Details for: SLC25A14

Gene ID: 9016

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: SLC25A14

Ensembl ID: ENSG00000102078

Description: solute carrier family 25 member 14

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • pancreatic A cell CL0000171
    CSI 3.89
    rCSI 4.08%
    PRS 97.53
  • pancreatic D cell CL0000173
    CSI 3.56
    rCSI 3.51%
    PRS 97.42
  • interneuron CL0000099
    CSI 3.5
    rCSI 7.02%
    PRS 94.97
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 3.2
    rCSI 5.66%
    PRS 91.87
  • retina horizontal cell CL0000745
    CSI 3.08
    rCSI 4.7%
    PRS 95.59
  • multi-ciliated epithelial cell CL0005012
    CSI 2.8
    rCSI 2.79%
    PRS 94.48
  • rod bipolar cell CL0000751
    CSI 2.67
    rCSI 4.8%
    PRS 94.69
  • ciliated epithelial cell CL0000067
    CSI 2.62
    rCSI 2.3%
    PRS 92.98
  • epithelial cell CL0000066
    CSI 2.55
    rCSI 3.93%
    PRS 89.84
  • ciliated cell CL0000064
    CSI 2.47
    rCSI 4%
    PRS 93.6
  • lung ciliated cell CL1000271
    CSI 2.36
    rCSI 2.73%
    PRS 94.63
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.33
    rCSI 2.9%
    PRS 90.58
  • type B pancreatic cell CL0000169
    CSI 2.04
    rCSI 4.51%
    PRS 96.97
  • sst GABAergic cortical interneuron CL4023017
    CSI 1.88
    rCSI 2.42%
    PRS 92.54
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.73
    rCSI 2.91%
    PRS 92.12
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 1.49
    rCSI 1.81%
    PRS 83.65
  • deuterosomal cell CL4033044
    CSI 1.03
    rCSI 3.49%
    PRS 93.51
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 1.01
    rCSI 2.3%
    PRS 93
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.65
    rCSI 2.33%
    PRS 90.72

