COX20

Summary

COX20 (cytochrome c oxidase assembly factor COX20, HGNC:26970) is a protein-coding gene on chromosome 1q44, encoding Cytochrome c oxidase assembly protein COX20, mitochondrial (Q5RI15). Essential for the assembly of the mitochondrial respiratory chain complex IV (CIV), also known as cytochrome c oxidase. It is a selective cancer dependency (DepMap: 35.4% of cell lines).

This gene encodes a protein that plays a role in the assembly of cytochrome C oxidase, an important component of the respiratory pathway. It contains two transmembrane helices and localizes to the mitochondrial membrane. Mutations in this gene can cause mitochondrial complex IV deficiency, which results in ataxia and muscle hypotonia. There are multiple pseudogenes for this gene. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 116228 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mitochondrial disease (Definitive, ClinGen) — +2 more curated relationships
• Clinical variants (ClinVar): 172 total — 10 pathogenic, 8 likely-pathogenic
• Phenotypes (HPO): 20
• Cancer dependency (DepMap): dependent in 35.4% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_198076

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26970
Approved symbol	COX20
Name	cytochrome c oxidase assembly factor COX20
Location	1q44
Locus type	gene with protein product
Status	Approved
Aliases	FLJ43269
Ensembl gene	ENSG00000203667
Ensembl biotype	protein_coding
OMIM	614698
Entrez	116228

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 8 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000366528, ENST00000391839, ENST00000411948, ENST00000464757, ENST00000498262, ENST00000873395, ENST00000925250, ENST00000925251, ENST00000925252, ENST00000925253, ENST00000925254

RefSeq mRNA: 5 — MANE Select: NM_198076 NM_001312871, NM_001312872, NM_001312873, NM_001312874, NM_198076

CCDS: CCDS31080, CCDS81434

Canonical transcript exons

ENST00000411948 — 4 exons

Exon	Start	End
ENSE00001679694	244835658	244835756
ENSE00003573027	244842195	244842258
ENSE00003643369	244843041	244845057
ENSE00003646512	244841944	244842058

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 98.63.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 63.2903 / max 1263.1084, expressed in 1823 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
9489	31.1229	1813
9490	25.8663	1799
9486	4.5531	1371
9487	1.6215	1044
9488	0.1265	52

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
kidney epithelium	UBERON:0004819	98.63	gold quality
endothelial cell	CL:0000115	98.09	gold quality
cortical plate	UBERON:0005343	97.56	gold quality
epithelial cell of pancreas	CL:0000083	97.37	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.32	gold quality
right atrium auricular region	UBERON:0006631	97.31	gold quality
lower esophagus	UBERON:0013473	97.31	gold quality
renal medulla	UBERON:0000362	97.00	gold quality
cardiac atrium	UBERON:0002081	96.91	gold quality
ganglionic eminence	UBERON:0004023	96.88	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.88	gold quality
pigmented layer of retina	UBERON:0001782	96.73	gold quality
heart left ventricle	UBERON:0002084	96.73	gold quality
cardiac ventricle	UBERON:0002082	96.60	gold quality
nucleus accumbens	UBERON:0001882	96.58	gold quality
popliteal artery	UBERON:0002250	96.49	gold quality
tibial artery	UBERON:0007610	96.49	gold quality
heart	UBERON:0000948	96.48	gold quality
ileal mucosa	UBERON:0000331	96.46	gold quality
calcaneal tendon	UBERON:0003701	96.45	gold quality
apex of heart	UBERON:0002098	96.44	gold quality
putamen	UBERON:0001874	96.36	gold quality
hypothalamus	UBERON:0001898	96.28	gold quality
amygdala	UBERON:0001876	96.27	gold quality
ventricular zone	UBERON:0003053	96.27	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.21	gold quality
caudate nucleus	UBERON:0001873	96.19	gold quality
metanephros cortex	UBERON:0010533	96.07	gold quality
left coronary artery	UBERON:0001626	96.05	gold quality
right coronary artery	UBERON:0001625	96.01	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.86
E-CURD-11	no	318.46
E-MTAB-9388	no	11.36

