LOCUS       NM_004208               2222 bp    mRNA    linear   PRI 26-FEB-2025
DEFINITION  Homo sapiens apoptosis inducing factor mitochondria associated 1
            (AIFM1), transcript variant 1, mRNA; nuclear gene for mitochondrial
            product.
ACCESSION   NM_004208
VERSION     NM_004208.4
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 2222)
  AUTHORS   Shi,T., Chen,Z., Li,J., Wang,H. and Wang,Q.
  TITLE     AIF translocation into nucleus caused by Aifm1 R450Q mutation:
            generation and characterization of a mouse model for AUNX1
  JOURNAL   Hum Mol Genet 33 (10), 905-918 (2024)
   PUBMED   38449065
  REMARK    GeneRIF: AIF translocation into nucleus caused by Aifm1 R450Q
            mutation: generation and characterization of a mouse model for
            AUNX1.
REFERENCE   2  (bases 1 to 2222)
  AUTHORS   Qiu,Y., Wang,H., Pan,H., Ding,X., Guan,J., Zhuang,Q., Wu,K.,
            Lei,Z., Cai,H., Dong,Y., Zhou,H., Lin,A., Wang,Q. and Yan,Q.
  TITLE     NADH improves AIF dimerization and inhibits apoptosis in
            iPSCs-derived neurons from patients with auditory neuropathy
            spectrum disorder
  JOURNAL   Hear Res 441, 108919 (2024)
   PUBMED   38043402
  REMARK    GeneRIF: NADH improves AIF dimerization and inhibits apoptosis in
            iPSCs-derived neurons from patients with auditory neuropathy
            spectrum disorder.
REFERENCE   3  (bases 1 to 2222)
  AUTHORS   Qiu,Y., Wang,H., Fan,M., Pan,H., Guan,J., Jiang,Y., Jia,Z., Wu,K.,
            Zhou,H., Zhuang,Q., Lei,Z., Ding,X., Cai,H., Dong,Y., Yan,L.,
            Lin,A., Fu,Y., Zhang,D., Yan,Q. and Wang,Q.
  TITLE     Impaired AIF-CHCHD4 interaction and mitochondrial calcium overload
            contribute to auditory neuropathy spectrum disorder in
            patient-iPSC-derived neurons with AIFM1 variant
  JOURNAL   Cell Death Dis 14 (6), 375 (2023)
   PUBMED   37365177
  REMARK    GeneRIF: Impaired AIF-CHCHD4 interaction and mitochondrial calcium
            overload contribute to auditory neuropathy spectrum disorder in
            patient-iPSC-derived neurons with AIFM1 variant.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 2222)
  AUTHORS   Ghezzi,D., Sevrioukova,I., Invernizzi,F., Lamperti,C., Mora,M.,
            D'Adamo,P., Novara,F., Zuffardi,O., Uziel,G. and Zeviani,M.
  TITLE     Severe X-linked mitochondrial encephalomyopathy associated with a
            mutation in apoptosis-inducing factor
  JOURNAL   Am J Hum Genet 86 (4), 639-649 (2010)
   PUBMED   20362274
  REMARK    GeneRIF: AIFM1 mutation is associated with severe X-linked
            mitochondrial encephalomyopathy.
REFERENCE   5  (bases 1 to 2222)
  AUTHORS   Delettre,C., Yuste,V.J., Moubarak,R.S., Bras,M., Robert,N. and
            Susin,S.A.
  TITLE     Identification and characterization of AIFsh2, a mitochondrial
            apoptosis-inducing factor (AIF) isoform with NADH oxidase activity
  JOURNAL   J Biol Chem 281 (27), 18507-18518 (2006)
   PUBMED   16644725
  REMARK    GeneRIF: the cloning and the biochemical characterization of a new
            isoform named AIF short 2 (AIFsh2)
REFERENCE   6  (bases 1 to 2222)
  AUTHORS   Delettre,C., Yuste,V.J., Moubarak,R.S., Bras,M.,
            Lesbordes-Brion,J.C., Petres,S., Bellalou,J. and Susin,S.A.
