Details for: NIPSNAP3A

Gene ID: 25934

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: NIPSNAP3A

Ensembl ID: ENSG00000136783

Description: nipsnap homolog 3A

Cell Significance Landscape

Associated with

Significant Cells

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

  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 10.19
    rCSI 9.2%
    PRS 70.91
  • ON-bipolar cell CL0000749
    CSI 5.12
    rCSI 7.6%
    PRS 73.96
  • type B pancreatic cell CL0000169
    CSI 5.06
    rCSI 11.21%
    PRS 72.34
  • Hofbauer cell CL3000001
    CSI 4.63
    rCSI 8.75%
    PRS 82.64
  • pancreatic ductal cell CL0002079
    CSI 4.33
    rCSI 8.42%
    PRS 76.7
  • CD1c-positive myeloid dendritic cell CL0002399
    CSI 4.16
    rCSI 5.03%
    PRS 81.83
  • erythroid progenitor cell CL0000038
    CSI 4.15
    rCSI 23.8%
    PRS 80.38
  • club cell CL0000158
    CSI 4.02
    rCSI 5.88%
    PRS 68.32
  • hematopoietic stem cell CL0000037
    CSI 3.27
    rCSI 2.18%
    PRS 76.3
  • hematopoietic multipotent progenitor cell CL0000837
    CSI 3.24
    rCSI 7.8%
    PRS 87.95
  • epithelial cell of lung CL0000082
    CSI 3.22
    rCSI 2.67%
    PRS 73.78
  • megakaryocyte CL0000556
    CSI 3.13
    rCSI 13.59%
    PRS 81.45
  • enteric smooth muscle cell CL0002504
    CSI 3.06
    rCSI 4.37%
    PRS 74.9
  • goblet cell CL0000160
    CSI 2.68
    rCSI 2.53%
    PRS 72.62
  • erythroid lineage cell CL0000764
    CSI 2.66
    rCSI 17.12%
    PRS 85.56
  • neural crest cell CL0011012
    CSI 2.61
    rCSI 2.07%
    PRS 60.98
  • pancreatic D cell CL0000173
    CSI 2.51
    rCSI 2.47%
    PRS 76.07
  • hematopoietic precursor cell CL0008001
    CSI 2.48
    rCSI 2.55%
    PRS 86.83
  • pro-B cell CL0000826
    CSI 2.46
    rCSI 2.04%
    PRS 75.82
  • intestine goblet cell CL0019031
    CSI 2.46
    rCSI 2.19%
    PRS 71.28
  • alternatively activated macrophage CL0000890
    CSI 2.44
    rCSI 3.07%
    PRS 83.95
  • pancreatic A cell CL0000171
    CSI 2.41
    rCSI 2.52%
    PRS 76.74
  • early lymphoid progenitor CL0000936
    CSI 2.38
    rCSI 2.09%
    PRS 78.69
  • plasmacytoid dendritic cell, human CL0001058
    CSI 2.37
    rCSI 1.65%
    PRS 76.59
  • duct epithelial cell CL0000068
    CSI 2.35
    rCSI 3.43%
    PRS 78.35
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 2.33
    rCSI 1.8%
    PRS 75.67
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 2.32
    rCSI 2.68%
    PRS 65.65
  • granulocyte monocyte progenitor cell CL0000557
    CSI 2.3
    rCSI 1.99%
    PRS 78
  • keratinocyte CL0000312
    CSI 2.26
    rCSI 1.89%
    PRS 76.67
  • intestinal epithelial cell CL0002563
    CSI 2.23
    rCSI 2.33%
    PRS 71.24
  • common myeloid progenitor CL0000049
    CSI 2.23
    rCSI 1.8%
    PRS 75.54
  • ciliated epithelial cell CL0000067
    CSI 2.19
    rCSI 1.93%
    PRS 61.83
  • myeloid leukocyte CL0000766
    CSI 2.11
    rCSI 1.95%
    PRS 75.08
  • enteroendocrine cell CL0000164
    CSI 2.1
    rCSI 2.87%
    PRS 73.99
  • peripheral nervous system neuron CL2000032
