UniProtKB/SwissProt variant VAR

Variant information

Variant position:

359

The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:

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:

From Arginine (R) to Glutamine (Q) at position 359 (R359Q, p.Arg359Gln).

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 (Q)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

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:

In MMAA; decreases protein levels.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs864309731 [ dbSNP | Ensembl ]

Sequence information

Variant position:

359

The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:

418

The length of the canonical sequence.

Location on the sequence:

WDKMKDFQDLMLASGELTAK R RKQQKVWMWNLIQESVLEHF

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                         WDKMKDFQDLMLASGELTAKRRKQQKVWMWNLIQES--VLEHF

Mouse                         WDTMREFQHQMLASGELAAKRQTQHKVWMWNLIQEN--VLE

Rabbit                        WNVGYDARILGPNTCQRGAACQTTKATESLDVEPHSGKRVR

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	66 – 418	Methylmalonic aciduria type A protein, mitochondrial
Helix	354 – 381

Literature citations

Mutations in the MMAA gene in patients with the cblA disorder of vitamin B(12) metabolism.
Lerner-Ellis J.P.; Dobson C.M.; Wai T.; Watkins D.; Tirone J.C.; Leclerc D.; Dore C.; Lepage P.; Gravel R.A.; Rosenblatt D.S.;
Hum. Mutat. 24:509-516(2004)
Cited for: VARIANTS MMAA 22-ARG--ASP-418 DEL; 54-TRP--ASP-418 DEL; PRO-89; 129-TYR--ASP-418 DEL; 145-ARG--ASP-418 DEL; GLN-145; GLU-147; CYS-207; GLU-218; 248-GLN--ASP-418 DEL; 320-TRP--ASP-418 DEL; 330-ARG--ASP-418 DEL AND GLN-359; VARIANT HIS-363;

High resolution melting analysis of the MMAA gene in patients with cblA and in those with undiagnosed methylmalonic aciduria.
Dempsey-Nunez L.; Illson M.L.; Kent J.; Huang Q.; Brebner A.; Watkins D.; Gilfix B.M.; Wittwer C.T.; Rosenblatt D.S.;
Mol. Genet. Metab. 107:363-367(2012)
Cited for: VARIANTS MMAA SER-209; LYS-250; ASP-274; SER-274; GLU-276 AND GLN-359;

Protein destabilization and loss of protein-protein interaction are fundamental mechanisms in cblA-type methylmalonic aciduria.
Plessl T.; Buerer C.; Lutz S.; Yue W.W.; Baumgartner M.R.; Froese D.S.;
Hum. Mutat. 38:988-1001(2017)
Cited for: VARIANTS MMAA 24-TYR--ASP-418 DEL; 68-GLN--ASP-418 DEL; PRO-89; 95-GLN--ASP-418 DEL; GLY-98; 100-CYS--ALA-104 DEL; 145-ARG--ASP-418 DEL; GLN-145; GLU-147; ARG-188; ASP-192; 196-ARG--ASP-418 DEL; GLN-196; CYS-207; SER-209; GLU-218; MET-220; PHE-241; ASN-243; 248-GLN--ASP-418 DEL; LYS-250; ASN-258; SER-274; GLU-276; ASP-287; VAL-292; 330-ARG--ASP-418 DEL; 359-ARG--ASP-418 DEL; GLN-359; GLY-359 AND VAL-399; CHARACTERIZATION OF VARIANTS MMAA PRO-89; GLY-98; GLN-145; GLU-147; ARG-188; ASP-192; GLN-196; CYS-207; SER-209; GLU-218; MET-220; PHE-241; ASN-243; LYS-250; SER-274; GLU-276; ASP-287; VAL-292; GLN-359; GLY-359 AND VAL-399; FUNCTION; GTP-BINDING; MUTAGENESIS OF LYS-290 AND ASP-292; BIOPHYSICOCHEMICAL PROPERTIES; ACTIVITY REGULATION; CATALYTIC ACTIVITY; PATHWAY;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q8IVH4: Variant p.Arg359Gln