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(Top) 1 Function 2 Tissue distribution 3 Roles 4 Clinical significance 5 Interactions 6 See also 7 References 8 Further reading 9 External links

TRPC4

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TRPC4

Identifiers

Aliases

TRPC4, HTRP-4, HTRP4, TRP4, transient receptor potential cation channel subfamily C member 4

External IDs

OMIM: 603651; MGI: 109525; HomoloGene: 22955; GeneCards: TRPC4; OMA:TRPC4 - orthologs

Gene location (Human)

Chr.	Chromosome 13 (human)^[1]

Band	13q13.3	Start	37,632,063 bp^[1]
Band	13q13.3	End	37,869,802 bp^[1]

Gene location (Mouse)

Chr.	Chromosome 3 (mouse)^[2]

Band	3 C\|3 25.43 cM	Start	54,063,456 bp^[2]
Band	3 C\|3 25.43 cM	End	54,225,892 bp^[2]

RNA expression pattern

Bgee

Human

Mouse (ortholog)

Top expressed in

stromal cell of endometrium

decidua

smooth muscle tissue

testicle

body of uterus

right coronary artery

myometrium

left coronary artery

prostate

gallbladder

Top expressed in

lateral septal nucleus

subiculum

Region I of hippocampus proper

CA3 field

dentate gyrus

anterior amygdaloid area

hippocampus proper

dentate gyrus of hippocampal formation granule cell

barrel cortex

secondary oocyte

More reference expression data

BioGPS


More reference expression data

Gene ontology
Molecular function	beta-catenin binding store-operated calcium channel activity cadherin binding inositol 1,4,5 trisphosphate binding ion channel activity protein binding calcium channel activity
Cellular component	integral component of membrane calcium channel complex membrane cell-cell junction cortical cytoskeleton plasma membrane cell surface basolateral plasma membrane caveola membrane raft integral component of plasma membrane protein-containing complex cation channel complex
Biological process	regulation of cytosolic calcium ion concentration calcium ion import oligodendrocyte differentiation ion transport calcium ion transmembrane transport manganese ion transport gamma-aminobutyric acid secretion calcium ion transport transmembrane transport
Sources:Amigo / QuickGO

Orthologs

Species

Human

Mouse

Entrez


7223


22066

Ensembl


ENSG00000133107


ENSMUSG00000027748

UniProt


Q9UBN4


Q9QUQ5

RefSeq (mRNA)

NM_001135955 NM_001135956 NM_001135957 NM_001135958 NM_003306
NM_016179 NM_001354799 NM_001354806 NM_001372055


NM_001253682 NM_001253683 NM_016984

RefSeq (protein)

NP_001129427 NP_001129428 NP_001129429 NP_001129430 NP_003297
NP_057263 NP_001341728 NP_001341735 NP_001358984


NP_001240611 NP_001240612 NP_058680

Location (UCSC)

Chr 13: 37.63 – 37.87 Mb

Chr 3: 54.06 – 54.23 Mb

PubMed search

^[3]

^[4]

Wikidata

View/Edit Human

View/Edit Mouse

The short transient receptor potential channel 4 (TrpC4), also known as Trp-related protein 4, is a protein that in humans is encoded by the TRPC4 gene.^[5]^[6]

Function[edit]

TrpC4 is a member of the transient receptor potential cation channels. This protein forms a non-selective calcium-permeable cation channel that is activated by Gαi-coupled receptors, Gαq-coupled receptors and tyrosine kinases, and plays a role in multiple processes including endothelial permeability, vasodilation, neurotransmitter release and cell proliferation.^[7]

Tissue distribution[edit]

The nonselective cation channel TrpC4 has been shown to be present in high abundance in the cortico-limbic regions of the brain.^[8] In addition, TRPC4 mRNA is present in midbrain dopaminergic neurons in the ventral tegmental area and the substantia nigra.^[9]

Roles[edit]

Deletion of the trpc4 gene decreases levels of sociability in a social exploration task. These results suggest that TRPC4 may play a role in regulating social anxiety in a number of different disorders.^[10] However deletion of the trpc4 gene had no impact on basic or complex strategic learning.^[11] Given that the trpc4 gene is expressed in a select population of midbrain dopamine neurons, it has been proposed that it may have an important role in dopamine related processes including addiction and attention.^[9]