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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  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
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    • 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 [SLC25A14](/details-gene/9016) is a protein-coding gene located on the X chromosome that encodes a member of the solute carrier family, specifically known as mitochondrial uncoupling protein 5 (UCP5). Functionally, it is an integral mitochondrial inner membrane protein involved in transporting various anions and protons, which contributes to [Mitochondrial uncoupling](/details-ontology/R-HSA-166187), a process that dissipates the proton gradient to produce heat instead of ATP. Expression data reveals that **Overall**, [SLC25A14](/details-gene/9016) shows pronounced significance in metabolically active and specialized cell types, most notably in endocrine cells of the pancreas, such as [pancreatic A cells](/details-cell/CL0000171) and [pancreatic D cells](/details-cell/CL0000173), as well as in various neuronal subtypes, including [interneurons](/details-cell/CL0000099). This expression pattern, coupled with its role in regulating mitochondrial potential and oxidative stress, suggests it plays a critical part in both neuroprotection and the bioenergetics of hormone secretion. Clinical associations for this gene are noted under OMIM entry [300242](https://omim.org/entry/300242). ## Cellular Roles and Expression Landscape The expression profile of [SLC25A14](/details-gene/9016) highlights its specialized role in discrete cell populations characterized by high metabolic or signaling activity. **Overall**, the gene exhibits its highest significance in two primary functional clusters: pancreatic islet cells and neurons. Within the pancreas, [SLC25A14](/details-gene/9016) is a significant marker for [pancreatic A cells](/details-cell/CL0000171) (CSI: 3.89) and [pancreatic D cells](/details-cell/CL0000173) (CSI: 3.56), and also shows relevance in [type B pancreatic cells](/details-cell/CL0000169) (CSI: 2.04). This enrichment in the primary endocrine cells of the pancreas suggests a role in modulating the energetic states required for the synthesis and secretion of glucagon, somatostatin, and insulin. The second major site of expression is the central nervous system, consistent with early reports identifying it as highly expressed in the CNS ([Link](https://pubmed.ncbi.nlm.nih.gov/9852133/)). It is a prominent marker in [interneurons](/details-cell/CL0000099) (CSI: 3.50), including specific subtypes such as [caudal ganglionic eminence derived cortical interneurons](/details-cell/CL4023064) (CSI: 3.20) and various GABAergic cortical interneurons. Furthermore, its high significance in specialized retinal neurons like [retina horizontal cells](/details-cell/CL0000745) (CSI: 3.08) and [rod bipolar cells](/details-cell/CL0000751) (CSI: 2.67) underscores its importance in neuronal circuits with high energy demands for signal processing. A third, distinct group of cells with high [SLC25A14](/details-gene/9016) expression includes [multi-ciliated epithelial cells](/details-cell/CL0005012) and [lung ciliated cells](/details-cell/CL1000271). This suggests a potential role in providing the high levels of ATP required to power ciliary motion. Notably, the expression landscape appears to be highly specific, with an absence of high significance in major cell lineages such as hematopoietic, muscle, or stromal cells, pointing towards a specialized function rather than a general housekeeping role. ## Pathways and Molecular Function The molecular functions of [SLC25A14](/details-gene/9016) are centered on its role as a transporter in the mitochondrial inner membrane. Gene Ontology annotations describe it as having [Proton transmembrane transporter activity](/details-ontology/GO0015078) and [Solute:inorganic anion antiporter activity](/details-ontology/GO0005452), which are central to its uncoupling function. This is explicitly captured in Reactome pathways such as [Mitochondrial uncoupling](/details-ontology/R-HSA-166187) and [Aerobic respiration and respiratory electron transport](/details-ontology/R-HSA-1428517). Its activity uncouples oxidative phosphorylation from ATP synthesis, a process critical for thermogenesis and for mitigating the production of reactive oxygen species (ROS). This function is directly linked to the biological process of [Regulation of cellular response to oxidative stress](/details-ontology/GO1900407). Research has demonstrated that [SLC25A14](/details-gene/9016) is neuroprotective by preserving mitochondrial membrane potential and reducing oxidative damage in models of dopamine toxicity ([Link](https://doi.org/10.1016/j.freeradbiomed.2010.06.017)). Recent studies have further refined its transport specificity, showing it can transport sulfur oxyanions, phosphate, and dicarboxylates, which may influence a wide range of metabolic pathways ([Link](https://doi.org/10.1016/j.bbabio.2019.07.010)). Its involvement in these core energetic and protective pathways aligns perfectly with its high expression in neurons and pancreatic endocrine cells, which are highly susceptible to metabolic stress and have stringent energy requirements. ## Research Directions The specific expression pattern and molecular function of [SLC25A14](/details-gene/9016) suggest several avenues for future investigation, particularly concerning its roles in metabolic regulation and neurobiology. 1. **Hypothesis 1:** Given its high significance in [pancreatic A](/details-cell/CL0000171), [D](/details-cell/CL0000173), and [B cells](/details-cell/CL0000169), [SLC25A14](/details-gene/9016) acts as a critical regulator of glucose homeostasis by fine-tuning the mitochondrial ATP/ADP ratio, a key signal for hormone exocytosis. In this model, its uncoupling activity would modulate the sensitivity of these cells to glucose and other secretagogues. 2. **Hypothesis 2:** In the central nervous system, particularly in high-firing [interneurons](/details-cell/CL0000099), the primary role of [SLC25A14](/details-gene/9016) is to prevent excitotoxic damage. By providing a "pressure-release" mechanism for the mitochondrial proton gradient during intense synaptic activity, it mitigates ROS production and preserves neuronal integrity under conditions of high metabolic stress. To test the role of [SLC25A14](/details-gene/9016) in pancreatic function (Hypothesis 1), a compelling experiment would involve the generation of a pancreas-specific knockout mouse model (e.g., *Slc25a14* flox/flox crossed with a Pdx1-Cre driver). These mice and control littermates could be subjected to glucose and insulin tolerance tests to assess systemic metabolic changes. Furthermore, islets isolated from these mice could be analyzed *ex vivo* for glucose-stimulated insulin, glucagon, and somatostatin secretion. Direct assessment of mitochondrial function using respirometry assays (e.g., Seahorse XF) would reveal the impact of [SLC25A14](/details-gene/9016) deletion on basal respiration, ATP production, and proton leak. From a therapeutic standpoint, [SLC25A14](/details-gene/9016) represents an intriguing target. Its demonstrated neuroprotective effects suggest that enhancing its activity or expression could be a strategy for treating neurodegenerative disorders associated with mitochondrial dysfunction and oxidative stress, such as Parkinson's or Alzheimer's disease. As an intracellular mitochondrial transporter, developing small molecules that can cross the blood-brain barrier and allosterically activate its transport function would be a key challenge. Activation, rather than inhibition, would be the likely therapeutic goal.

Genular Protein ID: 639938236

Symbol: UCP5_HUMAN

Name: Mitochondrial uncoupling protein 5

UniProtKB Accession Codes:

O95258 D3DTG2 Q0VDH7 Q9HC60 Q9HC61

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 3 CTD 1 ChEBI 36 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 9 Ensembl 5 ExpressionAtlas 1 GO 11 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRINTS 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 Pumba 1 RNAct 1 Reactome 1 RefSeq 4 Rhea 22 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9852133

Title: BMCP1, a novel mitochondrial carrier with high expression in the central nervous system of humans and rodents, and respiration uncoupling activity in recombinant yeast.

PubMed ID: 9852133

DOI: 10.1074/jbc.273.51.34611

PubMed ID: 10928996

Title: Characterization of novel UCP5/BMCP1 isoforms and differential regulation of UCP4 and UCP5 expression through dietary or temperature manipulation.

PubMed ID: 10928996

DOI: 10.1096/fj.14.11.1611

PubMed ID: 12975309

Title: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.

