ACO2

Summary

ACO2 (aconitase 2, HGNC:118) is a protein-coding gene on chromosome 22q13.2, encoding Aconitate hydratase, mitochondrial (Q99798). Catalyzes the isomerization of citrate to isocitrate via cis-aconitate. It is a selective cancer dependency (DepMap: 64.2% of cell lines).

The protein encoded by this gene belongs to the aconitase/IPM isomerase family. It is an enzyme that catalyzes the interconversion of citrate to isocitrate via cis-aconitate in the second step of the TCA cycle. This protein is encoded in the nucleus and functions in the mitochondrion. It was found to be one of the mitochondrial matrix proteins that are preferentially degraded by the serine protease 15(PRSS15), also known as Lon protease, after oxidative modification.

Source: NCBI Gene 50 — RefSeq curated summary.

At a glance

• Gene–disease (curated): optic atrophy 9 (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 5
• Clinical variants (ClinVar): 976 total — 53 pathogenic, 39 likely-pathogenic (top 3% of genes corpus-wide)
• Regional missense constraint (gnomAD): 1 of 5 regions constrained (≈4% of expected missense variation)
• GTEx eGene: eQTL in 29 tissues, sQTL in 29 (q < 0.05)
• Phenotypes (HPO): 32
• Cancer dependency (DepMap): dependent in 64.2% of screened cell lines
• Constraint (gnomAD): pLI 0.98 (loss-of-function intolerant), LOEUF 0.49 (moderately constrained)
• MANE Select transcript: NM_001098
• Interaction hub: 3,574 STRING partners (top 1% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:118
Approved symbol	ACO2
Name	aconitase 2
Location	22q13.2
Locus type	gene with protein product
Status	Approved
Aliases	ACONM
Ensembl gene	ENSG00000100412
Ensembl biotype	protein_coding
OMIM	100850
Entrez	50

Gene structure

Transcript identifiers

Ensembl transcripts: 69 — 34 protein_coding, 22 nonsense_mediated_decay, 12 retained_intron, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000216254

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 1, TSL 3: 3, TSL 5: 1

ENST00000216254, ENST00000396512, ENST00000466237, ENST00000471094, ENST00000478010, ENST00000482208, ENST00000676664, ENST00000676714, ENST00000676748, ENST00000676792, ENST00000676822, ENST00000676883, ENST00000676959, ENST00000677007, ENST00000677153, ENST00000677427, ENST00000677492, ENST00000677516, ENST00000677532, ENST00000677554, ENST00000677698, ENST00000678394, ENST00000678454, ENST00000678600, ENST00000678688, ENST00000678788, ENST00000678819, ENST00000679264, ENST00000679284, ENST00000679311, ENST00000679320, ENST00000878384, ENST00000878385, ENST00000878386, ENST00000878387, ENST00000878388, ENST00000878389, ENST00000878390, ENST00000878391, ENST00000923519, ENST00000923520, ENST00000953703, ENST00000953704, ENST00000953705, ENST00000953706, ENST00000953707, ENST00000953708, ENST00000953709, ENST00000953710, ENST00000984535, ENST00000984536, ENST00000984537, ENST00001043267, ENST00001043268, ENST00001043270, ENST00001043277, ENST00001043280, ENST00001043281, ENST00001043284, ENST00001065347, ENST00001065350, ENST00001065351, ENST00001065352, ENST00001104602, ENST00001104603, ENST00001104604, ENST00001119689, ENST00001130915, ENST00001132846

RefSeq mRNA: 1 — MANE Select: NM_001098 NM_001098

CCDS: CCDS14017

Canonical transcript exons

ENST00000216254 — 18 exons

Exon	Start	End
ENSE00000655866	41522830	41522987
ENSE00000655869	41523205	41523278
ENSE00000655874	41523830	41523941
ENSE00000655877	41524846	41524968
ENSE00000655880	41525193	41525348
ENSE00000655884	41526262	41526453
ENSE00000655886	41527288	41527420
ENSE00000655890	41527901	41528022
ENSE00001176200	41499726	41499862
ENSE00001340994	41469117	41469182
ENSE00003472516	41515767	41515917
ENSE00003509924	41520171	41520276
ENSE00003535455	41511876	41511968
ENSE00003540387	41515377	41515535
ENSE00003562818	41507791	41508049
ENSE00003607158	41517527	41517631
ENSE00003687143	41518481	41518572
ENSE00003848339	41528479	41528974

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 99.53.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 62.7078 / max 740.5226, expressed in 1826 samples.

Highest expression (Bgee): heart right ventricle, apex of heart, ventricle myocardium, cardiac ventricle, heart left ventricle.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ACO2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 29 tissues and its splicing (sQTL) in 29 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 58 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Skin Sun Exposed Lower leg	sqtl	1.7e-111	+1.17	22:41517473:T:C
Skin Not Sun Exposed Suprapubic	sqtl	6.7e-81	+1.10	22:41517473:T:C
Adipose Subcutaneous	sqtl	7.1e-66	+0.84	22:41517473:T:C
Nerve Tibial	sqtl	1.8e-62	+0.91	22:41517473:T:C
Artery Tibial	sqtl	1.3e-60	+0.86	22:41529531:T:C
Whole Blood	sqtl	7.5e-57	+0.87	22:41517473:T:C
Lung	sqtl	6.6e-49	+0.79	22:41517473:T:C
Esophagus Mucosa	sqtl	7.1e-45	+0.85	22:41517473:T:C
Adipose Visceral Omentum	sqtl	4.1e-41	+0.80	22:41529531:T:C
Breast Mammary Tissue	sqtl	1.3e-40	+0.95	22:41517473:T:C
Testis	sqtl	5.4e-36	-1.16	22:41517473:T:C
Artery Aorta	sqtl	1.6e-27	-0.86	22:41507739:G:T
Lung	eqtl	4.3e-25	+0.31	22:41554893:G:A
Spleen	sqtl	4.7e-22	+0.96	22:41545745:T:C
Nerve Tibial	eqtl	1.1e-21	-0.28	22:41460133:T:A
Stomach	sqtl	1.9e-19	-0.76	22:41517473:T:C
Pituitary	sqtl	6.9e-19	-0.99	22:41517473:T:C
Esophagus Gastroesophageal Junction	sqtl	1.1e-17	-0.73	22:41529531:T:C
Pancreas	sqtl	1.5e-15	-0.78	22:41517473:T:C
Prostate	sqtl	4.1e-15	-0.96	22:41517473:T:C

