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    TRPC4 transient receptor potential cation channel subfamily C member 4 [ Homo sapiens (human) ]

    Gene ID: 7223, updated on 10-Dec-2024

    Summary

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    Official Symbol
    TRPC4provided by HGNC
    Official Full Name
    transient receptor potential cation channel subfamily C member 4provided by HGNC
    Primary source
    HGNC:HGNC:12336
    See related
    Ensembl:ENSG00000133107 MIM:603651; AllianceGenome:HGNC:12336
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    TRP4; HTRP4; HTRP-4
    Summary
    This gene encodes a member of the canonical subfamily of transient receptor potential cation channels. The encoded protein forms a non-selective calcium-permeable cation channel that is activated by Gq-coupled receptors and tyrosine kinases, and plays a role in multiple processes including endothelial permeability, vasodilation, neurotransmitter release and cell proliferation. Single nucleotide polymorphisms in this gene may be associated with generalized epilepsy with photosensitivity. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2011]
    Expression
    Biased expression in endometrium (RPKM 6.2), prostate (RPKM 2.5) and 8 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See TRPC4 in Genome Data Viewer
    Location:
    13q13.3
    Exon count:
    11
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 13 NC_000013.11 (37632063..37869772, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 13 NC_060937.1 (36851454..37089250, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 13 NC_000013.10 (38206200..38443909, complement)

    Chromosome 13 - NC_000013.11Genomic Context describing neighboring genes Neighboring gene H3K27ac hESC enhancer GRCh37_chr13:38120407-38120907 Neighboring gene long intergenic non-protein coding RNA 547 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr13:38169125-38169774 Neighboring gene periostin Neighboring gene Sharpr-MPRA regulatory region 14178 Neighboring gene Sharpr-MPRA regulatory region 929 Neighboring gene uncharacterized LOC124903160 Neighboring gene RNA, 5S ribosomal pseudogene 26 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr13:38488805-38489357 Neighboring gene long intergenic non-protein coding RNA 2334 Neighboring gene heat shock protein family D (Hsp60) member 1 pseudogene 9 Neighboring gene long intergenic non-protein coding RNA 571

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. TRPC channels and their splice variants are essential for promoting human ovarian cancer cell proliferation and tumorigenesis. Zeng B, et al. Curr Cancer Drug Targets, 2013 Jan. PMID 22920441
    2. Association study of TRPC4 as a candidate gene for generalized epilepsy with photosensitivity. von Spiczak S, et al. Neuromolecular Med, 2010 Sep. PMID 20574736
    3. TRPC4α and TRPC4β Similarly Affect Neonatal Cardiomyocyte Survival during Chronic GPCR Stimulation. Kirschmer N, et al. PLoS One, 2016. PMID 27992507, Free PMC Article
    4. The regulation of transient receptor potential canonical 4 (TRPC4) channel by phosphodiesterase 5 inhibitor via the cyclic guanosine 3'5'-monophosphate. Wie J, et al. Pflugers Arch, 2017 Jun. PMID 28124739
    5. The PDZ-interacting domain of TRPC4 controls its localization and surface expression in HEK293 cells. Mery L, et al. J Cell Sci, 2002 Sep 1. PMID 12154080