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

101 targeting COX20, 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-5692A	100.00	74.40	6850
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-4728-5P	99.85	69.39	4718

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 35.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 9)

• These results suggest that HNRNPU, FAM36A, and NCRNA00201 are not major genes for microcephaly and corpus callosum abnormalities but are good candidates for intellectual disability (ID) and seizures. (PMID:22678713)
• The function of the human gene FAM36A/COX20 in complex IV assembly and role of the gene in complex IV deficiency. (PMID:23125284)
• This study deministrated that phenotypic spectrum of mutation in COX20 to a recessively inherited, early-onset dystonia-ataxia syndrome that is characterized by reduced complex IV activity. (PMID:24202787)
• COX20 cooperates with SCO1 and SCO2 to mature COX2 and promote the assembly of cytochrome c oxidase. (PMID:24403053)
• data shows that by unbalancing the amount of TMEM177, newly synthesized COX2 accumulates in a COX20-associated state. (PMID:29154948)
• Study reports on four subjects with features that include childhood hypotonia, areflexia, ataxia, dysarthria, dystonia, and sensory neuropathy. Exome sequencing in all four subjects identified the same novel COX20 variants. One variant affected the splice donor site of intron-one (c.41A>G), while the other variant (c.157+3G>C) affected the splice donor site of intron-two. (PMID:30656193)
• COX20 mutation are associated with autosomal recessive axonal neuropathy and static encephalopathy. (PMID:31079202)
• Bi-allelic loss of function variants in COX20 gene cause autosomal recessive sensory neuronopathy. (PMID:33751098)
• Clinical and genetic characteristics of children with COX20-associated mitochondrial disorder: case report and literature review. (PMID:37095481)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cox20	ENSMUSG00000026500
rattus_norvegicus	LOC120096563	ENSRNOG00000050982
rattus_norvegicus		ENSRNOG00000076247

Protein

Protein identifiers

Cytochrome c oxidase assembly protein COX20, mitochondrial — Q5RI15 (reviewed: Q5RI15)

All UniProt accessions (2): Q5RI15, B3KM21

UniProt curated annotations — full annotation on UniProt →

Function. Essential for the assembly of the mitochondrial respiratory chain complex IV (CIV), also known as cytochrome c oxidase. Acts as a chaperone in the early steps of cytochrome c oxidase subunit II (MT-CO2/COX2) maturation, stabilizing the newly synthesized protein and presenting it to metallochaperones SCO1/2 which in turn facilitates the incorporation of the mature MT-CO2/COX2 into the assembling CIV holoenzyme.

Subunit / interactions. Found in a complex with TMEM177, COA6, MT-CO2/COX2, COX18, SCO1 and SCO2. Interacts with SCO1, SCO2 and COA6 in a MT-CO2/COX2- and COX18-dependent manner. Interacts with COX18 in a MT-CO2/COX2-dependent manner. Interacts with MT-CO2/COX2. Interacts with TMEM177.

Subcellular location. Mitochondrion inner membrane.

Disease relevance. Mitochondrial complex IV deficiency, nuclear type 11 (MC4DN11) [MIM:619054] An autosomal recessive mitochondrial disorder with onset in childhood or adolescence. MC4DN11 is characterized by walking difficulties, cerebellar ataxia, dystonia, choreoathetotic movements and dysarthria. Additional features may include sensory axonal neuropathy, cerebellar atrophy, and mild speech delay. Cognitive function is normal. Serum lactate levels are increased. Patient tissues show decreased levels and activity of mitochondrial respiratory complex IV. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the COX20 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5RI15-1	1	yes
Q5RI15-2	2

RefSeq proteins (5): NP_001299800, NP_001299801, NP_001299802, NP_001299803, NP_932342* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR022533	Cox20	Family

Pfam: PF12597

UniProt features (11 total): topological domain 3, sequence variant 2, transmembrane region 2, initiator methionine 1, chain 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5RI15-F1	66.42	0.00

