Details for: NPAS1

Gene ID: 4861

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: NPAS1

Ensembl ID: ENSG00000130751

Description: neuronal PAS domain protein 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

  • Central nervous system development
    (GO:0007417)
  • Chromatin
    (GO:0000785)
  • Dna-binding transcription factor activity
    (GO:0003700)
  • Dna-binding transcription factor activity, rna polymerase ii-specific
    (GO:0000981)
  • Maternal behavior
    (GO:0042711)
  • Negative regulation of dna-templated transcription
    (GO:0045892)
  • Negative regulation of transcription by rna polymerase ii
    (GO:0000122)
  • Nucleus
    (GO:0005634)
  • Protein heterodimerization activity
    (GO:0046982)
  • Regulation of transcription by rna polymerase ii
    (GO:0006357)
  • Rna polymerase ii transcription regulatory region sequence-specific dna binding
    (GO:0000977)
  • Startle response
    (GO:0001964)

Significant Cells

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

  • sncg GABAergic cortical interneuron CL4023015
    CSI 10.06
    rCSI 16.18%
    PRS 94.15
  • cerebral cortex GABAergic interneuron CL0010011
    CSI 5.53
    rCSI 16.32%
    PRS 97.88
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 3.56
    rCSI 4.43%
    PRS 93.1
  • inhibitory interneuron CL0000498
    CSI 3
    rCSI 6.92%
    PRS 94.47
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.88
    rCSI 3.45%
    PRS 94.14
  • sst GABAergic cortical interneuron CL4023017
    CSI 2.82
    rCSI 3.64%
    PRS 94.66
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 2.52
    rCSI 4.45%
    PRS 94.06
  • retinal cone cell CL0000573
    CSI 1.99
    rCSI 3.2%
    PRS 94.8
  • neural cell CL0002319
    CSI 1.78
    rCSI 6.73%
    PRS 91.58
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.54
    rCSI 2.58%
    PRS 94.29
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.72
    rCSI 2.6%
    PRS 93.08

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 [NPAS1](/details-gene/4861), or Neuronal PAS Domain Protein 1, is a protein-coding gene located on chromosome 19q13.32. It encodes a basic helix-loop-helix (bHLH) PAS domain-containing transcription factor. As its name suggests, [NPAS1](/details-gene/4861) is selectively expressed in the central nervous system ([Link](https://doi.org/10.1073/pnas.94.2.713)). Functional annotations indicate its primary role as a DNA-binding transcription factor that negatively regulates gene expression. The expression data highlights its exceptional significance in specific subpopulations of inhibitory neurons, particularly GABAergic interneurons within the cerebral cortex, suggesting it is a key determinant of their cellular identity and function. ## Cellular Roles and Expression Landscape The expression profile of [NPAS1](/details-gene/4861) underscores its highly specialized role within the nervous system. **Overall**, the gene shows its most significant expression in various classes of inhibitory neurons. It serves as a preeminent marker for [sncg GABAergic cortical interneuron](/details-cell/CL4023015) (CSI: 10.06) and demonstrates high significance in broader categories like [cerebral cortex GABAergic interneuron](/details-cell/CL0010011) (CSI: 5.53) and [inhibitory interneuron](/details-cell/CL0000498) (CSI: 3.00). Its high CSI values extend to multiple, well-defined subtypes of cortical interneurons, including [pvalb GABAergic cortical interneuron](/details-cell/CL4023018), [VIP GABAergic cortical interneuron](/details-cell/CL4023016), [sst GABAergic cortical interneuron](/details-cell/CL4023017), and [lamp5 GABAergic cortical interneuron](/details-cell/CL4023011). This consistent high-level expression across diverse interneuron lineages suggests that [NPAS1](/details-gene/4861) is a fundamental regulator of the GABAergic fate in the cortex. Its significance is also noted, albeit to a lesser extent, in other neural cell types such as the [retinal cone cell](/details-cell/CL0000573) and [L5 extratelencephalic projecting glutamatergic cortical neuron](/details-cell/CL4023041), indicating a potential role in the function of other specialized neurons beyond the inhibitory system. ## Pathways and Molecular Function Functionally, [NPAS1](/details-gene/4861) operates as a sequence-specific transcription factor located within the [nucleus](/details-cell/GO:0005634) and associated with [chromatin](/details-cell/GO:0000785). Its molecular activities are centered around [DNA-binding transcription factor activity](/details-cell/GO:0003700) and [protein heterodimerization activity](/details-cell/GO:0046982), consistent with the function of other bHLH-PAS proteins which often form heterodimers to bind DNA. This molecular machinery is primarily directed towards the [negative regulation of dna-templated transcription](/details-cell/GO:0045892) by RNA polymerase II. This repressive function is highly relevant to its biological roles in [central nervous system development](/details-cell/GO:0007417). By suppressing specific gene programs, [NPAS1](/details-gene/4861) likely plays a critical role in guiding the differentiation and maturation of the GABAergic interneurons where it is most prominently expressed. Early studies have also shown that it can interact with components of the dioxin signaling pathway, suggesting potential cross-talk with environmental sensor pathways ([Link](https://doi.org/10.1074/jbc.272.13.8581)). ## Research Directions The highly specific expression pattern of [NPAS1](/details-gene/4861) in GABAergic interneurons, coupled with its role as a transcriptional repressor, provides a foundation for several compelling research avenues. **Proposed Hypotheses:** 1. [NPAS1](/details-gene/4861) is a master regulator required for the terminal differentiation and functional specification of cortical interneuron subtypes. Its loss during development would lead to a failure of these cells to acquire their mature identity and properly integrate into cortical circuits. 2. During neurogenesis, [NPAS1](/details-gene/4861) functions by actively suppressing alternative neuronal fates, such as the glutamatergic lineage, thereby committing precursor cells to the GABAergic inhibitory lineage. **Suggested Experimental Approach:** To test the first hypothesis, a conditional knockout (cKO) mouse model could be generated using a Cre-loxP system with a Cre driver specific to interneuron progenitors (e.g., *Nkx2-1-Cre*). Postnatal analysis of the cortex in cKO mice using single-cell RNA sequencing (scRNA-seq) would reveal whether specific interneuron subtypes ([sncg GABAergic cortical interneuron](/details-cell/CL4023015), [pvalb GABAergic cortical interneuron](/details-cell/CL4023018), etc.) are absent or exhibit aberrant transcriptomic profiles. This could be complemented with electrophysiological recordings to assess their functional deficits. **Therapeutic Potential:** As an intracellular transcription factor, [NPAS1](/details-gene/4861) is a challenging direct therapeutic target for small molecule inhibitors or biologics. However, its exquisite specificity for inhibitory interneurons makes it a valuable biomarker. Its dysregulation could be implicated in neurodevelopmental or psychiatric disorders characterized by an imbalance of excitation and inhibition, such as epilepsy or schizophrenia. Furthermore, understanding its role as a master regulator could inform novel cell-based therapies, where [NPAS1](/details-gene/4861) could be used as a tool to direct the differentiation of pluripotent stem cells into specific, therapeutically relevant interneuron subtypes for transplantation.

