Details for: SLC25A53

Gene ID: 401612

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: SLC25A53

Ensembl ID: ENSG00000269743

Description: solute carrier family 25 member 53

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • mucosal invariant T cell CL0000940
    CSI 4.71
    rCSI 3.81%
    PRS 96.96
  • pancreatic D cell CL0000173
    CSI 3.94
    rCSI 3.88%
    PRS 94.74
  • melanocyte CL0000148
    CSI 3.45
    rCSI 2.56%
    PRS 91.42
  • renal alpha-intercalated cell CL0005011
    CSI 3.31
    rCSI 4.43%
    PRS 95.75
  • renal beta-intercalated cell CL0002201
    CSI 2.9
    rCSI 6.91%
    PRS 94.29
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 2.68
    rCSI 4.88%
    PRS 88.93
  • pancreatic A cell CL0000171
    CSI 2.65
    rCSI 2.78%
    PRS 94.89
  • choroid plexus epithelial cell CL0000706
    CSI 2.56
    rCSI 4.19%
    PRS 88.55
  • cerebral cortex endothelial cell CL1001602
    CSI 2.4
    rCSI 4.15%
    PRS 89.97
  • hepatic stellate cell CL0000632
    CSI 2.14
    rCSI 8.03%
    PRS 90.9
  • erythrocyte CL0000232
    CSI 2.12
    rCSI 4.81%
    PRS 91.78
  • chondrocyte CL0000138
    CSI 1.96
    rCSI 3.11%
    PRS 90.31
  • astrocyte of the cerebral cortex CL0002605
    CSI 1.8
    rCSI 4.02%
    PRS 84.38
  • type B pancreatic cell CL0000169
    CSI 1.7
    rCSI 3.76%
    PRS 93.61
  • regular ventricular cardiac myocyte CL0002131
    CSI 1.63
    rCSI 10.17%
    PRS 88.62
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.52
    rCSI 2.69%
    PRS 83.61
  • kidney connecting tubule epithelial cell CL1000768
    CSI 1.47
    rCSI 3.72%
    PRS 89.79
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 0.96
    rCSI 2.34%
    PRS 82.04
  • pulmonary alveolar type 1 cell CL0002062
    CSI 0.91
    rCSI 5.28%
    PRS 91.68
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.74
    rCSI 2.68%
    PRS 82.37
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.74
    rCSI 2.31%
    PRS 85.12
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 0.65
    rCSI 2.47%
    PRS 84.3
  • direct pathway medium spiny neuron CL4023026
    CSI 0.56
    rCSI 13.5%
    PRS 82.03
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.42
    rCSI 2.5%
    PRS 84.48
  • indirect pathway medium spiny neuron CL4023029
    CSI 0.4
    rCSI 9.66%
    PRS 81.97

