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AIFM1 apoptosis inducing factor mitochondria associated 1 [ Homo sapiens (human) ]

Gene ID: 9131, updated on 5-Mar-2024

Summary

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Official Symbol
AIFM1provided by HGNC
Official Full Name
apoptosis inducing factor mitochondria associated 1provided by HGNC
Primary source
HGNC:HGNC:8768
See related
Ensembl:ENSG00000156709 MIM:300169; AllianceGenome:HGNC:8768
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
AIF; AUNX1; CMT2D; CMTX4; COWCK; DFNX5; NADMR; NAMSD; PDCD8; COXPD6; SEMDHL
Summary
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 cognitive disability. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 10. [provided by RefSeq, Aug 2015]
Expression
Broad expression in kidney (RPKM 48.3), heart (RPKM 22.2) and 24 other tissues See more
Orthologs
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Genomic context

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Location:
Xq26.1
Exon count:
18
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) X NC_000023.11 (130129362..130165841, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) X NC_060947.1 (128448167..128484647, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) X NC_000023.10 (129263337..129299815, complement)

Chromosome X - NC_000023.11Genomic Context describing neighboring genes Neighboring gene BCL6 corepressor like 1 Neighboring gene uncharacterized LOC124905216 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29932 Neighboring gene H3K4me1 hESC enhancer GRCh37_chrX:129159157-129159656 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20986 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20987 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20988 Neighboring gene Sharpr-MPRA regulatory region 15346 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29934 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29933 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29935 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29936 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29937 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20989 Neighboring gene E74 like ETS transcription factor 4 Neighboring gene Sharpr-MPRA regulatory region 9263 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20994 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20993 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20992 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20991 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20990 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29938 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20995 Neighboring gene ReSE screen-validated silencer GRCh37_chrX:129255011-129255220 Neighboring gene RAB33A, member RAS oncogene family Neighboring gene MED14-independent group 3 enhancer GRCh37_chrX:129280263-129281462 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29939 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29940 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20996 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20997 Neighboring gene H3K4me1 hESC enhancer GRCh37_chrX:129305519-129306473 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29941 Neighboring gene zinc finger protein 280C Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20998 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chrX:129413936-129414929 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chrX:129414930-129415922 Neighboring gene RNA, U6 small nuclear 1130, pseudogene

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Deep Brain Stimulation for the Management of AIFM1-Related Disabling Tremor: A Case Series. Tunyi J, et al. Pediatr Neurol, 2023 May. PMID 36907087
  2. AIFM1 variants associated with auditory neuropathy spectrum disorder cause apoptosis due to impaired apoptosis-inducing factor dimerization. Qiu Y, et al. J Zhejiang Univ Sci B, 2023 Feb 15. PMID 36751702, Free PMC Article
  3. Staurosporine-induced cleavage of apoptosis-inducing factor in human fibrosarcoma cells is independent of matrix metalloproteinase-2. Bassiouni W, et al. Can J Physiol Pharmacol, 2022 Feb. PMID 34597523
  4. Severe multisystem pathology, metabolic acidosis, mitochondrial dysfunction, and early death associated with an X-linked AIFM1 variant. Moss T, et al. Cold Spring Harb Mol Case Stud, 2021 Jun. PMID 34117073, Free PMC Article
  5. W196 and the β-Hairpin Motif Modulate the Redox Switch of Conformation and the Biomolecular Interaction Network of the Apoptosis-Inducing Factor. Romero-Tamayo S, et al. Oxid Med Cell Longev, 2021. PMID 33510840, Free PMC Article

