Human Disease Model Report: autism spectrum disorder, susceptibility to (postulated), TRPC6-related

General Information

Name

autism spectrum disorder, susceptibility to (postulated), TRPC6-related

FlyBase ID

FBhh0001488

Disease Ontology Term

autism spectrum disorder

Parent Disease

OMIM

Overview

The human ion channel gene TRPC6 has been identified as a potential susceptibilty locus for autism spectrum disorder (ASD: FBhh000514). There are multiple moderate-ranking orthologs for TRPC6 in Drosophila, Trpγ and its paralogs trp and trpl. Loss of function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated for Dmel\Trpγ. TRPC6 has also been implicated in focal segmental glomerulosclerosis-2 (MIM:603965)

The human TRPC6 gene has not been introduced into flies.

Loss of function mutations in Dmel\Trpγ result in behavioral anomalies that mirror those seen in ASD patients, including defective social interactions, hyperactivity, impaired learning and memory, and deficits in sleep homeostasis (FBrf0255132).

[updated Dec. 2022 by FlyBase; FBrf0222196]

Disease Summary Information

Disease Summary: autism spectrum disorder, susceptibility to (postulated), TRPC6-related

OMIM report

Human gene(s) implicated

Symptoms and phenotype

Genetics

The SFARI Gene autism database ( https:gene.sfari.org ) rates the gene-autism associations for TRPC6 as strong candidate (score 2). [2022.12.08]

(FlyBase Curators, 2013-)

Cellular phenotype and pathology

Molecular information

The TRPC6 gene encodes a receptor-activated calcium channel in the cell membrane. The channel is activated by diacylglycerol and is thought to be under the control of a phosphatidylinositol second messenger system. Activation of this channel occurs independently of protein kinase C and is not triggered by low levels of intracellular calcium. [RefSeq; Mar. 2009]

(FlyBase Curators, 2013-)

External links

Gene2Function (human gene): TRPC6
Gene Cards: TRPC6
MedlinePlus (condition): Autism spectrum disorder
MedlinePlus (gene): TRPC6
MARRVEL (human gene): TRPC6
NCBI MedGen: Autism spectrum disorders (ASD)
NCBI (Entrez) gene: TRPC6; transient receptor potential cation channel subfamily C member 6

Disease synonyms

Related Diseases

Related human health report(s)

autism spectrum disorder, susceptibility to

Ortholog Information

Human gene(s) in FlyBase

Human gene (HGNC)

Symbol / Name

TRPC6; transient receptor potential cation channel subfamily C member 6

D. melanogaster ortholog (based on DIOPT)

Dmel\trp

(DIOPT, 2013-)

Dmel\trpl

(DIOPT, 2013-)

Dmel\Trpγ

(DIOPT, 2013-)

Comments on ortholog(s)

many to many (6 human to 3 Drosophila).

Other mammalian ortholog(s) used

D. melanogaster Gene Information (3)

Dmel\Trpγ

Gene Snapshot

Contributions welcome

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

TRP
MECH-TRP

Comments on ortholog(s)

High-scoring ortholog of human (3 Drosophila to 6 human).

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Dmel\trp

Gene Snapshot

transient receptor potential (trp) encodes a non-selective plasma membrane cation channel with high Ca[2+] permeability. It is highly eye-enriched and contributes to the electrical response to light in photoreceptors. [Date last reviewed: 2019-03-14]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

Moderate-scoring ortholog of human TRPC6 (3 Drosophila to 6 human).

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Dmel\trpl

Gene Snapshot

transient receptor potential-like (trpl) encodes a non-selective plasma membrane cation channel with modest Ca[2+] permeability. It is highly eye-enriched and contributes to the electrical response to light in photoreceptors. [Date last reviewed: 2019-03-14]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

Moderate-scoring ortholog of human TRPC6 (3 Drosophila to 6 human).

