Details for: NOMO1

Gene ID: 23420

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: NOMO1

Ensembl ID: ENSG00000103512

Description: NODAL modulator 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • melanocyte CL0000148
    CSI 4.68
    rCSI 3.47%
    PRS 98.31
  • secretory cell CL0000151
    CSI 3.86
    rCSI 4.02%
    PRS 98.88
  • retina horizontal cell CL0000745
    CSI 2.8
    rCSI 4.27%
    PRS 98.05
  • amacrine cell CL0000561
    CSI 2.65
    rCSI 7.68%
    PRS 96.55
  • ciliated cell CL0000064
    CSI 2.58
    rCSI 4.18%
    PRS 96.92
  • cerebral cortex neuron CL0010012
    CSI 2.51
    rCSI 10.23%
    PRS 96.15
  • peripheral nervous system neuron CL2000032
    CSI 2.15
    rCSI 2.92%
    PRS 97.77
  • cardiac muscle cell CL0000746
    CSI 2.08
    rCSI 2.99%
    PRS 96.78

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 [NOMO1](/details-gene/23420) (NODAL modulator 1) is a protein-coding gene located on chromosome 16p13.1. It encodes a multi-pass transmembrane protein that resides in the endoplasmic reticulum membrane. Functionally, [NOMO1](/details-gene/23420) is recognized as a key component of a specialized translocon complex responsible for the biogenesis of multi-pass membrane proteins ([Link](https://doi.org/10.7554/elife.56889), [Link](https://doi.org/10.1038/s41586-022-05330-8)). It also plays a role in developmental signaling as a negative regulator of the Nodal pathway ([Link](https://doi.org/10.1074/jbc.m611033200)). **Overall**, expression data indicates that [NOMO1](/details-gene/23420) is a significant gene in a diverse array of specialized cell types with high protein processing demands, including [melanocyte](/details-cell/CL0000148)s, [secretory cell](/details-cell/CL0000151)s, and various neuronal populations. ## Cellular Roles and Expression Landscape The expression profile of [NOMO1](/details-gene/23420) suggests a crucial role in maintaining the function of cells characterized by complex and high-volume protein synthesis and trafficking. **Overall**, it shows the highest significance in [melanocyte](/details-cell/CL0000148)s (CSI: 4.68) and [secretory cell](/details-cell/CL0000151)s (CSI: 3.86), both of which rely heavily on the endoplasmic reticulum for producing and processing their specific protein products. Furthermore, [NOMO1](/details-gene/23420) is highly significant across various components of the nervous system. This includes specialized retinal cells such as [retina horizontal cell](/details-cell/CL0000745)s (CSI: 2.80) and [amacrine cell](/details-cell/CL0000561)s (CSI: 2.65), as well as [cerebral cortex neuron](/details-cell/CL0010012)s (CSI: 2.51) and [peripheral nervous system neuron](/details-cell/CL2000032)s (CSI: 2.15). This pattern is consistent with its function in the biogenesis of multi-pass transmembrane proteins, such as ion channels and receptors, which are fundamental to neuronal signaling. The gene also shows notable significance in [ciliated cell](/details-cell/CL0000064)s and [cardiac muscle cell](/details-cell/CL0000746)s, further underscoring its importance in cells with high metabolic activity and complex proteomes. ## Pathways and Molecular Function The functional annotations for [NOMO1](/details-gene/23420) align closely with its observed cellular expression pattern. Its localization to the [endoplasmic reticulum membrane](/details-cell/GO:0005789) is central to its function. Recent research has identified [NOMO1](/details-gene/23420) as a core component of the multi-pass translocon complex ([MPTC](/details-cell/GO:0160064)), alongside Nicalin and TMEM147, which facilitates the insertion of nascent multi-pass transmembrane proteins into the ER membrane ([Link](https://doi.org/10.7554/elife.56889), [Link](https://doi.org/10.1038/s41586-022-05330-8)). This molecular function likely explains its high significance in secretory and neuronal cells, which require robust machinery for synthesizing complex membrane proteins. In addition to this role in protein biogenesis, [NOMO1](/details-gene/23420) is annotated for its involvement in the [negative regulation of nodal signaling pathway](/details-cell/GO:1900108). The Nodal pathway is critical for establishing left-right asymmetry during embryonic development ([determination of left/right asymmetry in lateral mesoderm](/details-cell/GO:0003140)). [NOMO1](/details-gene/23420) forms a complex with Nicalin that appears to antagonize Nodal signaling at the cell surface or within the ER, ensuring its proper spatiotemporal restriction ([Link](https://doi.org/10.1074/jbc.m611033200)). While this function is primarily developmental, the components may be repurposed in adult tissues. ## Research Directions The widespread importance of [NOMO1](/details-gene/23420) in diverse, specialized cell types suggests that its role in facilitating the production of specific multi-pass transmembrane proteins is a key determinant of cellular identity and function. Future research should focus on dissecting the substrate specificity of the NOMO1-containing translocon and its potential role in disease. Based on the available data, several testable hypotheses can be proposed: 1. The high significance of [NOMO1](/details-gene/23420) in [melanocyte](/details-cell/CL0000148)s is due to a specific requirement for the NOMO1-translocon complex in the proper biogenesis of key melanosomal multi-pass transmembrane proteins (e.g., transporters like OCA2 or enzymes like TYRP1), and its disruption leads to defects in pigmentation. 2. In [cardiac muscle cell](/details-cell/CL0000746)s, [NOMO1](/details-gene/23420) is essential for the correct assembly and membrane integration of critical ion channels and gap junction proteins, and its reduced function could contribute to cardiac arrhythmias or cardiomyopathies. 3. The role of [NOMO1](/details-gene/23420) in regulating Nodal signaling is re-activated in certain pathological contexts, such as cancer or tissue regeneration, where developmental pathways are often re-engaged. To test the first hypothesis, a key experiment could be proposed. To investigate the role of [NOMO1](/details-gene/23420) in melanosome protein biogenesis, one could utilize CRISPR-Cas9 to knock out the gene in a human iPSC-derived [melanocyte](/details-cell/CL0000148) model. The functional consequences would be assessed by quantifying melanin production and melanosome maturation via electron microscopy. Concurrently, quantitative proteomics (mass spectrometry) combined with cellular fractionation could be used to identify specific multi-pass transmembrane proteins that are mislocalized or destabilized in the absence of [NOMO1](/details-gene/23420). Given its fundamental role as a component of the protein biogenesis machinery in numerous essential cell types, including neurons and cardiac muscle, [NOMO1](/details-gene/23420) is likely a challenging therapeutic target. Systemic inhibition would be expected to cause significant toxicity. However, if a specific cancer or disease state were found to be uniquely dependent on [NOMO1](/details-gene/23420) function for the expression of a key pathological protein, it could present a narrow therapeutic window. In such a scenario, a strategy involving inhibition, likely via a small molecule inhibitor that disrupts its interaction with other translocon components, would be the most plausible approach.

