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Aliases for AIFM1 Gene

Aliases for AIFM1 Gene

  • Apoptosis Inducing Factor, Mitochondria Associated 1 2 3 5
  • Apoptosis-Inducing Factor, Mitochondrion-Associated, 1 2 3
  • Programmed Cell Death 8 (Apoptosis-Inducing Factor) 2 3
  • PDCD8 3 4
  • AIF 3 4
  • Neuropathy, Axonal, Motor-Sensory With Deafness And Mental Retardation (Cowchock Syndrome) 2
  • Striatal Apoptosis-Inducing Factor 3
  • Testicular Secretory Protein Li 4 3
  • Programmed Cell Death Protein 8 4
  • EC 1.1.1.- 4
  • COXPD6 3
  • CMT2D 3
  • CMTX4 3
  • COWCK 3
  • DFNX5 3
  • NADMR 3
  • NAMSD 3

External Ids for AIFM1 Gene

Previous HGNC Symbols for AIFM1 Gene

  • PDCD8
  • NAMSD

Previous GeneCards Identifiers for AIFM1 Gene

  • GC0XM129092
  • GC0XM129263
  • GC0XM118659

Summaries for AIFM1 Gene

Entrez Gene Summary for AIFM1 Gene

  • This gene encodes a flavoprotein essential for nuclear disassembly in apoptotic cells, and it is found in the mitochondrial intermembrane space in healthy cells. Induction of apoptosis results in the translocation of this protein to the nucleus where it affects chromosome condensation and fragmentation. In addition, this gene product induces mitochondria to release the apoptogenic proteins cytochrome c and caspase-9. Mutations in this gene cause combined oxidative phosphorylation deficiency 6 (COXPD6), a severe mitochondrial encephalomyopathy, as well as Cowchock syndrome, also known as X-linked recessive Charcot-Marie-Tooth disease-4 (CMTX-4), a disorder resulting in neuropathy, and axonal and motor-sensory defects with deafness and mental retardation. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 10. [provided by RefSeq, Aug 2015]

GeneCards Summary for AIFM1 Gene

AIFM1 (Apoptosis Inducing Factor, Mitochondria Associated 1) is a Protein Coding gene. Diseases associated with AIFM1 include Combined Oxidative Phosphorylation Deficiency 6 and Cowchock Syndrome. Among its related pathways are AIF Pathway and Ceramide signaling pathway. GO annotations related to this gene include oxidoreductase activity and electron carrier activity. An important paralog of this gene is AIFM3.

UniProtKB/Swiss-Prot for AIFM1 Gene

  • Functions both as NADH oxidoreductase and as regulator of apoptosis. In response to apoptotic stimuli, it is released from the mitochondrion intermembrane space into the cytosol and to the nucleus, where it functions as a proapoptotic factor in a caspase-independent pathway. In contrast, functions as an antiapoptotic factor in normal mitochondria via its NADH oxidoreductase activity. The soluble form (AIFsol) found in the nucleus induces parthanatos i.e. caspase-independent fragmentation of chromosomal DNA. Interacts with EIF3G,and thereby inhibits the EIF3 machinery and protein synthesis, and activates casapse-7 to amplify apoptosis. Plays a critical role in caspase-independent, pyknotic cell death in hydrogen peroxide-exposed cells. Binds to DNA in a sequence-independent manner.

Gene Wiki entry for AIFM1 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for AIFM1 Gene

Genomics for AIFM1 Gene

Regulatory Elements for AIFM1 Gene

Enhancers for AIFM1 Gene
GeneHancer Identifier Score Enhancer Sources TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Other Gene Targets for Enhancer

Enhancers around AIFM1 on UCSC Golden Path with GeneCards custom track

Promoters for AIFM1 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around AIFM1 on UCSC Golden Path with GeneCards custom track

Transcription factor binding sites by QIAGEN in the AIFM1 gene promoter:

Genomic Location for AIFM1 Gene

Chromosome:
X
Start:
130,129,362 bp from pter
End:
130,165,887 bp from pter
Size:
36,526 bases
Orientation:
Minus strand

Genomic View for AIFM1 Gene

Genes around AIFM1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
AIFM1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for AIFM1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for AIFM1 Gene

Proteins for AIFM1 Gene

  • Protein details for AIFM1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O95831-AIFM1_HUMAN
    Recommended name:
    Apoptosis-inducing factor 1, mitochondrial
    Protein Accession:
    O95831
    Secondary Accessions:
    • A4QPB4
    • B1ALN1
    • B2RB08
    • D3DTE9
    • Q1L6K4
    • Q1L6K6
    • Q2QKE4
    • Q5JUZ7
    • Q6I9X6
    • Q9Y3I3
    • Q9Y3I4

    Protein attributes for AIFM1 Gene

    Size:
    613 amino acids
    Molecular mass:
    66901 Da
    Cofactor:
    Name=FAD; Xref=ChEBI:CHEBI:57692;
    Quaternary structure:
    • Monomer (oxidized form). Homodimer (reduced form). Also dimerizes with isoform 3 preventing its release from mitochondria. Interacts with XIAP/BIRC4. Interacts (via N-terminus) with EIF3G (via C-terminus). Interacts with PRELID1.