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
192477	61.7790	1825
192476	0.7558	432
192478	0.1730	84

Top tissues by expression

showing 100 of 298 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
heart right ventricle	UBERON:0002080	99.53	gold quality
apex of heart	UBERON:0002098	99.41	gold quality
left ventricle myocardium	UBERON:0006566	99.30	gold quality
cardiac ventricle	UBERON:0002082	99.24	gold quality
heart left ventricle	UBERON:0002084	99.23	gold quality
gastrocnemius	UBERON:0001388	99.13	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.12	gold quality
right atrium auricular region	UBERON:0006631	99.11	gold quality
cardiac atrium	UBERON:0002081	99.10	gold quality
myocardium	UBERON:0002349	99.06	gold quality
jejunal mucosa	UBERON:0000399	99.00	gold quality
cardiac muscle of right atrium	UBERON:0003379	98.98	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.84	gold quality
vastus lateralis	UBERON:0001379	98.80	gold quality
diaphragm	UBERON:0001103	98.75	gold quality
skeletal muscle tissue	UBERON:0001134	98.75	gold quality
right frontal lobe	UBERON:0002810	98.75	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.75	gold quality
muscle of leg	UBERON:0001383	98.70	gold quality
muscle organ	UBERON:0001630	98.65	gold quality
skeletal muscle organ	UBERON:0014892	98.65	gold quality
duodenum	UBERON:0002114	98.62	gold quality
triceps brachii	UBERON:0001509	98.60	gold quality
heart	UBERON:0000948	98.57	gold quality
deltoid	UBERON:0001476	98.56	gold quality
body of tongue	UBERON:0011876	98.56	gold quality
cingulate cortex	UBERON:0003027	98.55	gold quality
biceps brachii	UBERON:0001507	98.54	gold quality
anterior cingulate cortex	UBERON:0009835	98.52	gold quality
amygdala	UBERON:0001876	98.51	gold quality
prefrontal cortex	UBERON:0000451	98.47	gold quality
lateral nuclear group of thalamus	UBERON:0002736	98.42	gold quality
gluteal muscle	UBERON:0002000	98.41	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	98.41	gold quality
ileal mucosa	UBERON:0000331	98.40	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.37	gold quality
nucleus accumbens	UBERON:0001882	98.34	gold quality
quadriceps femoris	UBERON:0001377	98.32	gold quality
adult mammalian kidney	UBERON:0000082	98.22	gold quality
adult organism	UBERON:0007023	98.18	gold quality
muscle tissue	UBERON:0002385	98.15	gold quality
caudate nucleus	UBERON:0001873	98.14	gold quality
putamen	UBERON:0001874	98.13	gold quality
temporal lobe	UBERON:0001871	98.11	gold quality
frontal cortex	UBERON:0001870	98.06	gold quality
postcentral gyrus	UBERON:0002581	98.03	gold quality
jejunum	UBERON:0002115	98.00	gold quality
lateral globus pallidus	UBERON:0002476	97.99	gold quality
neocortex	UBERON:0001950	97.97	gold quality
cerebral cortex	UBERON:0000956	97.93	gold quality
telencephalon	UBERON:0001893	97.92	gold quality
Ammon’s horn	UBERON:0001954	97.91	gold quality
parietal lobe	UBERON:0001872	97.87	gold quality
mucosa of transverse colon	UBERON:0004991	97.87	gold quality
Brodmann (1909) area 46	UBERON:0006483	97.79	gold quality
substantia nigra pars compacta	UBERON:0001965	97.77	gold quality
superior frontal gyrus	UBERON:0002661	97.72	gold quality
colonic mucosa	UBERON:0000317	97.65	gold quality
entorhinal cortex	UBERON:0002728	97.64	gold quality
hypothalamus	UBERON:0001898	97.63	gold quality
parotid gland	UBERON:0001831	97.60	gold quality
body of stomach	UBERON:0001161	97.58	gold quality
tibialis anterior	UBERON:0001385	97.54	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.50	gold quality
mucosa of sigmoid colon	UBERON:0004993	97.50	gold quality
transverse colon	UBERON:0001157	97.43	gold quality
forebrain	UBERON:0001890	97.42	gold quality
substantia nigra	UBERON:0002038	97.41	gold quality
small intestine	UBERON:0002108	97.34	gold quality
inferior olivary complex	UBERON:0002127	97.34	gold quality
midbrain	UBERON:0001891	97.31	gold quality
brain	UBERON:0000955	97.28	gold quality
central nervous system	UBERON:0001017	97.26	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.25	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.25	gold quality
lower esophagus	UBERON:0013473	97.23	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.17	gold quality
orbitofrontal cortex	UBERON:0004167	97.16	gold quality
right adrenal gland	UBERON:0001233	97.08	gold quality
pons	UBERON:0000988	97.07	gold quality
cerebellar hemisphere	UBERON:0002245	97.06	gold quality
cerebellar cortex	UBERON:0002129	97.05	gold quality
dorsal plus ventral thalamus	UBERON:0001897	97.03	gold quality
right adrenal gland cortex	UBERON:0035827	97.01	gold quality
middle temporal gyrus	UBERON:0002771	97.00	gold quality
kidney	UBERON:0002113	96.94	gold quality
cerebellum	UBERON:0002037	96.92	gold quality
vena cava	UBERON:0004087	96.91	gold quality
stomach	UBERON:0000945	96.82	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.80	gold quality
left adrenal gland	UBERON:0001234	96.74	gold quality
tongue	UBERON:0001723	96.73	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.72	gold quality
superior vestibular nucleus	UBERON:0007227	96.71	gold quality
colon	UBERON:0001155	96.70	gold quality
intestine	UBERON:0000160	96.69	gold quality
large intestine	UBERON:0000059	96.67	gold quality
inferior vagus X ganglion	UBERON:0005363	96.65	gold quality
metanephros cortex	UBERON:0010533	96.62	gold quality
spinal cord	UBERON:0002240	96.61	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.19