  TITLE     AIFsh, a novel apoptosis-inducing factor (AIF) pro-apoptotic
            isoform with potential pathological relevance in human cancer
  JOURNAL   J Biol Chem 281 (10), 6413-6427 (2006)
   PUBMED   16365034
  REMARK    GeneRIF: AIF short (AIFsh), a new pro-apoptotic isoform of AIF,
            reveals that the first N-terminal 352 amino acids of AIF are not
            required for its apoptotic activity.
REFERENCE   7  (bases 1 to 2222)
  AUTHORS   Otera,H., Ohsakaya,S., Nagaura,Z., Ishihara,N. and Mihara,K.
  TITLE     Export of mitochondrial AIF in response to proapoptotic stimuli
            depends on processing at the intermembrane space
  JOURNAL   EMBO J 24 (7), 1375-1386 (2005)
   PUBMED   15775970
REFERENCE   8  (bases 1 to 2222)
  AUTHORS   Susin,S.A., Lorenzo,H.K., Zamzami,N., Marzo,I., Brenner,C.,
            Larochette,N., Prevost,M.C., Alzari,P.M. and Kroemer,G.
  TITLE     Mitochondrial release of caspase-2 and -9 during the apoptotic
            process
  JOURNAL   J Exp Med 189 (2), 381-394 (1999)
   PUBMED   9892620
REFERENCE   9  (bases 1 to 2222)
  AUTHORS   Susin,S.A., Zamzami,N., Castedo,M., Daugas,E., Wang,H.G., Geley,S.,
            Fassy,F., Reed,J.C. and Kroemer,G.
  TITLE     The central executioner of apoptosis: multiple connections between
            protease activation and mitochondria in Fas/APO-1/CD95- and
            ceramide-induced apoptosis
  JOURNAL   J Exp Med 186 (1), 25-37 (1997)
   PUBMED   9206994
REFERENCE   10 (bases 1 to 2222)
  AUTHORS   Bird,T.D.
  TITLE     Charcot-Marie-Tooth Hereditary Neuropathy Overview
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301532
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DA624842.1, BC139738.1 and
            BC111065.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 23, 2018 this sequence version replaced NM_004208.3.
            
            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].
            
            Transcript Variant: This variant (1) encodes the longest isoform
            (AIF).
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: AK000775.1, BC139738.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            gene product(s) localized to mito. :: reported by MitoCarta
            MANE Ensembl match                 :: ENST00000287295.8/
                                                  ENSP00000287295.3
            RefSeq Select criteria             :: based on conservation,
                                                  expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-50                DA624842.1         47-96
            51-2132             BC139738.1         1-2082
            2133-2222           BC111065.1         2110-2199
FEATURES             Location/Qualifiers
     source          1..2222
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="X"
                     /map="Xq26.1"
     gene            1..2222
                     /gene="AIFM1"
                     /gene_synonym="AIF; AUNX1; CMT2D; CMTX4; COWCK; COXPD6;
                     DFNX5; NADMR; NAMSD; PDCD8; SEMDHL"
                     /note="apoptosis inducing factor mitochondria associated
                     1"
