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

Summary

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: mouse all
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Genomic context

Location:: Xq26.1

Exon count:: 18

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	X	NC_000023.11 (130129362..130165841, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	X	NC_060947.1 (128448167..128484647, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	X	NC_000023.10 (129263337..129299815, complement)

Chromosome X - NC_000023.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

AIF translocation into nucleus caused by Aifm1 R450Q mutation: generation and characterization of a mouse model for AUNX1.
Title: AIF translocation into nucleus caused by Aifm1 R450Q mutation: generation and characterization of a mouse model for AUNX1.
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.
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.
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.
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.
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.
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.
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.
Cyclophosphamide-induced GPX4 degradation triggers parthanatos by activating AIFM1.
Title: Cyclophosphamide-induced GPX4 degradation triggers parthanatos by activating AIFM1.
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.

Submit: New GeneRIF Correction See all GeneRIFs (136)

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

Associated conditions

Description	Tests
Charcot-Marie-Tooth disease X-linked recessive 4 MedGen: C0795910 OMIM: 310490 GeneReviews: Charcot-Marie-Tooth Hereditary Neuropathy Overview	Compare labs
Deafness, X-linked 5 MedGen: C1845095 OMIM: 300614 GeneReviews: Not available	Compare labs
Severe X-linked mitochondrial encephalomyopathy MedGen: C3151753 OMIM: 300816 GeneReviews: Not available	Compare labs
Spondyloepimetaphyseal dysplasia, Bieganski type MedGen: C1846148 OMIM: 300232 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

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

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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

NoName (e-PCR)
- UniSTS:489761

STS-AA001364 (e-PCR)
- UniSTS:35186

RH80030 (e-PCR)
- UniSTS:87680

RH12533 (e-PCR)
- UniSTS:72334

DXS7034E (e-PCR)
- UniSTS:29141

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 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 I assembly	IMP Inferred from Mutant Phenotype more info	PubMed
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 neuron differentiation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of apoptotic process	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of cysteine-type endopeptidase activity	IDA Inferred from Direct Assay 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 mitochondrial intermembrane space	IMP Inferred from Mutant Phenotype more info	PubMed
located_in mitochondrion	HDA more info	PubMed
located_in mitochondrion	HTP more info	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

EC 1.1.1.-

NP_001124319.1

EC 1.1.1.-

NP_004199.1

EC 1.1.1.-

NP_665811.1

EC 1.1.1.-

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

NG_013217.2 RefSeqGene

Range

5000..41479

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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
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
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

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_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000023.11 Reference GRCh38.p14 Primary Assembly

Range

130129362..130165841 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

NC_060947.1 Alternate T2T-CHM13v2.0

Range

128448167..128484647 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

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.