UniProtKB/Swiss-Prot Q16595: Variant p.Ile154Phe

Frataxin, mitochondrial
Gene: FXN
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Variant information Variant position:

154 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 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
Variant description:

In FRDA; reduces interaction with the core iron-sulfur cluster assembly complex; does not affect mitochondrial localization; does not affect proteolytic processing; 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; decreases the level of covalent incorporation of sulfur into both NFS1 and ISCU. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs104894106 [ dbSNP | Ensembl ]

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        VNVSKSVGTYVINKQSPNKQIWLSSPMSGPKRYDL---EEE

Drosophila                    VNLGGQHGTYVINRQTPNKQIWLSSPTSGPKRYDFVGTVAA

Slime mold                    IIVGNK-GTYVINKQTPNRQIWWSSPLSGPKRFDY--DSVE

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

Fission yeast                 LMLGEK-GTYVINKQPPAHQIWLSSPVSGPKHYEY--SLKS

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	42 – 210	Frataxin intermediate form
Chain	56 – 210	Frataxin(56-210)
Chain	78 – 210	Frataxin(78-210)
Chain	81 – 210	Extramitochondrial frataxin
Chain	81 – 210	Frataxin mature form
Mutagenesis	146 – 146	N -> A. Does not affect interaction with the core iron-sulfur cluster assembly complex. Does not affect mitochondrial localization. Does not affect proteolytic processing.
Mutagenesis	173 – 173	W -> G. Loss of interaction with the core iron-sulfur cluster assembly complex. Does not affect mitochondrial localization. Does not affect proteolytic processing.
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; Mammalian frataxin: an essential function for cellular viability through an interaction with a preformed ISCU/NFS1/ISD11 iron-sulfur assembly complex.
Schmucker S.; Martelli A.; Colin F.; Page A.; Wattenhofer-Donze M.; Reutenauer L.; Puccio H.;
PLoS ONE 6:e16199-e16199(2011)
Cited for: COMPONENT OF CORE (FE-S) CLUSTER ASSEMBLY COMPLEX; MUTAGENESIS OF GLU-96; ASP-104; GLU-108; GLU-111; ASP-115; ASP-124; ASN-146 AND TRP-173; SUBCELLULAR LOCATION; PROTEOLYTIC PROCESSING; CHARACTERIZATION OF VARIANTS FRDA TYR-122; VAL-130 AND PHE-154; Human frataxin activates Fe-S cluster biosynthesis by facilitating sulfur transfer chemistry.
Bridwell-Rabb J.; Fox N.G.; Tsai C.L.; Winn A.M.; Barondeau D.P.;
Biochemistry 53:4904-4913(2014)
Cited for: VARIANTS FRDA PHE-154; ARG-155 AND CYS-165; CHARACTERIZATION OF VARIANTS FRDA PHE-154; ARG-155 AND CYS-165; FUNCTION; 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.