AIFM3

Summary

AIFM3 (AIF family member 3, HGNC:26398) is a protein-coding gene on chromosome 22q11.21, encoding Apoptosis-inducing factor 3 (Q96NN9). Induces apoptosis through a caspase dependent pathway.

Predicted to enable oxidoreductase activity, acting on NAD(P)H. Involved in execution phase of apoptosis. Located in cytosol; endoplasmic reticulum; and mitochondrial inner membrane.

Source: NCBI Gene 150209 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 404 total — 215 pathogenic, 28 likely-pathogenic
• Phenotypes (HPO): 4
• MANE Select transcript: NM_001386814

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26398
Approved symbol	AIFM3
Name	AIF family member 3
Location	22q11.21
Locus type	gene with protein product
Status	Approved
Aliases	AIFL, FLJ30473
Ensembl gene	ENSG00000183773
Ensembl biotype	protein_coding
OMIM	617298
Entrez	150209

Gene structure

Transcript identifiers

Ensembl transcripts: 50 — 38 protein_coding, 6 retained_intron, 4 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000399163, ENST00000399167, ENST00000405089, ENST00000417515, ENST00000426113, ENST00000434714, ENST00000440238, ENST00000441376, ENST00000465606, ENST00000467926, ENST00000468124, ENST00000472575, ENST00000479523, ENST00000483107, ENST00000484206, ENST00000486003, ENST00000495869, ENST00000496097, ENST00000683034, ENST00000884440, ENST00000884441, ENST00000884442, ENST00000884443, ENST00000884444, ENST00000884445, ENST00000884446, ENST00000884447, ENST00000884448, ENST00000884449, ENST00000884450, ENST00000884451, ENST00000884452, ENST00000884453, ENST00000884454, ENST00000884455, ENST00000884456, ENST00000884457, ENST00000884458, ENST00000884459, ENST00000961517, ENST00000961518, ENST00000961519, ENST00000961520, ENST00000961521, ENST00000961522, ENST00000961523, ENST00000961524, ENST00000961525, ENST00000961526, ENST00000961527

RefSeq mRNA: 4 — MANE Select: NM_001386814 NM_001018060, NM_001146288, NM_001386814, NM_144704

CCDS: CCDS13786, CCDS33605, CCDS54503

Canonical transcript exons

ENST00000440238 — 21 exons

Exon	Start	End
ENSE00001296842	20974704	20974816
ENSE00001313897	20980747	20980767
ENSE00001562354	20967255	20967303
ENSE00001618630	20980992	20981358
ENSE00003459056	20974252	20974296
ENSE00003460702	20979271	20979369
ENSE00003469659	20967805	20967975
ENSE00003501740	20977700	20977776
ENSE00003510245	20974063	20974172
ENSE00003511686	20974525	20974621
ENSE00003521701	20977032	20977095
ENSE00003552534	20977888	20978005
ENSE00003587102	20979627	20979702
ENSE00003590512	20980020	20980124
ENSE00003615716	20976215	20976306
ENSE00003617023	20976651	20976766
ENSE00003640960	20973758	20973867
ENSE00003670753	20976867	20976938
ENSE00003671229	20976408	20976538
ENSE00003690609	20973307	20973520
ENSE00003784931	20975692	20975778

Expression profiles

Bgee: expression breadth ubiquitous, 180 present calls, max score 97.84.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.4580 / max 81.1222, expressed in 152 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
191176	1.0274	102
191174	0.3446	120
191175	0.0860	60