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Other Genes Used: Viral, Bacterial, Synthetic (0)

Summary of Physical Interactions (16 groups)

trp

protein-protein

Interacting group

Assay

References

trp

coimmunoprecipitation, anti tag western blot, two hybrid, anti tag coimmunoprecipitation, western blot, pull down, autoradiography

(Voolstra et al., 2017, Katz et al., 2013, Xu et al., 1997)

trp - Cam

nuclear magnetic resonance, pull down, molecular weight estimation by staining, western blot, static light scattering, predetermined participant, molecular sieving, confirmation by molecular weight, x-ray crystallography, isothermal titration calorimetry, cosedimentation

(Chen et al., 2021, Sun et al., 2018, Chevesich et al., 1997)

trp - Gαq

anti bait coimmunoprecipitation, western blot

(Bahner et al., 2000)

trp - inaC

anti bait coimmunoprecipitation, molecular weight estimation by staining, pull down, Identification by mass spectrometry, enzymatic study, autoradiography, western blot, peptide massfingerprinting

(Chen and Montell, 2020, Peng et al., 2008, Popescu et al., 2006, Bahner et al., 2000, Liu et al., 2000)

trp - inaD

far western blotting, autoradiography, anti bait coimmunoprecipitation, western blot, pull down, molecular sieving, fluorescence polarization spectroscopy, predetermined participant, anti tag coimmunoprecipitation, molecular weight estimation by staining, nuclear magnetic resonance, Identification by mass spectrometry, cosedimentation

(Chen and Montell, 2020, Voolstra et al., 2017, Ye et al., 2016, Chen et al., 2015, Katz et al., 2013, Liu et al., 2011, Peng et al., 2008, Bahner et al., 2000, Li and Montell, 2000, Wes et al., 1999, Tsunoda et al., 1997, Shieh and Zhu, 1996)

trp - inaF-B

anti tag coimmunoprecipitation, western blot, anti bait coimmunoprecipitation, anti tag western blot, pull down, Identification by mass spectrometry

(Chen and Montell, 2020, Cheng and Nash, 2007)

trp - inaF-C

anti tag coimmunoprecipitation, western blot, pull down, Identification by mass spectrometry, anti tag western blot

(Chen and Montell, 2020)

trp - ninaE

anti bait coimmunoprecipitation, western blot

(Chevesich et al., 1997)

trp - norpA

pull down, western blot, Identification by mass spectrometry, anti bait coimmunoprecipitation, molecular weight estimation by staining

(Chen and Montell, 2020, Peng et al., 2008, Bahner et al., 2000, Chevesich et al., 1997)

trp - trpl

anti bait coimmunoprecipitation, western blot, pull down, autoradiography, two hybrid, coimmunoprecipitation, anti tag coimmunoprecipitation, anti tag western blot

(Xu et al., 1997)

trp - Xport-A

western blot, anti bait coimmunoprecipitation

(Rosenbaum et al., 2011)

trpl

protein-protein

Interacting group

Assay

References

trpl

anti tag coimmunoprecipitation, western blot, pull down, autoradiography, two hybrid

(Schopf et al., 2019, Katz et al., 2013, Xu et al., 1997)

trpl - Cam

lambda phage display

(Xu et al., 1998, Phillips et al., 1992)

trpl - Fkbp59

anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation, anti tag western blot, affinity chromatography technology

(Goel et al., 2001)

trpl - inaD

anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation, pull down, autoradiography, anti tag western blot

(Goel et al., 2001, Xu et al., 1998)

trpl - trp

anti bait coimmunoprecipitation, western blot, pull down, autoradiography, two hybrid, coimmunoprecipitation, anti tag coimmunoprecipitation, anti tag western blot

(Xu et al., 1997)

trpl - Ube3a

anti tag coimmunoprecipitation, anti tag western blot

(Zhang et al., 2013)

Alleles Reported to Model Human Disease (Disease Ontology) (5 alleles)

Trpγ

Models Based on Experimental Evidence ( 3 )

Allele

Disease

Evidence

References

Trpγ¹