FXN frataxin [Homo sapiens] - Gene

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Summary

Official Symbol: FXNprovided by HGNC
Official Full Name: frataxinprovided by HGNC
Primary source: HGNC:3951
See related: Ensembl:ENSG00000165060; HPRD:06013; MIM:606829; Vega:OTTHUMG00000019977
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: FA; X25; CyaY; FARR; FRDA; MGC57199
Summary: This nuclear gene encodes a mitochondrial protein which belongs to FRATAXIN family. The protein functions in regulating mitochondrial iron transport and respiration. The expansion of intronic trinucleotide repeat GAA results in Friedreich ataxia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2009]

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Genomic context

Location :: 9q21.11

Sequence :: Chromosome: 9; NC_000009.11 (71650479..71715094)

See FXN in Epigenomics, MapViewer

Chromosome 9 - NC_000009.11 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

role of frataxin in Fe-S assembly
Title: Effector role reversal during evolution: the case of frataxin in Fe-S cluster biosynthesis.
frataxin is involved in various processes related to iron homeostasis and metabolism. [review]
Title: Exploring frataxin function.
Results describe novel deletion-insertion mutation in exon 3 of frataxin in siblings with severe Friedreich ataxia.
Title: A novel deletion-insertion mutation identified in exon 3 of FXN in two siblings with a severe Friedreich ataxia phenotype.
dual, pro-proliferative but chemosensitizing role in astrocytic tumors
Title: Dual role of the mitochondrial protein frataxin in astrocytic tumors.
The data provide strong evidence that FXN deficiency in FRDA patients results from a block of transition from initiation to a productive elongation of FXN transcription due to heterochromatin-like structures formed near the hyperexpanded GAAs.
Title: Hyperexpansion of GAA repeats affects post-initiation steps of FXN transcription in Friedreich's ataxia.
the number of GAA repeats in the smaller allele of the FXN gene, whereas septal E; was not correlated with GAA repeat number. At 5 years, there was a reduction in lateral S; and E; but no change in septal TDI velocities.
Title: Early changes in left ventricular long-axis function in Friedreich ataxia: relation with the FXN gene mutation and cardiac structural change.
Friedreich's ataxia mutants reveals determinants of frataxin binding and activation of the Fe-S assembly complex.
Title: Structure-function analysis of Friedreich's ataxia mutants reveals determinants of frataxin binding and activation of the Fe-S assembly complex.
Silencing of frataxin gene expression triggers p53-dependent apoptosis in human neuron-like cells.
Title: Silencing of frataxin gene expression triggers p53-dependent apoptosis in human neuron-like cells.
Computational analyses were performed on the 21.3 kb region upstream of exon 1 of the human FXN gene and orthologs from other species in order to identify conserved non-coding DNA sequences with potential regulatory functions.
Title: Long range regulation of human FXN gene expression.
Fxn facilitates sulfur transfer from Nfs1 to Isu2.
Title: Friedreich's ataxia variants I154F and W155R diminish frataxin-based activation of the iron-sulfur cluster assembly complex.

Submit: New GeneRIF Correction See all (81)

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Phenotypes

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Friedreich ataxia with retained reflexes

MIM: 229300

Friedreich ataxia (FRDA) is characterized by slowly progressive ataxia with mean onset between age ten and 15 years and usually before age 25 years. FRDA is typically associated with dysarthria, muscle weakness, spasticity in the lower limbs, scoliosis, bladder dysfunction, absent lower limb reflexes, and loss of position and vibration sense. Approximately two-thirds of individuals with FRDA have cardiomyopathy; up to 30% have diabetes mellitus; and approximately 25% have an "atypical" presentation with later onset or retained tendon reflexes.

Diagnosis Testing

Individuals with FRDA have identifiable mutations in FXN. The most common type of mutation, which is observed on both alleles in more than 98% of individuals with FRDA, is a GAA triplet-repeat expansion in intron 1 of FXN. Approximately 2% of individuals with FRDA are compound heterozygotes for a GAA expansion in the disease-causing range in one FXN allele and another inactivating FXN mutation in the other allele. Molecular genetic testing is available on a clinical basis.

Genetic Counseling

FRDA is inherited in an autosomal recessive manner. Each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of having no mutation. Carrier testing of at-risk relatives and prenatal testing for pregnancies at increased risk are possible if both FXN mutations have been identified in an affected family member.

