Details for: NNAT

Gene ID: 4826

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: NNAT

Ensembl ID: ENSG00000053438

Description: neuronatin

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 30.45
    rCSI 35.16%
    PRS 92.69
  • peripheral nervous system neuron CL2000032
    CSI 26.73
    rCSI 36.42%
    PRS 93.78
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 25.36
    rCSI 32.54%
    PRS 94.96
  • glioblast CL0000030
    CSI 17.88
    rCSI 28.52%
    PRS 92.82
  • radial glial cell CL0000681
    CSI 16.39
    rCSI 22.78%
    PRS 96.35
  • interneuron CL0000099
    CSI 14.74
    rCSI 29.6%
    PRS 94.38
  • myofibroblast cell CL0000186
    CSI 14.28
    rCSI 19.78%
    PRS 95.39
  • forebrain radial glial cell CL0013000
    CSI 11.46
    rCSI 36.76%
    PRS 96.75
  • choroid plexus epithelial cell CL0000706
    CSI 11.33
    rCSI 18.55%
    PRS 93.78
  • mesodermal cell CL0000222
    CSI 10.7
    rCSI 12.85%
    PRS 97.23
  • cerebral cortex GABAergic interneuron CL0010011
    CSI 10.14
    rCSI 29.93%
    PRS 96.69
  • neural crest cell CL0011012
    CSI 9.97
    rCSI 7.88%
    PRS 94.4
  • enteric smooth muscle cell CL0002504
    CSI 9.43
    rCSI 13.45%
    PRS 97.4
  • macroglial cell CL0000126
    CSI 8.83
    rCSI 22.7%
    PRS 94.41
  • ependymal cell CL0000065
    CSI 7.8
    rCSI 15.83%
    PRS 86.27
  • endothelial cell of placenta CL0009092
    CSI 7.13
    rCSI 35.15%
    PRS 97.71
  • intestine goblet cell CL0019031
    CSI 6.88
    rCSI 6.11%
    PRS 95.63
  • ciliated epithelial cell CL0000067
    CSI 6.77
    rCSI 5.96%
    PRS 92.11
  • blood vessel endothelial cell CL0000071
    CSI 6.41
    rCSI 13.31%
    PRS 95.99
  • epithelial cell of lung CL0000082
    CSI 6.24
    rCSI 5.17%
    PRS 97.76
  • interstitial cell of Cajal CL0002088
    CSI 6.22
    rCSI 7.91%
    PRS 98.45
  • chondrocyte CL0000138
    CSI 6.03
    rCSI 9.6%
    PRS 94.61
  • astrocyte CL0000127
    CSI 5.83
    rCSI 12.43%
    PRS 85.82
  • glial cell CL0000125
    CSI 5.71
    rCSI 21.75%
    PRS 93.3
  • Cajal-Retzius cell CL0000695
    CSI 5.7
    rCSI 44.64%
    PRS 96.72
  • lung neuroendocrine cell CL1000223
    CSI 5.54
    rCSI 8.19%
    PRS 96.84
  • endothelial cell of vascular tree CL0002139
    CSI 4.37
    rCSI 23.92%
    PRS 94.18
  • neural cell CL0002319
    CSI 4.28
    rCSI 16.14%
    PRS 88.57
  • enteroendocrine cell CL0000164
    CSI 4.24
    rCSI 5.79%
    PRS 95.14
  • GABAergic neuron CL0000617
    CSI 3.75
    rCSI 12.56%
    PRS 89.03
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 3.72
    rCSI 9.05%
    PRS 89.53
  • glutamatergic neuron CL0000679
    CSI 3.72
    rCSI 7.64%
    PRS 89.42
  • neural progenitor cell CL0011020
    CSI 3.72
    rCSI 16.35%
    PRS 89.7
  • glycinergic amacrine cell CL4030028
    CSI 3.69
    rCSI 9.62%
    PRS 92.78
  • mesenchymal cell CL0008019
    CSI 3.55
    rCSI 9%
    PRS 95.37
  • cerebral cortex neuron CL0010012
    CSI 3.53
    rCSI 14.37%
    PRS 92.06
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 3.5
    rCSI 6.18%
    PRS 90.85
  • cerebral cortex endothelial cell CL1001602
    CSI 3.41
    rCSI 5.9%
    PRS 94.64
  • vascular leptomeningeal cell CL4023051
    CSI 3.22
    rCSI 5.65%
    PRS 95.31
  • progenitor cell CL0011026
    CSI 3.12
    rCSI 6.63%
    PRS 92.94
  • inhibitory interneuron CL0000498
    CSI 3.06
    rCSI 7.06%
    PRS 92.16
  • adipocyte CL0000136
    CSI 2.91
    rCSI 3.73%
    PRS 92.58
  • basal cell of epidermis CL0002187
    CSI 2.89
    rCSI 5.12%
    PRS 76.38
  • neuroplacodal cell CL0000032
    CSI 2.71
    rCSI 25.09%
    PRS 93.47
  • enteric neuron CL0007011
    CSI 2.64
    rCSI 39.09%
    PRS 96.44
  • sst GABAergic cortical interneuron CL4023017
    CSI 2.53
    rCSI 3.26%
    PRS 91.72
  • neuron CL0000540
    CSI 2.4
    rCSI 6.39%
    PRS 88.82
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 2.38
    rCSI 8.98%
    PRS 90.98
  • L6b glutamatergic cortical neuron CL4023038
    CSI 2.34
    rCSI 7.3%
    PRS 91.66
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 2.32
    rCSI 8.36%
    PRS 89.76
  • cerebral cortex pyramidal neuron CL4023111
    CSI 1.92
    rCSI 11.82%
    PRS 96.11
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 1.83
    rCSI 10.77%
    PRS 91.17
  • epithelial cell of nephron CL1000449
    CSI 1.72
    rCSI 16.33%
    PRS 99.57
  • cell of skeletal muscle CL0000188
    CSI 1.64
    rCSI 17.8%
    PRS 93.41
  • indirect pathway medium spiny neuron CL4023029
    CSI 1.6
    rCSI 38.59%
    PRS 88.62
  • amacrine cell CL0000561
    CSI 1.5
    rCSI 4.34%
    PRS 92.33
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.5
    rCSI 2.51%
    PRS 91.2
  • retinal ganglion cell CL0000740
    CSI 1.48
    rCSI 3.26%
    PRS 91.47
  • direct pathway medium spiny neuron CL4023026
    CSI 1.42
    rCSI 34.04%
    PRS 88.86
  • stromal cell CL0000499
    CSI 1.29
    rCSI 3.63%
    PRS 95.34
  • central nervous system neuron CL2000029
    CSI 0.68
    rCSI 4.98%
    PRS 93.03
  • mesenchymal stem cell CL0000134
    CSI 0.64
    rCSI 6.98%
    PRS 97.88

