TMEM126B

Summary

TMEM126B (transmembrane protein 126B, HGNC:30883) is a protein-coding gene on chromosome 11q14.1, encoding Complex I assembly factor TMEM126B, mitochondrial (Q8IUX1). As part of the MCIA complex, involved in the assembly of the mitochondrial complex I.

This gene encodes a mitochondrial transmembrane protein which is a component of the mitochondrial complex I assembly complex. The encoded protein serves as an assembly factor that is required for formation of the membrane arm of the complex. It interacts with NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 13. Naturally occurring mutations in this gene are associated with isolated complex I deficiency. A pseudogene of this gene has been defined on chromosome 9.

Source: NCBI Gene 55863 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mitochondrial disease (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 126 total — 9 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 57
• MANE Select transcript: NM_018480

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30883
Approved symbol	TMEM126B
Name	transmembrane protein 126B
Location	11q14.1
Locus type	gene with protein product
Status	Approved
Aliases	HT007
Ensembl gene	ENSG00000171204
Ensembl biotype	protein_coding
OMIM	615533
Entrez	55863

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 7 nonsense_mediated_decay, 4 protein_coding

ENST00000358867, ENST00000393375, ENST00000526822, ENST00000528361, ENST00000529197, ENST00000530783, ENST00000530901, ENST00000531274, ENST00000531477, ENST00000531718, ENST00000534341

RefSeq mRNA: 8 — MANE Select: NM_018480 NM_001193537, NM_001193538, NM_001256546, NM_001256547, NM_001350393, NM_001350394, NM_001350396, NM_018480

CCDS: CCDS53686, CCDS8267

Canonical transcript exons

ENST00000358867 — 5 exons

Exon	Start	End
ENSE00002194853	85636046	85636536
ENSE00003516708	85634086	85634279
ENSE00003588154	85635667	85635778
ENSE00003600377	85631687	85631808
ENSE00003900182	85628593	85628688

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 96.40.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 33.0671 / max 653.9018, expressed in 1805 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
116083	33.0671	1805

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pigmented layer of retina	UBERON:0001782	96.40	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.91	gold quality
islet of Langerhans	UBERON:0000006	95.80	gold quality
hypothalamus	UBERON:0001898	95.50	gold quality
heart right ventricle	UBERON:0002080	95.45	gold quality
anterior cingulate cortex	UBERON:0009835	95.27	gold quality
spinal cord	UBERON:0002240	95.26	gold quality
caudate nucleus	UBERON:0001873	95.25	gold quality
cingulate cortex	UBERON:0003027	95.22	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	95.19	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.07	gold quality
pons	UBERON:0000988	94.97	gold quality
rectum	UBERON:0001052	94.97	gold quality
prefrontal cortex	UBERON:0000451	94.95	gold quality
right frontal lobe	UBERON:0002810	94.92	gold quality
amygdala	UBERON:0001876	94.86	gold quality
nucleus accumbens	UBERON:0001882	94.82	gold quality
cerebellar hemisphere	UBERON:0002245	94.82	gold quality
cerebellar cortex	UBERON:0002129	94.80	gold quality
calcaneal tendon	UBERON:0003701	94.75	gold quality
monocyte	CL:0000576	94.71	gold quality
mononuclear cell	CL:0000842	94.65	gold quality
metanephros cortex	UBERON:0010533	94.63	gold quality
left coronary artery	UBERON:0001626	94.58	gold quality
putamen	UBERON:0001874	94.50	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.45	gold quality
leukocyte	CL:0000738	94.41	gold quality
right adrenal gland cortex	UBERON:0035827	94.31	gold quality
right atrium auricular region	UBERON:0006631	94.25	gold quality
frontal cortex	UBERON:0001870	94.20	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	12.08
E-GEOD-75367	no	278.60

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4

miRNA regulators (miRDB)