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	97.84	gold quality
right frontal lobe	UBERON:0002810	96.11	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.54	gold quality
anterior cingulate cortex	UBERON:0009835	95.33	gold quality
Brodmann (1909) area 9	UBERON:0013540	94.82	gold quality
caudate nucleus	UBERON:0001873	94.61	gold quality
cerebellar hemisphere	UBERON:0002245	94.43	gold quality
amygdala	UBERON:0001876	94.41	gold quality
cerebellar cortex	UBERON:0002129	94.28	gold quality
nucleus accumbens	UBERON:0001882	93.55	gold quality
putamen	UBERON:0001874	93.48	gold quality
prefrontal cortex	UBERON:0000451	92.67	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	92.52	gold quality
cerebellum	UBERON:0002037	92.46	gold quality
hypothalamus	UBERON:0001898	91.84	gold quality
transverse colon	UBERON:0001157	90.90	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	90.70	gold quality
frontal cortex	UBERON:0001870	90.61	gold quality
neocortex	UBERON:0001950	90.28	gold quality
primary visual cortex	UBERON:0002436	88.89	gold quality
cerebral cortex	UBERON:0000956	88.67	gold quality
forebrain	UBERON:0001890	88.34	gold quality
substantia nigra	UBERON:0002038	88.22	gold quality
spinal cord	UBERON:0002240	88.16	gold quality
brain	UBERON:0000955	88.15	gold quality
Ammon’s horn	UBERON:0001954	87.90	gold quality
rectum	UBERON:0001052	87.67	gold quality
temporal lobe	UBERON:0001871	86.74	gold quality
midbrain	UBERON:0001891	85.05	gold quality
granulocyte	CL:0000094	84.96	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.66

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

22 targeting AIFM3, 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-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-4763-5P	98.75	63.89	854
HSA-MIR-6873-5P	98.45	66.14	1417
HSA-MIR-6742-3P	97.95	64.50	1490
HSA-MIR-6747-3P	97.73	64.84	1596
HSA-MIR-4313	97.18	63.15	420
HSA-MIR-5588-3P	94.96	65.59	500
HSA-MIR-210-3P	92.54	65.16	165

Literature-anchored findings (GeneRIF, showing 10)

• AIFL has 598 amino acids, with a characteristic Rieske domain and a pyridine nucleotide-disulfide oxidoreductase domain (Pyr_redox). AIFL shares 35% homology with AIF, mainly in the Pyr_redox domain. (PMID:15764604)
• AIF maintains the transformed state of colon cancer cells through its NADH oxidase activity, by mechanisms that involve complex I function. (PMID:16001080)
• H. pylori triggers apoptosis in AGS cells via interaction with death receptors in the plasma membrane, leading to the cleavage of procaspase-8, release of cytochrome c and AIF from mitochondria, and activation of subsequent downstream apoptotic events (PMID:19166416)
• AIFM3 is a direct target of miR-210 in human hepatoma cells. (PMID:22387901)
• The expression of apoptosis-inducing factor was identified in pineal gland and thymus, but it did not change with age. (PMID:22550867)
• Upregulated expression of AIFM3 is associated with cholangiocarcinoma. (PMID:27473083)
• AIFM3 was significantly more expressed in breast cancer tissues than in normal tissues. There was a significant association of AIFM3 expression with tumor size, lymph node metastasis, molecular typing and TNM staging. Lymph node metastasis and TNM stage were independent factors of AIFM3 expression. High AIFM3 expression was related to a shorter OS and DFS. (PMID:31088422)
• Apoptosis-Inducing Factor, Mitochondrion-Associated 3 (AIFM3) Protein Level in the Sera as a Prognostic Marker of Cholangiocarcinoma Patients. (PMID:32664187)
• CRKL, AIFM3, AIF, BCL2, and UBASH3A during Human Kidney Development. (PMID:34502088)
• Bioinformatic Prediction of Novel Signaling Pathways of Apoptosis-inducing Factor, Mitochondrion-associated 3 (AIFM3) and Their Roles in Metastasis of Cholangiocarcinoma Cells. (PMID:34949658)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	aifm3	ENSDARG00000062780
mus_musculus	Aifm3	ENSMUSG00000022763
rattus_norvegicus	Aifm3	ENSRNOG00000037957
drosophila_melanogaster	CG4199	FBGN0025628
drosophila_melanogaster	CG10700	FBGN0032754
caenorhabditis_elegans		WBGENE00017640

