AIFM1

Summary

AIFM1 (apoptosis inducing factor mitochondria associated 1, HGNC:8768) is a protein-coding gene on chromosome Xq26.1, encoding Apoptosis-inducing factor 1, mitochondrial (O95831). Functions both as NADH oxidoreductase and as regulator of apoptosis. It is a selective cancer dependency (DepMap: 49.0% of cell lines).

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.

Source: NCBI Gene 9131 — RefSeq curated summary.

At a glance

• Gene–disease (curated): X-linked hereditary sensory and autonomic neuropathy with hearing loss (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 710 total — 9 pathogenic, 30 likely-pathogenic
• Phenotypes (HPO): 130
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 49.0% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_004208

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8768
Approved symbol	AIFM1
Name	apoptosis inducing factor mitochondria associated 1
Location	Xq26.1
Locus type	gene with protein product
Status	Approved
Aliases	AIF, CMTX4, DFNX5
Ensembl gene	ENSG00000156709
Ensembl biotype	protein_coding
OMIM	300169
Entrez	9131

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 18 protein_coding, 11 nonsense_mediated_decay, 6 retained_intron

ENST00000287295, ENST00000319908, ENST00000346424, ENST00000416073, ENST00000460436, ENST00000527892, ENST00000529877, ENST00000533719, ENST00000535724, ENST00000674546, ENST00000674555, ENST00000674582, ENST00000674591, ENST00000674601, ENST00000674722, ENST00000674957, ENST00000674997, ENST00000675015, ENST00000675037, ENST00000675050, ENST00000675092, ENST00000675111, ENST00000675240, ENST00000675427, ENST00000675774, ENST00000675857, ENST00000676048, ENST00000676144, ENST00000676229, ENST00000676328, ENST00000676436, ENST00000903845, ENST00000903846, ENST00000903847, ENST00000921976

RefSeq mRNA: 4 — MANE Select: NM_004208 NM_001130846, NM_001130847, NM_004208, NM_145812

CCDS: CCDS14618, CCDS14619, CCDS48166, CCDS48167

Canonical transcript exons

ENST00000287295 — 16 exons

Exon	Start	End
ENSE00001027915	130156461	130156603
ENSE00003506245	130129970	130130166
ENSE00003520937	130140533	130140617
ENSE00003521291	130138593	130138701
ENSE00003538247	130131675	130131799
ENSE00003556673	130136643	130136731
ENSE00003562335	130137078	130137185
ENSE00003617268	130139795	130139871
ENSE00003618975	130129362	130129628
ENSE00003625505	130147752	130147876
ENSE00003629885	130147493	130147623
ENSE00003658970	130136045	130136185
ENSE00003681204	130133313	130133455
ENSE00003691885	130145479	130145569
ENSE00003722876	130149469	130149568
ENSE00003844546	130165551	130165841

Expression profiles

Bgee: expression breadth ubiquitous, 273 present calls, max score 97.13.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.9710 / max 162.7070, expressed in 1813 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
200467	13.9860	1772
200469	7.3544	1747
200468	1.9655	1101
200466	0.3544	162
200470	0.3105	125

Top tissues by expression

291 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	97.13	gold quality
adult mammalian kidney	UBERON:0000082	96.78	gold quality
heart left ventricle	UBERON:0002084	96.50	gold quality
right adrenal gland cortex	UBERON:0035827	96.32	gold quality
cardiac ventricle	UBERON:0002082	96.31	gold quality
right adrenal gland	UBERON:0001233	96.27	gold quality
mucosa of transverse colon	UBERON:0004991	96.20	gold quality
right lobe of liver	UBERON:0001114	96.19	gold quality
right atrium auricular region	UBERON:0006631	96.01	gold quality
left adrenal gland	UBERON:0001234	95.94	gold quality
left adrenal gland cortex	UBERON:0035825	95.61	gold quality
cardiac atrium	UBERON:0002081	95.55	gold quality
left ventricle myocardium	UBERON:0006566	95.19	gold quality
gastrocnemius	UBERON:0001388	94.78	gold quality
adrenal gland	UBERON:0002369	94.70	gold quality
adrenal cortex	UBERON:0001235	94.69	gold quality
heart	UBERON:0000948	94.67	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.44	gold quality
muscle of leg	UBERON:0001383	94.39	gold quality
rectum	UBERON:0001052	94.04	gold quality
liver	UBERON:0002107	93.98	gold quality
kidney	UBERON:0002113	93.87	gold quality
heart right ventricle	UBERON:0002080	93.49	gold quality
muscle organ	UBERON:0001630	93.24	gold quality
skeletal muscle organ	UBERON:0014892	93.24	gold quality
right uterine tube	UBERON:0001302	93.09	gold quality
myocardium	UBERON:0002349	93.01	gold quality
duodenum	UBERON:0002114	92.91	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	92.54	gold quality
transverse colon	UBERON:0001157	92.51	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-70580	no	287.43
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CELF1, PARP1, SFPQ, TP53

miRNA regulators (miRDB)

10 targeting AIFM1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-32-3P	99.36	68.20	2517
HSA-MIR-4427	99.34	70.33	1854
HSA-MIR-6071	99.16	67.77	1780
HSA-MIR-6074	98.89	69.64	2187
HSA-MIR-6829-5P	98.86	65.12	1480
HSA-MIR-93-3P	98.15	66.65	1309
HSA-MIR-6772-3P	97.04	65.89	784