Functional residue map

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

Post-translational modifications (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9864848	Complex IV assembly

MSigDB gene sets: 189 (showing top): GOBP_RESPIRATORY_CHAIN_COMPLEX_IV_ASSEMBLY, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_MITOCHONDRIAL_RESPIRATORY_CHAIN_COMPLEX_ASSEMBLY, GOBP_CYTOCHROME_COMPLEX_ASSEMBLY, GOCC_MITOCHONDRIAL_ENVELOPE, FISCHER_DREAM_TARGETS, BASAKI_YBX1_TARGETS_UP, MILI_PSEUDOPODIA_CHEMOTAXIS_UP, chr1q44, SENESE_HDAC3_TARGETS_DN, GOCC_ORGANELLE_INNER_MEMBRANE, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_DN, GOCC_ORGANELLE_ENVELOPE, GSE13522_CTRL_VS_T_CRUZI_G_STRAIN_INF_SKIN_UP

GO Biological Process (1): mitochondrial respiratory chain complex IV assembly (GO:0033617)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (3): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Respiratory electron transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitochondrion	1
respiratory chain complex IV assembly	1
mitochondrial respiratory chain complex assembly	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

620 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COX20	COX18	Q8N8Q8	807
COX20	TMEM177	Q53S58	775
COX20	COA6	Q5JTJ3	697
COX20	MT-CO2	P00403	680
COX20	SCO1	O75880	670
COX20	COX14	Q96I36	645
COX20	COA3	Q9Y2R0	642
COX20	PET100	P0DJ07	602
COX20	OXA1L	Q15070	592
COX20	COA5	Q86WW8	590
COX20	SCO2	O43819	583
COX20	PET117	Q6UWS5	583
COX20	COX16	Q9P0S2	580
COX20	ZBTB18	Q99592	540
COX20	SURF1	Q15526	540

IntAct

101 interactions, top by confidence:

A	B	Type	Score
COX20	CREB3L1	psi-mi:“MI:0915”(physical association)	0.560
COX20	GET1	psi-mi:“MI:0915”(physical association)	0.560
	COX20	psi-mi:“MI:0915”(physical association)	0.560
SLC10A6	COX20	psi-mi:“MI:0915”(physical association)	0.560
COX20	MENT	psi-mi:“MI:0915”(physical association)	0.560
TCEA2	COX20	psi-mi:“MI:0915”(physical association)	0.560
COX20	DYNC1H1	psi-mi:“MI:0915”(physical association)	0.560
COX20	TMX2	psi-mi:“MI:0915”(physical association)	0.560
PGRMC2	COX20	psi-mi:“MI:0915”(physical association)	0.560
GET1	COX20	psi-mi:“MI:0915”(physical association)	0.560
AQP6	COX20	psi-mi:“MI:0915”(physical association)	0.560
GJA8	COX20	psi-mi:“MI:0915”(physical association)	0.560
TMEM35A	COX20	psi-mi:“MI:0915”(physical association)	0.560
COX20	FUNDC2	psi-mi:“MI:0915”(physical association)	0.560
COX20	ERGIC3	psi-mi:“MI:0915”(physical association)	0.560
SLC10A1	COX20	psi-mi:“MI:0915”(physical association)	0.560
COX20	NCBP2AS2	psi-mi:“MI:0915”(physical association)	0.560
COX20	GOLT1A	psi-mi:“MI:0915”(physical association)	0.560
MAOB	COX20	psi-mi:“MI:0915”(physical association)	0.560
COX20	CHIA	psi-mi:“MI:0915”(physical association)	0.560
TEX44	COX20	psi-mi:“MI:0915”(physical association)	0.560
COX20	JAGN1	psi-mi:“MI:0915”(physical association)	0.560
CEP170	COX20	psi-mi:“MI:0915”(physical association)	0.400
MED12	WBP2	psi-mi:“MI:0914”(association)	0.350
		psi-mi:“MI:0914”(association)	0.350
	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (60): COX2 (Affinity Capture-Western), COX20 (Affinity Capture-MS), COMMD4 (Affinity Capture-MS), UQCC1 (Affinity Capture-MS), UQCC2 (Affinity Capture-MS), GK (Affinity Capture-MS), COX20 (Affinity Capture-MS), COX20 (Affinity Capture-MS), COX20 (Affinity Capture-MS), COX20 (Affinity Capture-MS), UQCC1 (Affinity Capture-MS), UQCC2 (Affinity Capture-MS), C16orf91 (Affinity Capture-MS), ECM1 (Affinity Capture-MS), COX20 (Affinity Capture-MS)

