TRPC6

transient receptor potential cation channel subfamily C member 6, the group of Ankyrin repeat domain containing|MicroRNA protein coding host genes|Transient receptor potential cation channels

Basic information

Region (hg38): 11:101451563-101872562

Previous symbols: [ "FSGS2" ]

Links

ENSG00000137672 ∙ NCBI:7225 ∙ OMIM:603652 ∙ HGNC:12338 ∙ Uniprot:Q9Y210 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• focal segmental glomerulosclerosis 2 (Strong), mode of inheritance: AD
• familial idiopathic steroid-resistant nephrotic syndrome (Supportive), mode of inheritance: AD
• focal segmental glomerulosclerosis 2 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Focal segmental glomerulosclerosis 2	AD	Renal	The condition can involve renal failure, and early diagnosis may allow early management; Renal transplant has been described	Renal	10200986; 15924139; 15879175; 21415313; 21511817; 21734084

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TRPC6 gene.

• not provided (197 variants)
• Focal segmental glomerulosclerosis 2 (130 variants)
• Inborn genetic diseases (22 variants)
• not specified (17 variants)
• Focal segmental glomerulosclerosis (17 variants)
• TRPC6-related condition (9 variants)
• Kidney disorder (5 variants)
• Nephrotic syndrome (5 variants)
• Atypical hemolytic-uremic syndrome (1 variants)
• Prednisolone response (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TRPC6 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			8	40	10	58
missense	2	4	97	4	3	110
nonsense	1	1	2			4
start loss			1			1
frameshift	1	4	2			7
inframe indel			1	1		2
splice donor/acceptor (+/-2bp)			3			3
splice region				6	1	7
non coding			35	30	42	107
Total	4	9	149	75	55

Highest pathogenic variant AF is 0.0000132

Variants in TRPC6

This is a list of pathogenic ClinVar variants found in the TRPC6 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-101451569-G-C		Focal segmental glomerulosclerosis 2	Uncertain significance (Jan 13, 2018)
11-101451575-C-T		Focal segmental glomerulosclerosis 2	Uncertain significance (Jan 13, 2018)
11-101451606-A-G		Focal segmental glomerulosclerosis 2	Uncertain significance (Jan 12, 2018)
11-101451779-A-G		Focal segmental glomerulosclerosis 2	Uncertain significance (Jan 12, 2018)
11-101451808-T-C		Focal segmental glomerulosclerosis 2	Uncertain significance (Jan 12, 2018)
11-101451866-G-A		Focal segmental glomerulosclerosis 2	Benign (Jan 13, 2018)
11-101451917-A-C		Focal segmental glomerulosclerosis 2	Uncertain significance (Jan 13, 2018)
11-101451923-T-C		Focal segmental glomerulosclerosis 2	Uncertain significance (Jan 13, 2018)
11-101451935-C-T		Focal segmental glomerulosclerosis 2	Uncertain significance (Jan 13, 2018)
11-101451985-T-C		Focal segmental glomerulosclerosis 2	Benign (Jan 13, 2018)
11-101451995-C-G		Focal segmental glomerulosclerosis 2	Uncertain significance (Jan 13, 2018)
11-101452134-G-A		Focal segmental glomerulosclerosis 2	Uncertain significance (Jan 12, 2018)
11-101452135-G-A		Focal segmental glomerulosclerosis 2	Uncertain significance (Jan 12, 2018)
11-101452163-C-T		Focal segmental glomerulosclerosis 2	Uncertain significance (Jan 12, 2018)
11-101452244-C-CTAAA		Focal segmental glomerulosclerosis	Benign (Jun 14, 2016)
11-101452287-C-T		Focal segmental glomerulosclerosis 2	Uncertain significance (Jan 13, 2018)
11-101452380-G-T		Focal segmental glomerulosclerosis 2	Uncertain significance (Jan 12, 2018)
11-101452402-A-C		Focal segmental glomerulosclerosis 2	Benign (Jan 13, 2018)
11-101452425-A-G		Focal segmental glomerulosclerosis 2	Benign (Jan 13, 2018)
11-101452442-A-ATAAG		Focal segmental glomerulosclerosis	Likely benign (Jun 14, 2016)
11-101452448-A-T		Focal segmental glomerulosclerosis 2	Uncertain significance (Jan 13, 2018)
11-101452618-C-T		Focal segmental glomerulosclerosis 2	Benign (Jan 13, 2018)
11-101452619-G-A		Focal segmental glomerulosclerosis 2	Benign (Jan 12, 2018)
11-101452641-G-C		Focal segmental glomerulosclerosis 2	Benign (Jan 13, 2018)
11-101452662-C-G		Focal segmental glomerulosclerosis 2	Uncertain significance (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TRPC6	protein_coding	protein_coding	ENST00000344327	13	420999