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 78 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Tongue	tissue	650.0
Skeletal muscle	tissue	618.6	medium
Caudate putamen	tissue	456.9
Heart muscle	tissue	442.8	high
Frontal cortex	tissue	414.3
Parathyroid gland	tissue	219.6	high
Postcentral gyrus	tissue	213.3
Choroid plexus	tissue	188.8
Cerebral cortex	tissue	178.5	high
Somatosensory cortex	tissue	178.5
Motor cortex	tissue	177.6
Superior colliculi	tissue	167.6
Thalamus	tissue	167.1
Hippocampus	tissue	163.1	high
Putamen	tissue	160.0
Occipital cortex	tissue	157.4
Duodenum	tissue	153.4	high
Pons	tissue	152.8
Small intestine	tissue	149.5	high
Prefrontal cortex	tissue	149.1
Midbrain	tissue	147.1
Nucleus accumbens	tissue	146.9
Temporal cortex	tissue	145.5
Hippocampal formation	tissue	144.1
Entorhinal cortex	tissue	144.1
Spinal cord	tissue	142.9
Retrosplenial cortex	tissue	142.4
Basal ganglia	tissue	141.2	high
Insular cortex	tissue	140.6
Medulla oblongata	tissue	140.2
Retrosplenial and cingulate cortex	tissue	140.0
Locus coeruleus	tissue	133.8
Ventral forebrain	tissue	132.0
Kidney	tissue	129.8	high
Substantia nigra	tissue	127.9
Amygdala	tissue	111.0
Septum	tissue	107.9
Hypothalamus	tissue	106.0
Periaqueductal gray	tissue	105.9
Cerebellum	tissue	99.3	high
Corpus callosum	tissue	88.9
Colon	tissue	85.6	high
Adipose tissue	tissue	83.4	not detected
Olfactory bulb	tissue	80.2
Stomach 1	tissue	69.3	high
Salivary gland	tissue	68.0	high
Rectum	tissue	65.5	high
Esophagus	tissue	56.8	high
Fallopian tube	tissue	50.5	high
Thyroid gland	tissue	50.4	high
Liver	tissue	48.7	high
Adrenal gland	tissue	47.2	high
Seminal vesicle	tissue	46.6	high
Pancreas	tissue	45.8	high
Retina	tissue	43.6
Urinary bladder	tissue	43.3	high
Smooth muscle	tissue	40.8	medium
Tonsil	tissue	40.6	high
Prostate	tissue	38.8	high
Lymph node	tissue	38.0	high

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Posterior thalamic nucleus (248.0), Medial dorsal thalamic nucleus (211.1), Lateral thalamic nuclei (204.1), Lateral geniculate body (203.4), Pulvinar (202.1).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

Targeting ACO2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 31 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-4320	99.75	65.80	793
HSA-MIR-5004-3P	99.54	68.27	1371
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-4489	99.50	65.56	785
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-12113	99.32	67.54	1072
HSA-MIR-888-5P	99.30	70.15	1855
HSA-MIR-6846-5P	98.81	65.86	1121
HSA-MIR-6848-5P	98.81	65.49	1126
HSA-MIR-4539	98.78	67.18	888
HSA-MIR-502-5P	98.77	66.51	906
HSA-MIR-5011-3P	98.63	64.81	638
HSA-MIR-4720-3P	98.50	68.88	988
HSA-MIR-4704-3P	98.28	69.33	1300
HSA-MIR-4691-3P	98.11	66.83	1204
HSA-MIR-6841-3P	98.08	66.54	604
HSA-MIR-3157-5P	97.41	67.61	998
HSA-MIR-517-5P	97.13	68.43	781
HSA-MIR-664B-5P	96.74	67.50	509
HSA-MIR-4772-5P	95.60	68.04	617
HSA-MIR-184	94.24	64.40	152
HSA-MIR-127-3P	93.92	66.42	36
HSA-MIR-4749-5P	92.16	62.26	179

Functional genomics

gnomAD constraint: pLI 0.981, LOEUF 0.489, missense Z 4.34 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000216254 splits into 5 regions with different missense tolerance; 1 is missense-constrained (≈4% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
22:41,469,147–41,507,866	98 / 107.6	0.91	no
22:41,507,867–41,515,783	92 / 203.7	0.45	no
22:41,515,784–41,525,297	311 / 441.6	0.70	no
22:41,525,298–41,526,313	10 / 39.7	0.25	yes (p 2.4e-06)
22:41,526,314–41,528,610	174 / 236.6	0.74	no
DepMap (CRISPR cell-line fitness): dependent in 64.2% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): Caov-4 (-2.822), PE/CA-PJ15 (-2.76), SW 1990 (-2.721), SNU-61 (-2.577), KP-N-YN (-2.475), Panc 03.27 (-2.434), SW1116 (-2.216), HUP-T4 (-2.179), A-375 (-2.119), SNU-216 (-1.998), HCC1143 (-1.987), T.T (-1.899), PC-14 (-1.862), HCC38 (-1.853), HCC1187 (-1.821).

