Details for: SLC44A5

Gene ID: 204962

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: SLC44A5

Ensembl ID: ENSG00000137968

Description: solute carrier family 44 member 5

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • VIP GABAergic cortical interneuron CL4023016
    CSI 36.5
    rCSI 43.6%
    PRS 94.11
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 35.38
    rCSI 44.02%
    PRS 93.06
  • sst GABAergic cortical interneuron CL4023017
    CSI 32.76
    rCSI 42.23%
    PRS 94.64
  • sncg GABAergic cortical interneuron CL4023015
    CSI 28.92
    rCSI 46.51%
    PRS 94.13
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 20.84
    rCSI 34.99%
    PRS 94.26
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 20.12
    rCSI 35.53%
    PRS 94.03
  • neural crest cell CL0011012
    CSI 19.96
    rCSI 15.78%
    PRS 96.62
  • rod bipolar cell CL0000751
    CSI 19.75
    rCSI 35.48%
    PRS 95.82
  • inhibitory interneuron CL0000498
    CSI 16.28
    rCSI 37.59%
    PRS 94.43
  • neuron CL0000540
    CSI 15.93
    rCSI 42.42%
    PRS 91.34
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 15.62
    rCSI 22.15%
    PRS 97.6
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 15.16
    rCSI 36.85%
    PRS 92.74
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 15.01
    rCSI 35.89%
    PRS 93.13
  • oligodendrocyte precursor cell CL0002453
    CSI 12.42
    rCSI 27.32%
    PRS 89.13
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 12.03
    rCSI 13.89%
    PRS 95.19
  • L2/3 intratelencephalic projecting glutamatergic neuron CL4030059
    CSI 11.96
    rCSI 25.94%
    PRS 92.06
  • L6b glutamatergic cortical neuron CL4023038
    CSI 11.83
    rCSI 36.96%
    PRS 94.38
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 11.69
    rCSI 44.2%
    PRS 93.62
  • radial glial cell CL0000681
    CSI 11.48
    rCSI 15.95%
    PRS 97.92
  • glioblast CL0000030
    CSI 11.32
    rCSI 18.06%
    PRS 95.18
  • retinal bipolar neuron CL0000748
    CSI 10.83
    rCSI 20.28%
    PRS 94.79
  • retinal rod cell CL0000604
    CSI 10.7
    rCSI 18.86%
    PRS 95.99
  • ependymal cell CL0000065
    CSI 10.38
    rCSI 21.07%
    PRS 90.33
  • GABAergic amacrine cell CL4030027
    CSI 9.95
    rCSI 34.06%
    PRS 91.74
  • lung secretory cell CL1000272
    CSI 9.64
    rCSI 23.86%
    PRS 98.86
  • interneuron CL0000099
    CSI 9.25
    rCSI 18.57%
    PRS 96.26
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 8.9
    rCSI 11.42%
    PRS 96.94
  • astrocyte of the cerebral cortex CL0002605
    CSI 8.37
    rCSI 18.77%
    PRS 94.15
  • cardiac muscle cell CL0000746
    CSI 8.31
    rCSI 11.92%
    PRS 94.55
  • blood vessel endothelial cell CL0000071
    CSI 8.19
    rCSI 17%
    PRS 97.59
  • cerebral cortex endothelial cell CL1001602
    CSI 8.03
    rCSI 13.89%
    PRS 96.34
  • neural cell CL0002319
    CSI 7.93