Genular Protein ID: 2565311860

Symbol: NPAS1_HUMAN

Name: Neuronal PAS domain-containing protein 1

UniProtKB Accession Codes:

Q99742 B4DR69 Q99632 Q9BY83

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 2 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 6 Ensembl 3 ExpressionAtlas 1 GO 12 Gene3D 2 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyGen 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 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 2 SIGNOR 1 SMART 2 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 9012850

Title: Molecular characterization of two mammalian bHLH-PAS domain proteins selectively expressed in the central nervous system.

PubMed ID: 9012850

DOI: 10.1073/pnas.94.2.713

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15057824

Title: The DNA sequence and biology of human chromosome 19.

PubMed ID: 15057824

DOI: 10.1038/nature02399

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: 9079689

Title: Characterization of a subset of the basic-helix-loop-helix-PAS superfamily that interacts with components of the dioxin signaling pathway.

PubMed ID: 9079689

DOI: 10.1074/jbc.272.13.8581

Sequence Information:

  • Length: 590
  • Mass: 62702
  • Checksum: CE893A0C7CEEDB09
  • Sequence:
    • MAAPYPGSGG GSEVKCVGGR GASVPWDFLP GLMVKAPSGP CLQAQRKEKS RNAARSRRGK 
ENLEFFELAK LLPLPGAISS QLDKASIVRL SVTYLRLRRF AALGAPPWGL RAAGPPAGLA 
PGRRGPAALV SEVFEQHLGG HILQSLDGFV FALNQEGKFL YISETVSIYL GLSQVEMTGS 
SVFDYIHPGD HSEVLEQLGL RTPTPGPPTP PSVSSSSSSS SSLADTPEIE ASLTKVPPSS 
LVQERSFFVR MKSTLTKRGL HVKASGYKVI HVTGRLRAHA LGLVALGHTL PPAPLAELPL 
HGHMIVFRLS LGLTILACES RVSDHMDLGP SELVGRSCYQ FVHGQDATRI RQSHVDLLDK 
GQVMTGYYRW LQRAGGFVWL QSVATVAGSG KSPGEHHVLW VSHVLSQAEG GQTPLDAFQL 
PASVACEEAS SPGPEPTEPE PPTEGKQAAP AENEAPQTQG KRIKVEPGPR ETKGSEDSGD 
EDPSSHPATP RPEFTSVIRA GVLKQDPVRP WGLAPPGDPP PTLLHAGFLP PVVRGLCTPG 
TIRYGPAELG LVYPHLQRLG PGPALPEAFY PPLGLPYPGP AGTRLPRKGD