30 targeting TMEM126B, 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-4673	100.00	66.64	1490
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-4639-5P	99.81	67.37	1028
HSA-MIR-200A-5P	99.76	69.10	949
HSA-MIR-200B-5P	99.76	69.05	948
HSA-MIR-6757-3P	99.63	66.88	1089
HSA-MIR-183-3P	99.41	69.41	1598
HSA-MIR-5582-5P	99.27	71.42	1879
HSA-MIR-1911-3P	99.15	66.17	528
HSA-MIR-3125	99.14	68.49	2269
HSA-MIR-877-3P	99.09	68.10	1637
HSA-MIR-3916	98.99	68.04	2155
HSA-MIR-6859-5P	98.99	68.07	2049
HSA-MIR-4738-3P	98.98	67.98	1846
HSA-MIR-4742-5P	98.89	68.41	1542
HSA-MIR-496	98.66	69.80	931
HSA-MIR-6852-3P	98.54	67.60	1468
HSA-MIR-4768-3P	98.16	66.02	2330
HSA-MIR-1243	97.07	65.44	719
HSA-MIR-6753-5P	94.70	64.08	470

Literature-anchored findings (GeneRIF, showing 4)

• results show that TMEM126B defects can lead to complex I deficiencies and, interestingly, that symptoms can occur only after exercise (PMID:27374773)
• functional experimentation including viral rescue and complexome profiling of subject cell lines has confirmed TMEM126B as the tenth complex I assembly factor associated with human disease and validates the importance of both genome-wide sequencing and proteomic approaches in characterizing disease-associated genes whose physiological roles have been previously undetermined (PMID:27374774)
• Data show that attenuating a functional complex I assembly appears critical for cellular adaptation towards chronic hypoxia and is linked to destruction of the mitochondrial assembly factor transmembrane protein 126B (TMEM126B). (PMID:29464284)
• Novel biallelic mutations in TMEM126B cause splicing defects and lead to Leigh-like syndrome with severe complex I deficiency. (PMID:36482121)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmem126a	ENSDARG00000014506
mus_musculus	Tmem126b	ENSMUSG00000030614
rattus_norvegicus	Tmem126b	ENSRNOG00000022732
drosophila_melanogaster	CG13392	FBGN0032033

Paralogs (1): TMEM126A (ENSG00000171202)

Protein

Protein identifiers

Complex I assembly factor TMEM126B, mitochondrial — Q8IUX1 (reviewed: Q8IUX1)

Alternative names: Transmembrane protein 126B

All UniProt accessions (6): E9PJQ6, E9PKZ7, E9PKZ9, H0YD74, Q8IUX1, H0YEG5

UniProt curated annotations — full annotation on UniProt →

Function. As part of the MCIA complex, involved in the assembly of the mitochondrial complex I. Participates in constructing the membrane arm of complex I.

Subunit / interactions. Part of the mitochondrial complex I assembly/MCIA complex that comprises at least the core subunits TMEM126B, NDUFAF1, ECSIT and ACAD9 and complement subunits such as COA1 and TMEM186. Associates with the intermediate 370 kDa subcomplex of incompletely assembled complex I. Interacts with TMEM70.

Subcellular location. Mitochondrion membrane.

Disease relevance. Mitochondrial complex I deficiency, nuclear type 29 (MC1DN29) [MIM:618250] A form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. MC1DN29 transmission pattern is consistent with autosomal recessive inheritance. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the TMEM126 family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q8IUX1-1	1	yes
Q8IUX1-2	2
Q8IUX1-3	3
Q8IUX1-4	4
Q8IUX1-5	5

RefSeq proteins (8): NP_001180466, NP_001180467, NP_001243475, NP_001243476, NP_001337322, NP_001337323, NP_001337325, NP_060950* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009801	TMEM126	Family

Pfam: PF07114

UniProt features (16 total): splice variant 6, transmembrane region 4, sequence variant 3, initiator methionine 1, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IUX1-F1	82.06	0.60