    See all (84) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. In vitro and in vivo inhibition of the host TRPC4 channel attenuates Zika virus infection.
      Title: In vitro and in vivo inhibition of the host TRPC4 channel attenuates Zika virus infection.
    2. Pan-Cancer Analysis of the TRP Family, Especially TRPV4 and TRPC4, and Its Expression Correlated with Prognosis, Tumor Microenvironment, and Treatment Sensitivity.
      Title: Pan-Cancer Analysis of the TRP Family, Especially TRPV4 and TRPC4, and Its Expression Correlated with Prognosis, Tumor Microenvironment, and Treatment Sensitivity.
    3. Expression of pH-Sensitive TRPC4 in Common Skin Tumors.
      Title: Expression of pH-Sensitive TRPC4 in Common Skin Tumors.
    4. Downregulation of TRPC4 and TRPC5 Inhibits Smooth Muscle Cell Proliferation without Affecting Endothelial Cell Proliferation.
      Title: Downregulation of TRPC4 and TRPC5 Inhibits Smooth Muscle Cell Proliferation without Affecting Endothelial Cell Proliferation.
    5. Transient Receptor Potential C 1/4/5 Is a Determinant of MTI-101 Induced Calcium Influx and Cell Death in Multiple Myeloma.
      Title: Transient Receptor Potential C 1/4/5 Is a Determinant of MTI-101 Induced Calcium Influx and Cell Death in Multiple Myeloma.
    6. Differential PI(4,5)P2 sensitivities of TRPC4, C5 homomeric and TRPC1/4, C1/5 heteromeric channels.
      Title: Differential PI(4,5)P(2) sensitivities of TRPC4, C5 homomeric and TRPC1/4, C1/5 heteromeric channels.
    7. Study reports a novel mechanism of self-limiting activation of TRPC1/4 and TRPC1/5 channels by G protein-coupled receptor stimulation. Galphaq protein directly interacts with either TRPC4 or TRPC5 of the heterotetrameric channels to permit activation. Simultaneously, Galphaq-coupled PLCbeta activation leads to the breakdown of PI(4,5)P2, which inhibits activity of TRPC1/4 and 1/5 channels.
      Title: Dual action of the Gα(q)-PLCβ-PI(4,5)P(2) pathway on TRPC1/4 and TRPC1/5 heterotetramers.
    8. We found that the inhibitory Galphai3 protein selectively bound to the G-protein-binding domain on the C-terminus of PC1. The dissociation of Galphai3 upon cleavage of PC1 increased TRPC4 activity.
      Title: Gα(i)-mediated TRPC4 activation by polycystin-1 contributes to endothelial function via STAT1 activation.
    9. Our results suggest that OGR1-dependent increases in TRPC4 expression may favor formation of highly Ca(2+) -permeable TRPC4-containing channels that promote transformed granule cell migration. Increased motility of cancer cells is a prerequisite for cancer invasion and metastasis, and our findings may point towards a key role for TRPC4 in progression of certain types of medullablastoma.
      Title: Functional expression of calcium-permeable canonical transient receptor potential 4-containing channels promotes migration of medulloblastoma cells.
    10. Protein levels of TRPC4 were elevated in FCD II and tuberous sclerosis complex cortical samples compared to those of control samples.
      Title: Elevated Expression of TRPC4 in Cortical Lesions of Focal Cortical Dysplasia II and Tuberous Sclerosis Complex.
    Submit: New GeneRIF Correction See all GeneRIFs (48)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    Cross-Disorder Genome-Wide Analyses Suggest a Complex Genetic Relationship Between Tourette's Syndrome and OCD.
    EBI GWAS Catalog
    Insights into the genetic architecture of early stage age-related macular degeneration: a genome-wide association study meta-analysis.
    EBI GWAS Catalog
    Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    HIV-1 interactions

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    Replication interactions

    Interaction Pubs
    Knockdown of transient receptor potential cation channel, subfamily C, member 4 (TRPC4) by siRNA inhibits HIV-1 replication in HeLa P4/R5 cells PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC119570, MGC119571, MGC119572, MGC119573

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables beta-catenin binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables cadherin binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables calcium channel activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables calcium channel activity TAS
    Traceable Author Statement
    more info
    		  
    enables inositol 1,4,5 trisphosphate binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables store-operated calcium channel activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables store-operated calcium channel activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in calcium ion import IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in calcium ion transmembrane transport IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in calcium ion transmembrane transport IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in calcium ion transmembrane transport TAS
    Traceable Author Statement
    more info
    		  
    involved_in calcium ion transport TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in gamma-aminobutyric acid secretion IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in oligodendrocyte differentiation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of cytosolic calcium ion concentration IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    located_in basolateral plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of calcium channel complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of cation channel complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in caveola IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in cell surface IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    colocalizes_with cell-cell junction IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cortical cytoskeleton IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    short transient receptor potential channel 4
    Names
    trp-related protein 4

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_029849.2 RefSeqGene

      Range
      5654..243363
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001135955.3 → NP_001129427.1  short transient receptor potential channel 4 isoform beta

      See identical proteins and their annotated locations for NP_001129427.1

      Status: REVIEWED

      Source sequence(s)
      AL138679, AL354802, AL356495
      Consensus CDS
      CCDS45038.1
      UniProtKB/TrEMBL
      B2R6C6, Q2M2U7
      Related
      ENSP00000351264.2, ENST00000358477.6
      Conserved Domains (2) summary
      TIGR00870
      Location:17 → 749
      trp; transient-receptor-potential calcium channel protein
      sd00045
      Location:122 → 167
      ANK; ANK repeat [structural motif]

    2. NM_001135956.3 → NP_001129428.1  short transient receptor potential channel 4 isoform gamma

      See identical proteins and their annotated locations for NP_001129428.1

      Status: REVIEWED

      Source sequence(s)
      AL138679, AL354802, AL356495
      Consensus CDS
      CCDS45036.1
      UniProtKB/TrEMBL
      B2R6C6, Q2M2U7
      Related
      ENSP00000368995.2, ENST00000379673.2
      Conserved Domains (2) summary
      TIGR00870
      Location:17 → 684
      trp; transient-receptor-potential calcium channel protein
      sd00045
      Location:122 → 167
      ANK; ANK repeat [structural motif]