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 49.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• observations suggest that AIF-induced nuclear apoptosis requires a direct interaction with DNA (PMID:12198487)
• These data suggest that apoptosis-inducing factor (AIF) is expressed in human coronary artery endothelial cells (HCAECs) and is upregulated by oxidized low density lipoproteins. (PMID:12535654)
• Possible contribution of apoptosis-inducing factor and reactive oxygen species to UVB-induced caspase-independent cell death in the T cell (PMID:12629154)
• apoptosis-inducing factor has a role in oxidant-induced cell death in retinal pigment epithelium cells (PMID:12668724)
• AIF is not implicated in CD47-dependent cell death of T cells (PMID:14585540)
• AIF and CYPA cooperate in apoptosis-associated chromatinolysis. (PMID:14716299)
• endonuclease G and apoptosis-inducing factor are relocated and have roles in calcium induced signaling and oxidative stress-related impairment of mitochondria (PMID:15182854)
• suggests a role in mitochondrial-mediated death pathway (PMID:15286713)
• The oxidoreductase function of AIF is required for the maintenance of glutathione levels in stress conditions and that glutathione is a major regulator of SG. (PMID:15316071)
• AIF plays a role in oxidative phosphorylation (PMID:15526035)
• AIF is involved in NMDA- and kainic acid- but not AMPA-induced excitotoxicity. AIF plays an important role in both BAX-dependent and BAX-independent mechanisms of neuronal injury. (PMID:15703386)
• findings indicate that PARP-1 activation and a PARP-1-dependent, caspase-independent, nuclear translocation of AIF contribute to apoptotic cerebral endothelial cell death after ischemia-reperfusion (PMID:15729291)
• AIF is responsible for stage I nuclear morphology and HMW DNA degradation is a caspase-activated DNase and AIF-independent process (PMID:16049016)
• 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. (PMID:16365034)
• AIF-mediated cell death is regulated by the functional interplay of SIRT1 and PARP-1 in response to DNA damage (PMID:16628003)
• the cloning and the biochemical characterization of a new isoform named AIF short 2 (AIFsh2) (PMID:16644725)
• Moreover, in the absence of overt apoptotic signals, the constitutive induction of AIF by p53 may underpin a cytoprotective maintenance role, based on the role of AIF in ensuring proper mitochondrial function. (PMID:16729031)
• AIF overexpression specifically resulted in the activation of caspase-7, thereby amplifying the inhibition of protein (PMID:17094969)
• Hypochlorous acid induced Bax-dependent mitochondrial permeability which led to cell death without caspase activity by processes involving AIF/EndoG-dependent pathways. (PMID:17107772)
• study of cellular localization of the endonuclease G, AIF & AMID during apoptosis using bioinformatics and image analysis (PMID:17347867)
• Down-regulation of hSUV3 results in cell cycle perturbations and in apoptosis, which is both AIF- and caspase-dependent, and proceeds with the induction of p53. (PMID:17352692)
• PKB/Akt inhibits ceramide-induced apoptosis in neuroblastoma cells by blocking AIF translocation. (PMID:17471535)
• Data suggest that erythroblast chromatin degradation may involve caspase activated DNase and apoptosis inducing factor, enzymes distinct from those active in apoptotic cells. (PMID:17492772)
• AIF is associated with cisplatin induced apoptosis in prostate cancer (PMID:17560018)
• Inhibitor of apoptosis proteins, nuclear factor-kappa, Smac/DIABLO and apoptosis inducing factor were increased in colon cancer cells. (PMID:17603079)
• TULA enhances the apoptotic effect of AIF by facilitating the interactions of AIF with its apoptotic co-factors (PMID:17709377)
• Down-regulation of apoptosis inducing factor inhibits TAp63gamma-induced apoptosis. (PMID:17822623)
• Scythe regulates apoptosis-inducing factor stability during endoplasmic reticulum stress-induced apoptosis (PMID:18056262)
• Hibiscus syriacus extract exhibits a cytotoxic effect on lung cancer cells by activation p53 and AIF. (PMID:18306460)
• Promoting neuronal survival of GDNF might be related to the reduction of AIF nuclear translocation, indicating the high therapeutic potency of SeV/GDNF for cerebral ischemia. (PMID:18593521)
• These results provide novel insights into the mechanism of AIF release during cell death. (PMID:18806756)
• AIF translocation has a role in FK228-induced autophagy in malignant rhabdoid tumor cells (PMID:18821579)
• AIF is essential for maintaining beta-cell mass and for oxidative stress response. (PMID:19197367)
• These findings suggest that an acute energy reduction by H(2)O(2) causes caspase-independent and AIF-dependent cell death. (PMID:19418225)
• TAp63gamma could induce apoptosis in human esophageal squamous cancer EC9706 cells, through at least releasing AIF and Bit1 from mitochindria into cytosol and nucleus, where apoptotic cascade takes place. (PMID:19578750)
• The positive rates of AIF and caspase-3 in colorectal adenoma were higher than those in normal mucosa. The positive rate of AIF in adenoma showed no significant difference compared to colorectal carcinoma. (PMID:19598027)
• Our results provide evidence for persistent cleavage and nuclear translocation of AIF in amyotrophic lateral sclerosis spinal cord, suggesting implications for the AIF-mediated motor neuron death in this disease. (PMID:19669652)
• Studies showed the manifold roles of AIF in cell life and death. (PMID:19723031)
• Data show that in cells with fragmented chromatin (i.e., in late apoptosis), the immunolabeling for AIF appeared to be distinct from chromatin, being mainly confined to mitochondria. (PMID:19723032)
• nuclear translocation of apoptosis-inducing factor and endonuclease G play a crucial role in (-)-Epigallocatechin-3-gallate -induced apoptosis of human laryngeal epidermoid carcinoma Hep2 cells (PMID:19781850)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	aifm1	ENSDARG00000058088
mus_musculus	Aifm1	ENSMUSG00000036932
rattus_norvegicus	Aifm1	ENSRNOG00000006067
drosophila_melanogaster	AIF	FBGN0031392
caenorhabditis_elegans		WBGENE00006937