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): 34

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-6799198	Complex I biogenesis
R-HSA-1428517	Aerobic respiration and respiratory electron transport
R-HSA-1430728	Metabolism
R-HSA-611105	Respiratory electron transport

MSigDB gene sets: 224 (showing top): WWTAAGGC_UNKNOWN, NKX25_02, GOBP_MITOCHONDRIAL_RESPIRATORY_CHAIN_COMPLEX_ASSEMBLY, GOBP_RESPONSE_TO_FOOD, CAGCTG_AP4_Q5, WEI_MYCN_TARGETS_WITH_E_BOX, NF1_Q6_01, ZIC1_01, GOCC_MITOCHONDRIAL_ENVELOPE, NKX22_01, NKX25_01, HNF1_C, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, NIKOLSKY_BREAST_CANCER_11Q12_Q14_AMPLICON, CTGYNNCTYTAA_UNKNOWN

GO Biological Process (3): response to food (GO:0032094), mitochondrial respiratory chain complex I assembly (GO:0032981), mitochondrion organization (GO:0007005)

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

GO Cellular Component (4): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), membrane (GO:0016020), mitochondrial membrane (GO:0031966)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Respiratory electron transport	1
Metabolism	1
Aerobic respiration and respiratory electron transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to nutrient levels	1
response to chemical	1
NADH dehydrogenase complex assembly	1
mitochondrial respiratory chain complex assembly	1
organelle organization	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
cellular anatomical structure	1
mitochondrion	1
mitochondrial envelope	1
organelle membrane	1

Protein interactions and networks

STRING

1208 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM126B	ACAD9	Q9H845	990
TMEM126B	ECSIT	Q9BQ95	979
TMEM126B	NDUFAF1	Q9Y375	977
TMEM126B	TMEM186	Q96B77	896
TMEM126B	TIMMDC1	Q9NPL8	896
TMEM126B	AASDHPPT	Q9NRN7	825
TMEM126B	FOXRED1	Q96CU9	817
TMEM126B	ATP5F1B	P06576	794
TMEM126B	SDHA	P31040	717
TMEM126B	NDUFAF6	Q330K2	697
TMEM126B	MT-ND2	P03891	656
TMEM126B	NDUFAF5	Q5TEU4	646
TMEM126B	NDUFAF7	Q7L592	622
TMEM126B	NDUFAF4	Q9P032	609
TMEM126B	MT-ND3	P03897	587

IntAct

44 interactions, top by confidence:

A	B	Type	Score
NDUFAF1	NDUFS3	psi-mi:“MI:0914”(association)	0.790
NDUFS3	NDUFS8	psi-mi:“MI:0914”(association)	0.730
NDUFA13	NDUFS8	psi-mi:“MI:0914”(association)	0.640
NDUFAF4	NDUFS8	psi-mi:“MI:0914”(association)	0.640
TMEM126B	MRFAP1L1	psi-mi:“MI:0915”(physical association)	0.560
MRFAP1L1	TMEM126B	psi-mi:“MI:0915”(physical association)	0.560
TIMMDC1	NDUFS8	psi-mi:“MI:0914”(association)	0.530
APLNR	METTL15	psi-mi:“MI:0914”(association)	0.530
PDCD1	RTL8C	psi-mi:“MI:0914”(association)	0.530
ECSIT	NDUFS8	psi-mi:“MI:0914”(association)	0.530
NDUFS5	NDUFS4	psi-mi:“MI:0914”(association)	0.530
NDUFC2	NDUFS4	psi-mi:“MI:0914”(association)	0.530
TMEM126B	ECSIT	psi-mi:“MI:0914”(association)	0.530
ACAD9	NDUFS2	psi-mi:“MI:0914”(association)	0.350
ECSIT	NDUFS2	psi-mi:“MI:0914”(association)	0.350
NDUFA13	SLC22A20P	psi-mi:“MI:0914”(association)	0.350
GPR17	TMEM120B	psi-mi:“MI:0914”(association)	0.350
MAGEA8	METTL15	psi-mi:“MI:0914”(association)	0.350
OPRL1	METTL15	psi-mi:“MI:0914”(association)	0.350
GLMP	RTL8C	psi-mi:“MI:0914”(association)	0.350
SLC22A4	RTL8C	psi-mi:“MI:0914”(association)	0.350
SLC18A2	UBXN8	psi-mi:“MI:0914”(association)	0.350
NDUFB11	NDUFS8	psi-mi:“MI:0914”(association)	0.350
SLC22A6	YIF1A	psi-mi:“MI:0914”(association)	0.350
GPR182	SLC12A8	psi-mi:“MI:0914”(association)	0.350
MFSD4A	UBXN8	psi-mi:“MI:0914”(association)	0.350

