Focal segmental glomerulosclerosis 2

disease

On this page

Also known as focal segmental glomerulosclerosis caused by mutation in TRPC6focal segmental glomerulosclerosis type 2FSGS2TRPC6 focal segmental glomerulosclerosis

Summary

Focal segmental glomerulosclerosis 2 (MONDO:0011390) is a disease caused by TRPC6 (GenCC Strong), with 1 cohort gene.

At a glance

Causal gene: TRPC6 (GenCC Strong)
Cohort genes: 1
ClinVar variants: 258

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	focal segmental glomerulosclerosis 2
Mondo ID	MONDO:0011390
MeSH	C565831
OMIM	603965
DOID	DOID:0111129
UMLS	C1858915
MedGen	349053
GARD	0015362
Is cancer (heuristic)	no

Also known as: focal segmental glomerulosclerosis 2 · focal segmental glomerulosclerosis caused by mutation in TRPC6 · focal segmental glomerulosclerosis type 2 · FSGS2 · TRPC6 focal segmental glomerulosclerosis

Data availability: 258 ClinVar variants · 3 GenCC gene-disease records · 2 cell lines.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inherited kidney disorder › inherited focal segmental glomerulosclerosis › focal segmental glomerulosclerosis 2

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

258 retrieved; paginated sample, class counts are floors:

161 uncertain significance, 25 conflicting classifications of pathogenicity, 25 benign, 17 likely pathogenic, 11 benign/likely benign, 10 likely benign, 6 pathogenic, 3 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1344650	NM_004621.6(TRPC6):c.2684G>T (p.Arg895Leu)	TRPC6	Pathogenic	criteria provided, multiple submitters, no conflicts
222850	NM_004621.6(TRPC6):c.523C>T (p.Arg175Trp)	TRPC6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3598781	NM_004621.6(TRPC6):c.2665C>A (p.Gln889Lys)	TRPC6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3598815	NM_004621.6(TRPC6):c.1195C>T (p.Arg399Ter)	TRPC6	Pathogenic	criteria provided, single submitter
6151	NM_004621.6(TRPC6):c.335C>A (p.Pro112Gln)	TRPC6	Pathogenic	criteria provided, single submitter
6153	NM_004621.6(TRPC6):c.808T>A (p.Ser270Thr)	TRPC6	Pathogenic	no assertion criteria provided
6155	NM_004621.6(TRPC6):c.2683C>T (p.Arg895Cys)	TRPC6	Pathogenic	criteria provided, multiple submitters, no conflicts
6156	NM_004621.6(TRPC6):c.2689G>A (p.Glu897Lys)	TRPC6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
974548	NM_004621.6(TRPC6):c.2643dup (p.Gly882fs)	TRPC6	Pathogenic	criteria provided, single submitter
2506480	NM_004621.6(TRPC6):c.2592_2595dup (p.Tyr866fs)	TRPC6	Likely pathogenic	criteria provided, single submitter
2572471	NM_004621.6(TRPC6):c.2415_2418del (p.Asn805fs)	TRPC6	Likely pathogenic	criteria provided, single submitter
2585357	NM_004621.6(TRPC6):c.1090dup (p.Ser364fs)	TRPC6	Likely pathogenic	criteria provided, single submitter
2681752	NM_004621.6(TRPC6):c.1891_1894del (p.Val631fs)	TRPC6	Likely pathogenic	criteria provided, single submitter
2681753	NM_004621.6(TRPC6):c.991G>A (p.Gly331Arg)	TRPC6	Likely pathogenic	criteria provided, single submitter
2681754	NM_004621.6(TRPC6):c.430G>C (p.Glu144Gln)	TRPC6	Likely pathogenic	criteria provided, single submitter
3235004	NM_004621.6(TRPC6):c.368C>G (p.Ser123Ter)	TRPC6	Likely pathogenic	criteria provided, single submitter
3236154	NM_004621.6(TRPC6):c.2619_2626del (p.Asp873fs)	TRPC6	Likely pathogenic	criteria provided, single submitter
3377201	NM_004621.6(TRPC6):c.2665del (p.Gln889fs)	TRPC6	Likely pathogenic	criteria provided, single submitter
3598783	NM_004621.6(TRPC6):c.2578_2581dup (p.Arg861fs)	TRPC6	Likely pathogenic	criteria provided, single submitter
3598799	NM_004621.6(TRPC6):c.1753_1754del (p.Lys585fs)	TRPC6	Likely pathogenic	criteria provided, single submitter
3598809	NM_004621.6(TRPC6):c.1540del (p.Trp514fs)	TRPC6	Likely pathogenic	criteria provided, single submitter
3598821	NM_004621.6(TRPC6):c.946-1G>C	TRPC6	Likely pathogenic	criteria provided, single submitter
3598839	NM_004621.6(TRPC6):c.129C>A (p.Cys43Ter)	TRPC6	Likely pathogenic	criteria provided, single submitter
829823	NM_004621.6(TRPC6):c.524G>A (p.Arg175Gln)	TRPC6	Likely pathogenic	criteria provided, multiple submitters, no conflicts
974547	NM_004621.6(TRPC6):c.2641G>T (p.Glu881Ter)	TRPC6	Likely pathogenic	criteria provided, single submitter
988133	NM_004621.6(TRPC6):c.644G>A (p.Arg215Gln)	TRPC6	Likely pathogenic	criteria provided, single submitter
1039436	NM_004621.6(TRPC6):c.1065T>G (p.Ser355Arg)	TRPC6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1047192	NM_004621.6(TRPC6):c.271C>T (p.Arg91Cys)	TRPC6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1399058	NM_004621.6(TRPC6):c.2732A>G (p.Glu911Gly)	TRPC6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1436639	NM_004621.6(TRPC6):c.1678G>A (p.Ala560Thr)	TRPC6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
TRPC6	Strong	Autosomal dominant	focal segmental glomerulosclerosis 2	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TRPC6	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TRPC6	HGNC:12338	ENSG00000137672	Q9Y210	Short transient receptor potential channel 6	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TRPC6	Short transient receptor potential channel 6	Forms a receptor-activated non-selective calcium permeant cation channel.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Ion channel	1	111.5×	0.009