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 [SLC25A53](/details-gene/401612) is a protein-coding gene located on the X chromosome that encodes Solute Carrier Family 25 Member 53, a transporter protein localized to the mitochondrial inner membrane. Based on its functional annotation, the primary role of [SLC25A53](/details-gene/401612) is to transport nicotinamide adenine dinucleotide (NAD+) into the mitochondrial matrix, a process essential for cellular energy metabolism. Expression data reveals its significance across a diverse range of metabolically active cell types, including [mucosal invariant T cell](/details-cell/CL0000940), various pancreatic islet cells such as [pancreatic D cell](/details-cell/CL0000173), and [melanocyte](/details-cell/CL0000148). Clinically, loss-of-function mutations in [SLC25A53](/details-gene/401612) are associated with a congenital NAD+ transporter deficiency ([300941](https://omim.org/entry/300941)), underscoring its critical, non-redundant role in human physiology. The gene has been characterized as part of large-scale sequencing and cDNA projects ([Link](https://doi.org/10.1038/nature03440), [Link](https://doi.org/10.1101/gr.2596504)). ## Cellular Roles and Expression Landscape The expression profile of [SLC25A53](/details-gene/401612) highlights its importance in a wide array of specialized cell types with high metabolic demands. **Overall**, the gene shows the highest significance in the immune system, particularly in [mucosal invariant T cell](/details-cell/CL0000940) (CSI: 4.71), suggesting a key role in the metabolic support of this unique T cell lineage. Its prominence extends to endocrine tissues, where it is a significant marker in multiple pancreatic islet cells, including [pancreatic D cell](/details-cell/CL0000173), [pancreatic A cell](/details-cell/CL0000171), and [type B pancreatic cell](/details-cell/CL0000169). This is consistent with the high energy requirements for hormone synthesis and secretion. Further, [SLC25A53](/details-gene/401612) is highly significant in other diverse, specialized cells such as: * Pigment-producing [melanocyte](/details-cell/CL0000148) * Ion-transporting renal cells like [renal alpha-intercalated cell](/details-cell/CL0005011) and [renal beta-intercalated cell](/details-cell/CL0002201) * Central nervous system cells, including [differentiation-committed oligodendrocyte precursor](/details-cell/CL4023059) and [astrocyte of the cerebral cortex](/details-cell/CL0002605) * Contractile cells like [regular ventricular cardiac myocyte](/details-cell/CL0002131) This broad but specific expression pattern across disparate lineages underscores a fundamental role for [SLC25A53](/details-gene/401612)-mediated NAD+ transport in supporting the specialized bioenergetic needs of these distinct cell types, rather than being a ubiquitous housekeeping gene. ## Pathways and Molecular Function [SLC25A53](/details-gene/401612) is an integral component of the [mitochondrial inner membrane](/details-ontology/GO0005743), where it executes its primary molecular function of `Nad transmembrane transporter activity` ([GO:0051724](https://www.ebi.ac.uk/QuickGO/term/GO:0051724)). This activity facilitates the biological process of `Nad transmembrane transport` ([GO:0035352](https://www.ebi.ac.uk/QuickGO/term/GO:0035352)), ensuring the mitochondrial matrix is supplied with NAD+. Mitochondrial NAD+ is an indispensable cofactor for core metabolic pathways, including the tricarboxylic acid (TCA) cycle, beta-oxidation of fatty acids, and the electron transport chain, which are central to ATP production. By controlling the influx of cytosolic NAD+ into the [mitochondrion](/details-ontology/GO0005739), [SLC25A53](/details-gene/401612) directly regulates the cell's capacity for oxidative phosphorylation. This function aligns with its high expression in cells with substantial energy demands, such as pancreatic cells for insulin secretion and cardiac myocytes for continuous contraction. ## Research Directions The established role of [SLC25A53](/details-gene/401612) in a severe congenital disorder ([300941](https://omim.org/entry/300941)) and its specific expression profile provide clear avenues for future research. The clinical presentation of the associated deficiency, which includes cardiac and neurological defects, correlates well with the observed expression in [regular ventricular cardiac myocyte](/details-cell/CL0002131) and various CNS cell types. Understanding how partial or complete loss of function impacts the metabolism of these specific cells is a key research priority. Based on the available data, several testable hypotheses can be proposed: 1. The high significance of [SLC25A53](/details-gene/401612) in [mucosal invariant T cell](/details-cell/CL0000940) suggests that mitochondrial NAD+ availability is a critical checkpoint for their activation and effector functions. It can be hypothesized that reduced [SLC25A53](/details-gene/401612) activity impairs MAIT cell metabolic reprogramming upon stimulation, leading to diminished anti-microbial capacity. 2. Given its consistent high expression across pancreatic islet cells ([pancreatic D cell](/details-cell/CL0000173), [pancreatic A cell](/details-cell/CL0000171), [type B pancreatic cell](/details-cell/CL0000169)), it is plausible that [SLC25A53](/details-gene/401612) activity is a rate-limiting factor for hormone production and regulated secretion. Therefore, a functional impairment in this transporter could contribute to islet cell dysfunction and may be a modifier in metabolic diseases like type 2 diabetes. **Experimental Approach to Test Hypothesis 2:** To investigate the role of [SLC25A53](/details-gene/401612) in pancreatic beta-cell function, a cell-specific knockout mouse model could be generated using the Cre-Lox system, crossing a floxed *Slc25a53* mouse with a line expressing Cre recombinase under the control of the insulin promoter (e.g., *Ins1*-Cre). Pancreatic islets would be isolated from control and knockout mice to perform functional assays. Glucose-stimulated insulin secretion (GSIS) assays would directly test the impact on the primary function of beta cells. Furthermore, metabolic analysis using a Seahorse XF Analyzer to measure oxygen consumption rate (OCR) would quantify the effect of [SLC25A53](/details-gene/401612) deletion on mitochondrial respiration. A significant defect in both GSIS and OCR in the knockout islets would provide strong evidence for its critical role in beta-cell bioenergetics. **Therapeutic Potential:** As [SLC25A53](/details-gene/401612) deficiency is a monogenic loss-of-function disorder, therapeutic strategies should focus on **restoration or activation** of its function. Inhibition is not a viable strategy and would likely be toxic due to its role in fundamental metabolism across many tissues. Potential therapeutic avenues could include AAV-mediated gene therapy to deliver a functional copy of the gene to affected tissues like the heart and brain. For patients with missense mutations that produce a partially active but unstable protein, the development of pharmacological chaperones to improve protein folding and stability could be a promising approach. Finally, strategies aimed at boosting mitochondrial NAD+ levels by supplementing with cell-permeable NAD+ precursors that can bypass the need for this specific transporter may offer a metabolic workaround to ameliorate disease symptoms.

Genular Protein ID: 1740029442

Symbol: S2553_HUMAN

Name: Solute carrier family 25 member 53

UniProtKB Accession Codes:

Q5H9E4 B2RTT9

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 EMBL 4 Ensembl 1 GO 3 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 5 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 15772651

Title: The DNA sequence of the human X chromosome.

PubMed ID: 15772651

DOI: 10.1038/nature03440

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: 307
  • Mass: 34481
  • Checksum: 830E366B62DC87AD
  • Sequence:
    • MGEQNHSPGK ELQHRTRAEA PGKKSWHSQA YALGAVSNFM STFLTFPIYK VVFRQQIHAM 
AVSEAVRQLW HEGPQYFYRG IYPPLLSKTL QGTLLFGTYD SLLCFLSPVG PHTLGHRWAA 
GLMSGVVEAV ALSPFERVQN VLQDGRKQAR FPSTFSILKE FNSYGLWGRL SLGYYRGFWP 
VLARNSLGSA LYFSFKDPIQ DGLAEQGLPH WVPALVSGSV NGTITCLVLY PLIVLVANMQ 
SHIGWQNMPS LWASAQDVWN TRGRKLLLIY RGGSLVILRS SVTWGLTTAI HDFLQRKSHS 
RKELKTD