BioGRID (73): MRFAP1L1 (Two-hybrid), TMEM126B (Affinity Capture-MS), TMEM126B (Affinity Capture-MS), TMEM126B (Affinity Capture-MS), TMEM126B (Affinity Capture-MS), TMEM126B (Affinity Capture-MS), NDUFAF1 (Affinity Capture-MS), NDUFC2 (Affinity Capture-MS), TMEM126B (Affinity Capture-MS), TMEM126B (Affinity Capture-MS), TMEM126B (Affinity Capture-MS), TMEM126B (Affinity Capture-MS), TMEM126B (Affinity Capture-MS), TMEM126B (Synthetic Lethality), TMEM126B (Affinity Capture-MS)

ESM2 similar proteins: A0A096LP01, A2AJB2, A3LP48, A5DJS9, A5E5Y6, A7TQD5, B2RZD2, B9WD58, C4XZH2, C4YPM0, C5DE77, C5DQU6, C5M8B9, G2TRP9, O22912, O95167, P0DN34, P0DN35, P19173, Q02371, Q04935, Q0D285, Q0MQ95, Q12082, Q2KP58, Q3E776, Q3E823, Q3SZU9, Q42841, Q56VL3, Q59LP6, Q6BYM1, Q6C0R5, Q6CMH6, Q75D07, Q86IZ2, Q8IUX1, Q8VY39, Q8VY40, Q941A6

Diamond homologs: B2RZD2, Q32L86, Q8IUX1, Q9D1R1, Q5HZA9, Q5RAY9, Q9D8Y1, Q9H061

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 51 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Complex I biogenesis	14	74.8×	7e-22
Respiratory electron transport	13	39.9×	1e-16
Aerobic respiration and respiratory electron transport	13	37.1×	2e-16

GO biological processes:

GO term	Partners	Fold	FDR
mitochondrial respiratory chain complex I assembly	12	112.1×	4e-20
mitochondrial electron transport, NADH to ubiquinone	8	65.2×	2e-11
proton motive force-driven mitochondrial ATP synthesis	9	53.9×	8e-12
aerobic respiration	9	50.7×	9e-12

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	2
Uncertain significance	52
Likely benign	35
Benign	10

Top pathogenic / likely-pathogenic (11)

Variant ID	HGVS	Classification
1431700	NM_018480.7(TMEM126B):c.241del (p.Thr81fs)	Pathogenic
1953147	NM_018480.7(TMEM126B):c.187del (p.Tyr63fs)	Pathogenic
2072804	NM_018480.7(TMEM126B):c.77_81del (p.Pro26fs)	Pathogenic
2095260	NM_018480.7(TMEM126B):c.585dup (p.Leu196fs)	Pathogenic
2152794	NM_018480.7(TMEM126B):c.587T>G (p.Leu196Ter)	Pathogenic
236208	NM_018480.7(TMEM126B):c.401del (p.Asn134fs)	Pathogenic
253167	NM_018480.7(TMEM126B):c.208C>T (p.Gln70Ter)	Pathogenic
3695445	NM_018480.7(TMEM126B):c.269del (p.Asn90fs)	Pathogenic
4778794	NM_018480.7(TMEM126B):c.148del (p.Arg50fs)	Pathogenic
2153373	NM_018480.7(TMEM126B):c.203+2T>C	Likely pathogenic
2630644	NM_018480.7(TMEM126B):c.290dup (p.Lys98fs)	Likely pathogenic

