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UniProtKB/Swiss-Prot P07954: Variant p.Lys230Arg

Fumarate hydratase, mitochondrial
Gene: FH
Variant information

Variant position:  230
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 Lysine (K) to Arginine (R) at position 230 (K230R, p.Lys230Arg).
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 large size and basic.
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:  In FMRD and HLRCC.
Any additional useful information about the variant.

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

Sequence information

Variant position:  230
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  510
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 45 – 510 Fumarate hydratase, mitochondrial
Active site 235 – 235 Proton donor/acceptor
Binding site 234 – 234
Modified residue 213 – 213 N6-acetyllysine
Modified residue 223 – 223 N6-acetyllysine; alternate
Modified residue 223 – 223 N6-succinyllysine; alternate
Modified residue 236 – 236 Phosphothreonine; by PRKDC
Mutagenesis 236 – 236 T -> A. Abolished interaction with H2AZ1 and localization to chromatin in response to DNA damage.
Mutagenesis 236 – 236 T -> D. Phosphomimetic mutant; promotes interaction with H2AZ1, leading to increased localization to chromatin in response to DNA damage.
Beta strand 229 – 234

Literature citations

Molecular analysis and prenatal diagnosis of human fumarase deficiency.
Coughlin E.M.; Christensen E.; Kunz P.L.; Krishnamoorthy K.S.; Walker V.; Dennis N.R.; Chalmers R.A.; Elpeleg O.N.; Whelan D.; Pollitt R.J.; Ramesh V.; Mandell R.; Shih V.E.;
Mol. Genet. Metab. 63:254-262(1998)
Cited for: VARIANTS FMRD ARG-230; THR-308; CYS-312 AND VAL-425;

Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer.
Tomlinson I.P.M.; Alam N.A.; Rowan A.J.; Barclay E.; Jaeger E.E.M.; Kelsell D.; Leigh I.; Gorman P.; Lamlum H.; Rahman S.; Roylance R.R.; Olpin S.; Bevan S.; Barker K.; Hearle N.; Houlston R.S.; Kiuru M.; Lehtonen R.; Karhu A.; Vilkki S.; Laiho P.; Eklund C.; Vierimaa O.; Aittomaeki K.; Hietala M.; Sistonen P.; Paetau A.; Salovaara R.; Herva R.; Launonen V.; Aaltonen L.A.;
Nat. Genet. 30:406-410(2002)
Cited for: VARIANTS HLRCC THR-107; PRO-117; ARG-180; ARG-185; ARG-230; HIS-233; VAL-282 AND ARG-328;

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.