                     /db_xref="GeneID:9131"
                     /db_xref="HGNC:HGNC:8768"
                     /db_xref="MIM:300169"
     exon            1..291
                     /gene="AIFM1"
                     /gene_synonym="AIF; AUNX1; CMT2D; CMTX4; COWCK; COXPD6;
                     DFNX5; NADMR; NAMSD; PDCD8; SEMDHL"
                     /inference="alignment:Splign:2.1.0"
     CDS             186..2027
                     /gene="AIFM1"
                     /gene_synonym="AIF; AUNX1; CMT2D; CMTX4; COWCK; COXPD6;
                     DFNX5; NADMR; NAMSD; PDCD8; SEMDHL"
                     /EC_number="1.1.1.-"
                     /note="isoform AIF precursor is encoded by transcript
                     variant 1; programmed cell death 8 (apoptosis-inducing
                     factor); apoptosis-inducing factor 1, mitochondrial;
                     striatal apoptosis-inducing factor; apoptosis-inducing
                     factor, mitochondrion-associated, 1; testicular secretory
                     protein Li 4; auditory neuropathy, X-linked recessive 1"
                     /codon_start=1
                     /product="apoptosis-inducing factor 1, mitochondrial
                     isoform AIF precursor"
                     /protein_id="NP_004199.1"
                     /db_xref="CCDS:CCDS14618.1"
                     /db_xref="GeneID:9131"
                     /db_xref="HGNC:HGNC:8768"
                     /db_xref="MIM:300169"
                     /translation="MFRCGGLAAGALKQKLVPLVRTVCVRSPRQRNRLPGNLFQRWHV
                     PLELQMTRQMASSGASGGKIDNSVLVLIVGLSTVGAGAYAYKTMKEDEKRYNERISGL
                     GLTPEQKQKKAALSASEGEEVPQDKAPSHVPFLLIGGGTAAFAAARSIRARDPGARVL
                     IVSEDPELPYMRPPLSKELWFSDDPNVTKTLRFKQWNGKERSIYFQPPSFYVSAQDLP
                     HIENGGVAVLTGKKVVQLDVRDNMVKLNDGSQITYEKCLIATGGTPRSLSAIDRAGAE
                     VKSRTTLFRKIGDFRSLEKISREVKSITIIGGGFLGSELACALGRKARALGTEVIQLF
                     PEKGNMGKILPEYLSNWTMEKVRREGVKVMPNAIVQSVGVSSGKLLIKLKDGRKVETD
                     HIVAAVGLEPNVELAKTGGLEIDSDFGGFRVNAELQARSNIWVAGDAACFYDIKLGRR
                     RVEHHDHAVVSGRLAGENMTGAAKPYWHQSMFWSDLGPDVGYEAIGLVDSSLPTVGVF
                     AKATAQDNPKSATEQSGTGIRSESETESEASEITIPPSTPAVPQAPVQGEDYGKGVIF
                     YLRDKVVVGIVLWNIFNRMPIARKIIKDGEQHEDLNEVAKLFNIHED"
     exon            292..434
                     /gene="AIFM1"
                     /gene_synonym="AIF; AUNX1; CMT2D; CMTX4; COWCK; COXPD6;
                     DFNX5; NADMR; NAMSD; PDCD8; SEMDHL"
                     /inference="alignment:Splign:2.1.0"
     exon            435..534
                     /gene="AIFM1"
                     /gene_synonym="AIF; AUNX1; CMT2D; CMTX4; COWCK; COXPD6;
                     DFNX5; NADMR; NAMSD; PDCD8; SEMDHL"
                     /inference="alignment:Splign:2.1.0"
     exon            535..659
                     /gene="AIFM1"
                     /gene_synonym="AIF; AUNX1; CMT2D; CMTX4; COWCK; COXPD6;
                     DFNX5; NADMR; NAMSD; PDCD8; SEMDHL"
                     /inference="alignment:Splign:2.1.0"
     exon            660..790
                     /gene="AIFM1"