Paralogs (7): DLD (ENSG00000091140), GSR (ENSG00000104687), PYROXD1 (ENSG00000121350), AIFM3 (ENSG00000183773), TXNRD2 (ENSG00000184470), TXNRD3 (ENSG00000197763), TXNRD1 (ENSG00000198431)

Protein

Protein identifiers

Apoptosis-inducing factor 1, mitochondrial — O95831 (reviewed: O95831)

Alternative names: Programmed cell death protein 8

All UniProt accessions (18): O95831, A0A6Q8PF87, A0A6Q8PFA7, A0A6Q8PFE1, A0A6Q8PFM5, A0A6Q8PFN1, A0A6Q8PFQ8, A0A6Q8PFS4, A0A6Q8PFW2, A0A6Q8PG15, A0A6Q8PGB7, A0A6Q8PHC0, A0A6Q8PHJ4, A0A6Q8PHJ9, A0A7I2PK44, A0A7I2RLJ8, E9PMA0, E9PMQ8

UniProt curated annotations — full annotation on UniProt →

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. Release into the cytoplasm is mediated upon binding to poly-ADP-ribose chains. The soluble form (AIFsol) found in the nucleus induces ‘parthanatos’ i.e. caspase-independent fragmentation of chromosomal DNA. Binds to DNA in a sequence-independent manner. Interacts with EIF3G, and thereby inhibits the EIF3 machinery and protein synthesis, and activates caspase-7 to amplify apoptosis. Plays a critical role in caspase-independent, pyknotic cell death in hydrogen peroxide-exposed cells. In contrast, participates in normal mitochondrial metabolism. Plays an important role in the regulation of respiratory chain biogenesis by interacting with CHCHD4 and controlling CHCHD4 mitochondrial import. Has NADH oxidoreductase activity. Does not induce nuclear apoptosis. Pro-apoptotic isoform.

Subunit / interactions. Monomer (oxidized form). Homodimer (reduced form). Upon reduction with NADH, undergoes dimerization and forms tight, long-lived FADH2-NAD charge transfer complexes (CTC) resistant to oxidation. 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. Interacts with CHCHD4; the interaction increases in presence of NADH. Interacts with processed form of PARP1 (Poly [ADP-ribose] polymerase 1, processed C-terminus); interaction is mediated with poly-ADP-ribose chains attached to PARP1, promoting translocation into the nucleus.

Subcellular location. Mitochondrion intermembrane space. Mitochondrion inner membrane. Cytoplasm. Nucleus. Perinuclear region Mitochondrion intermembrane space. Mitochondrion inner membrane Mitochondrion. Cytosol Cytoplasm.

Tissue specificity. Expressed in all tested tissues. Detected in muscle and skin fibroblasts (at protein level). Expressed in osteoblasts (at protein level). Brain specific. Expressed in all tested tissues except brain. Isoform 5 is frequently down-regulated in human cancers.

Post-translational modifications. 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 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.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry. Charcot-Marie-Tooth disease, X-linked recessive, 4, with or without cerebellar ataxia (CMTX4) [MIM:310490] A neuromuscular disorder characterized by progressive sensorimotor axonal neuropathy, distal sensory impairment, difficulty walking due to peripheral neuropathy and/or cerebellar ataxia, and deafness due to auditory neuropathy. Additional features include cognitive impairment, cerebellar atrophy, dysarthria, abnormal extraocular movements, tremor, dysmetria and spasticity. The age at onset ranges from infancy to young adulthood. The disease is caused by variants affecting the gene represented in this entry. Deafness, X-linked, 5, with peripheral neuropathy (DFNX5) [MIM:300614] A form of hearing loss characterized by absent or severely abnormal auditory brainstem response, abnormal middle ear reflexes, abnormal speech discrimination, loss of outer hair cell function, and cochlear nerve hypoplasia. DFNX5 patients manifest auditory neuropathy with childhood onset, associated with distal sensory impairment affecting the peripheral nervous system. The disease is caused by variants affecting the gene represented in this entry. Spondyloepimetaphyseal dysplasia, X-linked, with hypomyelinating leukodystrophy (SEMDHL) [MIM:300232] An X-linked recessive developmental disorder characterized by slowly progressive skeletal and neurologic abnormalities, including short stature, large and deformed joints, significant motor impairment, visual defects, and sometimes cognitive deficits. Affected individuals typically have normal early development in the first year or so of life, followed by development regression and the development of symptoms. Brain imaging shows white matter abnormalities consistent with hypomyelinating leukodystrophy. The disease is caused by variants affecting the gene represented in this entry.

Induction. Strongly down-regulated in many tumor cells, up-regulated by gamma-irradiation.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the FAD-dependent oxidoreductase family.