Paralogs (7): DLD (ENSG00000091140), GSR (ENSG00000104687), PYROXD1 (ENSG00000121350), AIFM1 (ENSG00000156709), TXNRD2 (ENSG00000184470), TXNRD3 (ENSG00000197763), TXNRD1 (ENSG00000198431)

Protein

Protein identifiers

Apoptosis-inducing factor 3 — Q96NN9 (reviewed: Q96NN9)

Alternative names: Apoptosis-inducing factor-like protein

All UniProt accessions (5): C9JPU8, C9K029, Q96NN9, F8WC30, F8WFB6

UniProt curated annotations — full annotation on UniProt →

Function. Induces apoptosis through a caspase dependent pathway. Reduces mitochondrial membrane potential.

Subcellular location. Mitochondrion.

Tissue specificity. Ubiquitous. Expressed in bone marrow, cerebral cortex, liver, ovary, thymus, thyroid gland and tongue (at protein level).

Domain organisation. The Rieske domain induces apoptosis.

Similarity. Belongs to the FAD-dependent oxidoreductase family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96NN9-1	1	yes
Q96NN9-2	2
Q96NN9-3	3

RefSeq proteins (4): NP_001018070, NP_001139760, NP_001373743, NP_653305 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR016156	FAD/NAD-linked_Rdtase_dimer_sf	Homologous_superfamily
IPR017941	Rieske_2Fe-2S	Domain
IPR023753	FAD/NAD-binding_dom	Domain
IPR028202	Reductase_C	Domain
IPR036188	FAD/NAD-bd_sf	Homologous_superfamily
IPR036922	Rieske_2Fe-2S_sf	Homologous_superfamily
IPR050446	FAD-oxidoreductase/Apoptosis	Family

Pfam: PF00355, PF07992, PF14759

UniProt features (17 total): binding site 10, splice variant 2, chain 1, domain 1, sequence variant 1, sequence conflict 1, region of interest 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
6SK8	X-RAY DIFFRACTION	1.87
6SK2	X-RAY DIFFRACTION	1.9
6SJZ	X-RAY DIFFRACTION	2
5O9V	X-RAY DIFFRACTION	2.2
6QRM	X-RAY DIFFRACTION	2.3
6SK3	X-RAY DIFFRACTION	2.7
6SKJ	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96NN9-F1	88.47	0.81

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 (10): 270; 467; 514; 109; 111; 128; 131; 201–205; 235; 240

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 46 (showing top): RNGTGGGC_UNKNOWN, TGACCTY_ERR1_Q2, GOCC_MITOCHONDRIAL_ENVELOPE, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_NAD_P_H, CCCNNGGGAR_OLF1_01, GOBP_EXECUTION_PHASE_OF_APOPTOSIS, GOCC_ORGANELLE_INNER_MEMBRANE, GOMF_METAL_CLUSTER_BINDING, GOMF_2_IRON_2_SULFUR_CLUSTER_BINDING, MIKKELSEN_MCV6_HCP_WITH_H3K27ME3, GOCC_ORGANELLE_ENVELOPE, MIKKELSEN_MEF_HCP_WITH_H3K27ME3, MARTENS_TRETINOIN_RESPONSE_UP, CAHOY_ASTROCYTIC, ZNF436_TARGET_GENES

GO Biological Process (2): execution phase of apoptosis (GO:0097194), apoptotic process (GO:0006915)

GO Molecular Function (5): oxidoreductase activity, acting on NAD(P)H (GO:0016651), metal ion binding (GO:0046872), 2 iron, 2 sulfur cluster binding (GO:0051537), oxidoreductase activity (GO:0016491), iron-sulfur cluster binding (GO:0051536)

GO Cellular Component (4): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), endoplasmic reticulum (GO:0005783), cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	3
intracellular membrane-bounded organelle	2
apoptotic process	1
cellular process	1
bleb assembly	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
oxidoreductase activity	1
cation binding	1
iron-sulfur cluster binding	1
catalytic activity	1
metal cluster binding	1
organelle inner membrane	1
mitochondrial membrane	1
endomembrane system	1
cellular anatomical structure	1