                     /gene_synonym="AIF; AUNX1; CMT2D; CMTX4; COWCK; COXPD6;
                     DFNX5; NADMR; NAMSD; PDCD8; SEMDHL"
                     /inference="alignment:Splign:2.1.0"
     exon            791..881
                     /gene="AIFM1"
                     /gene_synonym="AIF; AUNX1; CMT2D; CMTX4; COWCK; COXPD6;
                     DFNX5; NADMR; NAMSD; PDCD8; SEMDHL"
                     /inference="alignment:Splign:2.1.0"
     exon            882..966
                     /gene="AIFM1"
                     /gene_synonym="AIF; AUNX1; CMT2D; CMTX4; COWCK; COXPD6;
                     DFNX5; NADMR; NAMSD; PDCD8; SEMDHL"
                     /inference="alignment:Splign:2.1.0"
     exon            967..1043
                     /gene="AIFM1"
                     /gene_synonym="AIF; AUNX1; CMT2D; CMTX4; COWCK; COXPD6;
                     DFNX5; NADMR; NAMSD; PDCD8; SEMDHL"
                     /inference="alignment:Splign:2.1.0"
     exon            1044..1152
                     /gene="AIFM1"
                     /gene_synonym="AIF; AUNX1; CMT2D; CMTX4; COWCK; COXPD6;
                     DFNX5; NADMR; NAMSD; PDCD8; SEMDHL"
                     /inference="alignment:Splign:2.1.0"
     exon            1153..1260
                     /gene="AIFM1"
                     /gene_synonym="AIF; AUNX1; CMT2D; CMTX4; COWCK; COXPD6;
                     DFNX5; NADMR; NAMSD; PDCD8; SEMDHL"
                     /inference="alignment:Splign:2.1.0"
     exon            1261..1349
                     /gene="AIFM1"
                     /gene_synonym="AIF; AUNX1; CMT2D; CMTX4; COWCK; COXPD6;
                     DFNX5; NADMR; NAMSD; PDCD8; SEMDHL"
                     /inference="alignment:Splign:2.1.0"
     exon            1350..1490
                     /gene="AIFM1"
                     /gene_synonym="AIF; AUNX1; CMT2D; CMTX4; COWCK; COXPD6;
                     DFNX5; NADMR; NAMSD; PDCD8; SEMDHL"
                     /inference="alignment:Splign:2.1.0"
     exon            1491..1633
                     /gene="AIFM1"
                     /gene_synonym="AIF; AUNX1; CMT2D; CMTX4; COWCK; COXPD6;
                     DFNX5; NADMR; NAMSD; PDCD8; SEMDHL"
                     /inference="alignment:Splign:2.1.0"
     exon            1634..1758
                     /gene="AIFM1"
                     /gene_synonym="AIF; AUNX1; CMT2D; CMTX4; COWCK; COXPD6;
                     DFNX5; NADMR; NAMSD; PDCD8; SEMDHL"
                     /inference="alignment:Splign:2.1.0"
     exon            1759..1955
                     /gene="AIFM1"
                     /gene_synonym="AIF; AUNX1; CMT2D; CMTX4; COWCK; COXPD6;
                     DFNX5; NADMR; NAMSD; PDCD8; SEMDHL"
                     /inference="alignment:Splign:2.1.0"
     exon            1956..2222
                     /gene="AIFM1"
                     /gene_synonym="AIF; AUNX1; CMT2D; CMTX4; COWCK; COXPD6;
                     DFNX5; NADMR; NAMSD; PDCD8; SEMDHL"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2196..2201
                     /regulatory_class="polyA_signal_sequence"
                     /gene="AIFM1"
                     /gene_synonym="AIF; AUNX1; CMT2D; CMTX4; COWCK; COXPD6;