SpliceAI

1101 predictions. Top by Δscore:

Variant	Effect	Δscore
11:85631804:GAAAT:G	donor_gain	1.0000
11:85631809:G:GG	donor_gain	1.0000
11:85634570:G:GG	donor_gain	1.0000
11:85634589:T:G	donor_gain	1.0000
11:85634608:G:GG	donor_gain	1.0000
11:85635661:TTCCA:T	acceptor_loss	1.0000
11:85635662:TCCAG:T	acceptor_loss	1.0000
11:85635663:CCAGA:C	acceptor_loss	1.0000
11:85635664:CAGA:C	acceptor_loss	1.0000
11:85635665:AG:A	acceptor_loss	1.0000
11:85635666:GATA:G	acceptor_gain	1.0000
11:85635776:CAAG:C	donor_loss	1.0000
11:85635778:AGTAA:A	donor_loss	1.0000
11:85635779:G:GG	donor_gain	1.0000
11:85635779:GT:G	donor_loss	1.0000
11:85635780:TAAG:T	donor_loss	1.0000
11:85629986:TTCA:T	donor_gain	0.9900
11:85631317:G:GG	donor_gain	0.9900
11:85631765:A:AG	donor_gain	0.9900
11:85631992:G:GA	donor_gain	0.9900
11:85634081:ATTAG:A	acceptor_gain	0.9900
11:85634082:TTA:T	acceptor_loss	0.9900
11:85634083:TAG:T	acceptor_loss	0.9900
11:85634084:A:AG	acceptor_gain	0.9900
11:85634084:AG:A	acceptor_gain	0.9900
11:85634085:G:GG	acceptor_gain	0.9900
11:85634085:GG:G	acceptor_gain	0.9900
11:85634085:GGAC:G	acceptor_gain	0.9900
11:85634214:C:G	donor_gain	0.9900
11:85634589:T:TG	donor_gain	0.9900

AlphaMissense

1513 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:85634152:C:A	N90K	0.977
11:85634152:C:G	N90K	0.977
11:85635761:T:A	N164K	0.976
11:85635761:T:G	N164K	0.976
11:85636092:T:A	W186R	0.967
11:85636092:T:C	W186R	0.967
11:85634164:A:C	R94S	0.960
11:85634164:A:T	R94S	0.960
11:85635738:A:C	S157R	0.960
11:85635740:T:A	S157R	0.960
11:85635740:T:G	S157R	0.960
11:85635750:T:C	F161L	0.958
11:85635752:T:A	F161L	0.958
11:85635752:T:G	F161L	0.958
11:85634163:G:C	R94T	0.954
11:85635699:A:C	S144R	0.953
11:85635701:C:A	S144R	0.953
11:85635701:C:G	S144R	0.953
11:85635772:C:A	A168E	0.952
11:85635751:T:C	F161S	0.948
11:85635720:T:C	C151R	0.947
11:85635771:G:C	A168P	0.946
11:85635748:C:A	A160D	0.941
11:85634139:G:A	G86E	0.938
11:85634127:C:A	A82D	0.935
11:85634225:T:C	F115L	0.935
11:85634227:T:A	F115L	0.935
11:85634227:T:G	F115L	0.935
11:85634241:T:A	V120D	0.935
11:85634223:C:G	P114R	0.934

dbSNP variants (sampled 300 via entrez): RS1000228247 (11:85636795 T>A), RS1000802507 (11:85635869 T>TGTCTATG), RS1000855097 (11:85636248 G>A,C), RS1000960160 (11:85629125 T>A,C), RS1000969503 (11:85635159 A>G), RS1001283923 (11:85636572 T>A,C), RS1001413929 (11:85629397 G>A,C,T), RS1001733340 (11:85636332 T>C), RS1002886211 (11:85628334 G>A), RS1003176485 (11:85626758 G>A), RS1003244460 (11:85628140 G>A), RS1003353153 (11:85633490 C>T), RS1003424282 (11:85632590 G>A), RS1003461812 (11:85627996 C>A,T), RS1003512736 (11:85628263 C>G)