ESM2 similar proteins: A4IFL0, B1H3B1, D3ZLY0, D3ZXD8, E1BD52, E1BWM5, F1N5S9, O14925, O35093, O35094, O43615, P00130, Q08DM5, Q0VCK9, Q28851, Q2KHV4, Q3B8P0, Q4RY26, Q58EA0, Q5BJS4, Q5R5H4, Q5R9K4, Q5RDD0, Q5RI15, Q5SRD1, Q5XH94, Q5XIA8, Q5XJY4, Q68EQ9, Q6DFJ3, Q6DH87, Q6INE8, Q6INU6, Q6NYY9, Q6P4H8, Q7YRC0, Q864V5, Q8IVP5, Q8MJN0, Q91ZQ0

Diamond homologs: Q5RI15, Q6DH88, Q9D7J4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	10
Likely pathogenic	8
Uncertain significance	67
Likely benign	57
Benign	16

Top pathogenic / likely-pathogenic (18)

Variant ID	HGVS	Classification
1339430	NM_198076.6(COX20):c.222G>T (p.Trp74Cys)	Pathogenic
1339431	NM_198076.6(COX20):c.98C>T (p.Ser33Leu)	Pathogenic
1339432	NM_198076.6(COX20):c.157+7A>G	Pathogenic
1807770	GRCh37/hg19 1q44(chr1:244960357-245040680)x1	Pathogenic
2446887	NM_198076.6(COX20):c.42+1G>A	Pathogenic
3063232	GRCh37/hg19 1q44(chr1:245007762-245037711)x1	Pathogenic
3247852	NC_000001.10:g.(?244999017)(245020178_?)dup	Pathogenic
55889	NM_198076.6(COX20):c.154A>C (p.Thr52Pro)	Pathogenic
565252	GRCh37/hg19 1q44(chr1:244971506-245024284)x1	Pathogenic
687320	GRCh37/hg19 1q44(chr1:244991997-245117237)x1	Pathogenic
3343177	NM_198076.6(COX20):c.296TAT[1] (p.Leu100del)	Likely pathogenic
3582926	NM_198076.6(COX20):c.16G>T (p.Glu6Ter)	Likely pathogenic
3582958	NM_198076.6(COX20):c.53_54insAGGAT (p.Leu19fs)	Likely pathogenic
3582981	NM_198076.6(COX20):c.91del (p.Arg31fs)	Likely pathogenic
3583010	NM_198076.6(COX20):c.158-4_159delinsGAC	Likely pathogenic
3583041	NM_198076.6(COX20):c.222-1G>A	Likely pathogenic
3779546	NM_198076.6(COX20):c.108T>A (p.Tyr36Ter)	Likely pathogenic
432104	NM_198076.6(COX20):c.157+1G>A	Likely pathogenic

SpliceAI

559 predictions. Top by Δscore:

Variant	Effect	Δscore
1:244841942:A:AG	acceptor_gain	1.0000
1:244841943:G:GG	acceptor_gain	1.0000
1:244842268:C:G	donor_gain	1.0000
1:244843038:AAG:A	acceptor_gain	1.0000
1:244843039:A:G	acceptor_gain	1.0000
1:244835753:G:GT	donor_gain	0.9900
1:244835754:A:T	donor_gain	0.9900
1:244842056:CTA:C	donor_gain	0.9900
1:244842059:G:GG	donor_gain	0.9900
1:244842194:GGTA:G	acceptor_gain	0.9900
1:244842267:GC:G	donor_gain	0.9900
1:244842268:C:CG	donor_gain	0.9900
1:244843038:A:AG	acceptor_gain	0.9900
1:244843039:A:T	acceptor_loss	0.9900
1:244843040:G:A	acceptor_gain	0.9900
1:244843040:G:C	acceptor_loss	0.9900
1:244843040:G:GG	acceptor_gain	0.9900
1:244842297:G:GG	donor_gain	0.9800
1:244843040:GGTTT:G	acceptor_gain	0.9800
1:244845343:ACCT:A	acceptor_loss	0.9800
1:244835749:A:T	donor_gain	0.9700
1:244841943:GTC:G	acceptor_gain	0.9700
1:244841943:GTCC:G	acceptor_gain	0.9700
1:244842057:TA:T	donor_gain	0.9700
1:244842246:C:G	donor_gain	0.9700
1:244843039:AG:A	acceptor_gain	0.9700
1:244843040:GGT:G	acceptor_gain	0.9700
1:244845345:C:CC	acceptor_gain	0.9700
1:244835732:GCCCG:G	donor_gain	0.9600
1:244835753:GAAGG:G	donor_loss	0.9600

AlphaMissense

762 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:244842257:T:A	W74R	0.984
1:244842257:T:C	W74R	0.984
1:244842046:T:C	F49L	0.981
1:244842048:T:A	F49L	0.981
1:244842048:T:G	F49L	0.981
1:244842019:G:A	G40R	0.976
1:244842019:G:C	G40R	0.976
1:244842251:G:A	G72R	0.976
1:244842251:G:C	G72R	0.976
1:244842233:T:C	F66L	0.975
1:244842235:T:A	F66L	0.975
1:244842235:T:G	F66L	0.975
1:244842252:G:A	G72E	0.970
1:244842035:G:A	G45D	0.969
1:244842230:G:A	G65R	0.968
1:244842230:G:C	G65R	0.968
1:244842020:G:A	G40E	0.967
1:244842011:G:A	G37D	0.962
1:244842032:C:A	A44D	0.962
1:244843052:G:T	R78M	0.962
1:244842002:T:A	I34K	0.961
1:244842047:T:C	F49S	0.958
1:244842221:G:A	G62R	0.958
1:244842221:G:C	G62R	0.958
1:244842222:G:A	G62E	0.958
1:244842034:G:C	G45R	0.956
1:244842041:G:A	G47E	0.956
1:244842195:G:T	S53I	0.954
1:244842228:G:A	G64E	0.954
1:244842219:T:A	V61D	0.952

dbSNP variants (sampled 300 via entrez): RS1000024972 (1:244840186 C>T), RS1000062183 (1:244843364 C>G,T), RS1000194292 (1:244842578 A>G), RS1000244820 (1:244834562 CAT>C), RS1000413609 (1:244843569 T>A), RS1001021267 (1:244838965 C>A,G), RS1001099729 (1:244834412 G>A), RS1001365467 (1:244844650 CAGG>C), RS1001516065 (1:244839384 G>A), RS1001519339 (1:244839675 G>A), RS1001576473 (1:244839082 C>A), RS1001592846 (1:244839344 T>C), RS1001689661 (1:244844722 G>A), RS1001851275 (1:244840552 C>G,T), RS1001903691 (1:244840254 T>A,C,G)

Disease associations

OMIM: gene MIM:614698 | disease phenotypes: MIM:619054, MIM:220110, MIM:617391

GenCC curated gene-disease

Disease	Classification	Inheritance
mitochondrial complex IV deficiency, nuclear type 11	Strong	Autosomal recessive
cytochrome-c oxidase deficiency disease	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
mitochondrial disease	Definitive	AR

Mondo (5): mitochondrial complex IV deficiency, nuclear type 11 (MONDO:0033645), mitochondrial disease (MONDO:0044970), mitochondrial complex IV deficiency, nuclear type 1 (MONDO:0700250), developmental and epileptic encephalopathy, 54 (MONDO:0033363), (MONDO:0009068)

