# US 7,745,597 B2 · TRPC6 involved in glomerulonephritis > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 7,745,597 B2 - Document ID: US7745597B2 - Status: Granted - Kind: B2 - Application number: 11/716,050 - Filed: 2007-03-09 - Published: 2008-02-14 - Granted: 2010-06-29 - Earliest claimed: 2005-05-05 - Assignees: Duke University - Inventors: Michelle Winn; Margaret A. Pericak-Vance; Jeffery M. Vance - Web page: https://patentgrep.com/patent/US7745597B2 ## CPC - C12Q 1/6883: for diseases caused by alterations of genetic material - A61K 31/4174: Arylalkylimidazoles, e.g. oxymetazolin, naphazoline, miconazole - A61K 31/69: Boron compounds - A61K 33/24: Heavy metals; Compounds thereof - A61P 13/12: of the kidneys - C07K 14/705: Receptors; Cell surface antigens; Cell surface determinants {(tumour specific antigens C07K14/4748)} - G01N 33/6872: {Intracellular protein regulatory factors and their receptors, e.g. including ion channels} - A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) - C12Q 2600/118: Prognosis of disease development - C12Q 2600/136: Screening for pharmacological compounds - C12Q 2600/156: Polymorphic or mutational markers - C12Q 2600/158: Expression markers - G01N 2333/705: Assays involving receptors, cell surface antigens or cell surface determinants - G01N 2500/04: Screening involving studying the effect of compounds C directly on molecule A (e.g. C are potential ligands for a receptor A, or potential substrates for an enzyme A) - G01N 2800/347: Renal failures; Glomerular diseases; Tubulointerstitial diseases, e.g. nephritic syndrome, glomerulonephritis; Renovascular diseases, e.g. renal artery occlusion, nephropathy - G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis - C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) ## Abstract Focal and segmental glomerulosclerosis (FSGS) is a kidney disorder of unknown etiology and up to 20% of patients on dialysis have this diagnosis. A large family with hereditary FSGS carries a missense mutation in the TRPC6 gene on chromosome 11q, encoding the ion channel protein Transient Receptor Potential Cation Channel 6. The missense mutation is a P112Q substitution, which occurs in a highly conserved region of the protein, enhances TRPC6-mediated calcium signals in response to agonists such as angiotensin II, and alters the intracellular distribution of TRPC6 protein. Previous work has emphasized the importance of cytoskeletal and structural proteins in proteinuric kidney diseases. Our findings suggest a novel mechanism for glomerular disease pathogenesis. ## Claims ### Claim 1 A method of identifying a subject at increased risk of developing Focal and Segmental Glomerulosclerosis (FSGS), comprising: analyzing the nucleotide sequence of a Transient Receptor Potential Cation Channel, Subfamily C, Member 6 (TRPC6) gene in a nucleic acid sample obtained from the subject; comparing the nucleotide sequence of the sample gene to the nucleotide sequence of a reference wild-type TRPC6 gene comprising SEQ ID NO: 64 to determine one or more differences between the nucleotide sequence of the sample gene and the reference gene; and identifying the subject as being at increased risk of developing FSGS if the sequence of the gene of the subject differs from the reference gene at position 335 of the coding sequence of the reference gene, or identifying the subject as being at no increased risk if the sequence of the gene of the subject does not differ from the reference gene at position 335 of the coding sequence. ### Claim 2 (depends on 1) The method of claim 1 wherein the sequence difference of the sample TRPC6 gene is a non-synonymous difference with respect to the reference wild-type TRPC6 gene. ### Claim 3 (depends on 1) The method of claim 1 wherein the sequence difference is an adenine at nucleotide 335. ### Claim 4 (depends on 1) The method of claim 1 wherein the sequence difference is in a codon which encodes glutamine at residue 112 of a TRPC6 protein comprising SEQ ID NO: 63 or 65. ### Claim 5 (depends on 1) The method of claim 1 wherein oligonucleotide probes are used to detect the sequence difference. ### Claim 6 (depends on 1) The method of claim 1 wherein an amplification reaction is used to determine the sequence difference. ### Claim 7 A method of identifying a subject with Focal and Segmental Glomerulosclerosis (FSGS), comprising: analyzing the nucleotide sequence of a Transient Receptor Potential Cation Channel Subfamily C, Member 6 (TRCP6) gene in a nucleic acid sample obtained from the subject; comparing the nucleotide sequence of the sample gene to the nucleotide sequence of a reference wild-type-TRPC6 gene comprising SEQ ID NO: 64 to determine one or more differences between the nucleotide sequence of the sample gene and the reference gene; and identifying the subject as having FSGS if the sequence of the gene of the subject differs from the reference gene at position 335 of the coding sequence of the reference gene, or identifying the subject as not having FSGS if the sequence of the gene of the subject does not differ from the reference gene at position 335 of the coding sequence. ### Claim 8 (depends on 7) The method of claim 7 wherein the sequence difference of the sample TRPC6 gene is a non-synonymous difference with respect to the reference wild-type TRPC6 gene. ### Claim 9 (depends on 7) The method of claim 7 wherein the sequence difference is an adenine at nucleotide 335. ### Claim 10 (depends on 7) The method of claim 7 wherein the sequence difference is in a codon which encodes glutamine at reside 112 of a TRPC6 protein comprising SEQ ID NO: 63 or 65. ### Claim 11 (depends on 7) The method of claim 7 wherein oligonucleotide probes are used to detect the sequence difference. ### Claim 12 (depends on 7) The method of claim 7 wherein an amplification reaction is used to determine the sequence difference. ### Claim 13 A method of identifying a subject at increased risk of developing Focal and Segmental Glomerulosclerosis (FSGS), comprising: analyzing the nucleotide sequence of a Transient Receptor Potential Cation Channel, Subfamily C, Member 6 (TRPC6) gene in a nucleic acid sample obtained from the subject; comparing the nucleotide sequence of the sample gene to the nucleotide sequence of SEQ ID NO: 64 to determine one or more differences between the nucleotide sequence of the sample gene and SEQ ID NO: 64; and identifying the subject as being at increased risk of developing FSGS if the sequence of the gene of the subject differs from SEQ ID NO: 64 leotide position 335 of the coding sequence, or identifying the subject as being at no increased risk if the sequence of the gene of the subject does not differ from SEQ ID NO: 64 at nucleotide position 335 of the coding sequence. ### Claim 14 (depends on 13) The method of claim 13 wherein the sequence difference is an adenine at nucleotide 335 of the coding sequence. ### Claim 15 (depends on 13) The method of claim 13 wherein the sequence difference is in a codon which encodes glutamine at residue 112 of a TRPC6 protein comprising SEQ ID NO: 63 or 65.