    rCSI 29.94%
    PRS 91.54
  • GABAergic neuron CL0000617
    CSI 7.91
    rCSI 26.51%
    PRS 91.49
  • amacrine cell CL0000561
    CSI 7.9
    rCSI 22.91%
    PRS 94.54
  • vascular leptomeningeal cell CL4023051
    CSI 7.8
    rCSI 13.68%
    PRS 96.58
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 7.59
    rCSI 13.8%
    PRS 95.22
  • glutamatergic neuron CL0000679
    CSI 7.49
    rCSI 15.4%
    PRS 91.79
  • mesothelial cell CL0000077
    CSI 6.66
    rCSI 26.03%
    PRS 92.18
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 6.35
    rCSI 19.86%
    PRS 94.88
  • diffuse bipolar 6 cell CL4033032
    CSI 6.23
    rCSI 32.77%
    PRS 92.29
  • glycinergic amacrine cell CL4030028
    CSI 5.87
    rCSI 15.28%
    PRS 94.45
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 5.74
    rCSI 14.85%
    PRS 97.45
  • parietal epithelial cell CL1000452
    CSI 5.27
    rCSI 14.08%
    PRS 96.68
  • L5/6 near-projecting glutamatergic neuron CL4030067
    CSI 5.24
    rCSI 17.23%
    PRS 92.34
  • serotonergic neuron CL0000850
    CSI 4.81
    rCSI 21.51%
    PRS 89.99
  • dopaminergic neuron CL0000700
    CSI 4.73
    rCSI 26.75%
    PRS 93.03
  • cerebral cortex neuron CL0010012
    CSI 4.73
    rCSI 19.29%
    PRS 94
  • central nervous system neuron CL2000029
    CSI 4.64
    rCSI 34.13%
    PRS 94.89
  • Bergmann glial cell CL0000644
    CSI 4.59
    rCSI 6.29%
    PRS 94.86
  • endocardial cell CL0002350
    CSI 4.2
    rCSI 20.09%
    PRS 96.71
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 3.92
    rCSI 14.09%
    PRS 93.05
  • cerebellar granule cell CL0001031
    CSI 3.53
    rCSI 5.19%
    PRS 95.77
  • basal cell of epidermis CL0002187
    CSI 3.46
    rCSI 6.13%
    PRS 81.12
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 3.27
    rCSI 19.27%
    PRS 93.92
  • epithelial cell of lower respiratory tract CL0002632
    CSI 3.22
    rCSI 2.5%
    PRS 99.02
  • invaginating midget bipolar cell CL4033034
    CSI 2.79
    rCSI 16.46%
    PRS 93.02
  • neuroplacodal cell CL0000032
    CSI 2.65
    rCSI 24.5%
    PRS 95.1
  • medium spiny neuron CL1001474
    CSI 2.64
    rCSI 22.78%
    PRS 94.5
  • Mueller cell CL0000636
    CSI 2.61
    rCSI 5.96%
    PRS 95.57
  • retinal ganglion cell CL0000740
    CSI 2.54
    rCSI 5.61%
    PRS 93.99
  • extravillous trophoblast CL0008036
    CSI 2.4
    rCSI 2.97%
    PRS 97.42
  • chondrocyte CL0000138
    CSI 2.14
    rCSI 3.41%
    PRS 96.39
  • diffuse bipolar 4 cell CL4033031
    CSI 1.71
    rCSI 19.64%
    PRS 89.55
  • cardiac blood vessel endothelial cell CL0010006
    CSI 1.67
    rCSI 11.83%
    PRS 95.45
  • starburst amacrine cell CL0004232
    CSI 1.61
    rCSI 13.59%
    PRS 89.98
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 1.48
    rCSI 3.37%
    PRS 94.49
  • neural progenitor cell CL0011020
    CSI 1.46
    rCSI 6.4%
    PRS 92.4