    CSI 2.06
    rCSI 2.81%
    PRS 64.73
  • transit amplifying cell of colon CL0009011
    CSI 1.99
    rCSI 2.34%
    PRS 75.44
  • retinal bipolar neuron CL0000748
    CSI 1.91
    rCSI 3.57%
    PRS 61.29
  • conventional dendritic cell CL0000990
    CSI 1.9
    rCSI 1.59%
    PRS 77.55
  • colon epithelial cell CL0011108
    CSI 1.88
    rCSI 1.97%
    PRS 70.56
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.88
    rCSI 3.32%
    PRS 53.86
  • common dendritic progenitor CL0001029
    CSI 1.86
    rCSI 2.33%
    PRS 82.96
  • promyelocyte CL0000836
    CSI 1.85
    rCSI 2.67%
    PRS 80.83
  • Langerhans cell CL0000453
    CSI 1.83
    rCSI 2.79%
    PRS 86.41
  • ependymal cell CL0000065
    CSI 1.81
    rCSI 3.67%
    PRS 51.59
  • multi-ciliated epithelial cell CL0005012
    CSI 1.81
    rCSI 1.81%
    PRS 66.98
  • radial glial cell CL0000681
    CSI 1.8
    rCSI 2.5%
    PRS 71.99
  • lung neuroendocrine cell CL1000223
    CSI 1.8
    rCSI 2.66%
    PRS 78.12
  • rod bipolar cell CL0000751
    CSI 1.77
    rCSI 3.18%
    PRS 66.47
  • glioblast CL0000030
    CSI 1.69
    rCSI 2.7%
    PRS 65.02
  • lung ciliated cell CL1000271
    CSI 1.69
    rCSI 1.95%
    PRS 64.82
  • lung macrophage CL1001603
    CSI 1.59
    rCSI 3.56%
    PRS 81.25
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 1.58
    rCSI 2.03%
    PRS 69.81
  • common lymphoid progenitor CL0000051
    CSI 1.55
    rCSI 2.07%
    PRS 89.92
  • fraction A pre-pro B cell CL0002045
    CSI 1.5
    rCSI 1.72%
    PRS 86.95
  • erythrocyte CL0000232
    CSI 1.48
    rCSI 3.35%
    PRS 75.11
  • promonocyte CL0000559
    CSI 1.45
    rCSI 2.49%
    PRS 80.86
  • podocyte CL0000653
    CSI 1.4
    rCSI 6.23%
    PRS 73.72
  • intermediate monocyte CL0002393
    CSI 1.32
    rCSI 2%
    PRS 78.63
  • myeloid dendritic cell CL0000782
    CSI 1.16
    rCSI 1.67%
    PRS 87.04
  • mesenchymal cell CL0008019
    CSI 1.15
    rCSI 2.92%
    PRS 67.06
  • forebrain radial glial cell CL0013000
    CSI 1.1
    rCSI 3.53%
    PRS 76.65
  • kidney epithelial cell CL0002518
    CSI 1.04
    rCSI 1.98%
    PRS 88.92
  • primitive red blood cell CL0002355
    CSI 0.98
    rCSI 5.3%
    PRS 81.71
  • colon goblet cell CL0009039
    CSI 0.96
    rCSI 2.28%
    PRS 80.42
  • placental villous trophoblast CL2000060
    CSI 0.93
    rCSI 1.44%
    PRS 72.46
  • pancreatic PP cell CL0002275
    CSI 0.72
    rCSI 2.85%
    PRS 82.76
  • microcirculation associated smooth muscle cell CL0008035
    CSI 0.7
    rCSI 2.04%
    PRS 73.84
  • myeloid lineage restricted progenitor cell CL0000839
    CSI 0.65
    rCSI 3.36%
    PRS 90.47
  • endothelial cell of placenta CL0009092
    CSI 0.58
    rCSI 2.84%
    PRS 82.88
  • Cajal-Retzius cell CL0000695
    CSI 0.57
    rCSI 4.46%
    PRS 80.82
  • eosinophil CL0000771
    CSI 0.55
    rCSI 3.6%
    PRS 92.4
  • megakaryocyte progenitor cell CL0000553
    CSI 0.27
    rCSI 4.97%
    PRS 92.95
  • pre-conventional dendritic cell CL0002010
    CSI 0.23
    rCSI 3.07%
    PRS 92.75