Clinical significance[edit]

Single nucleotide polymorphisms in this gene may be associated with generalized epilepsy with photosensitivity.^[12]

Interactions[edit]

TRPC4 has been shown to interact with ITPR1,^[13]^[14] TRPC1,^[15]^[16] and TRPC5.^[16]

References[edit]

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000133107 – Ensembl, May 2017

^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000027748 – Ensembl, May 2017

^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

^ Zhu X, Jiang M, Peyton M, Boulay G, Hurst R, Stefani E, Birnbaumer L (May 1996). "trp, a novel mammalian gene family essential for agonist-activated capacitative Ca2+ entry". Cell. 85 (5): 661–71. doi:10.1016/S0092-8674(00)81233-7. PMID 8646775.

^ Clapham DE, Julius D, Montell C, Schultz G (December 2005). "International Union of Pharmacology. XLIX. Nomenclature and structure-function relationships of transient receptor potential channels". Pharmacol. Rev. 57 (4): 427–50. doi:10.1124/pr.57.4.6. PMID 16382100. S2CID 17936350.

^ "Entrez Gene: transient receptor potential cation channel, subfamily C, member 4".

^ Fowler MA, Sidiropoulou K, Ozkan ED, Phillips CW, Cooper DC (2007). "Corticolimbic expression of TRPC4 and TRPC5 channels in the rodent brain". PLOS ONE. 2 (6): e573. Bibcode:2007PLoSO...2..573F. doi:10.1371/journal.pone.0000573. PMC 1892805. PMID 17593972.

^ ^a ^b Cooper D, Illig K, Varnell A, Ostertag E, Klipec W (2011). "TRPC4 ion channel protein is selectively expressed in a subpopulation of dopamine neurons in the ventral tegmental area". Nature Precedings. arXiv:1204.0142. doi:10.1038/npre.2011.6577.1. S2CID 19188350.

^ Cooper D, Rasmus K, Wang J-G, Varnell A, Ostertag E (2011). "Sociability is decreased following deletion of the trpc4 gene". Nature Precedings. doi:10.1038/npre.2011.6367.1.

^ Cooper D, Collins M, Drish A, Swenson L, Ostertag E, Klipec W, Nguyen P, Deeney B, Williamson C, Wenzel K, Stumme J (2012). "Deletion of the trpc4 gene and its role in simple and complex strategic learning". Nature Precedings. doi:10.1038/npre.2012.6929.1.

^ von Spiczak S, Muhle H, Helbig I, de Kovel CG, Hampe J, Gaus V, Koeleman BP, Lindhout D, Schreiber S, Sander T, Stephani U (September 2010). "Association study of TRPC4 as a candidate gene for generalized epilepsy with photosensitivity". Neuromolecular Med. 12 (3): 292–9. doi:10.1007/s12017-010-8122-x. hdl:11858/00-001M-0000-0029-429E-D. PMID 20574736. S2CID 20930490.

^ Yuan JP, Kiselyov K, Shin DM, Chen J, Shcheynikov N, Kang SH, Dehoff MH, Schwarz MK, Seeburg PH, Muallem S, Worley PF (September 2003). "Homer binds TRPC family channels and is required for gating of TRPC1 by IP3 receptors". Cell. 114 (6): 777–89. doi:10.1016/S0092-8674(03)00716-5. PMID 14505576.

^ Mery L, Magnino F, Schmidt K, Krause KH, Dufour JF (January 2001). "Alternative splice variants of hTrp4 differentially interact with the C-terminal portion of the inositol 1,4,5-trisphosphate receptors". FEBS Lett. 487 (3): 377–83. doi:10.1016/S0014-5793(00)02362-0. PMID 11163362. S2CID 44945442.

^ Strübing C, Krapivinsky G, Krapivinsky L, Clapham DE (October 2003). "Formation of novel TRPC channels by complex subunit interactions in embryonic brain". J. Biol. Chem. 278 (40): 39014–9. doi:10.1074/jbc.M306705200. PMID 12857742.