See all (403) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. NADH improves AIF dimerization and inhibits apoptosis in iPSCs-derived neurons from patients with auditory neuropathy spectrum disorder.
    Title: NADH improves AIF dimerization and inhibits apoptosis in iPSCs-derived neurons from patients with auditory neuropathy spectrum disorder.
  2. Newly synthesized AIFM1 determines the hypersensitivity of T lymphocytes to STING activation-induced cell apoptosis.
    Title: Newly synthesized AIFM1 determines the hypersensitivity of T lymphocytes to STING activation-induced cell apoptosis.
  3. Impaired AIF-CHCHD4 interaction and mitochondrial calcium overload contribute to auditory neuropathy spectrum disorder in patient-iPSC-derived neurons with AIFM1 variant.
    Title: Impaired AIF-CHCHD4 interaction and mitochondrial calcium overload contribute to auditory neuropathy spectrum disorder in patient-iPSC-derived neurons with AIFM1 variant.
  4. Deep Brain Stimulation for the Management of AIFM1-Related Disabling Tremor: A Case Series.
    Title: Deep Brain Stimulation for the Management of AIFM1-Related Disabling Tremor: A Case Series.
  5. AIFM1 variants associated with auditory neuropathy spectrum disorder cause apoptosis due to impaired apoptosis-inducing factor dimerization.
    Title: AIFM1 variants associated with auditory neuropathy spectrum disorder cause apoptosis due to impaired apoptosis-inducing factor dimerization.
  6. AIFM1 is a component of the mitochondrial disulfide relay that drives complex I assembly through efficient import of NDUFS5.
    Title: AIFM1 is a component of the mitochondrial disulfide relay that drives complex I assembly through efficient import of NDUFS5.
  7. REDD1 interacts with AIF and regulates mitochondrial reactive oxygen species generation in the keratinocyte response to UVB.
    Title: REDD1 interacts with AIF and regulates mitochondrial reactive oxygen species generation in the keratinocyte response to UVB.
  8. Cyclophosphamide-induced GPX4 degradation triggers parthanatos by activating AIFM1.
    Title: Cyclophosphamide-induced GPX4 degradation triggers parthanatos by activating AIFM1.
  9. Silencing ESRP1 expression promotes caspase-independent cell death via nuclear translocation of AIF in colon cancer cells.
    Title: Silencing ESRP1 expression promotes caspase-independent cell death via nuclear translocation of AIF in colon cancer cells.
  10. Staurosporine-induced cleavage of apoptosis-inducing factor in human fibrosarcoma cells is independent of matrix metalloproteinase-2.
    Title: Staurosporine-induced cleavage of apoptosis-inducing factor in human fibrosarcoma cells is independent of matrix metalloproteinase-2.
Submit: New GeneRIF Correction See all GeneRIFs (135)

Phenotypes

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

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env Tandem affinity purification and mass spectrometry analysis identify mitochondrion-associated apoptosis-inducing factor 1 (AIFM1), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells PubMed
env Apoptosis induced by HIV-1 gp120/gp41 is involved in the translocation of cytochrome c and apoptosis-inducing factor (AIF) from mitochondria to an extra-mitochondrial localization and in the dissipation of the mitochondrial transmembrane potential PubMed
Gag-Pol gag-pol Tandem affinity purification and mass spectrometry analysis identify mitochondrion-associated apoptosis-inducing factor 1 (AIFM1), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells PubMed
Nef nef Tandem affinity purification and mass spectrometry analysis identify mitochondrion-associated apoptosis-inducing factor 1 (AIFM1), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells PubMed
Pr55(Gag) gag Tandem affinity purification and mass spectrometry analysis identify mitochondrion-associated apoptosis-inducing factor 1 (AIFM1), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells PubMed
Vif vif HIV-1 Vif interacts with AIFM1 PubMed
Vpr vpr A stable-isotope labeling by amino acids in cell culture coupled with mass spectrometry-based proteomics identifies downregulation of apoptosis-inducing factor 1 (AIFM1, PDCD8, mitochondrial) expression by HIV-1 Vpr in Vpr transduced macrophages PubMed
vpr HIV-1 Vpr induces apoptosis through a caspase-independent mitochondrial pathway controlled by AIF PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • MGC111425

