UniProtKB/Swiss-Prot Q6PIV2: Variant p.Met280Leu

Forkhead box protein R1
Gene: FOXR1
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Variant information Variant position:

280 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 Methionine (M) to Leucine (L) at position 280 (M280L, p.Met280Leu). 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:

Similar physico-chemical property. Both residues are medium size and hydrophobic. 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 a severe neurological disorder; uncertain significance; reduced protein expression due to protein instability; protein misfolding; formation of nuclear puncta in some cells; loss of activation of HSPA1A, HSPA6 and DHRS2. Any additional useful information about the variant.

Sequence information Variant position:

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

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

RFAEEARALASTRLESIQQC M SQPDVMPFLFDL 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                         RFAEEARALASTRLESIQQCMSQPDVMPFLFDL

Mouse                         RFSKEARTLASTQLQSIQQCMSQPGVKPFLFDL

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 – 292	Forkhead box protein R1
Alternative sequence	206 – 291	Missing. In isoform 2.
Mutagenesis	280 – 292	Missing. Reduced protein expression and formation of nuclear puncta in some cells.

Literature citations
FOXR1 regulates stress response pathways and is necessary for proper brain development.
Mota A.; Waxman H.K.; Hong R.; Lagani G.D.; Niu S.Y.; Bertherat F.L.; Wolfe L.; Malicdan C.M.; Markello T.C.; Adams D.R.; Gahl W.A.; Cheng C.S.; Beffert U.; Ho A.;
PLoS Genet. 17:e1009854-e1009854(2021)
Cited for: FUNCTION; SUBCELLULAR LOCATION; INDUCTION; CHARACTERIZATION OF VARIANT LEU-280; MUTAGENESIS OF 280-MET--LEU-292;

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.