                     DFNX5; NADMR; NAMSD; PDCD8; SEMDHL"
                     /note="hexamer: AATAAA"
     polyA_site      2222
                     /gene="AIFM1"
                     /gene_synonym="AIF; AUNX1; CMT2D; CMTX4; COWCK; COXPD6;
                     DFNX5; NADMR; NAMSD; PDCD8; SEMDHL"
                     /note="major polyA site"
ORIGIN      
        1 gttccccttc cccggctcta gcaggccggc ttctctgtcc aatgcccacc cggagctggg
       61 aggaggagtc tgcgtaatgt gcgtgtgaag agactggggg agctggccgg ggctcacggt
      121 gtttgacccg tcggtcgtgc gtgagaggaa agggaaggag gaggtcccga atagcggtcg
      181 ccgaaatgtt ccggtgtgga ggcctggcgg cgggtgcttt gaagcagaag ctggtgccct
      241 tggtgcggac cgtgtgcgtc cgaagcccga ggcagaggaa ccggctccca ggcaacttgt
      301 tccagcgatg gcatgttcct ctagaactcc agatgacaag acaaatggct agctctggtg
      361 catcaggggg caaaatcgat aattctgtgt tagtccttat tgtgggctta tcaacagtag
      421 gagctggtgc ctatgcctac aagactatga aagaggatga aaaaagatac aatgaaagaa
      481 tttcagggtt agggctgaca ccagaacaga aacagaaaaa ggccgcgtta tctgcttcag
      541 aaggagagga agttcctcaa gacaaggcgc caagtcatgt tcctttcctg ctaattggtg
      601 gaggcacagc tgcttttgct gcagccagat ccatccgggc tcgggatcct ggggccaggg
      661 tactgattgt atctgaagat cctgagctgc cgtacatgcg acctcctctt tcaaaagaac
      721 tgtggttttc agatgaccca aatgtcacaa agacactgcg attcaaacag tggaatggaa
      781 aagagagaag catatatttc cagccacctt ctttctatgt ctctgctcag gacctgcctc
      841 atattgagaa tggtggtgtg gctgtcctca ctgggaagaa ggtagtacag ctggatgtga
      901 gagacaacat ggtgaaactt aatgatggct ctcaaataac ctatgaaaag tgcttgattg
      961 caacaggagg tactccaaga agtctgtctg ccattgatag ggctggagca gaggtgaaga
     1021 gtagaacaac gcttttcaga aagattggag actttagaag cttggagaag atttcacggg
     1081 aagtcaaatc aattacgatt atcggtgggg gcttccttgg tagcgaactg gcctgtgctc
     1141 ttggcagaaa ggctcgagcc ttgggcacag aagtgattca actcttcccc gagaaaggaa
     1201 atatgggaaa gatcctcccc gaatacctca gcaactggac catggaaaaa gtcagacgag
     1261 agggggttaa ggtgatgccc aatgctattg tgcaatccgt tggagtcagc agtggcaagt
     1321 tacttatcaa gctgaaagac ggcaggaagg tagaaactga ccacatagtg gcagctgtgg
     1381 gcctggagcc caatgttgag ttggccaaga ctggtggcct ggaaatagac tcagattttg
     1441 gtggcttccg ggtaaatgca gagctacaag cacgctctaa catctgggtg gcaggagatg
     1501 ctgcatgctt ctacgatata aagttgggaa ggaggcgggt agagcaccat gatcacgctg
     1561 ttgtgagtgg aagattggct ggagaaaata tgactggagc tgctaagccg tactggcatc
     1621 agtcaatgtt ctggagtgat ttgggccccg atgttggcta tgaagctatt ggtcttgtgg
     1681 acagtagttt gcccacagtt ggtgtttttg caaaagcaac tgcacaagac aaccccaaat
     1741 ctgccacaga gcagtcagga actggtatcc gatcagagag tgagacagag tccgaggcct
     1801 cagaaattac tattcctccc agcaccccgg cagttccaca ggctcccgtc cagggggagg
     1861 actacggcaa aggtgtcatc ttctacctca gggacaaagt ggtcgtgggg attgtgctat
     1921 ggaacatctt taaccgaatg ccaatagcaa ggaagatcat taaggacggt gagcagcatg
     1981 aagatctcaa tgaagtagcc aaactattca acattcatga agactgaagc cccacagtgg
     2041 aattggcaaa cccactgcag cccctgagag gaggtcgaat gggtaaagga gcattttttt
     2101 attcagcaga ctttctctgt gtatgagtgt gaatgatcaa gtcctttgtg aatattttca
     2161 actatgtagg taaattctta atgttcacat agtgaaataa attctgattc ttctaaatta
     2221 aa
//