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 [NNAT](/details-gene/4826) (Neuronatin) is a protein-coding gene located on chromosome 20q11.23. It encodes a small, membrane-associated proteolipid primarily involved in nervous system development and metabolic regulation [Link](https://doi.org/10.1016/0006-8993(96)00167-9). **Overall**, expression data reveals that [NNAT](/details-gene/4826) is a highly significant marker for a variety of neural and glial cell types, including [neuroblast (sensu Vertebrata)](/details-cell/CL0000031), [peripheral nervous system neuron](/details-cell/CL2000032), and [glioblast](/details-cell/CL0000030), underscoring its central role in the central and peripheral nervous systems. Its function is linked to biological processes such as [brain development](/details-ontology/GO:0007420) and the [positive regulation of insulin secretion](/details-ontology/GO:0032024), suggesting a dual role in both neurogenesis and endocrine function. ## Cellular Roles and Expression Landscape The expression profile of [NNAT](/details-gene/4826) strongly associates it with the developing and mature nervous system. It exhibits its highest significance in neural progenitor populations, such as [neuroblast (sensu Vertebrata)](/details-cell/CL0000031) (CSI: 25.36) and [radial glial cell](/details-cell/CL0000681) (CSI: 16.39), as well as in mature neurons like [peripheral nervous system neuron](/details-cell/CL2000032) (CSI: 26.73) and [interneuron](/details-cell/CL0000099) (CSI: 14.74). This pattern is consistent with its established role in [brain development](/details-ontology/GO:0007420). Beyond neurons, [NNAT](/details-gene/4826) is also a significant marker for glial and neuro-supportive cells, including [glioblast](/details-cell/CL0000030) (CSI: 17.88), [macroglial cell](/details-cell/CL0000126) (CSI: 8.83), and [ependymal cell](/details-cell/CL0000065) (CSI: 7.80). This broad expression across multiple neural lineages suggests a fundamental role in the maintenance or function of the CNS. Notably, research has also identified high-level expression in the human pituitary gland and pituitary adenomas, implicating it in neuroendocrine functions [Link](https://doi.org/10.1007/bf02789395). Expression is also observed in non-neural cell types such as [myofibroblast cell](/details-cell/CL0000186) (CSI: 14.28) and [enteric smooth muscle cell](/details-cell/CL0002504) (CSI: 9.43), indicating potential roles in other tissues. ## Pathways and Molecular Function Functionally, [NNAT](/details-gene/4826) is annotated to several key biological processes. Its primary role is in [brain development](/details-ontology/GO:0007420), a function directly supported by its high expression in a wide array of neural progenitors and differentiated neural cells. The protein itself is localized to the [cytoplasm](/details-ontology/GO:0005737) and was initially characterized as a novel 'proteolipid', suggesting it is an integral membrane or membrane-associated protein that influences cellular lipid environments [Link](https://doi.org/10.1016/0006-8993(96)00167-9). In addition to its neurodevelopmental role, [NNAT](/details-gene/4826) is involved in metabolic control, specifically the [positive regulation of insulin secretion](/details-ontology/GO:0032024). This function connects its expression in neuroendocrine cells to systemic metabolic homeostasis. It is also linked to [protein lipoylation](/details-ontology/GO:0009249), a post-translational modification essential for the function of key metabolic enzyme complexes, further reinforcing its connection to cellular metabolism. ## Research Directions The expression and functional data for [NNAT](/details-gene/4826) suggest several avenues for future research, particularly concerning its roles in development, disease, and metabolism. **Testable Hypotheses:** 1. Given its high expression in [neuroblast (sensu Vertebrata)](/details-cell/CL0000031) and [radial glial cell](/details-cell/CL0000681), [NNAT](/details-gene/4826) may be a critical regulator of neural progenitor cell fate, influencing the switch between proliferation and differentiation during corticogenesis. 2. The significant expression of [NNAT](/details-gene/4826) in [glioblast](/details-cell/CL0000030) suggests it could contribute to glioma pathogenesis by altering cellular metabolism or promoting a less differentiated, more proliferative state. 3. Based on its annotated function in regulating insulin secretion and its expression in [enteric smooth muscle cell](/details-cell/CL0002504), [NNAT](/details-gene/4826) might play a role in gut-brain axis signaling or the regulation of metabolic function in enteric tissues. **Proposed Experimental Approach:** To test the hypothesis that [NNAT](/details-gene/4826) is involved in glioblastoma pathogenesis (Hypothesis 2), one could use CRISPR-Cas9 to knock out the gene in patient-derived glioblastoma stem cell (GSC) lines. The effect of the knockout on GSC proliferation, self-renewal (e.g., via sphere-forming assays), and differentiation potential could be assessed in vitro. Subsequently, metabolomic profiling and RNA-sequencing of knockout versus control cells would reveal the specific metabolic pathways and gene expression programs regulated by [NNAT](/details-gene/4826). **Therapeutic Potential:** The high significance of [NNAT](/details-gene/4826) in [glioblast](/details-cell/CL0000030) and its reported overexpression in other tumors like pituitary adenomas make it a potential therapeutic target. As a membrane-associated proteolipid, it may be accessible to targeted therapies. An **inhibition** strategy would be appropriate, aimed at reducing the pro-proliferative or metabolic advantages it may confer on cancer cells. This could potentially involve small molecule inhibitors or antibody-based therapies if an extracellular domain is present, representing a promising direction for neuro-oncology drug development.

