Details for: NRIP3

Gene ID: 56675

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: NRIP3

Ensembl ID: ENSG00000175352

Description: nuclear receptor interacting protein 3

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 19.26
    rCSI 32.33%
    PRS 94.24
  • sncg GABAergic cortical interneuron CL4023015
    CSI 11.72
    rCSI 18.86%
    PRS 94.1
  • retina horizontal cell CL0000745
    CSI 10.66
    rCSI 16.25%
    PRS 96.62
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 9.27
    rCSI 16.36%
    PRS 94.01
  • ionocyte CL0005006
    CSI 8.44
    rCSI 9.04%
    PRS 98.49
  • glycinergic amacrine cell CL4030028
    CSI 8.18
    rCSI 21.32%
    PRS 94.39
  • melanocyte CL0000148
    CSI 5.35
    rCSI 3.97%
    PRS 96.89
  • inhibitory interneuron CL0000498
    CSI 5.34
    rCSI 12.34%
    PRS 94.4
  • sst GABAergic cortical interneuron CL4023017
    CSI 5.25
    rCSI 6.77%
    PRS 94.61
  • retinal ganglion cell CL0000740
    CSI 5.1
    rCSI 11.27%
    PRS 93.97
  • H2 horizontal cell CL0004218
    CSI 5.05
    rCSI 25.09%
    PRS 95.01
  • interneuron CL0000099
    CSI 5.01
    rCSI 10.06%
    PRS 96.23
  • VIP GABAergic cortical interneuron CL4023016
    CSI 4.95
    rCSI 5.92%
    PRS 94.09
  • retinal cone cell CL0000573
    CSI 3.63
    rCSI 5.85%
    PRS 94.76
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 3.59
    rCSI 4.47%
    PRS 93.03
  • pulmonary ionocyte CL0017000
    CSI 3.16
    rCSI 3.84%
    PRS 98.76
  • cerebellar granule cell CL0001031
    CSI 3.15
    rCSI 4.64%
    PRS 95.71
  • H1 horizontal cell CL0004217
    CSI 3.15
    rCSI 12.46%
    PRS 94.38
  • cerebral cortex neuron CL0010012
    CSI 3.05
    rCSI 12.41%
    PRS 93.95
  • CD14-positive monocyte CL0001054
    CSI 2.95
    rCSI 3.68%
    PRS 99.63
  • amacrine cell CL0000561
    CSI 2.56
    rCSI 7.4%
    PRS 94.51
  • granulocyte CL0000094
    CSI 2.33
    rCSI 3.57%
    PRS 98.84
  • GABAergic neuron CL0000617
    CSI 2.19
    rCSI 7.34%
    PRS 91.45
  • L6b glutamatergic cortical neuron CL4023038
    CSI 2.11
    rCSI 6.6%
    PRS 94.36
  • ON parasol ganglion cell CL4033052
    CSI 1.61
    rCSI 22.86%
    PRS 93.91
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 1.55
    rCSI 4.86%
    PRS 94.85
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 1.4
    rCSI 5.29%
    PRS 93.6
  • GABAergic amacrine cell CL4030027
    CSI 1.21
    rCSI 4.14%
    PRS 91.69
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 1.02
    rCSI 3.67%
    PRS 93.03
  • ON midget ganglion cell CL4033046
    CSI 0.85
    rCSI 17.22%
    PRS 93.7
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.79
    rCSI 4.64%
    PRS 93.9
  • OFF midget ganglion cell CL4033047
    CSI 0.54
    rCSI 11.04%
    PRS 93.84
  • central nervous system neuron CL2000029
    CSI 0.49
    rCSI 3.57%
    PRS 94.85