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables DNA binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables FAD binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables FAD binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables NAD(P)H oxidase H2O2-forming activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables NAD(P)H oxidase H2O2-forming activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables NAD(P)H oxidase H2O2-forming activity TAS
Traceable Author Statement
more info
 PubMed 
enables NADH dehydrogenase activity IEA
Inferred from Electronic Annotation
more info
  
enables oxidoreductase activity, acting on NAD(P)H IDA
Inferred from Direct Assay
more info
 PubMed 
enables poly-ADP-D-ribose binding ISS
Inferred from Sequence or Structural Similarity
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein dimerization activity IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
involved_in activation of cysteine-type endopeptidase activity involved in apoptotic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in apoptotic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in apoptotic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in cellular response to aldosterone IEA
Inferred from Electronic Annotation
more info
  
involved_in cellular response to estradiol stimulus IEA
Inferred from Electronic Annotation
more info
  
involved_in cellular response to hydrogen peroxide IEA
Inferred from Electronic Annotation
more info
  
involved_in cellular response to hypoxia IEA
Inferred from Electronic Annotation
more info
  
involved_in cellular response to nitric oxide IEA
Inferred from Electronic Annotation
more info
  
involved_in chromosome condensation TAS
Traceable Author Statement
more info
 PubMed 
involved_in intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in mitochondrial respiratory chain complex assembly IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in mitochondrial respiratory chain complex assembly IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in neuron apoptotic process IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of apoptotic process TAS
Traceable Author Statement
more info
 PubMed 
involved_in positive regulation of necroptotic process ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in positive regulation of neuron apoptotic process IEA
Inferred from Electronic Annotation
more info
  
involved_in protein import into mitochondrial intermembrane space IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of apoptotic DNA fragmentation IEA
Inferred from Electronic Annotation
more info
  
involved_in response to L-glutamate IEA
Inferred from Electronic Annotation
more info
  
involved_in response to ischemia IEA
Inferred from Electronic Annotation
more info
  
involved_in response to toxic substance IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytosol ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in mitochondrial inner membrane TAS
Traceable Author Statement
more info
 PubMed 
located_in mitochondrial intermembrane space IDA
Inferred from Direct Assay
more info
 PubMed 
located_in mitochondrion HDA PubMed 
is_active_in mitochondrion IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in mitochondrion IDA
Inferred from Direct Assay
more info
  
located_in nucleus IDA
Inferred from Direct Assay
more info
 PubMed 
located_in nucleus ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in perinuclear region of cytoplasm IEA
Inferred from Electronic Annotation
more info
  

General protein information

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Preferred Names
apoptosis-inducing factor 1, mitochondrial
Names
apoptosis-inducing factor, mitochondrion-associated, 1
auditory neuropathy, X-linked recessive 1
programmed cell death 8 (apoptosis-inducing factor)
striatal apoptosis-inducing factor
testicular secretory protein Li 4
NP_001124318.2
NP_001124319.1
NP_004199.1
NP_665811.1

NCBI Reference Sequences (RefSeq)

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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

  1. NG_013217.2 RefSeqGene

    Range
    5000..41479
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001130846.4 → NP_001124318.2  apoptosis-inducing factor 1, mitochondrial isoform AIFsh

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) lacks several 5' exons but contains an alternate 5' terminal exon, and it thus differs in the 5' UTR and initiates translation at a downstream in-frame start codon, compared to variant 1. The encoded isoform (AIFsh, also known as AIFshort) is shorter at the N-terminus, compared to isoform AIF. This variant can initiate translation at alternative start codons according to protein N-terminal sequencing and in vitro translation studies in PMID:16365034. The 5'-most start codon is represented in this RefSeq.
    Source sequence(s)
    AI521711, DQ016496
    Consensus CDS
    CCDS48166.2
    UniProtKB/TrEMBL
    A0A140VK04, E9PMA0
    Related
    ENSP00000431222.1, ENST00000460436.6
    Conserved Domains (2) summary
    pfam14721
    Location:126 → 254
    AIF_C; Apoptosis-inducing factor, mitochondrion-associated, C-term
    cl26177
    Location:1 → 123
    Pyr_redox_2; Pyridine nucleotide-disulphide oxidoreductase