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.03e-7	1.00	125691	0	57	125748	0.000227

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.12	361	494	0.731	0.0000262	6173
Missense in Polyphen		200	311.53	0.64198		3838
Synonymous	-0.658	187	176	1.06	0.00000934	1715
Loss of Function	3.31	18	40.8	0.441	0.00000207	507

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000589	0.000566
Ashkenazi Jewish	0.00	0.00
East Asian	0.000218	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.000270	0.000264
Middle Eastern	0.000218	0.000217
South Asian	0.000266	0.000196
Other	0.000172	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Thought to form a receptor-activated non-selective calcium permeant cation channel (PubMed:19936226, PubMed:23291369). Probably is operated by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases or G-protein coupled receptors. Activated by diacylglycerol (DAG) in a membrane-delimited fashion, independently of protein kinase C (PubMed:26892346). Seems not to be activated by intracellular calcium store depletion. {ECO:0000269|PubMed:19936226, ECO:0000269|PubMed:23291369, ECO:0000269|PubMed:26892346}.
• Disease: DISEASE: Focal segmental glomerulosclerosis 2 (FSGS2) [MIM:603965]: A renal pathology defined by the presence of segmental sclerosis in glomeruli and resulting in proteinuria, reduced glomerular filtration rate and progressive decline in renal function. Renal insufficiency often progresses to end-stage renal disease, a highly morbid state requiring either dialysis therapy or kidney transplantation. {ECO:0000269|PubMed:15879175, ECO:0000269|PubMed:15924139, ECO:0000269|PubMed:19458060, ECO:0000269|PubMed:19936226, ECO:0000269|PubMed:20798252, ECO:0000269|PubMed:21511817, ECO:0000269|PubMed:21734084, ECO:0000269|PubMed:22732337, ECO:0000269|PubMed:23014460, ECO:0000269|PubMed:23291369, ECO:0000269|PubMed:26892346}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Axon guidance - Homo sapiens (human);cGMP-PKG signaling pathway - Homo sapiens (human);Primary Focal Segmental Glomerulosclerosis FSGS;BDNF-TrkB Signaling;Signaling by GPCR;Signal Transduction;ion channels and their functional role in vascular endothelium;Stimuli-sensing channels;Ion channel transport;Transport of small molecules;Effects of PIP2 hydrolysis;Platelet activation, signaling and aggregation;Hemostasis;TRP channels;Elevation of cytosolic Ca2+ levels;Platelet calcium homeostasis;Platelet homeostasis;G alpha (q) signalling events;GPCR downstream signalling;PAR1-mediated thrombin signaling events;Endothelins;Nephrin/Neph1 signaling in the kidney podocyte (Consensus)

Recessive Scores

• pRec: 0.185

Intolerance Scores

• loftool: 0.225
• rvis_EVS: -1.29
• rvis_percentile_EVS: 5.08

Haploinsufficiency Scores

• pHI: 0.165
• hipred: Y
• hipred_score: 0.624
• ghis: 0.546

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.577

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Trpc6
• Phenotype: vision/eye phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); muscle phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Gene ontology

• Biological process: cation transport;manganese ion transport;positive regulation of cytosolic calcium ion concentration;single fertilization;aging;positive regulation of peptidyl-threonine phosphorylation;platelet activation;neuron differentiation;positive regulation of ion transmembrane transporter activity;positive regulation of neuron differentiation;negative regulation of dendrite morphogenesis;regulation of cytosolic calcium ion concentration;positive regulation of calcium ion transport;cellular response to hydrogen peroxide;calcium ion transmembrane transport;cellular response to hypoxia
• Cellular component: cytoplasm;plasma membrane;integral component of plasma membrane;membrane;cation channel complex;slit diaphragm
• Molecular function: actin binding;cation channel activity;calcium channel activity;protein binding;store-operated calcium channel activity;clathrin binding;protein homodimerization activity;actinin binding;ATPase binding;inositol 1,4,5 trisphosphate binding