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

Gene ID: 7223, updated on 5-Mar-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
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Genomic context

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Location:
13q13.3
Exon count:
11
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 13 NC_000013.11 (37632063..37869772, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 13 NC_060937.1 (36851454..37089250, complement)
105.20220307 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. Expression of pH-Sensitive TRPC4 in Common Skin Tumors. Kurz B, et al. Int J Mol Sci, 2023 Jan 5. PMID 36674553, Free PMC Article
  2. Transient receptor potential (TRP) channel function in the reproductive axis. Götz V, et al. Cell Calcium, 2017 Nov. PMID 28522036
  3. Transient receptor potential (TRP) channels as molecular targets in lung toxicology and associated diseases. Dietrich A, et al. Cell Calcium, 2017 Nov. PMID 28499580
  4. Elevated Expression of TRPC4 in Cortical Lesions of Focal Cortical Dysplasia II and Tuberous Sclerosis Complex. Wang LK, et al. J Mol Neurosci, 2017 Jun. PMID 28455787
  5. 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

See all (83) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. Expression of pH-Sensitive TRPC4 in Common Skin Tumors.
    Title: Expression of pH-Sensitive TRPC4 in Common Skin Tumors.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. STIM1L and TRPC1/4 are working together in myotubes to ensure efficient store refilling and a proper differentiation program.
    Title: TRPC1 and TRPC4 channels functionally interact with STIM1L to promote myogenesis and maintain fast repetitive Ca(2+) release in human myotubes.
Submit: New GeneRIF Correction See all GeneRIFs (47)

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)

Genotypes

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 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 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_2023_10

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

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