    Three dimensional structures from OCA and Proteopedia for AIFM1 Gene

    Alternative splice isoforms for AIFM1 Gene

neXtProt entry for AIFM1 Gene

Proteomics data for AIFM1 Gene at MOPED

Post-translational modifications for AIFM1 Gene

  • Ubiquitination by XIAP/BIRC4 does not lead to proteasomal degradation. Ubiquitination at Lys-255 by XIAP/BIRC4 blocks its ability to bind DNA and induce chromatin degradation, thereby inhibiting its ability to induce cell death.
  • Under normal conditions, a 54-residue N-terminal segment is first proteolytically removed during or just after translocation into the mitochondrial intermembrane space (IMS) by the mitochondrial processing peptidase (MPP) to form the inner-membrane-anchored mature form (AIFmit). During apoptosis, it is further proteolytically processed at amino-acid position 101 leading to the generation of the mature form, which is confined to the mitochondrial IMS in a soluble form (AIFsol). AIFsol is released to the cytoplasm in response to specific death signals, and translocated to the nucleus, where it induces nuclear apoptosis in a caspase-independent manner.
  • Ubiquitination at Lys 109, Lys 189, and Lys 255
  • Modification sites at PhosphoSitePlus

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for AIFM1 (PDCD8)

No data available for DME Specific Peptides for AIFM1 Gene

Domains & Families for AIFM1 Gene

Suggested Antigen Peptide Sequences for AIFM1 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

O95831

UniProtKB/Swiss-Prot:

AIFM1_HUMAN :
  • Belongs to the FAD-dependent oxidoreductase family.
Family:
  • Belongs to the FAD-dependent oxidoreductase family.
genes like me logo Genes that share domains with AIFM1: view

No data available for Gene Families for AIFM1 Gene

Function for AIFM1 Gene

Molecular function for AIFM1 Gene

UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=1.53 mM for NADH {ECO:0000269 PubMed:23217327}; KM=26 uM for cytochrome c {ECO:0000269 PubMed:23217327};
UniProtKB/Swiss-Prot Function:
Functions both as NADH oxidoreductase and as regulator of apoptosis. In response to apoptotic stimuli, it is released from the mitochondrion intermembrane space into the cytosol and to the nucleus, where it functions as a proapoptotic factor in a caspase-independent pathway. In contrast, functions as an antiapoptotic factor in normal mitochondria via its NADH oxidoreductase activity. The soluble form (AIFsol) found in the nucleus induces parthanatos i.e. caspase-independent fragmentation of chromosomal DNA. Interacts with EIF3G,and thereby inhibits the EIF3 machinery and protein synthesis, and activates casapse-7 to amplify apoptosis. Plays a critical role in caspase-independent, pyknotic cell death in hydrogen peroxide-exposed cells. Binds to DNA in a sequence-independent manner.

Enzyme Numbers (IUBMB) for AIFM1 Gene

Gene Ontology (GO) - Molecular Function for AIFM1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0016174 NAD(P)H oxidase activity TAS 18309324
GO:0050660 flavin adenine dinucleotide binding IEA --
GO:0071949 FAD binding IEA --
genes like me logo Genes that share ontologies with AIFM1: view
genes like me logo Genes that share phenotypes with AIFM1: view

Human Phenotype Ontology for AIFM1 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for AIFM1 Gene

MGI Knock Outs for AIFM1:

Animal Model Products

CRISPR Products

miRNA for AIFM1 Gene

No data available for Transcription Factor Targets and HOMER Transcription for AIFM1 Gene

Localization for AIFM1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for AIFM1 Gene

Mitochondrion intermembrane space. Mitochondrion inner membrane. Cytoplasm. Nucleus. Cytoplasm, perinuclear region. Note=Proteolytic cleavage during or just after translocation into the mitochondrial intermembrane space (IMS) results in the formation of an inner-membrane-anchored mature form (AIFmit). During apoptosis, further proteolytic processing leads to a mature form, which is confined to the mitochondrial IMS in a soluble form (AIFsol). AIFsol is released to the cytoplasm in response to specific death signals, and translocated to the nucleus, where it induces nuclear apoptosis. Colocalizes with EIF3G in the nucleus and perinuclear region.
Isoform 3: Mitochondrion intermembrane space. Mitochondrion inner membrane. Note=Has a stronger membrane anchorage than isoform 1.
Isoform 5: Cytoplasm.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for AIFM1 Gene COMPARTMENTS Subcellular localization image for AIFM1 gene
Compartment Confidence
cytosol 5
mitochondrion 5
nucleus 5
endoplasmic reticulum 2
extracellular 2
vacuole 2
cytoskeleton 1
golgi apparatus 1
lysosome 1
peroxisome 1
plasma membrane 1

