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UniProtKB/Swiss-Prot O60313: Variant p.Arg445His

Dynamin-like 120 kDa protein, mitochondrial
Gene: OPA1
Variant information

Variant position:  445
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 Histidine (H) at position 445 (R445H, p.Arg445His).
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 (H)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
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 DOA+ and OPA1; decreased GTPase activity; loss of function in promoting mitochondrial fusion.
Any additional useful information about the variant.

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



Sequence information

Variant position:  445
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  960
The length of the canonical sequence.

Location on the sequence:   YMQNPNAIILCIQDGSVDAE  R SIVTDLVSQMDPHGRRTIFV
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                         YMQNPNAIILCIQDGSVDAERSIVTDLVSQMDPHGRRTIFV

Mouse                         YMQNPNAIILCIQDGSVDAERSIVTDLVSQMDPHGRRTIFV

Rat                           YMQNPNAIILCIQDGSVDAERSIVTDLVSQMDPHGRRTIFV

Chicken                       YMQNPNAIILCIQDGSVDAERSIVTDLVSQMDPQGKRTIFV

Zebrafish                     YMQNPNAIILCIQDGSVDAERSIVTDLVSQMDPQGKRTIFV

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.

TypePositionsDescription
Chain 88 – 960 Dynamin-like 120 kDa protein, mitochondrial
Chain 195 – 960 Dynamin-like 120 kDa protein, form S1
Topological domain 114 – 960 Mitochondrial intermembrane
Domain 285 – 561 Dynamin-type G
Helix 443 – 445


Literature citations

OPA1 disease alleles causing dominant optic atrophy have defects in cardiolipin-stimulated GTP hydrolysis and membrane tubulation.
Ban T.; Heymann J.A.; Song Z.; Hinshaw J.E.; Chan D.C.;
Hum. Mol. Genet. 19:2113-2122(2010)
Cited for: FUNCTION; CATALYTIC ACTIVITY; SUBUNIT; CHARACTERIZATION OF VARIANTS OPA1 GLU-300; VAL-439; HIS-445; ARG-545; LYS-728; ARG-785 AND PRO-939; CHARACTERIZATION OF VARIANTS VARIANT DOA+ THR-357; VAL-439; HIS-445; ARG-545 AND ASP-910;

A novel mutation in the OPA1 gene in a Japanese patient with optic atrophy.
Shimizu S.; Mori N.; Kishi M.; Sugata H.; Tsuda A.; Kubota N.;
Am. J. Ophthalmol. 135:256-257(2003)
Cited for: VARIANT OPA1 HIS-445;

Dominant optic atrophy, sensorineural hearing loss, ptosis, and ophthalmoplegia: a syndrome caused by a missense mutation in OPA1.
Payne M.; Yang Z.; Katz B.J.; Warner J.E.A.; Weight C.J.; Zhao Y.; Pearson E.D.; Treft R.L.; Hillman T.; Kennedy R.J.; Meire F.M.; Zhang K.;
Am. J. Ophthalmol. 138:749-755(2004)
Cited for: VARIANT DOA+ HIS-445;

OPA1 R445H mutation in optic atrophy associated with sensorineural deafness.
Amati-Bonneau P.; Guichet A.; Olichon A.; Chevrollier A.; Viala F.; Miot S.; Ayuso C.; Odent S.; Arrouet C.; Verny C.; Calmels M.-N.; Simard G.; Belenguer P.; Wang J.; Puel J.-L.; Hamel C.; Malthiery Y.; Bonneau D.; Lenaers G.; Reynier P.;
Ann. Neurol. 58:958-963(2005)
Cited for: VARIANT DOA+ HIS-445;

OPA1 mutations induce mitochondrial DNA instability and optic atrophy 'plus' phenotypes.
Amati-Bonneau P.; Valentino M.L.; Reynier P.; Gallardo M.E.; Bornstein B.; Boissiere A.; Campos Y.; Rivera H.; de la Aleja J.G.; Carroccia R.; Iommarini L.; Labauge P.; Figarella-Branger D.; Marcorelles P.; Furby A.; Beauvais K.; Letournel F.; Liguori R.; La Morgia C.; Montagna P.; Liguori M.; Zanna C.; Rugolo M.; Cossarizza A.; Wissinger B.; Verny C.; Schwarzenbacher R.; Martin M.A.; Arenas J.; Ayuso C.; Garesse R.; Lenaers G.; Bonneau D.; Carelli V.;
Brain 131:338-351(2008)
Cited for: VARIANTS DOA+ THR-357; VAL-439; HIS-445; ARG-545 AND ASP-910; 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.