EME2

Summary

EME2 (essential meiotic structure-specific endonuclease subunit 2, HGNC:27289) is a protein-coding gene on chromosome 16p13.3, encoding Structure-specific endonuclease subunit EME2 (A4GXA9). Non-catalytic subunit of the structure-specific, heterodimeric DNA endonuclease MUS81-EME2 which is involved in the maintenance of genome stability.

EME2 forms a heterodimer with MUS81 (MIM 606591) that functions as an XPF (MIM 278760)-type flap/fork endonuclease in DNA repair (Ciccia et al., 2007 [PubMed 17289582]).

Source: NCBI Gene 197342 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 182 total — 2 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_001257370

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27289
Approved symbol	EME2
Name	essential meiotic structure-specific endonuclease subunit 2
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ00151, SLX2B
Ensembl gene	ENSG00000197774
Ensembl biotype	protein_coding
OMIM	610886
Entrez	197342

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding

ENST00000561564, ENST00000561903, ENST00000564182, ENST00000565326, ENST00000568449, ENST00000570069

RefSeq mRNA: 1 — MANE Select: NM_001257370 NM_001257370

CCDS: CCDS58404

Canonical transcript exons

ENST00000568449 — 8 exons

Exon	Start	End
ENSE00001673805	1775041	1775132
ENSE00002593011	1772810	1773474
ENSE00002595308	1776068	1781702
ENSE00003476979	1775797	1775986
ENSE00003489161	1774260	1774352
ENSE00003601895	1773705	1773841
ENSE00003633647	1775569	1775684
ENSE00003694624	1775315	1775408

Expression profiles

Bgee: expression breadth ubiquitous, 231 present calls, max score 94.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2.7988 / max 54.1666, expressed in 1372 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
152130	2.1702	1264
152131	0.4302	229
152132	0.1984	110

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oviduct epithelium	UBERON:0004804	94.93	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.68	gold quality
cerebellar hemisphere	UBERON:0002245	92.94	gold quality
cerebellar cortex	UBERON:0002129	92.79	gold quality
cerebellum	UBERON:0002037	92.01	gold quality
pituitary gland	UBERON:0000007	91.50	gold quality
adenohypophysis	UBERON:0002196	91.05	gold quality
parotid gland	UBERON:0001831	89.63	silver quality
apex of heart	UBERON:0002098	87.14	gold quality
metanephros cortex	UBERON:0010533	86.88	gold quality
right frontal lobe	UBERON:0002810	86.55	gold quality
granulocyte	CL:0000094	86.41	gold quality
right lobe of thyroid gland	UBERON:0001119	86.06	gold quality
right adrenal gland cortex	UBERON:0035827	85.86	gold quality
right adrenal gland	UBERON:0001233	85.83	gold quality
prostate gland	UBERON:0002367	85.47	gold quality
left lobe of thyroid gland	UBERON:0001120	84.93	gold quality
metanephros	UBERON:0000081	84.74	gold quality
tendon of biceps brachii	UBERON:0008188	84.64	gold quality
lower esophagus mucosa	UBERON:0035834	84.61	gold quality
left adrenal gland	UBERON:0001234	84.15	gold quality
thyroid gland	UBERON:0002046	84.15	gold quality
spleen	UBERON:0002106	84.07	gold quality
left adrenal gland cortex	UBERON:0035825	83.95	gold quality
mucosa of transverse colon	UBERON:0004991	83.71	gold quality
adrenal cortex	UBERON:0001235	83.63	gold quality
cerebellar vermis	UBERON:0004720	83.58	gold quality
esophagus mucosa	UBERON:0002469	83.37	gold quality
small intestine Peyer’s patch	UBERON:0003454	83.05	gold quality
bone marrow cell	CL:0002092	82.96	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-7407	yes	10539.21
E-CURD-112	yes	6426.85
E-MTAB-9543	yes	3119.27
E-ANND-3	yes	4.48
E-ENAD-27	no	3.37

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 5)

• The results indicate that MUS81-EME2 is a more active endonuclease than MUS81-EME1 and exhibits broader substrate specificity. (PMID:24371268)
• The presence of a 5’ phosphate terminus at nicks and gaps rendered DNA significantly less susceptible to the cleavage by MUS81-EME2 than its absence. (PMID:24692662)
• Results define distinct and temporal roles for MUS81-EME1 and MUS81-EME2 in the maintenance of genome stability. (PMID:24813886)
• Avoiding damage formation through invalidation of Mus81-Eme2 and Mre11, or preventing damage signaling by turning off the ATM pathway, suppresses the replication phenotypes of Chk1-deficient cells. (PMID:26804904)
• Crystal structure of the human MUS81-EME2 complex. (PMID:35290797)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Eme2	ENSMUSG00000073436
rattus_norvegicus	Eme2	ENSRNOG00000024867
drosophila_melanogaster	mms4	FBGN0033549