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 [SLC44A5](/details-gene/204962) is a protein-coding gene that encodes Solute carrier family 44 member 5, a transmembrane protein. Functional annotations strongly indicate its role as a choline transporter ([GO:0015220](https://www.ebi.ac.uk/QuickGO/term/GO:0015220)) involved in the transport of choline across the plasma membrane ([GO:0005886](https://www.ebi.ac.uk/QuickGO/term/GO:0005886)). This function is integral to phospholipid metabolism, particularly the biosynthesis of phosphatidylcholine ([GO:0006656](https://www.ebi.ac.uk/QuickGO/term/GO:0006656), [R-HSA-1483191](https://reactome.org/content/detail/R-HSA-1483191)). Expression data reveals that **Overall**, [SLC44A5](/details-gene/204962) is a highly significant marker for various neuronal populations, showing exceptional specificity for cortical GABAergic interneurons, such as [VIP GABAergic cortical interneuron](/details-cell/CL4023016) and [pvalb GABAergic cortical interneuron](/details-cell/CL4023018). This suggests a critical role in maintaining membrane homeostasis and metabolic function in these specific, high-activity inhibitory neurons of the central nervous system. ## Cellular Roles and Expression Landscape The expression profile of [SLC44A5](/details-gene/204962) highlights its profound importance within the nervous system. The gene demonstrates its highest significance in a range of inhibitory interneurons, including [VIP GABAergic cortical interneuron](/details-cell/CL4023016) (CSI: 36.50), [pvalb GABAergic cortical interneuron](/details-cell/CL4023018) (CSI: 35.38), and [sst GABAergic cortical interneuron](/details-cell/CL4023017) (CSI: 32.76). Its high expression extends to other neuronal subtypes, such as [L2/3-6 intratelencephalic projecting glutamatergic neuron](/details-cell/CL4023040) and [rod bipolar cell](/details-cell/CL0000751), underscoring a broad but specialized role in neuronal biology. Beyond mature neurons, [SLC44A5](/details-gene/204962) is also significantly expressed in [oligodendrocyte precursor cell](/details-cell/CL0002453) (CSI: 12.42), suggesting a potential function in glial cell development, myelination, or metabolic support. Interestingly, a notable level of expression is also observed in a non-neuronal context, specifically in the [kidney loop of Henle thin descending limb epithelial cell](/details-cell/CL1001111) (CSI: 15.62), which may indicate a role in osmoregulation or solute transport in the kidney. The pronounced enrichment in these specific cell types suggests that its expression is comparatively low in other major lineages, such as hematopoietic or connective tissues, making it a specific marker for these cellular contexts. ## Pathways and Molecular Function The molecular function of [SLC44A5](/details-gene/204962) is centered on its activity as a choline transporter, as part of the larger solute carrier (SLC) family involved in [Slc-mediated transmembrane transport](/details-pathway/R-HSA-425407). It participates directly in [Choline transport](/details-go/GO:0015871) across the cell membrane, a critical step for multiple downstream processes. The primary metabolic pathway supported by this gene is [Glycerophospholipid biosynthesis](/details-pathway/R-HSA-1483206), and more specifically, the [synthesis of pc](/details-pathway/R-HSA-1483191) (phosphatidylcholine). Phosphatidylcholine is a major constituent of eukaryotic cell membranes, and its synthesis is essential for membrane integrity, signaling, and fluidity. This function is particularly vital for [neuron](/details-cell/CL0000540)s, which have extensive plasma membranes and high metabolic demands for membrane turnover and repair. Furthermore, research has suggested a link between related choline transporter-like proteins and non-neuronal acetylcholine synthesis, indicating that the choline transported by [SLC44A5](/details-gene/204962) could also serve as a precursor for signaling molecules in certain cellular contexts [Link](https://doi.org/10.1111/jnc.12298). ## Research Directions The highly specific expression of [SLC44A5](/details-gene/204962) in distinct cell populations, coupled with its fundamental role in metabolism, provides fertile ground for further investigation. **Testable Hypotheses:** 1. **Neurological Function:** The exceptional enrichment of [SLC44A5](/details-gene/204962) in cortical GABAergic interneurons suggests it is essential for their survival and function. We hypothesize that loss-of-function of [SLC44A5](/details-gene/204962) in these neurons would disrupt membrane lipid composition, leading to impaired inhibitory neurotransmission and a state of network hyperexcitability, potentially contributing to the pathology of disorders like epilepsy. 2. **Renal Physiology:** Given its specific expression in the [kidney loop of Henle thin descending limb epithelial cell](/details-cell/CL1001111), we hypothesize that [SLC44A5](/details-gene/204962) functions in renal osmoregulation by transporting choline, which can act as an organic osmolyte to protect cells from osmotic stress in the hypertonic environment of the kidney medulla. 3. **Glial Development:** The expression in [oligodendrocyte precursor cell](/details-cell/CL0002453) suggests a role beyond that of mature neurons. We hypothesize that [SLC44A5](/details-gene/204962) is critical for supplying the large amounts of choline required for the synthesis of sphingomyelin and phosphatidylcholine during the process of myelination. **Proposed Experiment:** To test the first hypothesis regarding the role of [SLC44A5](/details-gene/204962) in GABAergic neuron function, a conditional knockout mouse model could be generated using the Cre-lox system. By crossing a floxed-[SLC44A5](/details-gene/204962) mouse line with a line expressing Cre recombinase under the control of a GABAergic-specific promoter (e.g., Gad2-Cre or Pvalb-Cre), the gene can be selectively deleted in inhibitory interneurons. The resulting phenotype can be assessed through a combination of techniques: electrophysiological recordings (patch-clamp) from cortical slices to measure changes in synaptic inhibition, lipidomic analysis of sorted neurons to confirm alterations in membrane composition, and behavioral assays to assess seizure susceptibility (e.g., response to chemoconvulsants). **Therapeutic Potential:** As a direct therapeutic target, [SLC44A5](/details-gene/204962) presents challenges due to its likely critical role in the normal function of essential neurons. Inhibition of such a fundamental transporter could have severe neurotoxic effects. However, its high cellular specificity makes it a valuable asset for understanding disease. Genetic variants or mutations in [SLC44A5](/details-gene/204962) could be investigated as potential causes of inherited neurological or renal disorders. Furthermore, if its expression is dysregulated in specific disease states (e.g., neurodegeneration or brain tumors), it could serve as a highly specific diagnostic biomarker or a target for cell-specific drug delivery systems, rather than a target for functional modulation.