Genular Protein ID: 1060860797

Symbol: NOMO1_HUMAN

Name: Nodal modulator 1

UniProtKB Accession Codes:

Q15155 P78421 Q8IW21 Q96DG0

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChiTaRS 1 ComplexPortal 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 1 EMBL 3 Ensembl 2 ExpressionAtlas 1 GO 6 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyConnect 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 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 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 5 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 RefSeq 1 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 15616553

Title: The sequence and analysis of duplication-rich human chromosome 16.

PubMed ID: 15616553

DOI: 10.1038/nature03187

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: 1310294

Title: Cloning and characterization of a novel human cDNA that has DNA similarity to the conserved region of the collagenase gene family.

PubMed ID: 1310294

DOI: 10.1016/0888-7543(92)90425-r

PubMed ID: 19159218

Title: Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry.

PubMed ID: 19159218

DOI: 10.1021/pr8008012

PubMed ID: 17261586

Title: The Nicastrin-like protein Nicalin regulates assembly and stability of the Nicalin-nodal modulator (NOMO) membrane protein complex.

PubMed ID: 17261586

DOI: 10.1074/jbc.m611033200

PubMed ID: 20538592

Title: Transmembrane protein 147 (TMEM147) is a novel component of the Nicalin-NOMO protein complex.

