AIFM1

Protein identityUniProt · HPA

UniProt accession

O95831

Gene

AIFM1

Ensembl

ENSG00000156709

Chromosome

X

Canonical length

613 aa

Protein class

Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins

Subcellular location

Mitochondria,Connecting piece

Quaternary structure

Homodimer

OverviewNCBI 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 cognitive disability. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 10. [provided by RefSeq, Aug 2015]

Canonical amino-acid sequenceUniProt

613 residues, UniProt reviewed canonical sequence.

>O95831|AIFM1
     1  MFRCGGLAAG ALKQKLVPLV RTVCVRSPRQ RNRLPGNLFQ RWHVPLELQM TRQMASSGAS
    61  GGKIDNSVLV LIVGLSTVGA GAYAYKTMKE DEKRYNERIS GLGLTPEQKQ KKAALSASEG
   121  EEVPQDKAPS HVPFLLIGGG TAAFAAARSI RARDPGARVL IVSEDPELPY MRPPLSKELW
   181  FSDDPNVTKT LRFKQWNGKE RSIYFQPPSF YVSAQDLPHI ENGGVAVLTG KKVVQLDVRD
   241  NMVKLNDGSQ ITYEKCLIAT GGTPRSLSAI DRAGAEVKSR TTLFRKIGDF RSLEKISREV
   301  KSITIIGGGF LGSELACALG RKARALGTEV IQLFPEKGNM GKILPEYLSN WTMEKVRREG
   361  VKVMPNAIVQ SVGVSSGKLL IKLKDGRKVE TDHIVAAVGL EPNVELAKTG GLEIDSDFGG
   421  FRVNAELQAR SNIWVAGDAA CFYDIKLGRR RVEHHDHAVV SGRLAGENMT GAAKPYWHQS
   481  MFWSDLGPDV GYEAIGLVDS SLPTVGVFAK ATAQDNPKSA TEQSGTGIRS ESETESEASE
   541  ITIPPSTPAV PQAPVQGEDY GKGVIFYLRD KVVVGIVLWN IFNRMPIARK IIKDGEQHED
   601  LNEVAKLFNI HED

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against AIFM1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Other membrane

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.3

Highest tissue expression

77 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about AIFM1.

Disease | AllUniProt

Conditions AIFM1 is implicated in, by any mechanism.

• Combined oxidative phosphorylation deficiency 6 (COXPD6) MIM:300816
• Charcot-Marie-Tooth disease, X-linked recessive, 4, with or without cerebellar ataxia (CMTX4) MIM:310490
• Deafness, X-linked, 5, with peripheral neuropathy (DFNX5) MIM:300614
• Spondyloepimetaphyseal dysplasia, X-linked, with hypomyelinating leukodystrophy (SEMDHL) MIM:300232

Disease | GeneticClinVar

47 pathogenic / likely-pathogenic of 777 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Deafness, X-linked 5
• Severe X-linked mitochondrial encephalomyopathy
• Combined oxidative phosphorylation deficiency
• Charcot-Marie-Tooth Neuropathy X
• Spondyloepimetaphyseal dysplasia, Bieganski type

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.23

gnomAD pLI

1

gnomAD missense Z

2.49

DepMap mean gene effect

-0.36

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• apoptotic process
• cellular response to aldosterone
• cellular response to estradiol stimulus
• cellular response to hydrogen peroxide
• cellular response to hypoxia
• cellular response to nitric oxide
• intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
• mitochondrial disulfide relay system
• mitochondrial respiratory chain complex assembly
• neuron differentiation
• positive regulation of apoptotic process
• positive regulation of necroptotic process
• positive regulation of neuron apoptotic process
• protein import into mitochondrial intermembrane space
• response to ischemia
• response to L-glutamate
• response to toxic substance

Molecular functions

• DNA binding
• FAD binding
• NAD(P)H oxidase H2O2-forming activity
• NADH dehydrogenase activity
• oxidoreductase activity, acting on NAD(P)H
• poly-ADP-D-ribose binding
• protein dimerization activity

Cellular components

• cytosol
• mitochondrial inner membrane
• mitochondrial intermembrane space
• mitochondrion
• nucleus
• perinuclear region of cytoplasm
• sperm head-tail coupling apparatus

Protein domainsUniProt · Pfam · InterPro

• FAD/NAD-linked reductase, dimerisation domain superfamily
• FAD/NAD(P)-binding domain
• FAD/NAD(P)-binding domain superfamily
• FAD-dependent Oxidoreductases and Apoptosis Regulators
• Pyridine nucleotide-disulphide oxidoreductase
• Mitochondrial apoptosis-inducing factor, C-terminal domain
• Apoptosis-inducing factor, mitochondrion-associated, C-term

KeywordsUniProt

• Acetylation
• Apoptosis
• Charcot-Marie-Tooth disease
• Cytoplasm
• Deafness
• DNA-binding
• Dwarfism
• FAD
• Flavoprotein
• Intellectual disability
• Isopeptide bond
• Membrane
• Mitochondrion
• Mitochondrion inner membrane
• NAD
• Neurodegeneration
• Neuropathy
• Nucleus
• Oxidoreductase
• Phosphoprotein
• Primary mitochondrial disease
• Transit peptide
• Ubl conjugation

InteractionsUniProt · HPA

Protein binding partners of AIFM1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CHCHD4
• PRELID1
• XIAP
• KANK2
• BAG6
• EIF3G
• MLF2
• TSC22D4