Genular Protein ID: 1312125693

Symbol: CTL5_HUMAN

Name: Solute carrier family 44 member 5

UniProtKB Accession Codes:

Q8NCS7 A0A0A0MRP1 B5MCU3 Q4G0K0 Q8NA44 Q8NB86

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CTD 1 ChEBI 2 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 12 Ensembl 2 GO 8 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 1 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 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 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 2 RefSeq 8 Rhea 1 SMR 1 STRING 1 SignaLink 1 TCDB 1 TreeFam 1 UCSC 2 VEuPathDB 1 eggNOG 1 iPTMnet 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: 16710414

Title: The DNA sequence and biological annotation of human chromosome 1.

PubMed ID: 16710414

DOI: 10.1038/nature04727

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: 15715662

Title: Molecular characterization of the family of choline transporter-like proteins and their splice variants.

PubMed ID: 15715662

DOI: 10.1111/j.1471-4159.2004.02962.x

PubMed ID: 23651124

Title: Choline transporter-like protein 4 (CTL4) links to non-neuronal acetylcholine synthesis.

PubMed ID: 23651124

DOI: 10.1111/jnc.12298

Sequence Information:

  • Length: 719
  • Mass: 81694
  • Checksum: FF5B57849397F031
  • Sequence:
    • MNDTEKPADT PSEEEDFGDP RTYDPDFKGP VANRSCTDVL CCMIFLLCII GYIVLGLVAW 
VHGDPRRAAY PTDSQGHFCG QKGTPNENKT ILFYFNLLRC TSPSVLLNLQ CPTTQICVSK 
CPEKFLTYVE MQLLYTKDKS YWEDYRQFCK TTAKPVKSLT QLLLDDDCPT AIFPSKPFLQ 
RCFPDFSTKN GTLTIGSKMM FQDGNGGTRS VVELGIAANG INKLLDAKSL GLKVFEDYAR 
TWYWILIGLT IAMVLSWIFL ILLRFIAGCL FWVFMIGVIG IIGYGIWHCY QQYTNLQERP 
SSVLTIYDIG IQTNISMYFE LQQTWFTFMI ILCIIEVIVI LMLIFLRNRI RVAIILLKEG 
SKAIGYVPST LVYPALTFIL LSICICYWVV TAVFLATSGV PVYKVIAPGG HCIHENQTCD 
PEIFNTTEIA KACPGALCNF AFYGGKSLYH QYIPTFHVYN LFVFLWLINF VIALGQCALA 
GAFATYYWAM KKPDDIPRYP LFTAFGRAIR YHTGSLAFGS LIIALIQMFK IVLEYLDHRL 
KRTQNTLSKF LQCCLRCCFW CLENAIKFLN RNAYIMIAIY GRNFCRSAKD AFNLLMRNVL 
KVAVTDEVTY FVLFLGKLLV AGSIGVLAFL FFTQRLPVIA QGPASLNYYW VPLLTVIFGS 
YLIAHGFFSV YAMCVETIFI CFCEDLERND GSTEKPYFVT PNLHGILIKK QLVPQKQKE

Genular Protein ID: 2415175645

Symbol: B7Z5Y4_HUMAN

Name: N/A

UniProtKB Accession Codes:

B7Z5Y4

Database IDs:

ARBA 7 AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 ChEBI 2 DNASU 1 DisGeNET 1 EMBL 2 GO 3 InterPro 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PeptideAtlas 1 Pfam 1 RefSeq 3 Rhea 1 RuleBase 1

Sequence Information:

  • Length: 713
  • Mass: 80838
  • Checksum: 2ABD90C235895FC3
  • Sequence:
    • MAKKRKPPSI KGDPRTYDPD FKGPVANRSC TDVLCCMIFL LCIIGYIVLG LVAWVHGDPR 
RAAYPTDSQG HFCGQKGTPN ENKTILFYFN LLRCTSPSVL LNLQCPTTQI CVSKCPEKFL 
TYVEMQLLYT KDKSYWEDYR QFCKTTAKPV KSLTQLLLDD DCPTAIFPSK PSLQRCFPDF 
STKNGTLTIG SKMMFQDGNG GTRSVVELGI AANGINKLLD AKSLGLKVFE DYARTWYWIL 
IGLTIAMVLS WIFLILLRFI AGCLFWVFMI GVIGIIGYGI WHCYQQYTSL QERPSSVLTI 
YDIGIQTNIS MYFELQQTWF TFMIILCIIE VIVILMLIFL RNRIRVAIIL LKEGSKAIGY 
VPSTLVYPAL TFILLSICIC YWVVTAVFLA TSGVPVYKVI APGGHCIHEN QTCDPEIFNT 
TEIAKACPGA LCNFAFYGGK SLYHQYIPTF HVYNLFVFLW LINFVIALGQ CALAGAFATY 
YWAMKKPDDI PRYPLFTAFG RAIRYHTGSL AFGSSIIALI QMFKIVLEYL DHRLKRTQNT 
LSKFLQCCLR CCFWCLENAI KFLNRNAYIM IAIYGRNFCR SAKDAFNLLM RNVLKVAVTD 
EVTYFVLFLG KLLVAGSIGV LAFLFFTQRL PVIAQGPASL NYYWVPLLTV IFGSYLIAHG 
FFSVYAMCVE TIFICFCEDL GRNDGSTEKP YFVTPNLHGI LIKKQLVPQK QKE