References

PMID: 20301458

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Interactions

Products	Interactant	Other Gene	Source	Pubs	Description
Q16595	P12814	ACTN1	HPRD	PubMed
Q16595	Q9NRD5	PICK1	HPRD	PubMed
Q16595	O75439	PMPCB	HPRD	PubMed
BioGRID:108677	BioGRID:114889	PMPCB	BioGRID	PubMed	Reconstituted Complex; Two-hybrid
BioGRID:108677	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS

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General gene information

Markers

D8S2279 (e-PCR)
- UniSTS:473907

D8S2282 (e-PCR)
- UniSTS:473910

D11S3663 (e-PCR)
- UniSTS:152897

WI-17089 (e-PCR)
- UniSTS:78439

D1S1425 (e-PCR)
- UniSTS:149621

G35510 (e-PCR)
- UniSTS:44150

D11S3114 (e-PCR)
- UniSTS:152207

L17971 (e-PCR)
- UniSTS:43966

RH93216 (e-PCR)
- UniSTS:91898

Genotypes

See FXN SNP Geneview Report
See FXN SNP Genotype Report
See FXN SNP Variation Viewer Report

Related pseudogene(s)

2 found Review record(s) in Gene

Homology

Homologs of the FXN gene: The FXN gene is conserved in chimpanzee, , dog, cow, mouse, rat, chicken, zebrafish, S.pombe, A.thaliana, and rice.
Map Viewer (Mouse, Rat)

Pathways from BioSystems

HIF-2-alpha transcription factor network, organism-specific biosystem (from Pathway Interaction Database)
HIF-2-alpha transcription factor network, organism-specific biosystem
HIF-2-alpha transcription factor network
Metabolism of proteins, organism-specific biosystem (from REACTOME)
Metabolism of proteins, organism-specific biosystemProtein metabolism comprises the pathways of translation, post-translational modification and protein folding.
Mitochondrial Protein Import, organism-specific biosystem (from REACTOME)
Mitochondrial Protein Import, organism-specific biosystemA human mitochondrion contains about 1500 proteins, more than 99% of which are encoded in the nucleus, synthesized in the cytosol and imported into the mitochondrion. Proteins are targeted to four lo...

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
2 iron, 2 sulfur cluster binding	IDA Inferred from Direct Assay more info	PubMed
enzyme binding	IEA Inferred from Electronic Annotation more info
ferric iron binding	IDA Inferred from Direct Assay more info	PubMed
ferrous iron binding	IDA Inferred from Direct Assay more info	PubMed
ferroxidase activity	IDA Inferred from Direct Assay more info	PubMed
iron chaperone activity	IDA Inferred from Direct Assay more info	PubMed
iron-sulfur cluster binding	IDA Inferred from Direct Assay more info	PubMed
metal ion binding	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
adult walking behavior	IEA Inferred from Electronic Annotation more info
aerobic respiration	IEA Inferred from Electronic Annotation more info
cellular iron ion homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
cellular response to hydrogen peroxide	IDA Inferred from Direct Assay more info	PubMed
embryo development ending in birth or egg hatching	IEA Inferred from Electronic Annotation more info
heme biosynthetic process	NAS Non-traceable Author Statement more info	PubMed
ion transport	IEA Inferred from Electronic Annotation more info
iron incorporation into metallo-sulfur cluster	IDA Inferred from Direct Assay more info	PubMed
mitochondrion organization	IEA Inferred from Electronic Annotation more info
negative regulation of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of multicellular organism growth	IEA Inferred from Electronic Annotation more info
negative regulation of organ growth	IEA Inferred from Electronic Annotation more info
negative regulation of release of cytochrome c from mitochondria	IMP Inferred from Mutant Phenotype more info	PubMed
oxidative phosphorylation	IEA Inferred from Electronic Annotation more info
positive regulation of axon extension	IEA Inferred from Electronic Annotation more info
positive regulation of cell growth	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of lyase activity	IDA Inferred from Direct Assay more info
positive regulation of lyase activity	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of metalloenzyme activity	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of oxidoreductase activity	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of transferase activity	IMP Inferred from Mutant Phenotype more info	PubMed
proprioception	IEA Inferred from Electronic Annotation more info
protein autoprocessing	IDA Inferred from Direct Assay more info	PubMed
regulation of ferrochelatase activity	IDA Inferred from Direct Assay more info	PubMed
response to drug	IEA Inferred from Electronic Annotation more info
response to iron ion	IMP Inferred from Mutant Phenotype more info	PubMed
response to organic cyclic compound	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
cytoplasm	IEA Inferred from Electronic Annotation more info
cytosol	IDA Inferred from Direct Assay more info	PubMed
mitochondrial matrix	ISS Inferred from Sequence or Structural Similarity more info
mitochondrial matrix	NAS Non-traceable Author Statement more info	PubMed
mitochondrion	IDA Inferred from Direct Assay more info	PubMed

