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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9H0H5: Variant p.Leu396Gln

Rac GTPase-activating protein 1
Gene: RACGAP1
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Variant information Variant position: help 396 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 Leucine (L) to Glutamine (Q) at position 396 (L396Q, p.Leu396Gln). 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 medium size and hydrophobic (L) to medium size and polar (Q) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -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: help In CDAN3B; decreased function in erythropoiesis as shown by partial rescue of multinucleation defects in RACGAP1-deficient erythroid cells; decreased GAP activity towards RHOA, RAC1 and CDC42. Any additional useful information about the variant.


Sequence information Variant position: help 396 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 632 The length of the canonical sequence.
Location on the sequence: help RGLTETGLYRISGCDRTVKE L KEKFLRVKTVPLLSKVDDIH 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                         RGLTETGL------YRISGCDRTVKELK-----------------EKFLRVKTVPLL----SKVDDIH

Mouse                         RGLTEAGL------YRISGCDRTVKELK-------------

Slime mold                    EEPIDSDFILPCKGYKIDSGNSKCQQVNYDELIVLYTDEDE
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 – 632 Rac GTPase-activating protein 1
Domain 349 – 539 Rho-GAP
Modified residue 387 – 387 Phosphoserine; by AURKB
Modified residue 410 – 410 Phosphoserine; by AURKB
Cross 404 – 404 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)
Mutagenesis 385 – 385 R -> A. Abolishes GAP activity towards RAC1. Abolishes GAP activity towards CDC42 in prometaphase. Abolishes GAP activity towards RHOA. Induces multiple blebs during cytokinesis.
Helix 390 – 403



Literature citations
RACGAP1 variants in a sporadic case of CDA III implicate the dysfunction of centralspindlin as the basis of the disease.
Wontakal S.N.; Britto M.; Zhang H.; Han Y.; Gao C.; Tannenbaum S.; Durham B.H.; Lee M.T.; An X.; Mishima M.;
Blood 139:1413-1418(2022)
Cited for: VARIANTS CDAN3B GLN-396 AND SER-432; INVOLVEMENT IN CDAN3B; CHARACTERIZATION OF VARIANTS CDAN3B GLN-396 AND SER-432; MUTAGENESIS OF ARG-385; 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.