Literature-anchored findings (GeneRIF, showing 30)

• Gp50 was a class II ribonucleotide reductase having properties similar to that of the corresponding enzyme from Lactobacillus leichmanni. (PMID:18248423)
• Lon protease selectively recognizes and degrades the oxidized, hydrophobic form of aconitase after mild oxidative modification, but that severe oxidation results in aconitase aggregation, which makes it a poor substrate for Lon. (PMID:12198491)
• ACO2 is often deleted in colorectal cancer but is unlikely to be the true target of the deletions (PMID:12746427)
• The m-aconitase promoter is contained in a 153-bp 5’ fragment lacking a TATA or CAAT sequence. Sp1 binding to specific Sp1 site is needed for promoter activity. Other transcription factors are recruited through protein-protein interactions. (PMID:16598741)
• Manganese acts as an antagonist of iron, disrupting the enzymatic activity and gene expression of mACON and citrate metabolism in the prostate. (PMID:16625280)
• This protein has been found differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia. (PMID:19110265)
• This protein has been found differentially expressed in the Wernicke’s Area from patients with schizophrenia. (PMID:19405953)
• abolishes oxidant-induced apoptosis (PMID:19524665)
• these results suggest that p53 downregulation of mACON gene expression in human prostate carcinoma cells may not occur through the putative consensus p53 response elements found within the mACON promoter. (PMID:20607720)
• Homozygosity mapping followed by whole-exome sequencing disclosed a Ser112Arg mutation in ACO2. (PMID:22405087)
• Gastric cancer patients with lower ACO2 expression have a shorter survival time than those with higher ACO2 expression. (PMID:23550275)
• Hypoxia upregulates the gene expression of mitochondrial aconitase in prostate carcinoma cells (PMID:23709747)
• Ogg1 chaperoning of Aco-2 in preventing oxidant-mediated mtDNA damage and apoptosis may afford an innovative target for the molecular events underlying oxidant-induced toxicity. (PMID:24429287)
• immunofluorescence staining localized ACO2 to the human sperm mid-piece. By immunoblotting, we demonstrated that the level of ACO2 protein in asthenozoospermic samples was significantly decreased compared with that in normal fertile men (PMID:24785945)
• Results suggest that ACO2 activity is reduced in peripheral lymphocytes of subjects with Alzheimer’s disease and mild cognitive impairment and correlates with antioxidant protection (PMID:25322927)
• Our study shows that autosomal recessive ACO2 mutations can cause either isolated or syndromic optic neuropathy. (PMID:25351951)
• Dysfunctional mitochondrail Aco2, among the other bioenergetic parameters, is a key factor that could promote neurodegeneration (PMID:28814227)
• Aco2 activity correlated significantly with motor score, independence scale, and functional capacity of the Unified Huntington’s Disease Rating Scale as well as disease duration. Our study provides a potential biomarker to assess the disease status of HD patients and PreHD carriers. (PMID:29160844)
• Mutation in ACO2 gene is associated with optic neuropathy. (PMID:30118607)
• The study provides the most extensive cohort of patients and further delineates the clinical, radiological, biochemical, and molecular features of ACO2 deficiency. (PMID:30689204)
• Study showed that the expression of ACO2 was significantly increased in prostate cancer (PC) tissues and identified a positive correlation between ACO2 expression and the malignancy of prostate cancer. ACO2 protein expression and activity was higher in paclitaxel-resistant PC3 cells than in PTX-sensitive DU145 cells. These results indicate that ACO2 plays an important role in the development and drug resistance of PC. (PMID:30972978)
• This work identifies ACO2 as a relevant gene in cancer metabolic rewiring of MCF-7 cells, promoting a different utilisation of pyruvate and revealing the potential metabolic vulnerability of ACO2-associated malignancies. (PMID:31819175)
• ACO2 and ANPEP as novel prognostic markers for gallbladder squamous cell/adenosquamous carcinomas and adenocarcinomas. (PMID:32249333)
• Recessive ACO2 variants as a cause of isolated ophthalmologic phenotypes. (PMID:32449285)
• Expanding the clinical and phenotypic heterogeneity associated with biallelic variants in ACO2. (PMID:32519519)
• Haploinsufficiency due to a novel ACO2 deletion causes mitochondrial dysfunction in fibroblasts from a patient with dominant optic nerve atrophy. (PMID:33028849)
• Loss of mitochondrial aconitase promotes colorectal cancer progression via SCD1-mediated lipid remodeling. (PMID:33676027)
• ACO2 deficiency increases vulnerability to Parkinson’s disease via dysregulating mitochondrial function and histone acetylation-mediated transcription of autophagy genes. (PMID:38007539)
• AFG3L2 and ACO2-Linked Dominant Optic Atrophy: Genotype-Phenotype Characterization Compared to OPA1 Patients. (PMID:38278202)
• Mitochondrial Aconitase and Its Contribution to the Pathogenesis of Neurodegenerative Diseases. (PMID:39337438)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	aco2	ENSDARG00000007294
mus_musculus	Aco2	ENSMUSG00000022477
rattus_norvegicus	Aco2	ENSRNOG00000024128
drosophila_melanogaster	mAcon1	FBGN0010100
drosophila_melanogaster	mAcon2	FBGN0037862
caenorhabditis_elegans		WBGENE00000041

Paralogs (2): ACO1 (ENSG00000122729), IREB2 (ENSG00000136381)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:87880) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 1 distinct phenotype terms.