Gene Ontology (GO) - Cellular Components for AIFM1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IEA --
genes like me logo Genes that share ontologies with AIFM1: view

Pathways & Interactions for AIFM1 Gene

genes like me logo Genes that share pathways with AIFM1: view

Pathways by source for AIFM1 Gene

1 GeneTex pathway for AIFM1 Gene
1 Cell Signaling Technology pathway for AIFM1 Gene
2 BioSystems pathways for AIFM1 Gene
1 KEGG pathway for AIFM1 Gene
1 GeneGo (Thomson Reuters) pathway for AIFM1 Gene
1 R&D Systems pathway for AIFM1 Gene

SIGNOR curated interactions for AIFM1 Gene

Activates:
Is activated by:

Gene Ontology (GO) - Biological Process for AIFM1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002931 response to ischemia IEA --
GO:0010942 positive regulation of cell death IEA --
GO:0032981 mitochondrial respiratory chain complex I assembly IMP 20111043
GO:0045454 cell redox homeostasis IEA --
GO:0051402 neuron apoptotic process IEA --
genes like me logo Genes that share ontologies with AIFM1: view

Drugs & Compounds for AIFM1 Gene

(34) Drugs for AIFM1 Gene - From: DrugBank, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
FAD Approved Pharma Target 0
MCC Investigational Pharma Target 0

(27) Additional Compounds for AIFM1 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with AIFM1: view

Transcripts for AIFM1 Gene

Unigene Clusters for AIFM1 Gene

Apoptosis-inducing factor, mitochondrion-associated, 1:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for AIFM1 Gene

ExUns: 1a · 1b · 1c · 1d ^ 2 ^ 3 ^ 4a · 4b ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17
SP1: -
SP2: -
SP3: - - - - - - - - - -
SP4:

Relevant External Links for AIFM1 Gene

GeneLoc Exon Structure for
AIFM1
ECgene alternative splicing isoforms for
AIFM1

Expression for AIFM1 Gene

mRNA expression in normal human tissues for AIFM1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for AIFM1 Gene

This gene is overexpressed in Heart - Left Ventricle (x4.6) and Kidney - Cortex (x4.0).

Protein differential expression in normal tissues from HIPED for AIFM1 Gene

This gene is overexpressed in Liver, secretome (10.7), Heart (8.8), and Kidney (6.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MOPED, and MaxQB for AIFM1 Gene



SOURCE GeneReport for Unigene cluster for AIFM1 Gene Hs.424932

mRNA Expression by UniProt/SwissProt for AIFM1 Gene

O95831-AIFM1_HUMAN
Tissue specificity: Detected in muscle and skin fibroblasts (at protein level). Isoform 5 is frequently down-regulated in human cancers.
genes like me logo Genes that share expression patterns with AIFM1: view

Protein tissue co-expression partners for AIFM1 Gene

- Elite partner

Primer Products

Orthologs for AIFM1 Gene

This gene was present in the common ancestor of animals.

Orthologs for AIFM1 Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia AIFM1 35
  • 92.55 (n)
  • 94.13 (a)
AIFM1 36
  • 94 (a)
OneToOne
dog
(Canis familiaris)
Mammalia AIFM1 35
  • 93.26 (n)
  • 94.29 (a)
AIFM1 36
  • 94 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Aifm1 35
  • 90.69 (n)
  • 92.32 (a)
Aifm1 16
Aifm1 36
  • 92 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia AIFM1 35
  • 93.83 (n)
  • 92.62 (a)
AIFM1 36
  • 98 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Aifm1 35
  • 90.63 (n)
  • 92.65 (a)
oppossum
(Monodelphis domestica)
Mammalia AIFM1 36
  • 83 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia AIFM1 36
  • 44 (a)
OneToOne
chicken
(Gallus gallus)
Aves AIFM1 35
  • 71.99 (n)
  • 78.61 (a)
AIFM1 36
  • 77 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia AIFM1 36
  • 77 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia aifm1 35
  • 65.71 (n)
  • 73.25 (a)
Str.9724 35
zebrafish
(Danio rerio)
Actinopterygii aifm1 35
  • 67.17 (n)
  • 73.24 (a)
pdcd8 35
aifm1 36
  • 57 (a)
OneToOne
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.9123 35
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP008044 35
  • 56.78 (n)
  • 54.98 (a)
fruit fly
(Drosophila melanogaster)
Insecta AIF 35
  • 54.55 (n)
  • 51.28 (a)
AIF 36
  • 35 (a)
OneToOne
worm
(Caenorhabditis elegans)
Secernentea wah-1 35
  • 48.99 (n)
  • 40.91 (a)
wah-1 36
  • 29 (a)
OneToOne
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.5219 35
sea squirt
(Ciona savignyi)
Ascidiacea CSA.9420 36
  • 51 (a)
OneToOne
Species with no ortholog for AIFM1:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for AIFM1 Gene

