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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O75962: Variant p.Arg1428Gln

Triple functional domain protein
Gene: TRIO
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Variant information Variant position: help 1428 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] 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: help From Arginine (R) to Glutamine (Q) at position 1428 (R1428Q, p.Arg1428Gln). 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: help Change from large size and basic (R) to medium size and polar (Q) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 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: help In MRD44; severely decreased activation of RAC1-mediated signaling; severely decreased neurite outgrowth. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 1428 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 3097 The length of the canonical sequence.
Location on the sequence: help IQQRHGLANSISSYLIKPVQ R ITKYQLLLKELLTCCEEGKG 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences.
Human                         IQQRHGLANSISSYLIKPVQRITKYQLLLKELLTCCEEGKG

Mouse                         IQQRHGLANSISSYLIKPVQRITKYQLLLKELLTCCEEGKG

Rat                           IQQRHGLANSISSYLIKPVQRITKYQLLLKELLTCCEEGKG

Zebrafish                     IQQRHRLANSISSYLIKPVQRITKYQLLLKELLTCCEEGKG

Sequence annotation in neighborhood: help 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.
TypePositionsDescription
Chain 1 – 3097 Triple functional domain protein
Domain 1292 – 1467 DH 1
Alternative sequence 1 – 2501 Missing. In isoform 3.
Mutagenesis 1426 – 1426 V -> A. 90% decrease in nucleotide exchange activity.
Mutagenesis 1427 – 1427 Q -> A. 80% decrease in nucleotide exchange activity.
Mutagenesis 1428 – 1428 R -> A. 80% decrease in nucleotide exchange activity.
Mutagenesis 1430 – 1430 T -> A. 80% decrease in nucleotide exchange activity.
Mutagenesis 1431 – 1431 K -> A. Loss of nucleotide exchange activity.
Mutagenesis 1434 – 1434 L -> A. 40% decrease in nucleotide exchange activity.
Mutagenesis 1437 – 1437 K -> A. No change in nucleotide exchange activity.
Mutagenesis 1438 – 1438 E -> A. 30% decrease in nucleotide exchange activity.
Helix 1424 – 1441



Literature citations
Mutations specific to the Rac-GEF domain of TRIO cause intellectual disability and microcephaly.
Pengelly R.J.; Greville-Heygate S.; Schmidt S.; Seaby E.G.; Jabalameli M.R.; Mehta S.G.; Parker M.J.; Goudie D.; Fagotto-Kaufmann C.; Mercer C.; Debant A.; Ennis S.; Baralle D.;
J. Med. Genet. 53:735-742(2016)
Cited for: INVOLVEMENT IN MRD44; VARIANTS MRD44 GLN-1428 AND THR-1461; VARIANT MRD63 ILE-1080; CHARACTERIZATION OF VARIANT MRD44 GLN-1428; FUNCTION; Opposite modulation of RAC1 by mutations in TRIO is associated with distinct, domain-specific neurodevelopmental disorders.
Barbosa S.; Greville-Heygate S.; Bonnet M.; Godwin A.; Fagotto-Kaufmann C.; Kajava A.V.; Laouteouet D.; Mawby R.; Wai H.A.; Dingemans A.J.M.; Hehir-Kwa J.; Willems M.; Capri Y.; Mehta S.G.; Cox H.; Goudie D.; Vansenne F.; Turnpenny P.; Vincent M.; Cogne B.; Lesca G.; Hertecant J.; Rodriguez D.; Keren B.; Burglen L.; Gerard M.; Putoux A.; Cantagrel V.; Siquier-Pernet K.; Rio M.; Banka S.; Sarkar A.; Steeves M.; Parker M.; Clement E.; Moutton S.; Tran Mau-Them F.; Piton A.; de Vries B.B.A.; Guille M.; Debant A.; Schmidt S.; Baralle D.;
Am. J. Hum. Genet. 106:338-355(2020)
Cited for: VARIANTS MRD44 768-GLN--VAL-3097 DEL; LYS-1299; GLN-1428; THR-1461 AND ARG-1469; VARIANTS MRD63 ILE-1075; GLN-1078; GLY-1078; TRP-1078; ILE-1080 AND LEU-1461; INVOLVEMENT IN MRD63; FUNCTION; CHARACTERIZATION OF VARIANTS MRD63 ILE-1075; GLN-1078; GLY-1078; TRP-1078; ILE-1080 AND LEU-1461; CHARACTERIZATION OF VARIANTS MRD44 LYS-1299; GLN-1428 AND ARG-1469;
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.