Mouse phenotype (MP)	Records
preweaning lethality, complete penetrance	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Cryptococcus deneoformans JEC21	P0CM02	99.9%	Diamond
Cryptococcus deneoformans B-3501A	P0CM03	99.9%	Diamond
Sus scrofa	P16276	97.9%	Diamond
Bos taurus	P20004	97.9%	Diamond
Corynebacterium efficiens YS-314	Q8FTA8	92.6%	Diamond
Aspergillus nidulans FGSC A4	C8VG90	90.1%	Diamond
Aspergillus fumigatus Af293	Q4WLN1	90.1%	Diamond
Trichophyton benhamiae CBS 112371	D4AT77	87.3%	Diamond
Cucumis melo var. conomon	Q42669	85.2%	Diamond
Mycobacterium avium	O08451	82.8%	Diamond
Mycobacterium tuberculosis H37Rv	O53166	82.8%	Diamond
Saccharomyces cerevisiae S288C	P19414	81.8%	Diamond
Candida albicans SC5314	P82611	81.8%	Diamond
Schizosaccharomyces pombe 972h-	O13966	73.8%	Diamond
Streptomyces viridochromogenes DSM 40736	D9X0I3	72.5%	Diamond
Gracilaria gracilis	P49609	70.1%	Diamond
Dictyostelium discoideum	Q54XS2	69.3%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
TOB2	protein-coding	10766
POLR3H	protein-coding	171568
TEF	protein-coding	7008
PHF5A	protein-coding	84844
CSDC2	protein-coding	27254
PMM1	protein-coding	5372
DESI1	protein-coding	27351

Protein

Protein identifiers

Aconitate hydratase, mitochondrial — Q99798 (reviewed: Q99798)

Alternative names: Citrate hydro-lyase

All UniProt accessions (17): A0A7I2V2Y4, A0A7I2V3C8, A0A7I2V3F1, A0A7I2V3U0, A0A7I2V3U7, A0A7I2V499, A0A7I2V4I8, A0A7I2V538, A0A7I2V586, A0A7I2V5A1, A0A7I2V5T4, A0A7I2V5U4, A0A7I2V5W7, A0A7I2V614, A0A7I2V6A6, A2A274, Q99798

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the isomerization of citrate to isocitrate via cis-aconitate.

Subunit / interactions. Monomer.

Subcellular location. Mitochondrion.

Post-translational modifications. Forms covalent cross-links mediated by transglutaminase TGM2, between a glutamine and the epsilon-amino group of a lysine residue, forming homopolymers and heteropolymers.

Disease relevance. Infantile cerebellar-retinal degeneration (ICRD) [MIM:614559] A severe autosomal recessive neurodegenerative disorder characterized by onset between ages 2 and 6 months of truncal hypotonia, athetosis, seizures, and ophthalmologic abnormalities, particularly optic atrophy and retinal degeneration. Affected individuals show profound psychomotor retardation, with only some achieving rolling, sitting, or recognition of family. Brain MRI shows progressive cerebral and cerebellar degeneration. The disease is caused by variants affecting the gene represented in this entry. Optic atrophy 9 (OPA9) [MIM:616289] A condition that features progressive visual loss in association with optic atrophy. Atrophy of the optic disk indicates a deficiency in the number of nerve fibers which arise in the retina and converge to form the optic disk, optic nerve, optic chiasm and optic tracts. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 1 [4Fe-4S] cluster per subunit. Binding of a [3Fe-4S] cluster leads to an inactive enzyme.

Pathway. Carbohydrate metabolism; tricarboxylic acid cycle; isocitrate from oxaloacetate: step 2/2.

Similarity. Belongs to the aconitase/IPM isomerase family.

RefSeq proteins (1): NP_001089* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000573	AconitaseA/IPMdHydase_ssu_swvl	Domain
IPR001030	Acoase/IPM_deHydtase_lsu_aba	Domain
IPR006248	Aconitase_mito-like	Family
IPR015928	Aconitase/3IPM_dehydase_swvl	Homologous_superfamily
IPR015931	Acnase/IPM_dHydase_lsu_aba_1/3	Homologous_superfamily
IPR015932	Aconitase_dom2	Homologous_superfamily
IPR018136	Aconitase_4Fe-4S_BS	Binding_site
IPR036008	Aconitase_4Fe-4S_dom	Homologous_superfamily
IPR050926	Aconitase/IPM_isomerase	Family

Pfam: PF00330, PF00694

Enzyme classification (BRENDA)

• EC 4.2.1.3 — aconitate hydratase (BRENDA: 53 organisms, 72 substrates, 96 inhibitors, 82 Km, 22 kcat entries)

Substrate kinetics (BRENDA)

7 substrates with measured Km, best-characterized 7. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
CITRATE	0.12–21.1	27
ISOCITRATE	0.012–3.79	25
CIS-ACONITATE	0.0035–0.2	15
2-METHYL CIS-ACONITATE	0.0089–0.158	2
DL-ISOCITRATE	1.36–1.75	2
METHYLISOCITRATE	0.032–0.268	2
(2R,3S)-2-METHYLISOCITRATE	0.21	1

Catalyzed reactions (Rhea)

• citrate = D-threo-isocitrate (RHEA:10336)

UniProt features (61 total): modified residue 28, sequence conflict 12, binding site 9, sequence variant 7, compositionally biased region 2, transit peptide 1, chain 1, region of interest 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99798-F1	95.44	0.95