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TRPC6	Ion channel	yes		Ankyrin_rpt, TRPC_channel, TRPC6_channel

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
lower esophagus	1
lower esophagus muscularis layer	1
right lung	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TRPC6	180	broad	marker	right lung, lower esophagus muscularis layer, lower esophagus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TRPC6	1,819

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TRPC6	Q9Y210	6

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Role of second messengers in netrin-1 signaling	1	1038.2×	0.002	TRPC6
Elevation of cytosolic Ca2+ levels	1	713.8×	0.002	TRPC6
Effects of PIP2 hydrolysis	1	456.8×	0.002	TRPC6
TRP channels	1	407.9×	0.002	TRPC6

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of ion transmembrane transporter activity	1	16852.0×	7e-04	TRPC6
negative regulation of dendrite morphogenesis	1	1872.4×	0.003	TRPC6
monoatomic cation transport	1	766.0×	0.005	TRPC6
positive regulation of calcium ion transport	1	581.1×	0.005	TRPC6
regulation of cytosolic calcium ion concentration	1	383.0×	0.006	TRPC6
cellular response to hydrogen peroxide	1	234.1×	0.007	TRPC6
calcium ion transmembrane transport	1	210.7×	0.007	TRPC6
positive regulation of neuron differentiation	1	198.3×	0.007	TRPC6
single fertilization	1	183.2×	0.007	TRPC6
cellular response to hypoxia	1	121.2×	0.009	TRPC6
positive regulation of cytosolic calcium ion concentration	1	117.0×	0.009	TRPC6
neuron differentiation	1	100.3×	0.010	TRPC6

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TRPC6	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CLEMIZOLE	2	TRPC6

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
TRPC6	30	Binding:30

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

1 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
CLEMIZOLE	2	TRPC6

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	1	TRPC6
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: TRPC6