Isoforms (6)

UniProt ID	Names	Canonical?
O95831-1	1, AIF	yes
O95831-2	2
O95831-3	3, AIF-exB, AIF2
O95831-4	4, AIFsh2
O95831-5	5, AIFsh
O95831-6	6, AIFsh3

RefSeq proteins (4): NP_001124318, NP_001124319, NP_004199, NP_665811 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR016156	FAD/NAD-linked_Rdtase_dimer_sf	Homologous_superfamily
IPR023753	FAD/NAD-binding_dom	Domain
IPR029324	AIF_C	Domain
IPR036188	FAD/NAD-bd_sf	Homologous_superfamily
IPR050446	FAD-oxidoreductase/Apoptosis	Family

Pfam: PF07992, PF14721

Enzyme classification (BRENDA):

• EC 7.1.1.2 — NADH:ubiquinone reductase (H+-translocating) (BRENDA: 58 organisms, 186 substrates, 276 inhibitors, 132 Km, 34 kcat entries)

Substrate kinetics (BRENDA)

38 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
NADH	0.0001–1.1	41
DECYLUBIQUINONE	0.024–43	9
N-DECYLUBIQUINONE	0.007–0.039	8
UBIQUINONE-1	0.002–0.4	7
NADPH	0.025–1.87	6
COENZYME Q1	0.01–0.024	5
UBIQUINONE-2	0.0032–0.083	5
FERRICYTOCHROME C	0.012–0.0684	4
MENADIONE	0.002–0.239	4
FERRICYANIDE	0.055–4	3
NAD+	0.007–0.27	3
OXIDIZED 2,6-DICHLOROPHENOLINDOPHENOL	0.0062–0.55	3
UBIQUINONE-0	0.104–0.35	3
1,1’-CARBAMOYLMETHYLVIOLOGEN	0.55–1	2
MENAQUINONE	0.1	2

Catalyzed reactions (Rhea), 1 shown:

• A + NADH + H(+) = AH2 + NAD(+) (RHEA:11356)

UniProt features (134 total): strand 31, sequence variant 20, binding site 18, helix 18, modified residue 12, mutagenesis site 11, splice variant 7, turn 6, region of interest 3, short sequence motif 3, transit peptide 1, propeptide 1, chain 1, cross-link 1, compositionally biased region 1

Structure

Experimental structures (PDB)

26 structures.

PDB	Method	Resolution (Å)
5FS8	X-RAY DIFFRACTION	1.4
5FS9	X-RAY DIFFRACTION	1.75
1M6I	X-RAY DIFFRACTION	1.8
4BV6	X-RAY DIFFRACTION	1.8
5FMH	X-RAY DIFFRACTION	1.8
9SZQ	X-RAY DIFFRACTION	1.8
5FS7	X-RAY DIFFRACTION	1.85
4LII	X-RAY DIFFRACTION	1.88
5FS6	X-RAY DIFFRACTION	1.9
5KVI	X-RAY DIFFRACTION	2
8D3N	X-RAY DIFFRACTION	2.25
8D3O	X-RAY DIFFRACTION	2.25
5KVH	X-RAY DIFFRACTION	2.27
8D3K	X-RAY DIFFRACTION	2.3
8VGY	X-RAY DIFFRACTION	2.3
9GQZ	ELECTRON MICROSCOPY	2.36
8D3E	X-RAY DIFFRACTION	2.38
4FDC	X-RAY DIFFRACTION	2.4
8D3J	X-RAY DIFFRACTION	2.4
8D3H	X-RAY DIFFRACTION	2.51
8D3G	X-RAY DIFFRACTION	2.58
9GR0	ELECTRON MICROSCOPY	2.61
8D3I	X-RAY DIFFRACTION	2.65
9GQY	ELECTRON MICROSCOPY	2.8
4BUR	X-RAY DIFFRACTION	2.88
9FL7	ELECTRON MICROSCOPY	4.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95831-F1	85.97	0.76

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (18): 138–142; 164–165; 172; 177; 196; 233; 285; 308–311; 336; 342; 399; 438 …

Post-translational modifications (13): 105, 109, 116, 118, 268, 292, 371, 388, 521, 524, 530, 593, 255

Mutagenesis-validated functional residues (11):

Position	Phenotype
196	increases protein dimerization at lower nadh levels.
413–430	disrupts dimerization. lower efficiency in stabilizing charge-transfer complexes upon coenzyme reduction.
443–445	disrupts dimerization. disrupts dimerization; when associated with a-477.
454	allows dimerization in absence of nadh.
477	disrupts dimerization; when associated with a-443–445-a.
480	allows dimerization in absence of nadh.
485	increases protein dimerization at lower nadh levels.
529	increases protein dimerization at lower nadh levels.
531	increases protein dimerization at lower nadh levels.
533	increases protein dimerization at lower nadh levels.
535	increases protein dimerization at lower nadh levels.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 548 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, YAGI_AML_WITH_INV_16_TRANSLOCATION, TGCGCANK_UNKNOWN, GOBP_RESPONSE_TO_ESTRADIOL, GOBP_RESPONSE_TO_ACID_CHEMICAL, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_RESPONSE_TO_CORTICOSTEROID, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_MITOCHONDRIAL_RESPIRATORY_CHAIN_COMPLEX_ASSEMBLY, GOBP_NEUROGENESIS, TGACCTY_ERR1_Q2, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND

GO Biological Process (18): response to ischemia (GO:0002931), apoptotic process (GO:0006915), response to toxic substance (GO:0009636), neuron differentiation (GO:0030182), mitochondrial respiratory chain complex assembly (GO:0033108), positive regulation of apoptotic process (GO:0043065), positive regulation of neuron apoptotic process (GO:0043525), protein import into mitochondrial intermembrane space (GO:0045041), positive regulation of necroptotic process (GO:0060545), intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress (GO:0070059), cellular response to hydrogen peroxide (GO:0070301), cellular response to estradiol stimulus (GO:0071392), cellular response to hypoxia (GO:0071456), cellular response to nitric oxide (GO:0071732), protein import into the intermembrane space via the disulfide relay system (GO:0160203), response to L-glutamate (GO:1902065), cellular response to aldosterone (GO:1904045), positive regulation of programmed cell death (GO:0043068)