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Lyases, Metabolic proteins, Predicted intracellular proteins, Plasma proteins, Citric acid cycle related proteins, Disease related genes, Potential drug targets, Human disease related genes, Eye disease, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): mitochondria

Antibody reliability (HPA): IH enhanced · IF approved

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 (9)

Position	Role
474	substrate
479	substrate
607	substrate
670–671	substrate
99	substrate
192–194	substrate
385	[4Fe-4S] cluster
448	[4Fe-4S] cluster
451	[4Fe-4S] cluster

Post-translational modifications (28)

Type	Positions
N6-succinyllysine	31, 50, 138, 144, 233, 411, 549, 573, 577, 591, 605, 628, 689, 723, 730
N6-acetyllysine	50, 138, 144, 233, 573, 605, 723, 730, 736, 739, 743
Phosphoserine	559, 670

Function

Pathways and Gene Ontology

Reactome pathways

3 curated (TAS) of 8; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

8 pathways:

ID	Pathway	Evidence
R-HSA-71403	Citric acid cycle (TCA cycle)	curated
R-HSA-9854311	Maturation of TCA enzymes and regulation of TCA cycle	curated
R-HSA-9837999	Mitochondrial protein degradation	curated
R-HSA-1428517	Aerobic respiration and respiratory electron transport	—
R-HSA-1430728	Metabolism	—
R-HSA-392499	Metabolism of proteins	—
R-HSA-1268020	Mitochondrial protein import	electronic
R-HSA-9609507	Protein localization	—

MSigDB gene sets: 270 (showing top): E2F_Q4, E2F4DP1_01, RORA1_01, ENK_UV_RESPONSE_KERATINOCYTE_UP, TGACCTY_ERR1_Q2, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, NKX62_Q2, E2F1DP1_01, MCBRYAN_PUBERTAL_BREAST_4_5WK_DN, CATTTCA_MIR203, E2F1DP2_01, GOBP_TRICARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, FLECHNER_BIOPSY_KIDNEY_TRANSPLANT_REJECTED_VS_OK_DN, MODULE_295

GO Biological Process (3): generation of precursor metabolites and energy (GO:0006091), tricarboxylic acid cycle (GO:0006099), citrate metabolic process (GO:0006101)

GO Molecular Function (6): aconitate hydratase activity (GO:0003994), iron ion binding (GO:0005506), 4 iron, 4 sulfur cluster binding (GO:0051539), lyase activity (GO:0016829), metal ion binding (GO:0046872), iron-sulfur cluster binding (GO:0051536)

GO Cellular Component (3): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), cytosol (GO:0005829)

Reactome top-level categories

5 top-level categories:

Category	Pathways
Protein localization	1
Aerobic respiration and respiratory electron transport	1
Metabolism of proteins	1
Citric acid cycle (TCA cycle)	1
Metabolism	1

GO top-level categories

15 GO namespaces:

Category	Terms
cytoplasm	2
metabolic process	1
aerobic respiration	1
primary metabolic process	1
tricarboxylic acid metabolic process	1
hydro-lyase activity	1
transition metal ion binding	1
iron-sulfur cluster binding	1
catalytic activity	1
cation binding	1
metal cluster binding	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1
cellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 4 of 12 annotations. The rest are phylogenetic / computational / electronic (IEA).

4 experimentally-supported GO terms:

GO term	NS	Evidence
citrate metabolic process	BP	direct assay
tricarboxylic acid cycle	BP	direct assay
mitochondrion	CC	high-throughput assay
iron ion binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 3,574 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACO2	FXN	Q16595	933
ACO2	MDH2	P40926	910
ACO2	ISCU	Q9H1K1	904
ACO2	NFS1	Q9Y697	894
ACO2	IDH2	P48735	882
ACO2	CS	O75390	854
ACO2	IDH1	O75874	854
ACO2	FH	P07954	838
ACO2	F5H3C5	F5H3C5	822
ACO2	LONP1	P36776	820
ACO2	LYRM4	Q9HD34	815
ACO2	SDHA	P31040	808
ACO2	FECH	P22830	793
ACO2	OGDH	Q02218	791
ACO2	SOD2	P04179	787

IntAct

Human interaction partners of ACO2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

3 partners by confidence:

Partner	Interaction type	MIscore	Records
TCIM	physical association	0.400	1
C5AR2	physical association	0.370	1
MLH1	physical association	0.370	1

BioGRID (272 interactions; top human partners by supporting records): CLPP (Proximity Label-MS; 3 records), C21orf33 (Co-fractionation; 2 records), CLIC1 (Co-fractionation; 2 records), EPRS (Affinity Capture-MS; 2 records), ESD (Co-fractionation; 2 records), FH (Cross-Linking-MS (XL-MS); 2 records), GPI (Affinity Capture-MS; 2 records), HSPA9 (Affinity Capture-MS; 2 records), MDH2 (Cross-Linking-MS (XL-MS); 2 records), PARK2 (Affinity Capture-MS; 2 records), PSMD4 (Affinity Capture-MS; 2 records), SLC25A1 (Positive Genetic; 2 records), SOD1 (Affinity Capture-MS; 2 records), SQSTM1 (Proximity Label-MS; 2 records), TNIP1 (Affinity Capture-MS; 2 records)

SIGNOR signaling

showing 3 of 5 signaling interactions:

A	Effect	B	Mechanism
ACO2	“down-regulates quantity”	citrate(3-)	“chemical modification”
ACO2	“up-regulates quantity”	D-threo-isocitrate(3-)	“chemical modification”
FGR	unknown	ACO2	phosphorylation