Protein interactions and networks

STRING

2032 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AIFM3	THAP7	Q9BT49	646
AIFM3	SLC7A4	O43246	564
AIFM3	SNAP29	O95721	553
AIFM3	P2RX6	O15547	532
AIFM3	PI4KA	P42356	515
AIFM3	KLHL22	Q53GT1	502
AIFM3	ACAD9	Q9H845	460
AIFM3	SCARF2	Q96GP6	453
AIFM3	TANGO2	Q6ICL3	445
AIFM3	LZTR1	Q8N653	444
AIFM3	MED15	Q96RN5	428
AIFM3	ZNF74	Q16587	420
AIFM3	TBX1	O43435	410
AIFM3	CRKL	P46109	406
AIFM3	AIFM2	Q9BRQ8	403

IntAct

4 interactions, top by confidence:

A	B	Type	Score
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350
AIFM3	NMT2	psi-mi:“MI:0914”(association)	0.350
AIFM3	PRNP	psi-mi:“MI:0407”(direct interaction)	0.000

BioGRID (15): FDPS (Co-fractionation), PPIF (Co-fractionation), AIFM3 (Reconstituted Complex), AIFM3 (Affinity Capture-MS), NMT2 (Affinity Capture-MS), NMT1 (Affinity Capture-MS), PGK2 (Affinity Capture-MS), LZTR1 (Affinity Capture-MS), NMT1 (Affinity Capture-MS), PGK2 (Affinity Capture-MS), GRK6 (Affinity Capture-MS), NMT2 (Affinity Capture-MS), LZTR1 (Affinity Capture-MS), AIFM3 (Reconstituted Complex), APP (Reconstituted Complex)

ESM2 similar proteins: A0A6N3IN21, A3KCL7, A4IFH5, A7MBC0, A7MBI7, D3ZDK7, D3ZDM7, E1BNQ4, P09367, P10950, P11172, P13439, P17256, P20132, P24298, P25409, P31754, P46597, P50053, P97328, Q02974, Q03426, Q0VCW4, Q1JPD3, Q3B8E3, Q3TY86, Q3ZKN0, Q5BJJ5, Q5E9T8, Q5M7T9, Q5R514, Q5R824, Q5RD71, Q5RFE6, Q6PCB7, Q6SKR2, Q80W22, Q8CHP8, Q8CIM3, Q8HZJ0

Diamond homologs: A0KEJ2, A4STH3, A4XSQ1, A5W4E9, A6V3A6, A7ZPY5, A8A348, B1IVT5, B1LNJ8, B1XB17, B6I5B5, B7LDD4, B7N6C9, B7UZU5, C4ZXB7, D5IGG6, G2ITT5, G9F1Y9, O05940, O24679, O50286, O50311, P08087, P09063, P0C621, P14218, P16640, P17052, P31052, P32382, P33009, P37337, P43494, P43504, P48641, P52992, P54533, P57112, P75393, P77650