GO Molecular Function (9): DNA binding (GO:0003677), NADH dehydrogenase activity (GO:0003954), NAD(P)H oxidase H2O2-forming activity (GO:0016174), oxidoreductase activity, acting on NAD(P)H (GO:0016651), protein dimerization activity (GO:0046983), FAD binding (GO:0071949), poly-ADP-D-ribose binding (GO:0072572), protein binding (GO:0005515), oxidoreductase activity (GO:0016491)

GO Cellular Component (9): nucleus (GO:0005634), mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial intermembrane space (GO:0005758), cytosol (GO:0005829), perinuclear region of cytoplasm (GO:0048471), sperm head-tail coupling apparatus (GO:0120212), cytoplasm (GO:0005737), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cytoplasm	3
programmed cell death	2
cellular response to oxygen-containing compound	2
intracellular membrane-bounded organelle	2
response to stress	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
response to chemical	1
cell differentiation	1
generation of neurons	1
mitochondrion	1
mitochondrion organization	1
protein-containing complex assembly	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
positive regulation of apoptotic process	1
regulation of neuron apoptotic process	1
neuron apoptotic process	1
mitochondrial protein import pathway	1
regulation of necroptotic process	1
positive regulation of programmed necrotic cell death	1
necroptotic process	1
response to endoplasmic reticulum stress	1
intrinsic apoptotic signaling pathway	1
cellular response to reactive oxygen species	1
response to hydrogen peroxide	1
response to estradiol	1
cellular response to lipid	1
response to hypoxia	1
cellular response to stress	1
cellular response to decreased oxygen levels	1
response to nitric oxide	1
cellular response to reactive nitrogen species	1
protein import into mitochondrial intermembrane space	1
response to amino acid	1
response to nitrogen compound	1
response to oxygen-containing compound	1
cellular response to mineralocorticoid stimulus	1

Protein interactions and networks

STRING

3628 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AIFM1	ENDOG	Q14249	854
AIFM1	PARG	Q86W56	804
AIFM1	CHCHD4	Q8N4Q1	678
AIFM1	CASP3	P42574	671
AIFM1	TUFM	P49411	650
AIFM1	PRPS1	P09329	626
AIFM1	PRPS1L1	P21108	616
AIFM1	MRPS16	Q9Y3D3	595
AIFM1	CYCS	P00001	591
AIFM1	PDE1A	P54750	589
AIFM1	SIVA1	O15304	584
AIFM1	PARP1	P09874	579
AIFM1	HOGA1	Q86XE5	578
AIFM1	TSFM	P43897	572
AIFM1	MRPS22	P82650	542
AIFM1	SMPX	Q9UHP9	542

IntAct

232 interactions, top by confidence:

A	B	Type	Score
MED29	MED19	psi-mi:“MI:0914”(association)	0.890
ARL3	UNC119B	psi-mi:“MI:0914”(association)	0.730
CFTR	XPO1	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
RAF1	CALU	psi-mi:“MI:0914”(association)	0.640
CHCHD4	SSNA1	psi-mi:“MI:0914”(association)	0.640
RUVBL1	POLR3A	psi-mi:“MI:0914”(association)	0.640
PA	AIFM1	psi-mi:“MI:0915”(physical association)	0.610
AIFM1	PA	psi-mi:“MI:0914”(association)	0.610
KANK2	AIFM1	psi-mi:“MI:0914”(association)	0.600
AIFM1	KANK2	psi-mi:“MI:0915”(physical association)	0.600
KANK2	AIFM1	psi-mi:“MI:0403”(colocalization)	0.600
ERBB3	AIFM1	psi-mi:“MI:0914”(association)	0.570
AIFM1	AK2	psi-mi:“MI:0914”(association)	0.570
KANK2	AIFM1	psi-mi:“MI:0915”(physical association)	0.560
AIFM1	KANK2	psi-mi:“MI:0915”(physical association)	0.560
PA	IPO5	psi-mi:“MI:0914”(association)	0.550
ILK	HAX1	psi-mi:“MI:0914”(association)	0.530
IRAK1	SEC16A	psi-mi:“MI:0914”(association)	0.530
NDUFS5	NDUFS8	psi-mi:“MI:0914”(association)	0.530
TUBB3	POTEF	psi-mi:“MI:0914”(association)	0.530
PRKCZ	IPO5	psi-mi:“MI:0914”(association)	0.530

BioGRID (920): AIFM1 (Affinity Capture-RNA), AIFM1 (Affinity Capture-MS), AIFM1 (Affinity Capture-MS), AIFM1 (Affinity Capture-MS), AIFM1 (Affinity Capture-MS), AIFM1 (Affinity Capture-MS), AIFM1 (Affinity Capture-MS), AIFM1 (Affinity Capture-MS), AIFM1 (Affinity Capture-MS), AIFM1 (Affinity Capture-MS), AIFM1 (Affinity Capture-MS), AIFM1 (Co-fractionation), AIFM1 (Co-fractionation), AIFM1 (Co-fractionation), AIFM1 (Co-fractionation)