    3. NM_001135957.3 → NP_001129429.1  short transient receptor potential channel 4 isoform delta

      See identical proteins and their annotated locations for NP_001129429.1

      Status: REVIEWED

      Source sequence(s)
      AL138679, AL354802, AL356495
      Consensus CDS
      CCDS45039.1
      UniProtKB/TrEMBL
      B2R6C6
      Related
      ENSP00000348025.2, ENST00000355779.6
      Conserved Domains (2) summary
      TIGR00870
      Location:17 → 733
      trp; transient-receptor-potential calcium channel protein
      sd00045
      Location:122 → 167
      ANK; ANK repeat [structural motif]

    4. NM_001135958.3 → NP_001129430.1  short transient receptor potential channel 4 isoform zeta

      See identical proteins and their annotated locations for NP_001129430.1

      Status: REVIEWED

      Source sequence(s)
      AL138679, AL354802, AL356495
      Consensus CDS
      CCDS45035.1
      UniProtKB/TrEMBL
      B2R6C6, Q2M2U7
      Related
      ENSP00000342580.5, ENST00000338947.9
      Conserved Domains (1) summary
      TIGR00870
      Location:17 → 576
      trp; transient-receptor-potential calcium channel protein

    5. NM_001354799.2 → NP_001341728.1  short transient receptor potential channel 4 isoform eta

      Status: REVIEWED

      Source sequence(s)
      AL138679, AL354802, AL356495
      Conserved Domains (1) summary
      TIGR00870
      Location:1 → 329
      trp; transient-receptor-potential calcium channel protein

    6. NM_001354806.2 → NP_001341735.1  short transient receptor potential channel 4 isoform eta

      Status: REVIEWED

      Source sequence(s)
      AL138679, AL354802, AL356495
      Conserved Domains (1) summary
      TIGR00870
      Location:1 → 329
      trp; transient-receptor-potential calcium channel protein

    7. NM_001372055.1 → NP_001358984.1  short transient receptor potential channel 4 isoform eta

      Status: REVIEWED

      Source sequence(s)
      AL138679, AL354802, AL356495
      Conserved Domains (1) summary
      TIGR00870
      Location:1 → 329
      trp; transient-receptor-potential calcium channel protein

    8. NM_003306.3 → NP_003297.1  short transient receptor potential channel 4 isoform epsilon

      See identical proteins and their annotated locations for NP_003297.1

      Status: REVIEWED

      Source sequence(s)
      AL138679, AL354802, AL356495
      Consensus CDS
      CCDS45037.1
      UniProtKB/TrEMBL
      B2R6C6, Q2M2U7
      Related
      ENSP00000486109.1, ENST00000625583.2
      Conserved Domains (2) summary
      TIGR00870
      Location:17 → 754
      trp; transient-receptor-potential calcium channel protein
      sd00045
      Location:122 → 167
      ANK; ANK repeat [structural motif]

    9. NM_016179.4 → NP_057263.1  short transient receptor potential channel 4 isoform alpha

      See identical proteins and their annotated locations for NP_057263.1

      Status: REVIEWED

      Source sequence(s)
      AL138679, AL354802, AL356495
      Consensus CDS
      CCDS9365.1
      UniProtKB/Swiss-Prot
      B1ALE0, B1ALE1, B1ALE2, Q15721, Q3SWS6, Q96P03, Q96P04, Q96P05, Q9UBN4, Q9UIB0, Q9UIB1, Q9UIB2
      UniProtKB/TrEMBL
      B2R6C6, Q2M2U7
      Related
      ENSP00000369027.4, ENST00000379705.8
      Conserved Domains (2) summary
      TIGR00870
      Location:17 → 749
      trp; transient-receptor-potential calcium channel protein
      sd00045
      Location:122 → 167
      ANK; ANK repeat [structural motif]

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000013.11 Reference GRCh38.p14 Primary Assembly

      Range
      37632063..37869772 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011535206.2 → XP_011533508.1  short transient receptor potential channel 4 isoform X1

      Conserved Domains (1) summary
      TIGR00870
      Location:1 → 334
      trp; transient-receptor-potential calcium channel protein

    2. XM_017020723.2 → XP_016876212.1  short transient receptor potential channel 4 isoform X1

      Conserved Domains (1) summary
      TIGR00870
      Location:1 → 334
      trp; transient-receptor-potential calcium channel protein

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060937.1 Alternate T2T-CHM13v2.0

      Range
      36851454..37089250 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054374913.1 → XP_054230888.1  short transient receptor potential channel 4 isoform X1

    2. XM_054374914.1 → XP_054230889.1  short transient receptor potential channel 4 isoform X1

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9UBN4.1 GenPept UniProtKB/Swiss-Prot:Q9UBN4

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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