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	215
Likely pathogenic	28
Uncertain significance	140
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1172811	GRCh37/hg19 22q11.21(chr22:18873001-21469900)	Pathogenic
1180537	GRCh37/hg19 22q11.21(chr22:18841374-21465101)x3	Pathogenic
1180539	GRCh37/hg19 22q11.21(chr22:18889977-21463189)x3	Pathogenic
1180541	GRCh37/hg19 22q11.21(chr22:20730996-21465342)x1	Pathogenic
144398	GRCh38/hg38 22q11.21(chr22:18339130-21207225)x3	Pathogenic
144399	GRCh38/hg38 22q11.21(chr22:18339130-21207225)x1	Pathogenic
144405	GRCh38/hg38 22q11.21(chr22:18339130-21151128)x3	Pathogenic
144407	GRCh38/hg38 22q11.21(chr22:18339130-21151128)x4	Pathogenic
144617	GRCh38/hg38 22q11.21(chr22:18339130-21086226)x1	Pathogenic
144688	GRCh38/hg38 22q11.21(chr22:18178932-21151156)x3	Pathogenic
144691	GRCh38/hg38 22q11.21(chr22:18178932-21151156)x1	Pathogenic
145117	GRCh38/hg38 22q11.21(chr22:18339130-21107463)x3	Pathogenic
145118	GRCh38/hg38 22q11.21(chr22:18339130-21107463)x1	Pathogenic
145119	GRCh38/hg38 22q11.21(chr22:20726972-21086166)x3	Pathogenic
145469	GRCh38/hg38 22q11.21(chr22:18145380-21086226)x1	Pathogenic
145982	GRCh38/hg38 22q11.21(chr22:18168847-21086166)x3	Pathogenic
146133	GRCh38/hg38 22q11.21(chr22:18339130-21207225)x3	Pathogenic
146204	GRCh38/hg38 22q11.21(chr22:18178957-21086225)x3	Pathogenic
146309	GRCh38/hg38 22q11.21(chr22:20671366-21151128)x4	Pathogenic
146640	GRCh38/hg38 22q11.21(chr22:18339130-21003834)x3	Pathogenic
146800	GRCh38/hg38 22q11.21(chr22:20400117-21086226)x1	Pathogenic
147308	GRCh38/hg38 22q11.21(chr22:18178957-21307146)x3	Pathogenic
147591	GRCh38/hg38 22q11.21(chr22:18339130-21441926)x1	Pathogenic
147645	GRCh38/hg38 22q11.21(chr22:18339130-21028664)x1	Pathogenic
148430	GRCh38/hg38 22q11.21(chr22:18178957-21107522)x1	Pathogenic
148898	GRCh38/hg38 22q11.21(chr22:18339130-21109830)x1	Pathogenic
149111	GRCh38/hg38 22q11.21(chr22:18339130-21107522)x1	Pathogenic
149129	GRCh38/hg38 22q11.21(chr22:18339130-21454720)x3	Pathogenic
149307	GRCh38/hg38 22q11.21(chr22:18339130-21109830)x1	Pathogenic
149698	GRCh38/hg38 22q11.21(chr22:18178957-21109830)x1	Pathogenic

SpliceAI

3642 predictions. Top by Δscore:

Variant	Effect	Δscore
22:20973305:A:AG	acceptor_gain	1.0000
22:20973305:AGT:A	acceptor_gain	1.0000
22:20973305:AGTG:A	acceptor_gain	1.0000
22:20973306:G:GG	acceptor_gain	1.0000
22:20973306:GT:G	acceptor_gain	1.0000
22:20973306:GTG:G	acceptor_gain	1.0000
22:20973306:GTGG:G	acceptor_gain	1.0000
22:20973306:GTGGA:G	acceptor_gain	1.0000
22:20973504:G:GT	donor_gain	1.0000
22:20973521:G:GG	donor_gain	1.0000
22:20974058:CCCA:C	acceptor_loss	1.0000
22:20974059:CCAGG:C	acceptor_loss	1.0000
22:20974060:CAGG:C	acceptor_loss	1.0000
22:20974061:A:AG	acceptor_gain	1.0000
22:20974061:AG:A	acceptor_gain	1.0000
22:20974061:AGGC:A	acceptor_gain	1.0000
22:20974062:G:A	acceptor_loss	1.0000
22:20974062:G:GG	acceptor_gain	1.0000
22:20974062:GG:G	acceptor_gain	1.0000
22:20974062:GGC:G	acceptor_gain	1.0000
22:20974062:GGCG:G	acceptor_gain	1.0000
22:20974062:GGCGT:G	acceptor_gain	1.0000
22:20974168:TCCAG:T	donor_loss	1.0000
22:20974170:CAGG:C	donor_loss	1.0000
22:20974171:AG:A	donor_loss	1.0000
22:20974173:G:A	donor_loss	1.0000
22:20974699:CTCA:C	acceptor_loss	1.0000
22:20974700:TCA:T	acceptor_loss	1.0000
22:20974701:CA:C	acceptor_loss	1.0000
22:20974702:A:AT	acceptor_loss	1.0000