ESM2 similar proteins: A0A0E3D8M4, A0A0L1JEZ9, A0A140JWS7, A0A1C8AX29, A0A2I2F2K8, A0A411PQP8, A1A653, A7XRY0, A8NF99, B2KWH9, B2KWI1, D2E9W9, D4AU57, D4B1Y1, E9QYP0, G5EB76, I1RN13, J4W6X9, M2PP75, N4WYI1, O13907, O95831, P0DXV5, P0DXV6, P11637, P34229, P82861, Q09694, Q19910, Q2TZB2, Q2U6D4, Q4IER0, Q4U3U3, Q4U3U5, Q4WF56, Q4WVD1, Q4WZB3, Q5AYI6, Q5BH52, Q75BV4

Diamond homologs: O95831, P83966, Q9GRX6, Q9JM53, Q9VQ79, Q9Z0X1, P42435, P92947, Q40977, Q42711, Q43497, Q652L6, Q6ZJ08, Q84PW3, Q8S3R1, Q8S3R2, Q93WJ8, Q9LFA3, Q9LK94, Q9SR59

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
AIFM1	up-regulates	BAX
BAK1	up-regulates	AIFM1	relocalization
TP53	“up-regulates quantity by expression”	AIFM1	“transcriptional regulation”
XIAP	“down-regulates quantity by destabilization”	AIFM1	ubiquitination
PAK6	“down-regulates activity”	AIFM1	phosphorylation
PAK5	“down-regulates activity”	AIFM1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 202 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
CD209 (DC-SIGN) signaling	5	18.8×	4e-03
TRAF6 mediated NF-kB activation	5	16.6×	4e-03
TAK1-dependent IKK and NF-kappa-B activation	5	10.9×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
autophagosome maturation	6	11.9×	7e-03
cellular response to oxidative stress	8	7.0×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

710 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	30
Uncertain significance	212
Likely benign	205
Benign	20

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
11546	NM_004208.4(AIFM1):c.603_605del (p.Arg201del)	Pathogenic
1343826	NM_004208.4(AIFM1):c.1164+5G>A	Pathogenic
218110	NM_004208.4(AIFM1):c.778A>G (p.Thr260Ala)	Pathogenic
3061935	NM_004208.4(AIFM1):c.1463C>T (p.Pro488Leu)	Pathogenic
369972	NM_004208.4(AIFM1):c.1436A>G (p.Gln479Arg)	Pathogenic
58669	GRCh38/hg38 Xq25-26.2(chrX:128395951-132383344)x2	Pathogenic
694665	NM_004208.4(AIFM1):c.710A>G (p.Asp237Gly)	Pathogenic
694668	NM_004208.4(AIFM1):c.697-44T>G	Pathogenic
732674	NM_004208.4(AIFM1):c.422C>T (p.Thr141Ile)	Pathogenic
1327116	NM_004208.4(AIFM1):c.760G>A (p.Glu254Lys)	Likely pathogenic
1338853	NM_004208.4(AIFM1):c.1658C>T (p.Ala553Val)	Likely pathogenic
162472	NM_004208.4(AIFM1):c.-123G>C	Likely pathogenic
162473	NM_004208.4(AIFM1):c.434C>T (p.Ala145Val)	Likely pathogenic
162474	NM_004208.4(AIFM1):c.572_573delinsCT (p.Leu191Pro)	Likely pathogenic
162476	NM_004208.4(AIFM1):c.860T>C (p.Ile287Thr)	Likely pathogenic
162483	NM_004208.4(AIFM1):c.1678T>C (p.Tyr560His)	Likely pathogenic
162484	NM_004208.4(AIFM1):c.1319C>T (p.Ala440Val)	Likely pathogenic
162485	NM_004208.4(AIFM1):c.1078G>C (p.Gly360Arg)	Likely pathogenic
1677748	NM_004208.4(AIFM1):c.1426T>C (p.Tyr476His)	Likely pathogenic
1703042	NM_004208.4(AIFM1):c.1773C>G (p.Ile591Met)	Likely pathogenic
1703043	NM_004208.4(AIFM1):c.1705A>G (p.Arg569Gly)	Likely pathogenic
218108	NM_004208.4(AIFM1):c.1352G>A (p.Arg451Gln)	Likely pathogenic
2412786	NM_004208.4(AIFM1):c.742G>A (p.Gly248Ser)	Likely pathogenic
2444188	NM_004208.4(AIFM1):c.1267G>A (p.Val423Ile)	Likely pathogenic
2683856	NM_004208.4(AIFM1):c.1415C>T (p.Ala472Val)	Likely pathogenic
2683874	NM_004208.4(AIFM1):c.1408A>T (p.Thr470Ser)	Likely pathogenic
2683879	NM_004208.4(AIFM1):c.902A>T (p.Lys301Ile)	Likely pathogenic
2683882	NM_004208.4(AIFM1):c.1394C>T (p.Ala465Val)	Likely pathogenic
2933356	NM_004208.4(AIFM1):c.1195G>A (p.Gly399Ser)	Likely pathogenic
3061934	NM_004208.4(AIFM1):c.697G>A (p.Val233Ile)	Likely pathogenic

SpliceAI

2418 predictions. Top by Δscore:

Variant	Effect	Δscore
X:130129628:TCT:T	acceptor_loss	1.0000
X:130129965:CCTA:C	donor_loss	1.0000
X:130129966:CTA:C	donor_loss	1.0000
X:130129968:A:AT	donor_loss	1.0000
X:130129968:ACCTT:A	donor_gain	1.0000
X:130129969:C:A	donor_loss	1.0000
X:130129969:CCTTC:C	donor_gain	1.0000
X:130129972:T:A	donor_gain	1.0000
X:130130181:C:CT	acceptor_gain	1.0000
X:130130181:C:T	acceptor_gain	1.0000
X:130130195:A:C	acceptor_gain	1.0000
X:130131669:TCTTA:T	donor_loss	1.0000
X:130131670:CTTA:C	donor_loss	1.0000
X:130131671:TTA:T	donor_loss	1.0000
X:130131672:TAC:T	donor_loss	1.0000
X:130131673:A:AC	donor_gain	1.0000
X:130131673:A:T	donor_loss	1.0000
X:130131674:C:CC	donor_gain	1.0000
X:130131674:CCTGA:C	donor_gain	1.0000
X:130131795:CACTC:C	acceptor_gain	1.0000
X:130131796:ACTC:A	acceptor_gain	1.0000
X:130131797:CTC:C	acceptor_gain	1.0000
X:130131797:CTCC:C	acceptor_gain	1.0000
X:130131798:TC:T	acceptor_gain	1.0000
X:130131798:TCCT:T	acceptor_gain	1.0000
X:130131799:CC:C	acceptor_gain	1.0000
X:130131800:C:CC	acceptor_gain	1.0000
X:130131800:CTAAG:C	acceptor_loss	1.0000
X:130133336:CGG:C	donor_gain	1.0000
X:130133343:G:C	donor_gain	1.0000

AlphaMissense

3969 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:130129585:G:T	A605D	1.000
X:130129974:C:A	R589M	1.000
X:130129977:G:T	A588E	1.000
X:130130005:A:G	W579R	1.000
X:130130005:A:T	W579R	1.000
X:130130016:C:T	G575E	1.000
X:130130017:C:A	G575W	1.000
X:130130017:C:G	G575R	1.000
X:130130017:C:T	G575R	1.000
X:130130041:A:C	Y567D	1.000
X:130131761:C:T	G496D	1.000
X:130131762:C:G	G496R	1.000
X:130131768:C:G	A494P	1.000
X:130131796:A:C	S484R	1.000
X:130131796:A:T	S484R	1.000
X:130131798:T:G	S484R	1.000
X:130131799:C:A	W483C	1.000
X:130131799:C:G	W483C	1.000
X:130133314:A:G	W483R	1.000
X:130133314:A:T	W483R	1.000
X:130133329:G:C	H478D	1.000
X:130133357:A:C	N468K	1.000
X:130133357:A:T	N468K	1.000
X:130133364:C:T	G466E	1.000
X:130133365:C:G	G466R	1.000
X:130133365:C:T	G466R	1.000
X:130133367:G:T	A465D	1.000
X:130133376:C:A	G462V	1.000
X:130133376:C:T	G462E	1.000
X:130133377:C:G	G462R	1.000

dbSNP variants (sampled 300 via entrez): RS1000119357 (X:130148252 C>T), RS1000180109 (X:130153309 C>A,T), RS1000259157 (X:130167612 A>T), RS1000550847 (X:130156738 C>A), RS1000562438 (X:130158892 T>C), RS1000604565 (X:130156036 T>C), RS1000854317 (X:130143135 T>C), RS1001403094 (X:130129461 T>C), RS1001469686 (X:130138342 G>A), RS1001683287 (X:130143357 C>G), RS1001806170 (X:130132059 A>G), RS1001932126 (X:130166882 A>G), RS1002069137 (X:130140576 A>G,T), RS1002163788 (X:130151311 T>C), RS1002217874 (X:130150873 G>T)

Disease associations

OMIM: gene MIM:300169 | disease phenotypes: MIM:609060, MIM:300816, MIM:300232, MIM:310490, MIM:118220, MIM:128600, MIM:250620, MIM:300799, MIM:609129, MIM:312080, MIM:601042, MIM:209850

GenCC curated gene-disease

Disease	Classification	Inheritance
X-linked hereditary sensory and autonomic neuropathy with hearing loss	Definitive	X-linked
spondyloepimetaphyseal dysplasia, Bieganski type	Strong	X-linked
severe X-linked mitochondrial encephalomyopathy	Strong	X-linked
Charcot-Marie-Tooth disease X-linked recessive 4	Strong	X-linked

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
X-linked hereditary sensory and autonomic neuropathy with hearing loss	Definitive	XL
Leigh syndrome	Moderate	XL

Mondo (18): combined oxidative phosphorylation deficiency (MONDO:0000732), severe X-linked mitochondrial encephalomyopathy (MONDO:0010437), spondyloepimetaphyseal dysplasia, Bieganski type (MONDO:0010275), Charcot-Marie-Tooth disease X-linked recessive 4 (MONDO:0010689), Charcot-Marie-Tooth disease (MONDO:0015626), prostate cancer (MONDO:0008315), ear malformation (MONDO:0007500), 3-hydroxyisobutyryl-CoA hydrolase deficiency (MONDO:0009603), peripheral neuropathy (MONDO:0005244), syndromic X-linked intellectual disability Raymond type (MONDO:0010427), auditory neuropathy (MONDO:0021944), leukodystrophy (MONDO:0019046), flatfoot (MONDO:0005293), sensorineural hearing loss disorder (MONDO:0020678), dystonia 9 (MONDO:0010983)