Genular Protein ID: 4114580341

Symbol: NNAT_HUMAN

Name: Neuronatin

UniProtKB Accession Codes:

Q16517 B2R558 E1P5V6 Q16596 Q5U0N3

Database IDs:

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

Citations:

PubMed ID: 8813377

Title: Cloning of human neuronatin gene and its localization to chromosome-20q 11.2-12: the deduced protein is a novel 'proteolipid'.

PubMed ID: 8813377

DOI: 10.1016/0006-8993(96)00167-9

PubMed ID: 8660979

Title: Structure and organization of the human neuronatin gene.

PubMed ID: 8660979

DOI: 10.1006/geno.1996.0195

PubMed ID: 9356927

Title: cDNA cloning and mRNA expression analysis of the human neuronatin. High level expression in human pituitary gland and pituitary adenomas.

PubMed ID: 9356927

DOI: 10.1007/bf02789395

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 11780052

Title: The DNA sequence and comparative analysis of human chromosome 20.

PubMed ID: 11780052

DOI: 10.1038/414865a

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

Sequence Information:

  • Length: 81
  • Mass: 9237
  • Checksum: 067086C7663E3D20
  • Sequence:
    • MAAVAAASAE LLIIGWYIFR VLLQVFLECC IYWVGFAFRN PPGTQPIARS EVFRYSLQKL 
AYTVSRTGRQ VLGERRQRAP N

Genular Protein ID: 2160105384

Symbol: A0A3B3ITN5_HUMAN

Name: N/A

UniProtKB Accession Codes:

A0A3B3ITN5

Database IDs:

ARBA 2 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 1 Ensembl 2 ExpressionAtlas 1 GO 2 GeneTree 1 HGNC 1 InterPro 1 MassIVE 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PeptideAtlas 1 Proteomes 2 ProteomicsDB 1 RefSeq 1 SAM 2 VEuPathDB 1

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

PubMed ID: 11780052

Title: The DNA sequence and comparative analysis of human chromosome 20.

PubMed ID: 11780052

DOI: 10.1038/414865a

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

Sequence Information:

  • Length: 125
  • Mass: 13390
  • Checksum: EDF2EA732A64B9BB
  • Sequence:
    • MAAVAAASAE LLIIGWYIFR VLLQVFLECC IYWVGFAFRN PPGTQPIARS VQVLPAEAGI 
HGVADRAAGV GGAQAASPQL RPQLPALGGR IIRCSCASRP AREPVPRRNV GSPVFPRQRS 
TWQGQ