UniProtKB/Swiss-Prot Q9Y210: Variant p.Asn125Ser

Short transient receptor potential channel 6
Gene: TRPC6
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Variant information Variant position:

125 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

US The variants are classified into three categories: LP/P, LB/B and US.

LP/P: likely pathogenic or pathogenic.
LB/B: likely benign or benign.
US: uncertain significance

Residue change:

From Asparagine (N) to Serine (S) at position 125 (N125S, p.Asn125Ser). Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.
Physico-chemical properties:

Change from medium size and polar (N) to small size and polar (S) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

1 The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:

Lowest score: -4 (low probability of substitution).
Highest score: 11 (high probability of substitution).

More information can be found on the following page
Variant description:

In FSGS2; uncertain significance; decreases calcium ion transport. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs146776939 [ dbSNP | Ensembl ]

Sequence information Variant position:

125 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

931 The length of the canonical sequence.
Location on the sequence:

AAEYGNIPVVRKMLEECHSL N VNCVDYMGQNALQLAVANEH The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Residue conservation:

The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         AAEYGNIPVVRKMLEECHSLNVNCVDYMGQNALQLAVANEH

Mouse                         AAEYGNIPVVRKMLEECHSLNVNCVDYMGQNALQLAVANEH

Bovine                        AAEYGNIPVVRKMLEECLSLNVNCVDYMGQNALQLAVANEH

Sequence annotation in neighborhood:

The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:

Type: the type of sequence feature.
Positions: endpoints of the sequence feature.
Description: contains additional information about the feature.

Type	Positions	Description
Chain	1 – 931	Short transient receptor potential channel 6
Topological domain	1 – 438	Cytoplasmic
Repeat	97 – 126	ANK 1
Mutagenesis	110 – 110	N -> H. Increases calcium ion transport.
Mutagenesis	125 – 125	N -> A. No effect on RNF24-binding; when associated with A-127; A-128 and A-130.
Mutagenesis	127 – 127	N -> A. No effect on RNF24-binding; when associated with A-125; A-128 and A-130.
Mutagenesis	128 – 128	C -> A. No effect on RNF24-binding; when associated with A-125; A-127 and A-130.
Mutagenesis	130 – 130	D -> A. No effect on RNF24-binding; when associated with A-125; A-127 and A-128.
Mutagenesis	132 – 132	M -> T. Increases cation channel activity. Increases significantly inward and outward currents and does not show channel inactivation. Increases calcium ion transport.

Literature citations
TRPC6 mutational analysis in a large cohort of patients with focal segmental glomerulosclerosis.
Santin S.; Ars E.; Rossetti S.; Salido E.; Silva I.; Garcia-Maset R.; Gimenez I.; Ruiz P.; Mendizabal S.; Luciano Nieto J.; Pena A.; Camacho J.A.; Fraga G.; Cobo M.A.; Bernis C.; Ortiz A.; de Pablos A.L.; Sanchez-Moreno A.; Pintos G.; Mirapeix E.; Fernandez-Llama P.; Ballarin J.; Torra R.; Zamora I.; Lopez-Hellin J.; Madrid A.; Ventura C.; Vilalta R.; Espinosa L.; Garcia C.; Melgosa M.; Navarro M.; Gimenez A.; Cots J.V.; Alexandra S.; Caramelo C.; Egido J.; San Jose M.D.; de la Cerda F.; Sala P.; Raspall F.; Vila A.; Daza A.M.; Vazquez M.; Ecija J.L.; Espinosa M.; Justa M.L.; Poveda R.; Aparicio C.; Rosell J.; Muley R.; Montenegro J.; Gonzalez D.; Hidalgo E.; de Frutos D.B.; Trillo E.; Gracia S.; de los Rios F.J.;
Nephrol. Dial. Transplant. 24:3089-3096(2009)
Cited for: VARIANTS FSGS2 SER-109; SER-125 AND PRO-780; TRPC6 mutations in children with steroid-resistant nephrotic syndrome and atypical phenotype.
Gigante M.; Caridi G.; Montemurno E.; Soccio M.; d'Apolito M.; Cerullo G.; Aucella F.; Schirinzi A.; Emma F.; Massella L.; Messina G.; De Palo T.; Ranieri E.; Ghiggeri G.M.; Gesualdo L.;
Clin. J. Am. Soc. Nephrol. 6:1626-1634(2011)
Cited for: VARIANTS FSGS2 SER-125 AND LEU-218; VARIANT LEU-895; TRPC6 G757D Loss-of-Function Mutation Associates with FSGS.
Riehle M.; Buescher A.K.; Gohlke B.O.; Kassmann M.; Kolatsi-Joannou M.; Braesen J.H.; Nagel M.; Becker J.U.; Winyard P.; Hoyer P.F.; Preissner R.; Krautwurst D.; Gollasch M.; Weber S.; Harteneck C.;
J. Am. Soc. Nephrol. 27:2771-2783(2016)
Cited for: MUTAGENESIS OF ASN-110; MET-132; 755-GLU--GLY-757; 755-GLU-GLU-756; 826-LYS-LYS-827 AND GLN-889; VARIANTS FSGS2 SER-109; GLN-112; SER-125; SER-143; GLN-175; LEU-218; ALA-395; ASP-757; PRO-780; CYS-895; LEU-895 AND LYS-897; CHARACTERIZATION OF VARIANTS FSGS2 SER-109; GLN-112; SER-125; SER-143; GLN-175; LEU-218; ALA-395; ASP-757; PRO-780; CYS-895; LEU-895 AND LYS-897; VARIANT VAL-404; CHARACTERIZATION OF VARIANT VAL-404; FUNCTION; SUBCELLULAR LOCATION; SUBUNIT;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.