Orphanet (1): Mitochondrial disease (Orphanet:68380)

HPO phenotypes

20 total (20 of 20 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000473	Torticollis
HP:0000750	Delayed speech and language development
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001260	Dysarthria
HP:0001266	Choreoathetosis
HP:0001518	Small for gestational age
HP:0002151	Increased circulating lactate concentration
HP:0002198	Dilated fourth ventricle
HP:0002359	Frequent falls
HP:0002451	Limb dystonia
HP:0002490	Increased CSF lactate
HP:0003236	Elevated circulating creatine kinase concentration
HP:0003390	Sensory axonal neuropathy
HP:0003487	Babinski sign
HP:0003621	Juvenile onset
HP:0006855	Cerebellar vermis atrophy
HP:0008347	Decreased activity of mitochondrial complex IV
HP:0009027	Foot dorsiflexor weakness

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression	2
perfluorooctanoic acid	increases expression	2
bisphenol S	increases expression, affects cotreatment, decreases expression	2
Valproic Acid	affects expression, increases expression	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
perfluorohexanesulfonic acid	decreases expression	1
jinfukang	increases expression	1
bisphenol AF	increases expression	1
Temozolomide	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Doxorubicin	increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Indomethacin	decreases expression, affects cotreatment	1
Ivermectin	decreases expression	1
Lead	affects splicing	1
Methyl Methanesulfonate	decreases expression	1
Quercetin	decreases expression	1
Silver	increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Cyclosporine	decreases expression	1

Clinical trials (associated diseases)

103 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
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
NCT04086329	PHASE1	RECRUITING	Validation of Oxygen Nanosensor in Mitochondrial Myopathy
NCT04643249	PHASE1	COMPLETED	Drug-drug Interaction Study of KL1333 in Healthy Subjects
NCT05241262	PHASE1	RECRUITING	Study of N-acetylcysteine in the Treatment of Patients With the m.3243A>G Mutation and Low Brain Glutathione Levels
NCT05569122	PHASE1	RECRUITING	Applying pGz in Mitochondrial Disease
NCT06819683	PHASE1	RECRUITING	Validation of Nanosensor Oxygen Measurement
NCT07258667	PHASE1	NOT_YET_RECRUITING	Pilot Study of the Efficacy of Nicotinamide (Vitamin B3) in Leber’s Hereditary Optic Neuropathy
NCT04378075	PHASE2/PHASE3	TERMINATED	A Study to Evaluate Efficacy and Safety of Vatiquinone for Treating Mitochondrial Disease in Participants With Refractory Epilepsy
NCT01642056	PHASE1/PHASE2	COMPLETED	EPI-743 for Metabolism or Mitochondrial Disorders
NCT03384420	PHASE1/PHASE2	COMPLETED	A Study to Evaluate the Safety and Therapeutic Effects of Transplantation of MNV-BM-BLD in Pediatric Patients With Pearson Syndrome
NCT06051448	PHASE1/PHASE2	COMPLETED	Promoting Resilience in Stress Management (PRISM) and Clinical-focused Narrative (CFN) Pilot in Adults With Primary Mitochondrial Disease (PMD).
NCT01252979	EARLY_PHASE1	COMPLETED	Ketones & Mitochondrial Heteroplasmy
NCT00786539	Not specified	COMPLETED	Mitochondria Inborn Errors of Metabolism and ANT Defects in Mitochondria Diseases
NCT00829270	Not specified	COMPLETED	Economic and Medical Evaluation of the Whole Mitochondrial DNA Screening by Surveyor and Mitochips Techniques
NCT00831948	Not specified	UNKNOWN	Identification of Large-Scale Mutations of POLG Gene by QMPSF in Patients With Mitochondrial DNA Instability.
NCT01001585	Not specified	TERMINATED	Anesthetic Effects in Mitochondrial Disease
NCT01148550	Not specified	SUSPENDED	Longitudinal Study of Mitochondrial Hepatopathies