Paralogs (1): EME1 (ENSG00000154920)

Protein

Protein identifiers

Structure-specific endonuclease subunit EME2 — A4GXA9 (reviewed: A4GXA9)

Alternative names: Essential meiotic structure-specific endonuclease subunit 2

All UniProt accessions (3): A4GXA9, H3BSZ6, H3BV62

UniProt curated annotations — full annotation on UniProt →

Function. Non-catalytic subunit of the structure-specific, heterodimeric DNA endonuclease MUS81-EME2 which is involved in the maintenance of genome stability. In the complex, EME2 is required for DNA cleavage, participating in DNA recognition and bending. MUS81-EME2 cleaves 3’-flaps and nicked Holliday junctions, and exhibit limited endonuclease activity with 5’ flaps and nicked double-stranded DNAs. MUS81-EME2 which is active during the replication of DNA is more specifically involved in replication fork processing. Replication forks frequently encounter obstacles to their passage, including DNA base lesions, DNA interstrand cross-links, difficult-to-replicate sequences, transcription bubbles, or tightly bound proteins. One mechanism for the restart of a stalled replication fork involves nucleolytic cleavage mediated by the MUS81-EME2 endonuclease. By acting upon the stalled fork, MUS81-EME2 generates a DNA double-strand break (DSB) that can be repaired by homologous recombination, leading to the restoration of an active fork. MUS81-EME2 could also function in telomere maintenance.

Subunit / interactions. Part of the heterodimeric MUS81-EME2 complex; the complex forms specifically during the DNA replication phase of the cell cycle.

Subcellular location. Nucleus.

Similarity. Belongs to the EME1/MMS4 family.

Isoforms (2)

UniProt ID	Names	Canonical?
A4GXA9-1	1	yes
A4GXA9-2	2

RefSeq proteins (1): NP_001244299* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006166	ERCC4_domain	Domain
IPR033310	Mms4/EME1/EME2	Family
IPR042530	EME1/EME2_C	Homologous_superfamily
IPR047523	XPF_nuclease_EME2	Domain

Pfam: PF02732, PF21292

UniProt features (34 total): helix 12, strand 8, mutagenesis site 6, region of interest 3, turn 2, splice variant 2, chain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7F6L	X-RAY DIFFRACTION	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A4GXA9-F1	80.73	0.53

Functional residue map

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

Mutagenesis-validated functional residues (6):

Position	Phenotype
360	decreased cleavage of 3 prime flaps, nhjs and 5 prime flaps; when associated with e-361.
361	decreased cleavage of 3 prime flaps, nhjs and 5 prime flaps; when associated with e-360.
294	no effect on cleavage of 3 prime flaps, nhjs and 5 prime flaps; when associated with e-295.
295	no effect on cleavage of 3 prime flaps, nhjs and 5 prime flaps; when associated with e-294.
352	decreased cleavage of 3 prime flaps, nhjs and 5 prime flaps; when associated with e-353.
353	decreased cleavage of 3 prime flaps, nhjs and 5 prime flaps; when associated with e-353.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-5693568	Resolution of D-loop Structures through Holliday Junction Intermediates
R-HSA-6783310	Fanconi Anemia Pathway

MSigDB gene sets: 113 (showing top): GOBP_DNA_TEMPLATED_DNA_REPLICATION_MAINTENANCE_OF_FIDELITY, GOBP_CHROMOSOME_ORGANIZATION, GOMF_ENDONUCLEASE_ACTIVITY, GOMF_NUCLEASE_ACTIVITY, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_TELOMERE_ORGANIZATION, GOBP_MITOTIC_INTRA_S_DNA_DAMAGE_CHECKPOINT_SIGNALING, GOCC_NUCLEAR_REPLICATION_FORK, GOBP_ORGANELLE_FISSION, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE_PROCESS, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_NEGATIVE_REGULATION_OF_MITOTIC_CELL_CYCLE, GOBP_DNA_DAMAGE_RESPONSE, GOBP_MITOTIC_DNA_INTEGRITY_CHECKPOINT_SIGNALING

GO Biological Process (8): resolution of meiotic recombination intermediates (GO:0000712), telomere maintenance (GO:0000723), double-strand break repair (GO:0006302), replication fork processing (GO:0031297), mitotic intra-S DNA damage checkpoint signaling (GO:0031573), DNA repair (GO:0006281), DNA recombination (GO:0006310), DNA damage response (GO:0006974)