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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  • 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 Nuclear Receptor Interacting Protein 3, or [NRIP3](/details-gene/56675), is a protein-coding gene located on human chromosome 11p15.4. Functional annotations suggest that [NRIP3](/details-gene/56675) is an enzyme involved in [proteolysis](/details-go/GO:0006508), specifically exhibiting [aspartic-type endopeptidase activity](/details-go/GO:0004190). Expression data indicates a highly specialized role for this gene, with its most significant expression concentrated in specific neuronal subtypes within the central nervous system. In particular, it is a prominent marker for distinct populations of inhibitory GABAergic interneurons in the cortex and various cell types within the retina, suggesting a key function in neuronal homeostasis and signaling in these tissues. ## Cellular Roles and Expression Landscape The expression profile of [NRIP3](/details-gene/56675) demonstrates remarkable cell-type specificity, primarily within the nervous system. **Overall**, the gene's highest significance is observed in discrete subpopulations of cortical inhibitory neurons. It is an exceptional marker for [lamp5 GABAergic cortical interneuron](/details-cell/CL4023011) (CSI: 19.26) and [sncg GABAergic cortical interneuron](/details-cell/CL4023015) (CSI: 11.72), and shows notable significance across other interneuron classes, including [sst GABAergic cortical interneuron](/details-cell/CL4023017) and [VIP GABAergic cortical interneuron](/details-cell/CL4023016). In addition to its role in cortical circuits, [NRIP3](/details-gene/56675) is also highly significant in the retina. It is prominently expressed in [retina horizontal cell](/details-cell/CL0000745)s (CSI: 10.66), [glycinergic amacrine cell](/details-cell/CL4030028)s (CSI: 8.18), [retinal ganglion cell](/details-cell/CL0000740)s, and [retinal cone cell](/details-cell/CL0000573)s. This pattern suggests a fundamental role in processing and transmitting visual information. Beyond the central nervous system, significant expression is also noted in specialized cells such as the [ionocyte](/details-cell/CL0005006) and [melanocyte](/details-cell/CL0000148), indicating that its function may extend to other physiological contexts requiring precise protein regulation. ## Pathways and Molecular Function The functional annotations for [NRIP3](/details-gene/56675) strongly indicate its role as a protease. Its assigned molecular function of [aspartic-type endopeptidase activity](/details-go/GO:0004190) places it in a class of enzymes that cleave peptide bonds within proteins, driving the biological process of [proteolysis](/details-go/GO:0006508). The additional annotation for [protein binding](/details-go/GO:0005515) is consistent with an enzyme that must first recognize and bind to its specific substrates before catalysis. In the context of its cellular expression, this proteolytic function is likely critical for neuronal health and signaling. In highly specialized cells like [inhibitory interneuron](/details-cell/CL0000498)s and retinal neurons, precise protein turnover is essential for maintaining synaptic plasticity, processing neuropeptides, and regulating signal transduction pathways. The activity of [NRIP3](/details-gene/56675) may therefore be integral to the molecular machinery that governs the function of these specific neural circuits. ## Research Directions The highly specific expression and enzymatic function of [NRIP3](/details-gene/56675) suggest several avenues for future research. **Proposed Hypotheses:** 1. Given its high expression in multiple classes of cortical GABAergic interneurons, [NRIP3](/details-gene/56675) may be a key regulator of inhibitory neurotransmission. It could function by processing precursor proteins into mature neuropeptides (e.g., somatostatin, VIP) or by degrading specific synaptic proteins to modulate synaptic strength and plasticity. Dysregulation of [NRIP3](/details-gene/56675) could therefore contribute to an excitatory/inhibitory imbalance implicated in neurological disorders like epilepsy or schizophrenia. 2. The significant expression of [NRIP3](/details-gene/56675) across functionally distinct retinal cell types, including photoreceptors ([retinal cone cell](/details-cell/CL0000573)) and interneurons ([retina horizontal cell](/details-cell/CL0000745)), suggests it plays a role in the visual cycle or retinal signal processing. It might be involved in the turnover of phototransduction cascade proteins or the cleavage of signaling molecules that mediate communication between retinal layers. **Experimental Approach:** To test the hypothesis that [NRIP3](/details-gene/56675) regulates cortical interneuron function, a conditional knockout mouse model could be generated using a Lamp5-Cre driver to specifically delete the gene in the top-expressing interneuron subtype. Cortical slices from these mice could be analyzed using patch-clamp electrophysiology to measure changes in synaptic properties and intrinsic excitability. Concurrently, quantitative proteomics on fluorescence-activated cell sorted [lamp5 GABAergic cortical interneuron](/details-cell/CL4023011)s from knockout and control animals would identify the specific protein substrates of [NRIP3](/details-gene/56675), revealing the molecular pathways it directly modulates. **Therapeutic Potential:** As an enzyme, [NRIP3](/details-gene/56675) is a potentially druggable target. Its highly restricted expression pattern is advantageous, as it suggests that a targeted therapy could have minimal off-target effects in other tissues. If over-activity or gain-of-function mutations in [NRIP3](/details-gene/56675) were linked to neurodegenerative diseases or retinal disorders through aberrant proteolysis, developing specific small-molecule inhibitors would be a viable therapeutic strategy. Conversely, if its loss of function leads to the accumulation of toxic protein substrates, strategies for enhancing its activity could be explored. A thorough understanding of its substrates and physiological role is a critical first step before considering it as a clinical target.

Genular Protein ID: 3453431689

Symbol: NRIP3_HUMAN

Name: Nuclear receptor-interacting protein 3

UniProtKB Accession Codes:

Q9NQ35 Q86WD9

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 4 Ensembl 1 ExpressionAtlas 1 GO 2 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyConnect 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MEROPS 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 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: 11528127

Title: Comparative genomic sequencing reveals a strikingly similar architecture of a conserved syntenic region on human chromosome 11p15.3 (including gene ST5) and mouse chromosome 7.

PubMed ID: 11528127

DOI: 10.1159/000056999

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

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: 12601173

Title: Immunomic analysis of human sarcoma.

PubMed ID: 12601173

DOI: 10.1073/pnas.0437972100

Sequence Information:

  • Length: 241
  • Mass: 26975
  • Checksum: 3ECFE6A3CE3DB539
  • Sequence:
    • MFYSGLLTEG GRKETDMREA ASLRQQRRMK QAVQFIHKDS ADLLPLDGLK KLGSSKDMQP 
HNILQRRLME TNLSKLRSGP RVPWASKTNK LNQAKSEGLK KSEEDDMILV SCQCAGKDVK 
ALVDTGCLYN LISLACVDRL GLKEHVKSHK HEGEKLSLPR HLKVVGQIEH LVITLGSLRL 
DCPAAVVDDN EKNLSLGLQT LRSLKCIINL DKHRLIMGKT DKEEIPFVET VSLNEDNTSE 
A