLTGQQLAQE IKNLSGWMGR TGPGFTSPDE MAAQLHDLRK VEAAKREFEE YVRQQDVATK 
RIFSALRVLP DTMRNLLSTQ KDAILARHGV ALLCKGRDQT LEALEAELQA TAKAFMDSYT 
MRFCGHLAAV GGAVGAGLMG LAGGVVGAGM AAAALAAEAG MVAAGAAVGA TGAAVVGGGV 
GAGLAATVGC MEKEEDERLL EGDREPLLQE E