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 [NIPSNAP3A](/details-gene/25934) is a protein-coding gene located on chromosome 9q31.1. It is annotated as being involved in the selective degradation of mitochondria, a process known as [mitophagy](/details-go/GO:0000423), and is localized to the [mitochondrion](/details-go/GO:0005739), [cytosol](/details-go/GO:0005829), and [nucleus](/details-go/GO:0005634). **Overall**, expression data reveals that [NIPSNAP3A](/details-gene/25934) shows the highest significance in hematopoietic precursors, particularly [megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050)s, suggesting a key role in blood cell development. It is also notably significant in various metabolically active and secretory cell types, including [ON-bipolar cell](/details-cell/CL0000749)s and [type B pancreatic cell](/details-cell/CL0000169)s, indicating a potential function in cellular quality control and homeostasis across diverse tissues. ## Cellular Roles and Expression Landscape The expression profile of [NIPSNAP3A](/details-gene/25934) points to a specialized role in cellular differentiation and metabolic maintenance. Its most significant expression is observed in a cluster of hematopoietic progenitor cells, including [megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050) (CSI: 10.19), [erythroid progenitor cell](/details-cell/CL0000038), [hematopoietic stem cell](/details-cell/CL0000037), and [hematopoietic multipotent progenitor cell](/details-cell/CL0000837). This strong association with the erythroid and megakaryocytic lineages suggests that [NIPSNAP3A](/details-gene/25934) is likely involved in the extensive cellular remodeling, particularly mitochondrial clearance, that is a hallmark of the maturation of red blood cells and platelets. Beyond hematopoiesis, [NIPSNAP3A](/details-gene/25934) is also highly significant in a variety of specialized secretory and epithelial cells. These include [type B pancreatic cell](/details-cell/CL0000169)s, [pancreatic ductal cell](/details-cell/CL0002079)s, and pulmonary cells such as [club cell](/details-cell/CL0000158)s and [goblet cell](/details-cell/CL0000160)s. The high metabolic and secretory load in these cells necessitates robust mitochondrial quality control mechanisms to prevent cellular damage from oxidative stress. The significant expression of [NIPSNAP3A](/details-gene/25934) in these contexts is consistent with its putative role in mitophagy. Furthermore, its significance in unique cell types like the placental [Hofbauer cell](/details-cell/CL3000001) and the retinal [ON-bipolar cell](/details-cell/CL0000749) underscores a potentially broad, yet context-specific, role in maintaining cellular integrity. One study also identified it as a host cell target for a Salmonella virulence protein, suggesting a role in host-pathogen interactions ([Link](https://pubmed.ncbi.nlm.nih.gov/12427096/)). ## Pathways and Molecular Function The primary annotated biological process for [NIPSNAP3A](/details-gene/25934) is [mitophagy](/details-go/GO:0000423), the targeted autophagic removal of damaged or superfluous mitochondria. This function is directly supported by its localization to the [mitochondrion](/details-go/GO:0005739). This process is critical for cellular health and is particularly important in two key scenarios reflected in the gene's expression pattern. First, during terminal differentiation of certain cell types, such as erythrocytes, the entire mitochondrial population must be cleared. The high significance of [NIPSNAP3A](/details-gene/25934) in [erythroid progenitor cell](/details-cell/CL0000038)s and [megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050)s strongly supports its involvement in this programmed mitochondrial removal. Second, in cells with high energy demands and metabolic turnover, such as [type B pancreatic cell](/details-cell/CL0000169)s, efficient mitophagy is essential for removing mitochondria damaged by reactive oxygen species, thereby preventing apoptosis and maintaining secretory function. The gene's additional localizations in the [cytosol](/details-go/GO:0005829) and [nucleus](/details-go/GO:0005634), along with its capacity for [protein binding](/details-go/GO:0005515), suggest it may participate in signaling pathways that sense mitochondrial stress and initiate the autophagic response. ## Research Directions The strong association of [NIPSNAP3A](/details-gene/25934) with mitochondrial quality control in specific cellular contexts provides a foundation for several testable hypotheses. 1. **Hypothesis 1:** [NIPSNAP3A](/details-gene/25934) is a critical mediator of programmed mitochondrial clearance during the terminal differentiation of erythroid cells, and its absence impairs enucleation and the formation of mature reticulocytes. 2. **Hypothesis 2:** In pancreatic beta cells, [NIPSNAP3A](/details-gene/25934)-dependent mitophagy is a key protective mechanism against glucose-induced oxidative stress, and its dysfunction contributes to the pathogenesis of type 2 diabetes by promoting beta-cell failure. To investigate the primary hypothesis regarding its role in hematopoiesis, a key experiment could be designed. A CRISPR-Cas9-mediated knockout of [NIPSNAP3A](/details-gene/25934) could be generated in primary human CD34+ [hematopoietic stem cell](/details-cell/CL0000037)s. These modified cells would then be cultured *in vitro* under conditions that promote differentiation towards the erythroid lineage. The impact of the knockout would be assessed by quantifying mitochondrial mass over the differentiation time course using MitoTracker dyes and flow cytometry. Furthermore, the efficiency of terminal differentiation and enucleation could be measured, and the rate of mitophagy could be directly assayed using a reporter construct like mt-Keima. Given its fundamental role in cellular homeostasis, [NIPSNAP3A](/details-gene/25934) presents a complex therapeutic profile. It is unlikely to be a target for simple inhibition. Instead, its dysfunction could be implicated in diseases characterized by mitochondrial damage, such as certain congenital anemias, neurodegenerative disorders, or metabolic syndromes. Therefore, a therapeutic strategy might involve the development of small-molecule modulators that could enhance or restore its function in specific disease contexts. However, its expression in a range of progenitor and essential cell types suggests that systemic modulation would carry a high risk of off-target effects, making cell-specific delivery or *ex vivo* applications more plausible therapeutic avenues.