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General protein information

Preferred Names: frataxin, mitochondrial

Names: frataxin, mitochondrial; Friedreich ataxia protein

NP_000135.2

EC 1.16.3.1

NP_001155178.1

EC 1.16.3.1

NP_852090.1

EC 1.16.3.1

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NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_008845.2 RefSeqGene

Range

5001..69616

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000144.4 → NP_000135.2 frataxin, mitochondrial isoform 1 preproprotein

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1).

Source sequence(s)

AL162730, BC023633, U43747

Consensus CDS

CCDS6626.1

UniProtKB/Swiss-Prot

Q16595

Related

ENSP00000366482, OTTHUMP00000021428, ENST00000377270, OTTHUMT00000052568

Conserved Domains (1) summary

cd00503
Location:90 – 183
Blast Score: 301

Frataxin; Frataxin is a nuclear-encoded mitochondrial protein implicated in Friedreich's ataxia (FRDA), an human autosomal recessive neurodegenerative disease; Frataxin is found in eukaryotes and in purple bacteria; lack of frataxin causes iron to accumulate in ...
NM_001161706.1 → NP_001155178.1 frataxin, mitochondrial isoform 3 preproprotein

Status: REVIEWED

Description

Transcript Variant: Transcript Variant: This variant (3) uses an alternate exon in the 3' coding region, compared to variant 1, that results in a frameshift. It encodes isoform 3, which has a shorter and distinct C-terminus, compared to isoform 1.

Source sequence(s)

AL162730

Consensus CDS

CCDS55313.1

UniProtKB/Swiss-Prot

Q16595

Related

ENSP00000379650, ENST00000396364

Conserved Domains (1) summary

cl00238
Location:90 – 160
Blast Score: 226

Frataxin; Frataxin is a nuclear-encoded mitochondrial protein implicated in Friedreich's ataxia (FRDA), an human autosomal recessive neurodegenerative disease; Frataxin is found in eukaryotes and in purple bacteria; lack of frataxin causes iron to accumulate in ...
NM_181425.2 → NP_852090.1 frataxin, mitochondrial isoform 2 preproprotein

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate splice site in the 3' coding region, compared to variant 1, that results in a frameshift. It encodes isoform 2, which has a shorter and distinct C-terminus, compared to isoform 1.

Source sequence(s)

AA232366, AL162730, BC023633, BF058880

Consensus CDS

CCDS43834.1

UniProtKB/TrEMBL

A8MXJ6

UniProtKB/Swiss-Prot

Q16595

Related

ENSP00000379652, OTTHUMP00000215689, ENST00000396366, OTTHUMT00000355969

Conserved Domains (1) summary

cl00238
Location:90 – 160
Blast Score: 235

Frataxin; Frataxin is a nuclear-encoded mitochondrial protein implicated in Friedreich's ataxia (FRDA), an human autosomal recessive neurodegenerative disease; Frataxin is found in eukaryotes and in purple bacteria; lack of frataxin causes iron to accumulate in ...

RefSeqs of Annotated Genomes: Build 37.3

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000009.11 Reference GRCh37.p5 Primary Assembly

Range

71650479..71715094

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000141.1 Alternate HuRef

Range

41495732..41559839

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AF028240.1	AAB84047.1
genomic	AL162730.26	CAH71829.1
genomic	CH471089.1	EAW62473.1
		EAW62474.1
genomic	U43752.1	AAA98508.1
genomic	U43753.1	AAA98509.1
genomic	U93173.1	AAD00734.1
genomic	U93174.1	AAD00735.1
genomic	U93175.1	AAD00736.1
genomic	Y13751.1	CAA74077.1
mRNA	AA232366.1	None
mRNA	AI951739.1	None
mRNA	AK308620.1	None
mRNA	BC023633.2	AAH23633.1
mRNA	BC048097.1	AAH48097.1
mRNA	BF058880.1	None
mRNA	U43747.1	AAA98510.1
other-genetic	HQ447980.1	ADQ32463.1