PubMed ID: 12975309

DOI: 10.1101/gr.1293003

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

PubMed ID: 20600837

Title: Mitochondrial UCP5 is neuroprotective by preserving mitochondrial membrane potential, ATP levels, and reducing oxidative stress in MPP+ and dopamine toxicity.

PubMed ID: 20600837

DOI: 10.1016/j.freeradbiomed.2010.06.017

PubMed ID: 22524567

Title: Toward understanding the mechanism of ion transport activity of neuronal uncoupling proteins UCP2, UCP4, and UCP5.

PubMed ID: 22524567

DOI: 10.1021/bi3003378

PubMed ID: 26182433

Title: A biophysical study on molecular physiology of the uncoupling proteins of the central nervous system.

PubMed ID: 26182433

DOI: 10.1042/bsr20150130

PubMed ID: 31356773

Title: The human uncoupling proteins 5 and 6 (UCP5/SLC25A14 and UCP6/SLC25A30) transport sulfur oxyanions, phosphate and dicarboxylates.

PubMed ID: 31356773

DOI: 10.1016/j.bbabio.2019.07.010

Sequence Information:

  • Length: 325
  • Mass: 36202
  • Checksum: 0447E8E3B5374982
  • Sequence:
    • MGIFPGIILI FLRVKFATAA VIVSGHQKST TVSHEMSGLN WKPFVYGGLA SIVAEFGTFP 
VDLTKTRLQV QGQSIDARFK EIKYRGMFHA LFRICKEEGV LALYSGIAPA LLRQASYGTI 
KIGIYQSLKR LFVERLEDET LLINMICGVV SGVISSTIAN PTDVLKIRMQ AQGSLFQGSM 
IGSFIDIYQQ EGTRGLWRGV VPTAQRAAIV VGVELPVYDI TKKHLILSGM MGDTILTHFV 
SSFTCGLAGA LASNPVDVVR TRMMNQRAIV GHVDLYKGTV DGILKMWKHE GFFALYKGFW 
PNWLRLGPWN IIFFITYEQL KRLQI

Genular Protein ID: 1592435734

Symbol: F6SL11_HUMAN

Name: N/A

UniProtKB Accession Codes:

F6SL11

Database IDs:

ARBA 8 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 2 Ensembl 2 ExpressionAtlas 1 GO 2 Gene3D 1 GeneTree 1 HGNC 1 HOGENOM 1 InterPro 4 MassIVE 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PRINTS 1 PROSITE 1 PROSITE-ProRule 1 PeptideAtlas 2 Pfam 1 Proteomes 2 ProteomicsDB 1 RefSeq 1 RuleBase 1 SMR 1 SUPFAM 1 UCSC 1 VEuPathDB 1

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

PubMed ID: 15772651

Title: The DNA sequence of the human X chromosome.

PubMed ID: 15772651

DOI: 10.1038/nature03440

Sequence Information:

  • Length: 290
  • Mass: 32450
  • Checksum: DA3A5092741F4A85
  • Sequence:
    • MSGLNWKPFV YGGLASIVAE FGTFPVDLTK TRLQVQGQSI DARFKEIKYR GMFHALFRIC 
KEEGVLALYS GIAPALLRQA SYGTIKIGIY QSLKRLFVER LEDETLLINM ICGVVSGVIS 
STIANPTDVL KIRMQAQGSL FQGSMIGSFI DIYQQEGTRG LWRGVVPTAQ RAAIVVGVEL 
PVYDITKKHL ILSGMMGDTI LTHFVSSFTC GLAGALASNP VDVVRTRMMN QRAIVGHVDL 
YKGTVDGILK MWKHEGFFAL YKGFWPNWLR LGPWNIIFFI TYEQLKRLQI

Genular Protein ID: 2015438471

Symbol: B4DMK1_HUMAN

Name: N/A

UniProtKB Accession Codes:

B4DMK1

Database IDs:

ARBA 8 AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 GO 2 Gene3D 1 InterPro 4 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PRINTS 1 PROSITE 1 PROSITE-ProRule 1 PeptideAtlas 1 Pfam 1 ProteomicsDB 1 RefSeq 1 RuleBase 1 SAM 1 SUPFAM 1

Sequence Information:

  • Length: 240
  • Mass: 26386
  • Checksum: D3B34FD1E6933635
  • Sequence:
    • MGIFPGIILI FLRVKFATAA VIVSGHQKST TVSHEMSGLN WKPFVYGGLA SIVAEFGTFP 
VDLTKTRLQV QGQSIDARFK EIKYRGMFHA LFRICKEEGV LALYSGIAPA LLRQASYGTI 
KIGIYQSLKR LFVERLEDET LLINMICGVV SGVISSTIAN PTDVLKIRMQ AQGSLFQGSM 
IGSFIDIYQQ EGTRGLWRGV VPTAQRAAIV VGVELPVYDI TKKHLILSGM MGDTILTHFV