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UniProtKB/Swiss-Prot P22033: Variant p.Ala191Glu

Methylmalonyl-CoA mutase, mitochondrial
Gene: MMUT
Variant information

Variant position:  191
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 Alanine (A) to Glutamate (E) at position 191 (A191E, p.Ala191Glu).
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 small size and hydrophobic (A) to medium size and acidic (E)
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 MMAM; mut- and mut0; affects proper folding; reduced protein level; decreased methylmalonyl-CoA mutase activity.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.

Sequence information

Variant position:  191
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  750
The length of the canonical sequence.

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.






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.

Chain 33 – 750 Methylmalonyl-CoA mutase, mitochondrial

Literature citations

Seven novel mutations in mut methylmalonic aciduria.
Adjalla C.E.; Hosack A.R.; Gilfix B.M.; Lamothe E.; Sun S.; Chan A.; Evans S.; Matiaszuk N.V.; Rosenblatt D.S.;
Hum. Mutat. 11:270-274(1998)
Cited for: VARIANTS MMAM GLU-191; GLN-228; VAL-312; LEU-346 DEL; GLY-633; LEU-684 INS AND ARG-685;

Molecular basis of methylmalonyl-CoA mutase apoenzyme defect in 40 European patients affected by mut(o) and mut- forms of methylmalonic acidemia: identification of 29 novel mutations in the MUT gene.
Acquaviva C.; Benoist J.-F.; Pereira S.; Callebaut I.; Koskas T.; Porquet D.; Elion J.;
Hum. Mutat. 25:167-176(2005)
Cited for: VARIANTS MMAM HIS-108; LEU-148; ASN-156; VAL-158; GLU-191; ARG-203; SER-215; TYR-219; ASN-262; PRO-293; PHE-328; CYS-587; THR-615; ASN-621; ARG-623; ARG-624; ARG-627; GLU-637; ILE-638; TYR-640; ARG-642; TRP-694 AND LYS-700;

Genetic analysis of three genes causing isolated methylmalonic acidemia: identification of 21 novel allelic variants.
Martinez M.A.; Rincon A.; Desviat L.R.; Merinero B.; Ugarte M.; Perez B.;
Mol. Genet. Metab. 84:317-325(2005)
Cited for: VARIANTS MMAM ARG-109; GLU-191; TYR-219; THR-324; PRO-328; CYS-616 AND ARG-617; VARIANT VAL-69;

Spectrum of mutations in mut methylmalonic acidemia and identification of a common Hispanic mutation and haplotype.
Worgan L.C.; Niles K.; Tirone J.C.; Hofmann A.; Verner A.; Sammak A.; Kucic T.; Lepage P.; Rosenblatt D.S.;
Hum. Mutat. 27:31-43(2006)
Cited for: VARIANTS MMAM LEU-86; GLU-87; HIS-93; ARG-94; VAL-94; ARG-95; ARG-105; CYS-108; GLY-108; HIS-108; SER-145; SER-174; VAL-186; LYS-189; GLU-191; GLU-197; ARG-203; CYS-215; SER-215; HIS-218; TYR-219; GLN-228; ILE-230; ASN-231; ASN-262; TYR-265; SER-281; GLU-291; SER-305; PHE-306; VAL-312; CYS-316; THR-324; LEU-346 DEL; ARG-347; TYR-350; CYS-369; HIS-369; PRO-370; GLU-377; HIS-383; PRO-383; ARG-386; ASN-386; HIS-388; SER-389 DEL; ILE-412 DEL; ARG-426; ASP-427; PRO-518; TYR-560; ARG-566; SER-573; ARG-615; CYS-616; ARG-623; GLU-630; GLY-633; ARG-637; ARG-642; ARG-678; ARG-685; TRP-694; LYS-700; ARG-703 AND VAL-717; VARIANTS VAL-69; THR-499; HIS-532 AND VAL-671;

Mutation and biochemical analysis of 19 probands with mut0 and 13 with mut- methylmalonic aciduria: identification of seven novel mutations.
Lempp T.J.; Suormala T.; Siegenthaler R.; Baumgartner E.R.; Fowler B.; Steinmann B.; Baumgartner M.R.;
Mol. Genet. Metab. 90:284-290(2007)
Cited for: VARIANTS MMAM CYS-100; HIS-108; VAL-137; TYR-143; LEU-148; GLU-191; ARG-203; HIS-218; TYR-219; ASN-231; PRO-288; PHE-328; PHE-344; SER-366; HIS-369; GLU-454; THR-615; GLU-630; GLY-633; LEU-694; TRP-694 AND LYS-700;

Methylmalonic acidaemia: examination of genotype and biochemical data in 32 patients belonging to mut, cblA or cblB complementation group.
Merinero B.; Perez B.; Perez-Cerda C.; Rincon A.; Desviat L.R.; Martinez M.A.; Sala P.R.; Garcia M.J.; Aldamiz-Echevarria L.; Campos J.; Cornejo V.; Del Toro M.; Mahfoud A.; Martinez-Pardo M.; Parini R.; Pedron C.; Pena-Quintana L.; Perez M.; Pourfarzam M.; Ugarte M.;
J. Inherit. Metab. Dis. 31:55-66(2008)
Cited for: VARIANTS MMAM 7-GLN--VAL-750 DEL; VAL-69; ARG-109; 152-ARG--VAL-750 DEL; GLU-191; ARG-203; TYR-219; 228-ARG--VAL-750 DEL; ASN-231; THR-324; PRO-328; PRO-358; CYS-369; CYS-616; ARG-617 AND TRP-694;

Functional characterization and categorization of missense mutations that cause methylmalonyl-CoA mutase (MUT) deficiency.
Forny P.; Froese D.S.; Suormala T.; Yue W.W.; Baumgartner M.R.;
Hum. Mutat. 35:1449-1458(2014)
Cited for: CHARACTERIZATION OF VARIANTS MMAM LEU-86; CYS-100; GLU-191; HIS-218; TYR-219; ASN-231; CYS-316; PHE-328; PHE-344; SER-366; HIS-369; ILE-387; ARG-426; SER-573; LEU-615; THR-615; GLY-633; ASP-648; LEU-694; TRP-694; LYS-700; VAL-717 AND PHE-736; FUNCTION; CATALYTIC ACTIVITY; BIOPHYSICOCHEMICAL PROPERTIES;

Molecular genetic characterization of 151 mut-type methylmalonic aciduria patients and identification of 41 novel mutations in MUT.
Forny P.; Schnellmann A.S.; Buerer C.; Lutz S.; Fowler B.; Froese D.S.; Baumgartner M.R.;
Hum. Mutat. 37:745-754(2016)
Cited for: VARIANTS MMAM LYS-126; ARG-133; ASN-139; VAL-156; ARG-161; SER-187; ILE-189; GLU-205 DEL; ARG-230; ASP-276; ARG-284; GLU-284; ASP-325; LYS-326; LYS-388; LEU-424; GLU-426; VAL-552; PRO-618 AND GLY-625; CHARACTERIZATION OF VARIANTS MMAM HIS-93; ARG-133; ARG-161; ILE-189; GLU-191; ARG-203; ARG-230; PRO-288; SER-305; GLU-377; LYS-388; LEU-424; GLU-426; LEU-615; THR-615; ARG-624; VAL-625; GLY-625; PHE-674 AND TRP-694; FUNCTION; CATALYTIC ACTIVITY;

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.