Genular Protein ID: 876216719

Symbol: NPS3A_HUMAN

Name: Protein NipSnap homolog 3A

UniProtKB Accession Codes:

Q9UFN0 A6NM55 Q5VX32 Q9BRV7 Q9H843 Q9P083

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 6 Ensembl 1 GO 3 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 MetOSite 1 NCBI Taxonomy 1 OGP 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 Pumba 1 RNAct 1 RefSeq 2 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 17974005

Title: The full-ORF clone resource of the German cDNA consortium.

PubMed ID: 17974005

DOI: 10.1186/1471-2164-8-399

PubMed ID: 15164053

Title: DNA sequence and analysis of human chromosome 9.

PubMed ID: 15164053

DOI: 10.1038/nature02465

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: 12427096

Title: Identification of a NIPSNAP homologue as host cell target for Salmonella virulence protein SpiC.

PubMed ID: 12427096

DOI: 10.1046/j.1462-5822.2002.00225.x

PubMed ID: 19608861

Title: Lysine acetylation targets protein complexes and co-regulates major cellular functions.

PubMed ID: 19608861

DOI: 10.1126/science.1175371

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

PubMed ID: 25944712

Title: N-terminome analysis of the human mitochondrial proteome.

PubMed ID: 25944712

DOI: 10.1002/pmic.201400617

Sequence Information:

  • Length: 247
  • Mass: 28467
  • Checksum: DA668E2AD42BA1AA
  • Sequence:
    • MLVLRSALTR ALASRTLAPQ MCSSFATGPR QYDGIFYEFR SYYLKPSKMN EFLENFEKNA 
HLRTAHSELV GYWSVEFGGR MNTVFHIWKY DNFAHRTEVR KALAKDKEWQ EQFLIPNLAL 
IDKQESEITY LVPWCKLEKP PKEGVYELAT FQMKPGGPAL WGDAFKRAVH AHVNLGYTKL 
VGVFHTEYGA LNRVHVLWWN ESADSRAAGR HKSHEDPRVV AAVRESVNYL VSQQNMLLIP 
TSFSPLK