AlphaMissense

3950 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:20973837:T:C	C109R	0.999
22:20973867:G:C	G119R	0.999
22:20974089:T:C	C128R	0.999
22:20974280:T:A	V165D	0.999
22:20980045:A:C	S560R	0.999
22:20980047:C:A	S560R	0.999
22:20980047:C:G	S560R	0.999
22:20973823:C:A	A104D	0.998
22:20973837:T:A	C109S	0.998
22:20973838:G:C	C109S	0.998
22:20973839:T:G	C109W	0.998
22:20974091:C:G	C128W	0.998
22:20974110:T:C	F135L	0.998
22:20974112:C:A	F135L	0.998
22:20974112:C:G	F135L	0.998
22:20974734:T:C	L213P	0.998
22:20974737:G:C	R214P	0.998
22:20979283:C:A	A497D	0.998
22:20973796:T:C	L95P	0.997
22:20973843:C:G	H111D	0.997
22:20973859:T:C	L116P	0.997
22:20974063:G:A	G119D	0.997
22:20974090:G:A	C128Y	0.997
22:20974100:C:A	H131Q	0.997
22:20974100:C:G	H131Q	0.997
22:20974126:G:A	G140E	0.997
22:20974721:T:C	C209R	0.997
22:20974723:T:G	C209W	0.997
22:20974816:G:C	K240N	0.997
22:20974816:G:T	K240N	0.997

dbSNP variants (sampled 300 via entrez): RS1000008615 (22:20981672 C>T), RS1000135923 (22:20972547 C>T), RS1000184275 (22:20970593 T>A,C), RS1000208483 (22:20972862 T>C), RS1000422433 (22:20970862 C>G), RS1000769328 (22:20965841 C>G), RS1000811269 (22:20966882 C>A,T), RS1000878727 (22:20967700 C>T), RS1001390438 (22:20980663 C>T), RS1001426038 (22:20975594 C>T), RS1002215285 (22:20970285 C>G), RS1002301216 (22:20978297 T>TGG), RS1002318221 (22:20967911 C>T), RS1002337916 (22:20967759 A>C,G), RS1002478795 (22:20968827 C>A)

Disease associations

OMIM: gene MIM:617298 | disease phenotypes: MIM:608363, MIM:188400, MIM:611867, MIM:181500, MIM:209850, MIM:192430

GenCC curated gene-disease

Mondo (15): cerebral palsy (MONDO:0006497), chromosome 22q11.2 microduplication syndrome (MONDO:0012020), 22q11.2 deletion syndrome (MONDO:0018923), DiGeorge syndrome (MONDO:0008564), chromosome 22q11.2 deletion syndrome, distal (MONDO:0012740), schizophrenia (MONDO:0005090), autism (MONDO:0005260), neurodevelopmental disorder (MONDO:0700092), velocardiofacial syndrome (MONDO:0008644), oppositional defiant disorder (MONDO:0000495), attention deficit-hyperactivity disorder (MONDO:0007743), megacolon (MONDO:0001273), hydronephrosis (MONDO:0005510), intellectual disability (MONDO:0001071), epilepsy (MONDO:0005027)

Orphanet (7): 22q11.2 duplication syndrome (Orphanet:1727), Syndromic anorectal malformation (Orphanet:117573), 22q11.2 deletion syndrome (Orphanet:567), Distal 22q11.2 microdeletion syndrome (Orphanet:261330), Non-syndromic bicoronal craniosynostosis (Orphanet:35099), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

4 total (4 of 4 shown, HPO-id order):

HPO	Term
HP:0100021	Cerebral palsy
HP:0100753	Schizophrenia
HP:0000717	Autism
HP:0010865	Oppositional defiant disorder