Disease & clinical

Genetic variants

Variant evidence for ACO2: 976 ClinVar records (92 pathogenic / likely pathogenic); 5 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	53
Likely pathogenic	39
Uncertain significance	445
Likely benign	347
Benign	29

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 92 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
64477	NM_001098.3(ACO2):c.250C>T (p.Arg84Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
520987	NM_001098.3(ACO2):c.2105_2106del (p.Gln702fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
1213918	NM_001098.3(ACO2):c.1507G>T (p.Gly503Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
189314	NM_001098.3(ACO2):c.2328_2331del (p.Lys776fs)	Pathogenic	criteria provided, single submitter	2
430056	NM_001098.3(ACO2):c.34C>T (p.Gln12Ter)	Pathogenic	criteria provided, single submitter	1
803706	NM_001098.3(ACO2):c.1966_1969del (p.Arg656fs)	Pathogenic	criteria provided, single submitter	1
931020	NM_001098.3(ACO2):c.2253dup (p.Ile752fs)	Pathogenic	criteria provided, single submitter	1
1063268	NM_001098.3(ACO2):c.952del (p.Asn317_Leu318insTer)	Pathogenic	criteria provided, single submitter	1
1390490	NM_001098.3(ACO2):c.1835dup (p.Asn612fs)	Pathogenic	criteria provided, single submitter	1
1391740	NM_001098.3(ACO2):c.1534_1537del (p.Asp512fs)	Pathogenic	criteria provided, single submitter	1
1401215	NM_001098.3(ACO2):c.1416C>G (p.Tyr472Ter)	Pathogenic	criteria provided, single submitter	1
1413151	NM_001098.3(ACO2):c.1119G>A (p.Trp373Ter)	Pathogenic	criteria provided, single submitter	1
1418195	NM_001098.3(ACO2):c.1128_1134dup (p.Val379fs)	Pathogenic	criteria provided, single submitter	1
1420778	NM_001098.3(ACO2):c.499A>T (p.Lys167Ter)	Pathogenic	criteria provided, single submitter	1
1435000	NM_001098.3(ACO2):c.1002T>A (p.Tyr334Ter)	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore ACO2’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 34 predictions of 1,582):

Position(s)	Effect	Δscore	Sites
22:41499863–41499864	donor_loss	1.0000	4
22:41507789	acceptor_loss	1.0000
22:41508050–41508051	donor_loss	1.0000	5
22:41511874–41511875	acceptor_loss	1.0000	5
22:41515375	acceptor_loss	1.0000
22:41515536–41515537	donor_loss	1.0000	5
22:41517632–41517633	donor_loss	1.0000	5
22:41520156	acceptor_gain	1.0000
22:41523203–41523204	acceptor_loss	1.0000	6
22:41523824	acceptor_gain	1.0000

AlphaMissense

2,732 missense substitutions predicted likely pathogenic (of 5,122 scored), across 570 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M286	9	0.989	0.999
M105	9	0.975	0.999
M303	9	0.907	0.982
M217	9	0.894	0.998
M280	9	0.862	0.976
D192	8	1.000	1.000
D127	8	0.999	1.000
H128	8	0.999	1.000
H194	8	0.999	1.000
D595	8	0.999	1.000
D100	8	0.998	1.000
H174	8	0.998	1.000
H673	8	0.998	0.999
S670	8	0.997	1.000
D481	8	0.996	0.999
D392	8	0.995	0.999
F476	8	0.995	1.000
N475	8	0.994	1.000
H609	8	0.994	0.998
D212	8	0.993	0.999

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	8.29e-13
Kidney Renal Papillary Cell Carcinoma (TCGA)	favorable	1.15e-05
Kidney Renal Clear Cell Carcinoma (validation)	favorable	0.000332

Disease associations

OMIM: gene MIM:100850 | disease phenotypes: MIM:614559, MIM:616289

GenCC curated gene-disease

3 curated gene-disease records:

Disease	Classification	Inheritance	Records
infantile cerebellar-retinal degeneration	Definitive	Autosomal recessive	4
optic atrophy 9	Strong	Semidominant	4
autosomal recessive optic atrophy	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity

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

3 validity classifications:

Disease	Classification	Inheritance
optic atrophy 9	Definitive	SD
mitochondrial disease	Strong	AD
mitochondrial disease	Definitive	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (15 panels, 14 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

15 panels:

Panel	Rating
Ataxia and cerebellar anomalies - childhood onset	green
DDG2P	green
Hereditary ataxia and cerebellar anomalies, childhood onset	green
Hypotonic infant	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Likely inborn error of metabolism	green
Mitochondrial disorders	green
Optic neuropathy	green
Paediatric disorders	green
Possible mitochondrial disorder, nuclear genes	green
Retinal disorders	green
Undiagnosed metabolic disorders	green
Unexplained death in infancy and sudden unexplained death in childhood	green
Fetal anomalies	amber

Mondo (6): optic nerve disorder (MONDO:0002135), infantile cerebellar-retinal degeneration (MONDO:0013802), optic atrophy 9 (MONDO:0014571), optic atrophy (MONDO:0003608), inherited retinal dystrophy (MONDO:0019118), (MONDO:0014753)

Orphanet (2): Infantile cerebellar-retinal degeneration (Orphanet:313850), OBSOLETE: Inherited retinal disorder (Orphanet:71862)