Disease associations

OMIM: gene MIM:615533 | disease phenotypes: MIM:618250, MIM:252010

GenCC curated gene-disease

Disease	Classification	Inheritance
mitochondrial complex I deficiency, nuclear type 29	Definitive	Autosomal recessive
mitochondrial complex I deficiency	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 (4): mitochondrial complex I deficiency, nuclear type 29 (MONDO:0032633), mitochondrial complex I deficiency, nuclear type 1 (MONDO:0100224), mitochondrial disease (MONDO:0044970), mitochondrial complex I deficiency (MONDO:0100133)

Orphanet (2): Mitochondrial disease (Orphanet:68380), Isolated complex I deficiency (Orphanet:2609)

HPO phenotypes

57 total (30 of 57 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000114	Proximal tubulopathy
HP:0000252	Microcephaly
HP:0000407	Sensorineural hearing impairment
HP:0000486	Strabismus
HP:0000508	Ptosis
HP:0000543	Optic disc pallor
HP:0000618	Blindness
HP:0000639	Nystagmus
HP:0000817	Reduced eye contact
HP:0000819	Diabetes mellitus
HP:0001138	Optic neuropathy
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001254	Lethargy
HP:0001263	Global developmental delay
HP:0001298	Encephalopathy
HP:0001324	Muscle weakness
HP:0001508	Failure to thrive
HP:0001511	Intrauterine growth retardation
HP:0001627	Abnormal heart morphology
HP:0001639	Hypertrophic cardiomyopathy
HP:0001943	Hypoglycemia
HP:0001962	Palpitations
HP:0002013	Vomiting
HP:0002093	Respiratory insufficiency
HP:0002094	Dyspnea
HP:0002151	Increased circulating lactate concentration
HP:0002240	Hepatomegaly
HP:0002352	Leukoencephalopathy

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST000431_5	Height	3.000000e-06
GCST009391_1962	Metabolite levels	1.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008392	triiodothyronine measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C537475	Mitochondrial complex I deficiency (supp.)

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
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	2
Air Pollutants	decreases expression, increases abundance	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment	2
dicrotophos	decreases expression	1
arsenite	affects binding, increases reaction	1
beta-methylcholine	affects expression	1
ICG 001	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Vorinostat	increases expression	1
Ethanol	increases abundance, affects cotreatment, decreases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression, decreases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Coal	decreases expression, increases abundance	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Phthalic Acids	increases methylation	1
Plant Extracts	affects cotreatment, increases expression	1
Polycyclic Aromatic Hydrocarbons	increases abundance, affects cotreatment, decreases expression	1
Quercetin	decreases expression	1
Smoke	decreases expression, increases abundance	1
Tobacco Smoke Pollution	increases expression	1
Urethane	decreases expression	1
Aflatoxin B1	decreases methylation	1
Lactic Acid	decreases expression	1
1-Butanol	affects cotreatment, decreases expression, increases abundance	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3JH	Abcam HEK293T TMEM126B KO	Transformed cell line	Female

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
NCT05162768	PHASE3	COMPLETED	Study to Evaluate Efficacy and Safety of Elamipretide in Subjects With Primary Mitochondrial Disease From Nuclear DNA Mutations (nPMD)
NCT00432744	PHASE3	COMPLETED	Phase III Trial of Coenzyme Q10 in Mitochondrial Disease
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