GO Molecular Function (8): DNA binding (GO:0003677), nuclease activity (GO:0004518), enzyme-substrate adaptor activity (GO:0140767), endonuclease activity (GO:0004519), DNA endonuclease activity (GO:0004520), protein binding (GO:0005515), crossover junction DNA endonuclease activity (GO:0008821), hydrolase activity (GO:0016787)

GO Cellular Component (5): chromosome, telomeric region (GO:0000781), nuclear replication fork (GO:0043596), Holliday junction resolvase complex (GO:0048476), endodeoxyribonuclease complex (GO:1905347), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Resolution of D-Loop Structures	1
DNA Repair	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA metabolic process	3
reciprocal meiotic recombination	1
meiosis I cell cycle process	1
telomere organization	1
DNA repair	1
DNA-templated DNA replication maintenance of fidelity	1
mitotic S phase	1
mitotic DNA damage checkpoint signaling	1
DNA damage response	1
cellular response to stress	1
nucleic acid binding	1
catalytic activity, acting on a nucleic acid	1
protein-macromolecule adaptor activity	1
nuclease activity	1
endonuclease activity	1
DNA nuclease activity	1
binding	1
DNA endonuclease activity, producing 3’-phosphomonoesters	1
catalytic activity	1
chromosomal region	1
nuclear chromosome	1
nucleus	1
replication fork	1
CMG complex	1
endodeoxyribonuclease complex	1
endonuclease complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1242 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EME2	MUS81	Q96NY9	996
EME2	EME1	Q96AY2	853
EME2	ERCC4	Q92889	808
EME2	TERF2	Q15554	575
EME2	SLX4	Q8IY92	554
EME2	FAAP24	Q9BTP7	543
EME2	EEPD1	Q7L9B9	534
EME2	SLX1A	Q9BQ83	483
EME2	HLTF	Q14527	475
EME2	FANCM	Q8IYD8	466
EME2	DDA1	Q9BW61	444
EME2	GEN1	Q17RS7	417
EME2	CHLSN	Q9BRJ6	416
EME2	EXO1	Q9UQ84	398
EME2	RPA4	Q13156	394

IntAct

5 interactions, top by confidence:

A	B	Type	Score
EME2	MUS81	psi-mi:“MI:0915”(physical association)	0.540
EME2		psi-mi:“MI:0572”(dna cleavage)	0.440
FEN1	EME2	psi-mi:“MI:0914”(association)	0.350

BioGRID (8): EME2 (Synthetic Growth Defect), EME2 (Two-hybrid), EME2 (Negative Genetic), EME2 (Reconstituted Complex), EME2 (Affinity Capture-RNA), MUS81 (Reconstituted Complex), C19orf40 (Reconstituted Complex), FANCM (Reconstituted Complex)

ESM2 similar proteins: A4GXA9, A7E3N7, A8VU90, D3KCC4, D3ZZN9, G3V8H4, O08672, O95382, Q13608, Q13671, Q14296, Q17RN3, Q28616, Q3UR50, Q3UR97, Q3V3V9, Q4KM32, Q53GL7, Q56A04, Q58CQ5, Q58EX7, Q5BK61, Q5NVA9, Q62893, Q643R3, Q66H85, Q6F5E8, Q6NVH7, Q6ZW31, Q7T0L4, Q80UU1, Q80XL1, Q8BJW7, Q8BTN6, Q8CIE4, Q8CJ00, Q8K592, Q8N2G8, Q8NAG6, Q8VCI7

Diamond homologs: A4GXA9, Q0IHN5, Q56A04, Q5NVA9, Q8BJW7, Q96AY2, Q91ZJ0, Q4KM32, Q640B4, Q7SXA9, Q96NY9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	116
Likely benign	27
Benign	11

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
2837647	NC_000016.10:g.1772495_1773356del	Pathogenic
2876971	NM_023936.2(MRPS34):c.164G>A (p.Trp55Ter)	Pathogenic
430585	NM_023936.2(MRPS34):c.37G>A (p.Glu13Lys)	Likely pathogenic

SpliceAI

2339 predictions. Top by Δscore:

Variant	Effect	Δscore
16:1773696:C:CA	acceptor_gain	1.0000
16:1773837:GCAGC:G	donor_gain	1.0000
16:1773840:GC:G	donor_gain	1.0000
16:1773842:G:GG	donor_gain	1.0000
16:1775685:G:GG	donor_gain	1.0000
16:1777441:CAC:C	acceptor_gain	1.0000
16:1777442:ACCT:A	acceptor_loss	1.0000
16:1777444:CTGGA:C	acceptor_loss	1.0000
16:1777741:CCTCA:C	donor_loss	1.0000
16:1777742:CTCA:C	donor_loss	1.0000
16:1777743:TCAC:T	donor_loss	1.0000
16:1777745:ACCT:A	donor_loss	1.0000
16:1777746:C:T	donor_loss	1.0000
16:1777756:T:TA	donor_gain	1.0000
16:1777757:C:A	donor_gain	1.0000
16:1777873:C:CC	acceptor_gain	1.0000
16:1778129:CTTA:C	donor_loss	1.0000
16:1778130:TTACC:T	donor_loss	1.0000
16:1778131:TAC:T	donor_loss	1.0000
16:1778132:A:AC	donor_gain	1.0000
16:1778132:AC:A	donor_gain	1.0000
16:1778133:C:CA	donor_gain	1.0000
16:1778133:CC:C	donor_gain	1.0000
16:1778133:CCA:C	donor_gain	1.0000
16:1778133:CCAT:C	donor_gain	1.0000
16:1778133:CCATG:C	donor_gain	1.0000
16:1778319:AATCT:A	acceptor_loss	1.0000
16:1778320:ATCT:A	acceptor_loss	1.0000
16:1778321:TCT:T	acceptor_loss	1.0000
16:1778322:C:CA	acceptor_loss	1.0000

AlphaMissense

2382 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:1775960:T:C	F315L	0.987
16:1775962:C:A	F315L	0.987
16:1775962:C:G	F315L	0.987
16:1775949:T:A	V311D	0.985
16:1773806:T:A	W117R	0.979
16:1773806:T:C	W117R	0.979
16:1774324:T:C	F150S	0.979
16:1775825:T:C	F270L	0.977
16:1775827:C:A	F270L	0.977
16:1775827:C:G	F270L	0.977
16:1775894:T:A	W293R	0.977
16:1775894:T:C	W293R	0.977
16:1774323:T:C	F150L	0.976
16:1774325:T:A	F150L	0.976
16:1774325:T:G	F150L	0.976
16:1775896:G:C	W293C	0.973
16:1775896:G:T	W293C	0.973
16:1773808:G:C	W117C	0.971
16:1773808:G:T	W117C	0.971
16:1775108:T:A	V182D	0.968
16:1775907:T:C	I297T	0.964
16:1775916:T:C	F300S	0.963
16:1775961:T:C	F315S	0.959
16:1776183:T:C	I362T	0.956
16:1773469:A:T	D81V	0.953
16:1776179:C:A	R361S	0.951
16:1775907:T:G	I297S	0.950
16:1775105:C:A	A181D	0.946
16:1775635:A:C	S244R	0.944
16:1775637:T:A	S244R	0.944

dbSNP variants (sampled 300 via entrez): RS1000513546 (16:1776370 CAG>C), RS1000560342 (16:1778867 A>G), RS1000967235 (16:1779124 C>T), RS1000988298 (16:1773005 C>G,T), RS1001188624 (16:1770889 C>A,T), RS1001221004 (16:1780501 G>A), RS1001626436 (16:1780661 G>A), RS1002180875 (16:1771576 C>G,T), RS1003003991 (16:1781528 G>T), RS1003051504 (16:1781757 C>T), RS1003213252 (16:1772269 G>A), RS1003222824 (16:1774798 G>A), RS1003252289 (16:1774929 C>A,T), RS1003745212 (16:1775586 G>A,C), RS1003856156 (16:1779708 G>A,C)

Disease associations

OMIM: gene MIM:610886 | disease phenotypes: MIM:308350, MIM:616044, MIM:256000, MIM:617664

GenCC curated gene-disease

Mondo (5): mitochondrial disease (MONDO:0044970), developmental and epileptic encephalopathy, 1 (MONDO:0010632), autosomal dominant nonsyndromic hearing loss 65 (MONDO:0014470), Leigh syndrome (MONDO:0009723), combined oxidative phosphorylation deficiency 32 (MONDO:0054654)

Orphanet (3): Mitochondrial disease (Orphanet:68380), Rare autosomal dominant non-syndromic sensorineural deafness type DFNA (Orphanet:90635), Leigh syndrome (Orphanet:506)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D007888	Leigh Disease	C10.228.140.163.100.412; C16.320.565.189.412; C16.320.565.202.810.444; C18.452.132.100.412; C18.452.648.189.412; C18.452.648.202.810.444; C18.452.660.520