PubMed ID: 20538592

DOI: 10.1074/jbc.m110.132548

PubMed ID: 32820719

Title: An ER translocon for multi-pass membrane protein biogenesis.

PubMed ID: 32820719

DOI: 10.7554/elife.56889

PubMed ID: 36261522

Title: Substrate-driven assembly of a translocon for multipass membrane proteins.

PubMed ID: 36261522

DOI: 10.1038/s41586-022-05330-8

PubMed ID: 10835642

Title: Mutations in a gene encoding an ABC transporter cause pseudoxanthoma elasticum.

PubMed ID: 10835642

DOI: 10.1038/76102

PubMed ID: 11139250

Title: Identification of novel polymorphisms in the pM5 and MRP1 (ABCC1) genes at locus 16p13.1 and exclusion of both genes as responsible for pseudoxanthoma elasticum.

PubMed ID: 11139250

DOI: 10.1002/1098-1004(2001)17:1<74::aid-humu14>3.0.co;2-f

Sequence Information:

  • Length: 1222
  • Mass: 134324
  • Checksum: EE0A3BB552BAB72B
  • Sequence:
    • MLVGQGAGPL GPAVVTAAVV LLLSGVGPAH GSEDIVVGCG GFVKSDVEIN YSLIEIKLYT 
KHGTLKYQTD CAPNNGYFMI PLYDKGDFIL KIEPPLGWSF EPTTVELHVD GVSDICTKGG 
DINFVFTGFS VNGKVLSKGQ PLGPAGVQVS LRNTGTEAKI QSTVTQPGGK FAFFKVLPGD 
YEILATHPTW ALKEASTTVR VTNSNANAAS PLIVAGYNVS GSVRSDGEPM KGVKFLLFSS 
LVTKEDVLGC NVSPVPGFQP QDESLVYLCY TVSREDGSFS FYSLPSGGYT VIPFYRGERI 
TFDVAPSRLD FTVEHDSLKI EPVFHVMGFS VTGRVLNGPE GDGVPEAVVT LNNQIKVKTK 
ADGSFRLENI TTGTYTIHAQ KEHLYFETVT IKIAPNTPQL ADIIATGFSV CGQISIIRFP 
DTVKQMNKYK VVLSSQDKDK SLVTVETDAH GSFCFKAKPG TYKVQVMVPE AETRAGLTLK 
PQTFPLTVTN RPMMDVAFVQ FLASVSGKVS CLDTCGDLLV TLQSLSRQGE KRSLQLSGKV 
NAMTFTFDNV LPGKYKISIM HEDWCWKNKS LEVEVLEDDM SAVEFRQTGY MLRCSLSHAI 
TLEFYQDGNG RENVGIYNLS KGVNRFCLSK PGVYKVTPRS CHRFEQAFYT YDTSSPSILT 
LTAIRHHVLG TITTDKMMDV TVTIKSSIDS EPALVLGPLK SVQELRREQQ LAEIEARRQE 
REKNGNEEGE ERMTKPPVQE MVDELQGPFS YDFSYWARSG EKITVTPSSK ELLFYPPSME 
AVVSGESCPG KLIEIHGKAG LFLEGQIHPE LEGVEIVISE KGASSPLITV FTDDKGAYSV 
GPLHSDLEYT VTSQKEGYVL TAVEGTIGDF KAYALAGVSF EIKAEDDQPL PGVLLSLSGG 
LFRSNLLTQD NGILTFSNLS PGQYYFKPMM KEFRFEPSSQ MIEVQEGQNL KITITGYRTA 
YSCYGTVSSL NGEPEQGVAM EAVGQNDCSI YGEDTVTDEE GKFRLRGLLP GCVYHVQLKA 
EGNDHIERAL PHHRVIEVGN NDIDDVNIIV FRQINQFDLS GNVITSSEYL PTLWVKLYKS 
ENLDNPIQTV SLGQSLFFHF PPLLRDGENY VVLLDSTLPR SQYDYILPQV SFTAVGYHKH 
ITLIFNPTRK LPEQDIAQGS YIALPLTLLV LLAGYNHDKL IPLLLQLTSR LQGVRALGQA 
ASDNSGPEDA KRQAKKQKTR RT