TRPC6Transient receptor potential cation channel, subfamily C, member 6
Autism Reports / Total Reports
5 / 6Rare Variants / Common Variants
19 / 0Chromosome Band
11q22.1Associated Disorders
-Genetic Category
Rare Single Gene Mutation, FunctionalRelevance to Autism
A de novo balanced translocation [t(3;11)(p21;q22)] disrupting the TRPC6 gene was identified in an 8-year-old male proband presenting with non-syndromic autism; further functional studies using patient-specific iPSC-derived neuronal cells and mouse models demonstrated that TRPC6 reduction or haploinsufficiency resulted in altered neuronal development, morphology, and function (Griesi-Oliveira et al., 2014).
Molecular Function
The protein encoded by this gene forms 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. Defects in this gene are a cause of focal segmental glomerulosclerosis 2 (FSGS2) [MIM:603965].
External Links
SFARI Genomic Platforms
Reports related to TRPC6 (6 Reports)
# | Type | Title | Author, Year | Autism Report | Associated Disorders |
---|---|---|---|---|---|
1 | Support | Evidence for a supportive role of classical transient receptor potential 6 (TRPC6) in the exploration behavior of mice | Beis D , et al. (2010) | No | - |
2 | Primary | Modeling non-syndromic autism and the impact of TRPC6 disruption in human neurons | Griesi-Oliveira K , et al. (2014) | Yes | - |
3 | Support | Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks | Ruzzo EK , et al. (2019) | Yes | - |
4 | Support | - | Palacios-Muñoz A et al. (2022) | Yes | - |
5 | Support | - | Zhou X et al. (2022) | Yes | - |
6 | Support | - | Shin KC et al. (2023) | Yes | - |
Rare Variants (19)
Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
---|---|---|---|---|---|---|---|---|
- | - | translocation | De novo | - | Simplex | 25385366 | Griesi-Oliveira K , et al. (2014) | |
c.222G>C | p.Glu74Asp | missense_variant | De novo | - | Simplex | 35982159 | Zhou X et al. (2022) | |
c.70C>T | p.Arg24Trp | missense_variant | De novo | - | Multiplex | 35982159 | Zhou X et al. (2022) | |
c.1293+2T>C | - | splice_site_variant | Familial | Maternal | - | 35501408 | Palacios-Muñoz A et al. (2022) | |
c.7C>T | p.Gln3Ter | stop_gained | Familial | Paternal | Simplex | 25385366 | Griesi-Oliveira K , et al. (2014) | |
c.139C>G | p.Pro47Ala | missense_variant | Familial | Paternal | Simplex | 25385366 | Griesi-Oliveira K , et al. (2014) | |
c.620A>C | p.Tyr207Ser | missense_variant | Familial | Maternal | Simplex | 25385366 | Griesi-Oliveira K , et al. (2014) | |
c.1057C>T | p.Leu353Phe | missense_variant | Familial | Paternal | Simplex | 25385366 | Griesi-Oliveira K , et al. (2014) | |
c.1316C>G | p.Pro439Arg | missense_variant | Familial | Paternal | Simplex | 25385366 | Griesi-Oliveira K , et al. (2014) | |
c.1396G>A | p.Glu466Lys | missense_variant | Familial | Paternal | Simplex | 25385366 | Griesi-Oliveira K , et al. (2014) | |
c.1679C>T | p.Ala560Val | missense_variant | Familial | Maternal | Simplex | 25385366 | Griesi-Oliveira K , et al. (2014) | |
c.2385C>G | p.Phe795Leu | missense_variant | Familial | Maternal | Simplex | 25385366 | Griesi-Oliveira K , et al. (2014) | |
c.2424G>T | p.Lys808Asn | missense_variant | Familial | Maternal | Simplex | 25385366 | Griesi-Oliveira K , et al. (2014) | |
c.2T>A | p.Met1? | initiator_codon_variant | Familial | Maternal | Simplex | 25385366 | Griesi-Oliveira K , et al. (2014) | |
c.1208del | p.Met403ArgfsTer33 | frameshift_variant | Familial | Maternal | Multiplex | 31398340 | Ruzzo EK , et al. (2019) | |
c.1073dup | p.His358GlnfsTer14 | frameshift_variant | Familial | Maternal | - | 35501408 | Palacios-Muñoz A et al. (2022) | |
c.140del | p.Pro47ArgfsTer33 | frameshift_variant | Unknown | Not maternal | - | 35501408 | Palacios-Muñoz A et al. (2022) | |
c.1204_1206delinsCC | p.Thr402ProfsTer34 | frameshift_variant | Familial | Maternal | - | 35501408 | Palacios-Muñoz A et al. (2022) | |
c.177_178insATCTGACAACAGACTGGCTCACCGG | p.Ser60IlefsTer2 | frameshift_variant | Familial | Paternal | - | 35501408 | Palacios-Muñoz A et al. (2022) |
Common Variants
No common variants reported.