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Phenylmercuric Acetate	affects cotreatment, increases expression	2
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
butyraldehyde	decreases expression	1
manganese chloride	decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
Resveratrol	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	decreases expression	1
Atrazine	increases expression	1
Cisplatin	decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Estradiol	increases expression	1
Lead	increases expression	1
Manganese	decreases expression, increases abundance	1
Plant Extracts	affects cotreatment, decreases expression	1
Polychlorinated Biphenyls	affects expression	1
Silicon Dioxide	increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
Vincristine	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SL98	HAP1 EME2 (-) 1	Cancer cell line	Male
CVCL_SL99	HAP1 EME2 (-) 2	Cancer cell line	Male
CVCL_SM00	HAP1 EME2 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03351998	PHASE4	COMPLETED	Impact of Statin Therapy on Muscle Mitochondrial Function and Aerobic Capacity
NCT00432744	PHASE3	COMPLETED	Phase III Trial of Coenzyme Q10 in Mitochondrial Disease
NCT05162768	PHASE3	COMPLETED	Study to Evaluate Efficacy and Safety of Elamipretide in Subjects With Primary Mitochondrial Disease From Nuclear DNA Mutations (nPMD)
NCT06451757	PHASE3	RECRUITING	KHENERFIN Study: A Trial to Evaluate the Efficacy and Safety of Sonlicromanol in Primary Mitochondrial Diseases
NCT02398201	PHASE2	COMPLETED	A Study of Bezafibrate in Mitochondrial Myopathy
NCT02473445	PHASE2	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	PHASE2	COMPLETED	Heart Rate Variability in Response to Metformin Challenge
NCT02805790	PHASE2	COMPLETED	Safety, Tolerability, Efficacy of MTP-131 for Treatment of Mitochondrial Disease in Subjects From the MMPOWER Study
NCT02909400	PHASE2	COMPLETED	The KHENERGY Study
NCT02976038	PHASE2	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	PHASE2	COMPLETED	Mitochondria and Chronic Kidney Disease
NCT03866954	PHASE2	WITHDRAWN	Trial of Erythrocyte Encapsulated Thymidine Phosphorylase In Mitochondrial Neurogastrointestinal Encephalomyopathy
NCT04165239	PHASE2	COMPLETED	The KHENERGYZE Study
NCT04604548	PHASE2	COMPLETED	The KHENEREXT Study
NCT04802707	PHASE2	RECRUITING	Deoxynucleosides Pyrimidines as Treatment for Mitochondrial Depletion Syndrome
NCT04846036	PHASE2	SUSPENDED	The KHENERGYC Study
NCT05650229	PHASE2	RECRUITING	Efficacy of KL1333 in Adult Patients With Primary Mitochondrial Disease
NCT05972954	PHASE2	COMPLETED	OMT-28 in Patients With Primary Mitochondrial Disease (PMD) (PMD-OPTION)
NCT06017869	PHASE2	RECRUITING	Evaluate the Safety and Therapeutic Effects of a Single Intravenous Infusion (IV) of Autologous CD34+ Cells Enriched With Allogenic Placenta-derived Mitochondria in Patients With a Diagnosis of Pearson Syndrome (PS)
NCT07514338	PHASE2	NOT_YET_RECRUITING	Open Label Extension to Assess Long Term Safety and Efficacy of KL1333 in Patients With Primary Mitochondrial Disease
NCT01721733	PHASE2	COMPLETED	Safety and Efficacy Study of EPI-743 in Children With Leigh Syndrome
NCT02352896	PHASE2	COMPLETED	Long-Term Safety and Efficacy Evaluation of EPI-743 in Children With Leigh Syndrome
NCT03747328	PHASE2	WITHDRAWN	ABI-009 (Nab-sirolimus) in Patients With Genetically-confirmed Leigh or Leigh-like Syndrome
NCT06843811	PHASE2	ENROLLING_BY_INVITATION	Sirolimus for Leigh Syndrome
NCT06990984	PHASE2	NOT_YET_RECRUITING	A Dose-ranging Study of TTI-0102 in Adults and Children With Leigh Syndrome Spectrum (LSS)
NCT00060515	PHASE1	TERMINATED	RG2133 (2’,3’,5’-Tri-O-Acetyluridine) in Mitochondrial Disease
NCT02348125	PHASE1	UNKNOWN	Does Clinical Treatment of Mitochondrial Dysfunction Impact Autism Spectrum Disorder (ASD)?
NCT02544217	PHASE1	COMPLETED	A Dose-escalating Clinical Trial With KH176
NCT03888716	PHASE1	COMPLETED	A Phase Ia/Ib, SAD and MAD Study of of KL1333 in Healthy Subjects and Patients With Primary Mitochondrial Disease
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