  2. NM_001130847.4 → NP_001124319.1  apoptosis-inducing factor 1, mitochondrial isoform AIFsh2 precursor

    See identical proteins and their annotated locations for NP_001124319.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) contains an additional internal exon, which results in a distinct 3' coding region and differences in the 3' UTR, compared to variant 1. The encoded isoform (AIFsh2, also known as AIFshort2) has a distinct C-terminus and is shorter than isoform AIF.
    Source sequence(s)
    BC111065, DA624842, DQ016498
    Consensus CDS
    CCDS48167.1
    UniProtKB/Swiss-Prot
    O95831
    Related
    ENSP00000446113.2, ENST00000535724.6
    Conserved Domains (1) summary
    pfam07992
    Location:150 → 319
    Pyr_redox_2; Pyridine nucleotide-disulphide oxidoreductase

  3. NM_004208.4 → NP_004199.1  apoptosis-inducing factor 1, mitochondrial isoform AIF precursor

    See identical proteins and their annotated locations for NP_004199.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (AIF).
    Source sequence(s)
    BC111065, BC139738, DA624842
    Consensus CDS
    CCDS14618.1
    UniProtKB/Swiss-Prot
    A4QPB4, B1ALN1, B2RB08, D3DTE9, E9PRR0, O95831, Q1L6K4, Q1L6K6, Q2QKE4, Q5JUZ7, Q6I9X6, Q9Y3I3, Q9Y3I4
    UniProtKB/TrEMBL
    A0A6Q8PFM5, A0A6Q8PG15
    Related
    ENSP00000287295.3, ENST00000287295.8
    Conserved Domains (3) summary
    pfam07992
    Location:150 → 462
    Pyr_redox_2; Pyridine nucleotide-disulphide oxidoreductase
    pfam14721
    Location:465 → 593
    AIF_C; Apoptosis-inducing factor, mitochondrion-associated, C-term
    pfam14962
    Location:52 → 133
    AIF-MLS; Mitochondria localization Sequence

  4. NM_145812.3 → NP_665811.1  apoptosis-inducing factor 1, mitochondrial isoform AIF-exB precursor

    See identical proteins and their annotated locations for NP_665811.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an alternate in-frame exon but contains a different in-frame exon in the 5' coding region, compared to variant 1, resulting in an isoform (AIF-exB) that is shorter than isoform AIF.
    Source sequence(s)
    AK314446, BC111065, DA624842
    Consensus CDS
    CCDS14619.1
    UniProtKB/TrEMBL
    A0A6Q8PFM5, A0A6Q8PG15
    Related
    ENSP00000502184.1, ENST00000676229.1
    Conserved Domains (3) summary
    pfam07992
    Location:146 → 458
    Pyr_redox_2; Pyridine nucleotide-disulphide oxidoreductase
    pfam14721
    Location:461 → 589
    AIF_C; Apoptosis-inducing factor, mitochondrion-associated, C-term
    pfam14962
    Location:47 → 129
    AIF-MLS; Mitochondria localization Sequence

RNA

  1. NR_132647.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (6) lacks an alternate exon in the 5' region, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    AI521711, DA624842, DQ016500
    Related
    ENST00000527892.5

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000023.11 Reference GRCh38.p14 Primary Assembly

    Range
    130129362..130165841 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060947.1 Alternate T2T-CHM13v2.0

    Range
    128448167..128484647 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_145813.2: Suppressed sequence

    Description
    NM_145813.2: This RefSeq was removed because currently there is insufficient support for the transcript and the protein.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O95831.1 GenPept UniProtKB/Swiss-Prot:O95831

Gene LinkOut

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