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002592_12	Neuritic plaque	8.000000e-06
GCST004635_43	Testicular germ cell tumor	2.000000e-08
GCST90013442_36	Keratoconus	4.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006798	neuritic plaque measurement

MeSH disease descriptors (11)

Descriptor	Name	Tree numbers
D019958	Attention Deficit and Disruptive Behavior Disorders	F03.625.094
D001321	Autistic Disorder	F03.625.164.113.500
D002547	Cerebral Palsy	C10.228.140.140.254
D004062	DiGeorge Syndrome	C05.660.207.103.500; C14.240.400.021.500; C14.280.400.044.500; C15.604.451.249.500; C16.131.077.019.500; C16.131.240.400.021.500; C16.131.260.019.500; C16.131.482.249.500; C16.131.621.207.103.500; C16.320.180.019.500; C19.642.482.500.500
D004827	Epilepsy	C10.228.140.490
D006869	Hydronephrosis	C12.050.351.968.419.307; C12.200.777.419.307; C12.950.419.307
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008531	Megacolon	C06.405.469.158.701
D065886	Neurodevelopmental Disorders	F03.625
C567511	Chromosome 22q11.2 Deletion Syndrome, Distal (supp.)
C567224	Chromosome 22q11.2 Microduplication Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, increases methylation	4
(+)-JQ1 compound	decreases expression	2
Benzo(a)pyrene	affects methylation, increases methylation	2
aristolochic acid I	increases expression	1
OTX015	decreases expression	1
mivebresib	decreases expression	1
methylmercuric chloride	decreases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
trichostatin A	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	decreases expression	1
1-hydroxypyrene	decreases expression	1
pentanal	decreases expression	1
buprofezin	increases expression	1
pinostrobin	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Air Pollutants, Occupational	decreases expression	1
Camptothecin	decreases response to substance	1
Copper	affects cotreatment, decreases expression	1
Diazinon	increases methylation	1
Ozone	affects expression, increases abundance	1
Smoke	decreases expression	1
Urethane	decreases expression	1
Cyclosporine	decreases expression	1
Copper Sulfate	decreases expression	1
Particulate Matter	decreases expression, increases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7G2	Ubigene HEK293T AIFM3 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00154830	PHASE4	COMPLETED	Alterations of Functional Activities and Leg Stiffness After Hamstring Lengthening in Cerebral Palsy Children
NCT00432055	PHASE4	COMPLETED	Effects of Botulinum Toxin Type A in Adults With Cerebral Palsy
NCT00549471	PHASE4	TERMINATED	Improvement After Botulinum Toxin Injections to the Arms in Children With Cerebral Palsy
NCT00752934	PHASE4	TERMINATED	Does Oral Baclofen Improve Care and Comfort in Spastic Children in Nursing Homes?
NCT00964639	PHASE4	COMPLETED	Postoperative Pain in Children With Cerebral Palsy After Pelvic and Femoral Osteotomies
NCT01386255	PHASE4	WITHDRAWN	Placebo Controlled Study of Baclofen for GERD in Children With Cerebral Palsy
NCT02546999	PHASE4	COMPLETED	Does Botulinum Toxin A Make Walking Easier in Children With Cerebral Palsy?
NCT02633241	PHASE4	COMPLETED	A Pilot Study of Dexmedetomidine-Propofol in Children Undergoing Magnetic Resonance Imaging
NCT03117322	PHASE4	COMPLETED	Synbiotic, Prebiotics and Probiotics in Children With Cerebral Palsy and Constipation
NCT03648658	PHASE4	UNKNOWN	Paracetamol Study in Patients With Low Muscle Mass