^ ^a ^b Hofmann T, Schaefer M, Schultz G, Gudermann T (May 2002). "Subunit composition of mammalian transient receptor potential channels in living cells". Proc. Natl. Acad. Sci. U.S.A. 99 (11): 7461–6. Bibcode:2002PNAS...99.7461H. doi:10.1073/pnas.102596199. PMC 124253. PMID 12032305.

External links[edit]

TRPC4+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

Membrane transport protein: ion channels (TC 1A)

Ca²⁺: Calcium channel

Ligand-gated

Inositol trisphosphate receptor
- 1
- 2
- 3
Ryanodine receptor
- 1
- 2
- 3

Voltage-gated

L-type/Ca_vα
- 1.1
- 1.2
- 1.3
- 1.4
N-type/Ca_vα2.2
P-type/Ca_vα
- 2.1
Q-type/Ca_vα2.1
R-type/Ca_vα2.3
T-type/Ca_vα
- 3.1
- 3.2
- 3.3

α₂δ-subunits
- 1
- 2
β-subunits
- β1
- β2
- β3
- β4
γ-subunits
- γ1
- γ2
- γ3
- γ4

Cation channels of sperm
- 1
- 2
- 3
- 4
Two-pore channel
- 1
- 2

Na⁺: Sodium channel

Constitutively active

Epithelial sodium channel
- α
- β
- γ
- δ

Proton-gated

Amiloride-sensitive cation channel
- 1
- 2
- 3
- 4

Voltage-gated

Na_vα
- 1.1
- 1.2
- 1.3
- 1.4
- 1.5
- 1.6
- 1.7
- 1.8
- 1.9
- 7A
Na_vβ
- 1
- 2
- 3
- 4

K⁺: Potassium channel

Calcium-activated	BK channel α1 β1 β2 β3 β4 SK channel SK1 SK2 SK3 IK channel IK1 K_Ca 1.1 2.1 2.2 2.3 3.1 4.1 4.2 5.1
Inward-rectifier	K_ATP K_ir 1.1 2.1 2.2 2.3 2.4 2.6 GIRK/K_ir 3.1 3.2 3.3 3.4 K_ir 4.1 4.2 5.1 6.1 6.2 7.1
Tandem pore domain	K2P 1 2 3 4 5 6 7 9 10 12 13 15 16 17 18
Voltage-gated	K_vα1-6 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 2.1 2.2 3.1 3.2 3.3 3.4 4.1 4.2 4.3 5.1 6.1 6.2 6.3 6.4 K_vα7-12 7.1 7.2 7.3 7.4 7.5 8.1 8.2 9.1 9.2 9.3 10.1 10.2 11.1/hERG 11.2 11.3 12.1 12.2 12.3 K_vβ 1 2 3 KCNIP 1 2 3 4 minK/ISK minK/ISK-like MiRP 1 2 3 Shaker (gene)

Miscellaneous

Cl⁻: Chloride channel	Calcium-activated chloride channels Anoctamin ANO1 Bestrophin 1 2 Chloride Channel Accessory 1 2 3 4 CFTR CLCN 1 2 3 4 5 6 7 KA KB CLIC 1 2 3 4 5 6 L1 CLNS 1A 1B
H⁺: Proton channel	HVCN1
M⁺: CNG cation channel	α 1 2 3 4 β 1 2 3 HCN FC 1 2 3 4
M⁺: TRP cation channel	TRPA (1) TRPC 1 2 3 4 4AP 5 6 7 TRPM 1 2 3 4 5 6 7 8 TRPML 1 2 3 TRPN TRPP 1 2 TRPV 1 2 3 4 5 6
H₂O (+ solutes): Porin	Aquaporin 0 1 2 3 4 5 6 7 8 9 Voltage-dependent anion channel 1 2 3 General bacterial porin family
Cytoplasm: Gap junction	Connexin A GJA1 GJA3 GJA4 GJA5 GJA8 GJA9 GJA10 B GJB1 GJB2 GJB3 GJB4 GJB5 GJB6 GJB7 C GJC1 GJC2 GJC3 D GJD2 GJD3 GJD4 Innexin