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UniProtKB/Swiss-Prot Q16595: Variant p.Ile154Phe

Frataxin, mitochondrial
Gene: FXN
Variant information

Variant position:  154
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Isoleucine (I) to Phenylalanine (F) at position 154 (I154F, p.Ile154Phe).
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 medium size and hydrophobic (I) to large size and aromatic (F)
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

Involvement in disease:  Friedreich ataxia (FRDA) [MIM:229300]: Autosomal recessive, progressive degenerative disease characterized by neurodegeneration and cardiomyopathy it is the most common inherited ataxia. The disorder is usually manifest before adolescence and is generally characterized by incoordination of limb movements, dysarthria, nystagmus, diminished or absent tendon reflexes, Babinski sign, impairment of position and vibratory senses, scoliosis, pes cavus, and hammer toe. In most patients, FRDA is due to GAA triplet repeat expansions in the first intron of the frataxin gene. But in some cases the disease is due to mutations in the coding region. {ECO:0000269|PubMed:10732799, ECO:0000269|PubMed:10874325, ECO:0000269|PubMed:19629184, ECO:0000269|PubMed:9150176, ECO:0000269|PubMed:9779809, ECO:0000269|PubMed:9989622, ECO:0000269|Ref.36, ECO:0000269|Ref.7, ECO:0000269|Ref.8}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In FRDA; reduces interaction with LYRM4; the interaction is rescued by nickel; a murine cellular FRDA model, deleted for endogenous frataxin and expressing human mutant frataxin cDNA shows defects in mitochondrial structure, mitochondrial iron deposits, decreased enzymatic activity of some mitochondrial and cytoplasmic iron-sulfur cluster-containing enzymes, increased RNA-binding activity of ACO1 and increased sensitivity to oxidative stress.
Any additional useful information about the variant.

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



Sequence information

Variant position:  154
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  210
The length of the canonical sequence.

Location on the sequence:   VKLGGDLGTYVINKQTPNKQ  I WLSSPSSGPKRYDWTGKNWV
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                         VKLGGDLGTYVINKQTPNKQIWLSSPSSGPKRYDW----TGKNWV

Mouse                         IKLGGDLGTYVINKQTPNKQIWLSSPSSGPKRYDW----TG

Rat                           IKLGGDLGTYVINKQTPLLYLWFSGPCSGPKRYDW----TG

Bovine                        VKLGGDLGTYVINKQTPNKQIWLSSPSSGPKRYDW----TG

Caenorhabditis elegans        VNVSKSVGTYVINKQSPNKQIWLSSPMSGPKRYDLE---EE

Drosophila                    VNLGGQHGTYVINRQTPNKQIWLSSPTSGPKRYDFVGTVAA

Slime mold                    IIVGNK-GTYVINKQTPNRQIWWSSPLSGPKRFDYD--SVE

Baker's yeast                 LEIPAF-GTYVINKQPPNKQIWLASPLSGPNRFDL----LN

Fission yeast                 LMLGEK-GTYVINKQPPAHQIWLSSPVSGPKHYEYS--LKS

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 42 – 210 Frataxin intermediate form
Chain 56 – 210 Frataxin(56-210)
Chain 78 – 210 Frataxin(78-210)
Chain 81 – 210 Frataxin mature form
Beta strand 153 – 157


Literature citations

Friedreich's ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion.
Campuzano V.; Montermini L.; Molto M.D.; Pianese L.; Cossee M.; Cavalcanti F.; Monros E.; Rodius F.; Duclos F.; Monticelli A.; Zara F.; Canizares J.; Koutnikova H.; Bidichandani S.; Gellera C.; Brice A.; Trouillas P.; de Michele G.; Filla A.; de Frutos R.; Palau F.; Patel P.I.; di Donato S.; Mandel J.-L.; Cocozza S.; Koenig M.; Pandolfo M.;
Science 271:1423-1427(1996)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2); ALTERNATIVE SPLICING; VARIANT PHE-154;

Mitochondrial frataxin interacts with ISD11 of the NFS1/ISCU complex and multiple mitochondrial chaperones.
Shan Y.; Napoli E.; Cortopassi G.;
Hum. Mol. Genet. 16:929-941(2007)
Cited for: INTERACTION WITH LYRM4 AND HSPA9; CHARACTERIZATION OF VARIANTS PHE-154 AND ARG-155;

Atypical Friedreich ataxia caused by compound heterozygosity for a novel missense mutation and the GAA triplet-repeat expansion.
Bidichandani S.I.; Ashizawa T.; Patel P.I.;
Am. J. Hum. Genet. 60:1251-1256(1997)
Cited for: VARIANTS FRDA VAL-130 AND PHE-154;

The first cellular models based on frataxin missense mutations that reproduce spontaneously the defects associated with Friedreich ataxia.
Calmels N.; Schmucker S.; Wattenhofer-Donze M.; Martelli A.; Vaucamps N.; Reutenauer L.; Messaddeq N.; Bouton C.; Koenig M.; Puccio H.;
PLoS ONE 4:E6379-E6379(2009)
Cited for: CHARACTERIZATION OF VARIANT FRDA PHE-154;

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.