UniProtKB/Swiss-Prot Q13283: Variant p.Arg78Cys

Ras GTPase-activating protein-binding protein 1
Gene: G3BP1
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Variant information Variant position:

78 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 Arginine (R) to Cysteine (C) at position 78 (R78C, p.Arg78Cys). 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 large size and basic (R) to medium size and polar (C) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-3 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 a neurodevelopmental disorder; uncertain significance; decreased function in stress granule formation shown by rescue assays in transfected G3BP1-deficient cells. Any additional useful information about the variant.

Sequence information Variant position:

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

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

QKEIHRKVMSQNFTNCHTKI R HVDAHATLNDGVVVQVMGLL 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                         QKEIHRKVMSQNFTNCHTKIRHVDAHATLNDGVVVQVMGLL

Mouse                         QKEIHRKVMSQNFTNCHTKIRHVDAHATLNDGVVVQVMGLL

Bovine                        QKEIHRKVMSQNFTNCHTKIRHVDAHATLNDGVVVQVMGLL

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 – 466	Ras GTPase-activating protein-binding protein 1
Domain	11 – 133	NTF2
Cross	59 – 59	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Cross	64 – 64	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Cross	76 – 76	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Mutagenesis	59 – 59	K -> R. In 10KR; abolished ubiquitination in response to heat shock, leading to decreased stress granule disassembly when associated with R-36, R-50, R-64, R-76, R-123, R-353, R-357, R-376 and R-393. In 6KR; strongly decreased ubiquitination in response to heat shock, leading to decreased stress granule disassembly; when associated with R-36, R-50, R-64, R-76 and R-123. In 4KR; decreased ubiquitination in response to heat shock, leading to slightly decreased stress granule disassembly; when associated with R-36, R-50 and R-64.
Mutagenesis	64 – 64	K -> R. In 10KR; abolished ubiquitination in response to heat shock, leading to decreased stress granule disassembly when associated with R-36, R-50, R-59, R-76, R-123, R-353, R-357, R-376 and R-393. In 6KR; strongly decreased ubiquitination in response to heat shock, leading to decreased stress granule disassembly; when associated with R-36, R-50, R-59, R-76 and R-123. In 4KR; decreased ubiquitination in response to heat shock, leading to slightly decreased stress granule disassembly; when associated with R-36, R-50 and R-59.
Mutagenesis	76 – 76	K -> R. In 10KR; abolished ubiquitination in response to heat shock, leading to decreased stress granule disassembly when associated with R-36, R-50, R-59, R-64, R-123, R-353, R-357, R-376 and R-393. In 6KR; strongly decreased ubiquitination in response to heat shock, leading to decreased stress granule disassembly; when associated with R-36, R-50, R-59, R-64 and R-123.
Beta strand	74 – 84

Literature citations
De novo variants in genes regulating stress granule assembly associate with neurodevelopmental disorders.
Jia X.; Zhang S.; Tan S.; Du B.; He M.; Qin H.; Chen J.; Duan X.; Luo J.; Chen F.; Ouyang L.; Wang J.; Chen G.; Yu B.; Zhang G.; Zhang Z.; Lyu Y.; Huang Y.; Jiao J.; Chen J.Y.H.; Swoboda K.J.; Agolini E.; Novelli A.; Leoni C.; Zampino G.; Cappuccio G.; Brunetti-Pierri N.; Gerard B.; Ginglinger E.; Richer J.; McMillan H.; White-Brown A.; Hoekzema K.; Bernier R.A.; Kurtz-Nelson E.C.; Earl R.K.; Meddens C.; Alders M.; Fuchs M.; Caumes R.; Brunelle P.; Smol T.; Kuehl R.; Day-Salvatore D.L.; Monaghan K.G.; Morrow M.M.; Eichler E.E.; Hu Z.; Yuan L.; Tan J.; Xia K.; Shen Y.; Guo H.;
Sci. Adv. 8:eabo7112-eabo7112(2022)
Cited for: FUNCTION; VARIANTS CYS-78; ILE-132; CYS-208; CYS-320 AND MET-366; CHARACTERIZATION OF VARIANTS CYS-78; ILE-132; CYS-208; CYS-320 AND MET-366;

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.