ENSEMBL:
Gene Tree for AIFM1 (if available)
TreeFam:
Gene Tree for AIFM1 (if available)

Paralogs for AIFM1 Gene

Paralogs for AIFM1 Gene

Pseudogenes.org Pseudogenes for AIFM1 Gene

genes like me logo Genes that share paralogs with AIFM1: view

Variants for AIFM1 Gene

Sequence variations from dbSNP and Humsavar for AIFM1 Gene

SNP ID Clin Chr 0X pos Sequence Context AA Info Type
VAR_067334 Combined oxidative phosphorylation deficiency 6 (COXPD6)
VAR_069468 Cowchock syndrome (COWCK)
VAR_072791 -
rs747700217 -- 130,151,439(+) CGGCC(A/C)CATAA intron-variant
rs747762886 -- 130,138,915(+) TTGTC(C/T)CTATC intron-variant, upstream-variant-2KB

Structural Variations from Database of Genomic Variants (DGV) for AIFM1 Gene

Variant ID Type Subtype PubMed ID
nsv528290 CNV Gain 19592680

Variation tolerance for AIFM1 Gene

Residual Variation Intolerance Score: 32.5% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.10; 22.40% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for AIFM1 Gene

Human Gene Mutation Database (HGMD)
AIFM1

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for AIFM1 Gene

Disorders for AIFM1 Gene

MalaCards: The human disease database

(17) MalaCards diseases for AIFM1 Gene - From: OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
combined oxidative phosphorylation deficiency 6
  • coxpd6
cowchock syndrome
  • cowck
deafness, x-linked 5
  • deafness, x-linked, 5
severe x-linked mitochondrial encephalomyopathy
  • mitochondrial encephalomyopathy due to coxpd6
x-linked charcot-marie-tooth disease type 4
  • cowchock syndrome
- elite association - COSMIC cancer census association via MalaCards
Search AIFM1 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

AIFM1_HUMAN
  • Combined oxidative phosphorylation deficiency 6 (COXPD6) [MIM:300816]: A mitochondrial disease resulting in a neurodegenerative disorder characterized by psychomotor delay, hypotonia, areflexia, muscle weakness and wasting. Some patients manifest prenatal ventriculomegaly and severe postnatal encephalomyopathy. {ECO:0000269 PubMed:20362274, ECO:0000269 PubMed:22019070}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Cowchock syndrome (COWCK) [MIM:310490]: An X-linked recessive neuromuscular disorder characterized by early childhood onset of a slowly progressive axonal sensorimotor neuropathy associated in some patients with sensorineural deafness and cognitive impairment. {ECO:0000269 PubMed:23217327}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for AIFM1

Genetic Association Database (GAD)
AIFM1
Human Genome Epidemiology (HuGE) Navigator
AIFM1
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
AIFM1
genes like me logo Genes that share disorders with AIFM1: view

No data available for Genatlas for AIFM1 Gene

Publications for AIFM1 Gene

  1. Molecular characterization of mitochondrial apoptosis-inducing factor. (PMID: 9989411) Susin S.A. … Kroemer G. (Nature 1999) 2 3 4 23 67
  2. Cowchock syndrome is associated with a mutation in apoptosis-inducing factor. (PMID: 23217327) Rinaldi C. … Fischbeck K.H. (Am. J. Hum. Genet. 2012) 2 3
  3. Poly(ADP-ribose) polymerase (PARP)-1-independent apoptosis-inducing factor (AIF) release and cell death are induced by eleostearic acid and blocked by alpha-tocopherol and MEK inhibition. (PMID: 20177052) Kondo K. … Teshima R. (J. Biol. Chem. 2010) 3 23
  4. Severe X-linked mitochondrial encephalomyopathy associated with a mutation in apoptosis-inducing factor. (PMID: 20362274) Ghezzi D. … Zeviani M. (Am. J. Hum. Genet. 2010) 3 23
  5. [Apoptosis inducing factor mediates cisplatin-induced apoptosis of renal tubular epithelial cells]. (PMID: 20450583) Liu Y. … Guo M.Y. (Zhonghua Zhong Liu Za Zhi 2010) 3 23

Products for AIFM1 Gene

Sources for AIFM1 Gene

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