NCT04074265	PHASE4	COMPLETED	Peri-operative Use of a Pain Injection in Pediatric Patients With Cerebral Palsy
NCT04273737	PHASE4	TERMINATED	Amantadine in Treating Cognitive & Motor Impairments in Adolescents and Adults With Cerebral Palsy
NCT04523935	PHASE4	COMPLETED	Excessive Crying in Children With Cerebral Palsy and Communication Deficits
NCT05887765	PHASE4	COMPLETED	Effect of Systematic Dexamethasone on the Duration of Popliteal Nerve Block for Anesthesia After Pediatric Ankle Surgery
NCT06176430	PHASE4	UNKNOWN	Comparison of Twice Weekly Versus Daily Iron Therapy in Treating Anemia in Children With Cerebral Palsy
NCT06189781	PHASE4	RECRUITING	Pain Injection Versus Epidural Anesthesia for Hip Surgery in Pediatric Patients With Cerebral Palsy
NCT00014989	PHASE3	COMPLETED	Beneficial Effects of Antenatal Magnesium Sulfate (BEAM Trial)
NCT00065949	PHASE3	UNKNOWN	Magnesium Sulfate to Prevent Brain Injury in Premature Infants
NCT00367068	PHASE3	COMPLETED	Dutch National ITB Study in Children With Cerebral Palsy
NCT00491894	PHASE3	COMPLETED	Safety and Efficacy Study of Oral Glycopyrrolate Liquid for the Treatment of Pathologic (Chronic Moderate to Severe) Drooling in Pediatric Patients 3 to 18 Years of Age With Cerebral Palsy or Other Neurologic Conditions
NCT00632528	PHASE3	COMPLETED	MEOPA to Improve Physical Therapy Results After Multilevel Surgery
NCT00822029	PHASE3	TERMINATED	Use of Oral Bisphosphonates in the Treatment of Osteoporosis of Non-walking Children With Cerebral Palsy
NCT00922077	PHASE3	COMPLETED	Individualized Neurodevelopmental Treatment
NCT01249417	PHASE3	COMPLETED	Dysport® Pediatric Lower Limb Spasticity Study
NCT01251380	PHASE3	COMPLETED	Dysport® Pediatric Lower Limb Spasticity Follow-on Study
NCT01437644	PHASE3	COMPLETED	The Post-Operative Pain in Cerebral Palsy (POPPIES) Trial
NCT01492608	PHASE3	COMPLETED	Magnesium Sulphate for Preterm Birth (MASP Study)
NCT01603602	PHASE3	COMPLETED	BOTOX® Treatment in Pediatric Upper Limb Spasticity
NCT01603615	PHASE3	COMPLETED	BOTOX® Open-Label Treatment in Pediatric Upper Limb Spasticity
NCT01603628	PHASE3	COMPLETED	BOTOX® Treatment in Pediatric Lower Limb Spasticity
NCT01603641	PHASE3	COMPLETED	BOTOX® Open-Label Treatment in Pediatric Lower Limb Spasticity
NCT01633736	PHASE3	UNKNOWN	Targeted Hip Strength Training in Children With Cerebral Palsy (CP)
NCT01898520	PHASE3	COMPLETED	A Safety, Efficacy and Tolerability Study of Sativex for the Treatment of Spasticity in Children Aged 8 to 18 Years
NCT01929434	PHASE3	COMPLETED	Efficacy of Stem Cell Transplantation Compared to Rehabilitation Treatment of Patients With Cerebral Paralysis
NCT02002884	PHASE3	COMPLETED	Dose-response Study of Efficacy and Safety of Botulinum Toxin Type A to Treat Spasticity of the Arm(s) or of Arm(s) and Leg(s) in Cerebral Palsy
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02839785	PHASE3	TERMINATED	Analgesia and Physiotherapy in Children With Cerebral Palsy (ANTALKINECP)
NCT03110341	PHASE3	UNKNOWN	Effect of Erythropoietin in Premature Infants on White Matter Lesions and Neurodevelopmental Outcome
NCT03302871	PHASE3	COMPLETED	Integrated Management Enhances Functional Gains in Children With Cerebral Palsy Treated by BoNT-A
NCT03306212	PHASE3	COMPLETED	Efficacy of Intermittent Serial Casting on Spastic Wrist Flexion Deformity