SFARI Gene score
Strong Candidate
A de novo balanced translocation [t(3;11)(p21;q22)] disrupting the TRPC6 gene was identified in an 8-year-old male proband presenting with non-syndromic autism; further functional studies using patient-specific iPSC-derived neuronal cells and mouse models demonstrated that TRPC6 reduction or haploinsufficiency resulted in altered neuronal development, morphology, and function (PMID 25385366). In a previous publication, TRPC6-deficient mice had been shown to display reduced exploratory behavior (PMID 21059368). Genetic sequencing of TRPC6 in 1041 ASD individuals from the Simons Simplex Collection and 2872 controls in PMID 25385366 identified significantly more nonsynonymous mutations in cases compared to controls (10/1041 cases versus 1/942 controls; P = 0.013), and loss-of-function mutations in TRPC6 showing incomplete penetrance with ASD were observed in two cases.
Score Delta: Score remained at 2
criteria met
See SFARI Gene'scoring criteriaWe considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.
10/1/2019
Decreased from 3 to 2
New Scoring Scheme
Description
A de novo balanced translocation [t(3;11)(p21;q22)] disrupting the TRPC6 gene was identified in an 8-year-old male proband presenting with non-syndromic autism; further functional studies using patient-specific iPSC-derived neuronal cells and mouse models demonstrated that TRPC6 reduction or haploinsufficiency resulted in altered neuronal development, morphology, and function (PMID 25385366). In a previous publication, TRPC6-deficient mice had been shown to display reduced exploratory behavior (PMID 21059368). Genetic sequencing of TRPC6 in 1041 ASD individuals from the Simons Simplex Collection and 2872 controls in PMID 25385366 identified significantly more nonsynonymous mutations in cases compared to controls (10/1041 cases versus 1/942 controls; P = 0.013), and loss-of-function mutations in TRPC6 showing incomplete penetrance with ASD were observed in two cases.
Reports Added
[New Scoring Scheme]7/1/2019
Decreased from 3 to 3
Description
A de novo balanced translocation [t(3;11)(p21;q22)] disrupting the TRPC6 gene was identified in an 8-year-old male proband presenting with non-syndromic autism; further functional studies using patient-specific iPSC-derived neuronal cells and mouse models demonstrated that TRPC6 reduction or haploinsufficiency resulted in altered neuronal development, morphology, and function (PMID 25385366). In a previous publication, TRPC6-deficient mice had been shown to display reduced exploratory behavior (PMID 21059368). Genetic sequencing of TRPC6 in 1041 ASD individuals from the Simons Simplex Collection and 2872 controls in PMID 25385366 identified significantly more nonsynonymous mutations in cases compared to controls (10/1041 cases versus 1/942 controls; P = 0.013), and loss-of-function mutations in TRPC6 showing incomplete penetrance with ASD were observed in two cases.
10/1/2014
Increased from to 3
Description
A de novo balanced translocation [t(3;11)(p21;q22)] disrupting the TRPC6 gene was identified in an 8-year-old male proband presenting with non-syndromic autism; further functional studies using patient-specific iPSC-derived neuronal cells and mouse models demonstrated that TRPC6 reduction or haploinsufficiency resulted in altered neuronal development, morphology, and function (PMID 25385366). In a previous publication, TRPC6-deficient mice had been shown to display reduced exploratory behavior (PMID 21059368). Genetic sequencing of TRPC6 in 1041 ASD individuals from the Simons Simplex Collection and 2872 controls in PMID 25385366 identified significantly more nonsynonymous mutations in cases compared to controls (10/1041 cases versus 1/942 controls; P = 0.013), and loss-of-function mutations in TRPC6 showing incomplete penetrance with ASD were observed in two cases.
Krishnan Probability Score
Score 0.50539006678127
Ranking 1908/25841 scored genes
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ExAC Score
Score 0.0045641050533557
Ranking 10670/18225 scored genes
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Sanders TADA Score
Score 0.89115375773834
Ranking 5603/18665 scored genes
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Larsen Cumulative Evidence Score
Score 40
Ranking 48/461 scored genes
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Zhang D Score
Score 0.23994777027222
Ranking 3624/20870 scored genes
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