Orphanet (11): Severe X-linked mitochondrial encephalomyopathy (Orphanet:238329), Spondyloepimetaphyseal dysplasia, Bieganski type (Orphanet:168448), Leukoencephalopathy-spondyloepimetaphyseal dysplasia syndrome (Orphanet:83629), X-linked hereditary sensory and autonomic neuropathy with deafness (Orphanet:139583), X-linked Charcot-Marie-Tooth disease type 4 (Orphanet:101078), Charcot-Marie-Tooth disease/Hereditary motor and sensory neuropathy (Orphanet:166), Familial prostate cancer (Orphanet:1331), Neurodegeneration due to 3-hydroxyisobutyryl-CoA hydrolase deficiency (Orphanet:88639), Leukodystrophy (Orphanet:68356), Paroxysmal dystonic choreathetosis with episodic ataxia and spasticity (Orphanet:53583), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

130 total (30 of 130 shown, HPO-id order):

HPO	Term
HP:0000218	High palate
HP:0000272	Malar flattening
HP:0000280	Coarse facial features
HP:0000294	Low anterior hairline
HP:0000316	Hypertelorism
HP:0000360	Tinnitus
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000407	Sensorineural hearing impairment
HP:0000455	Broad nasal tip
HP:0000463	Anteverted nares
HP:0000470	Short neck
HP:0000505	Visual impairment
HP:0000543	Optic disc pallor
HP:0000545	Myopia
HP:0000574	Thick eyebrow
HP:0000587	Abnormal optic nerve morphology
HP:0000639	Nystagmus
HP:0000666	Horizontal nystagmus
HP:0000737	Irritability
HP:0000750	Delayed speech and language development
HP:0000762	Decreased nerve conduction velocity
HP:0000763	Sensory neuropathy
HP:0000883	Thin ribs
HP:0000884	Prominent sternum
HP:0000907	Anterior rib cupping
HP:0000926	Platyspondyly
HP:0001156	Brachydactyly
HP:0001169	Broad palm
HP:0001249	Intellectual disability

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008103_151	Bipolar disorder	5.000000e-06

MeSH disease descriptors (10)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D002607	Charcot-Marie-Tooth Disease	C10.500.300.200; C10.574.500.495.200; C10.668.829.800.300.200; C16.131.666.300.200; C16.320.400.375.200
D005413	Flatfoot	C05.330.488.655.250; C05.330.495.681.250; C05.660.585.512.380.813.250; C16.131.621.585.512.500.681.250
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750
C538268	Auditory neuropathy (supp.)
C562803	Beta-Hydroxyisobutyryl CoA Deacylase Deficiency (supp.)
C563401	Choreoathetosis-Spasticity, Episodic (supp.)
C564472	Deafness, X-Linked 5 (supp.)
C536671	Skeletal dysplasia coarse facies mental retardation (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295688 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.27	Kd	5.385	nM	CHEMBL3752910
8.27	ED50	5.385	nM	CHEMBL3752910
6.74	Kd	181.6	nM	CHEMBL5653589
6.74	ED50	181.6	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 5 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147823: Binding affinity to human AIFM1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0054	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147823: Binding affinity to human AIFM1 incubated for 45 mins by Kinobead based pull down assay	kd	0.1816	uM

CTD chemical–gene interactions

206 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Resveratrol	affects localization, decreases reaction, affects cotreatment, increases expression, increases reaction (+1 more)	9
Acetylcysteine	decreases reaction, increases expression, affects localization, increases localization, affects cotreatment	7
Sorafenib	affects localization, decreases reaction, affects cotreatment	6
bisphenol A	decreases expression, decreases methylation, increases expression, affects cotreatment, increases abundance (+1 more)	5
sodium arsenite	affects localization, affects cotreatment, increases expression, decreases expression, increases abundance	4
lead acetate	affects cotreatment, increases abundance, increases expression, increases reaction, affects reaction	3
bisphenol S	affects cotreatment, increases methylation, decreases expression, increases expression	3
Vorinostat	affects cotreatment, affects localization, increases secretion	3
Estradiol	increases reaction, decreases expression, affects localization, affects reaction, decreases reaction (+1 more)	3
Hydrogen Peroxide	affects localization, affects reaction, decreases reaction, increases reaction, affects expression	3
Lead	increases abundance, increases expression, increases reaction, decreases expression, affects reaction (+1 more)	3
Plant Extracts	affects cotreatment, increases expression, affects localization	3
Quercetin	affects localization, increases expression	3
Cyclosporine	affects localization, decreases reaction, decreases expression	3
Paclitaxel	affects cotreatment, increases expression, affects localization	3
bisphenol F	decreases expression, increases expression	2
trichostatin A	affects localization, affects cotreatment, increases secretion	2
fludarabine	affects cotreatment, increases secretion, affects localization	2
butylidenephthalide	increases expression	2
chromium hexavalent ion	affects localization, increases expression	2
pyrazolanthrone	affects localization, decreases reaction, increases expression	2
LAQ824	affects localization, affects cotreatment	2
Bortezomib	affects cotreatment, affects localization	2
Arsenic Trioxide	affects localization, decreases reaction	2
Acetaminophen	decreases expression	2
Acrolein	increases abundance, affects localization, affects cotreatment, increases oxidation	2
Butyrates	affects cotreatment, affects localization, increases secretion	2
Cadmium	affects localization, increases abundance, increases expression	2
Copper	affects binding, decreases expression, affects localization	2
Doxorubicin	affects cotreatment, increases expression	2

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118751	Binding	Binding affinity to AIFM1 in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Cellosaurus cell lines

3 cell lines: 1 induced pluripotent stem cell, 1 transformed cell line, 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A7IG	CPGHi003-A	Induced pluripotent stem cell	Male
CVCL_B2RA	Abcam HEK293T AIFM1 KO	Transformed cell line	Female
CVCL_SC02	HAP1 AIFM1 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
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NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
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NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
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NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
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