UniProtKB/Swiss-Prot Q9HB90: Variant p.Ser75Tyr

Ras-related GTP-binding protein C
Gene: RRAGC
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Variant information Variant position:

75 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 Serine (S) to Tyrosine (Y) at position 75 (S75Y, p.Ser75Tyr). 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 small size and polar (S) to large size and aromatic (Y) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-2 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:

Found in a patient with idiopathic dilated cardiomyopathy; renders cells partially insensitive to amino acid deprivation and result in activated mTORC1 signaling. Any additional useful information about the variant.

Sequence information Variant position:

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

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

GGADSSKPRILLMGLRRSGK S SIQKVVFHKMSPNETLFLES 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                         GGADSSKPRILLMGLRRSGKSSIQKVVFHKMSPNETLFLES

Mouse                         GGADSSKPRILLMGLRRSGKSSIQKVVFHKMSPNETLFLES

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	2 – 399	Ras-related GTP-binding protein C
Binding site	71 – 71
Binding site	72 – 72
Binding site	73 – 73
Binding site	74 – 74
Binding site	74 – 74
Binding site	75 – 75
Binding site	76 – 76
Binding site	90 – 90
Binding site	90 – 90
Binding site	94 – 94
Mutagenesis	75 – 75	S -> L. Constitutively active mutant. Increased RPTOR-binding.
Mutagenesis	92 – 92	F -> A. Promotes interaction with GATOR1 in the GAP mode.
Helix	74 – 82

Literature citations
De novo RRAGC mutation activates mTORC1 signaling in syndromic fetal dilated cardiomyopathy.
Long P.A.; Zimmermann M.T.; Kim M.; Evans J.M.; Xu X.; Olson T.M.;
Hum. Genet. 135:909-917(2016)
Cited for: VARIANT TYR-75; CHARACTERIZATION OF VARIANT TYR-75; INVOLVEMENT IN DISEASE; FUNCTION;

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.