HPO phenotypes

32 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000253	Progressive microcephaly
HP:0000407	Sensorineural hearing impairment
HP:0000486	Strabismus
HP:0000505	Visual impairment
HP:0000543	Optic disc pallor
HP:0000556	Retinal dystrophy
HP:0000639	Nystagmus
HP:0000642	Red-green dyschromatopsia
HP:0000648	Optic atrophy
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001265	Hyporeflexia
HP:0001272	Cerebellar atrophy
HP:0001284	Areflexia
HP:0001508	Failure to thrive
HP:0002069	Bilateral tonic-clonic seizure
HP:0002079	Hypoplasia of the corpus callosum
HP:0002120	Cerebral cortical atrophy
HP:0002305	Athetosis
HP:0002500	Abnormal cerebral white matter morphology
HP:0003593	Infantile onset
HP:0003621	Juvenile onset
HP:0004325	Decreased body weight
HP:0007108	Demyelinating peripheral neuropathy
HP:0007359	Focal-onset seizure
HP:0007663	Reduced visual acuity
HP:0010864	Severe intellectual disability
HP:0011344	Severe global developmental delay
HP:0011463	Childhood onset
HP:0030528	Paracentral scotoma

GWAS associations

5 associations:

Study	Trait	p-value
GCST010002_383	Refractive error	2e-27
GCST005232_27	Neuroticism	3e-18
GCST010043_2	Asthma	4e-12
GCST010988_210	Adult body size	3e-9
GCST010143_2	Meat-related diet	4e-8

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0007660	neuroticism measurement
EFO:0008111	diet measurement

MeSH disease descriptors

3 disease descriptors:

Descriptor	Name	Tree numbers
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
D009901	Optic Nerve Diseases	C10.292.700; C11.640
D058499	Retinal Dystrophies	C11.768.585.658

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, decreases methylation, increases expression	3
Doxorubicin	affects expression, decreases expression	2
bisphenol F	increases expression	1
2,4,6-tribromophenol	increases expression	1
lasiocarpine	decreases expression	1
nobiletin	decreases expression, decreases reaction	1
sodium arsenate	decreases expression, decreases reaction	1
pyrogallol 1,3-dimethyl ether	affects localization, decreases expression, affects cotreatment, increases expression	1
decabromobiphenyl ether	increases expression	1
ferric ammonium citrate	increases activity, decreases activity, decreases reaction	1
2,6-dichloro-4-nitrophenol	decreases expression	1
zinc chloride	affects cotreatment, decreases activity	1
cobaltous chloride	increases expression	1
linalool	increases expression	1
2-bromopalmitate	increases abundance, increases palmitoylation, decreases reaction	1
nickel chloride	decreases activity	1
perfluorooctanoic acid	increases expression	1
manganese chloride	decreases activity, decreases reaction, decreases expression	1
nickel sulfate	increases expression	1
CGP 52608	increases reaction, affects binding	1
nutlin 3	increases secretion, affects cotreatment	1
bisphenol B	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
bisphenol AF	increases expression	1
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	decreases expression	1
Acetaminophen	increases expression	1
Aluminum	decreases activity, decreases expression	1
Atrazine	decreases expression	1

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_SB24	HAP1 ACO2 (-) 1	Cancer cell line	Male
CVCL_SB25	HAP1 ACO2 (-) 2	Cancer cell line	Male
CVCL_XI73	IISHDOi006-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 153 trials:

NCT	Phase	Status	Title
NCT03351998	Phase 4	COMPLETED	Impact of Statin Therapy on Muscle Mitochondrial Function and Aerobic Capacity
NCT00432744	Phase 3	COMPLETED	Phase III Trial of Coenzyme Q10 in Mitochondrial Disease
NCT05162768	Phase 3	COMPLETED	Study to Evaluate Efficacy and Safety of Elamipretide in Subjects With Primary Mitochondrial Disease From Nuclear DNA Mutations (nPMD)
NCT06451757	Phase 3	RECRUITING	KHENERFIN Study: A Trial to Evaluate the Efficacy and Safety of Sonlicromanol in Primary Mitochondrial Diseases
NCT04224207	Phase 3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	Phase 3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT02398201	Phase 2	COMPLETED	A Study of Bezafibrate in Mitochondrial Myopathy
NCT02473445	Phase 2	TERMINATED	A Long-term Extension of Study RP103-MITO-001 (NCT02023866) to Assess Cysteamine Bitartrate Delayed-release Capsules (RP103) in Children With Inherited Mitochondrial Disease
NCT02500628	Phase 2	COMPLETED	Heart Rate Variability in Response to Metformin Challenge
NCT02805790	Phase 2	COMPLETED	Safety, Tolerability, Efficacy of MTP-131 for Treatment of Mitochondrial Disease in Subjects From the MMPOWER Study
NCT02909400	Phase 2	COMPLETED	The KHENERGY Study
NCT02976038	Phase 2	TERMINATED	Open-Label Extension Trial to Characterize the Long-term Safety and Tolerability of Elamipretide in Subjects With Genetically Confirmed Primary Mitochondrial Myopathy (PMM)
NCT03177798	Phase 2	COMPLETED	Mitochondria and Chronic Kidney Disease
NCT03866954	Phase 2	WITHDRAWN	Trial of Erythrocyte Encapsulated Thymidine Phosphorylase In Mitochondrial Neurogastrointestinal Encephalomyopathy
NCT04165239	Phase 2	COMPLETED	The KHENERGYZE Study
NCT04604548	Phase 2	COMPLETED	The KHENEREXT Study
NCT04802707	Phase 2	RECRUITING	Deoxynucleosides Pyrimidines as Treatment for Mitochondrial Depletion Syndrome
NCT04846036	Phase 2	SUSPENDED	The KHENERGYC Study
NCT05650229	Phase 2	RECRUITING	Efficacy of KL1333 in Adult Patients With Primary Mitochondrial Disease
NCT05972954	Phase 2	COMPLETED	OMT-28 in Patients With Primary Mitochondrial Disease (PMD) (PMD-OPTION)
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