TIMMDC1

Summary

TIMMDC1 (translocase of inner mitochondrial membrane domain containing 1, HGNC:1321) is a protein-coding gene on chromosome 3q13.33, encoding Complex I assembly factor TIMMDC1, mitochondrial (Q9NPL8). Chaperone protein involved in the assembly of the mitochondrial NADH:ubiquinone oxidoreductase complex (complex I). It is a selective cancer dependency (DepMap: 13.6% of cell lines).

Predicted to be involved in mitochondrial respiratory chain complex I assembly. Located in mitochondrion and nucleoplasm. Implicated in nuclear type mitochondrial complex I deficiency 31.

Source: NCBI Gene 51300 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mitochondrial disease (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 14
• Clinical variants (ClinVar): 153 total — 2 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 50
• Cancer dependency (DepMap): dependent in 13.6% of screened cell lines
• MANE Select transcript: NM_016589

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1321
Approved symbol	TIMMDC1
Name	translocase of inner mitochondrial membrane domain containing 1
Location	3q13.33
Locus type	gene with protein product
Status	Approved
Aliases	FLJ22597
Ensembl gene	ENSG00000113845
Ensembl biotype	protein_coding
OMIM	615534
Entrez	51300

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 7 protein_coding, 5 nonsense_mediated_decay, 1 retained_intron

ENST00000264244, ENST00000463927, ENST00000466984, ENST00000469324, ENST00000486418, ENST00000492164, ENST00000493694, ENST00000494664, ENST00000498399, ENST00000854204, ENST00000854205, ENST00000854206, ENST00000935160

RefSeq mRNA: 1 — MANE Select: NM_016589 NM_016589

CCDS: CCDS33831

Canonical transcript exons

ENST00000494664 — 7 exons

Exon	Start	End
ENSE00001810119	119498547	119498927
ENSE00001945356	119523606	119525090
ENSE00003578554	119503532	119503620
ENSE00003602109	119500695	119500860
ENSE00003621705	119513641	119513719
ENSE00003684644	119503954	119504021
ENSE00003784761	119517205	119517315

Expression profiles

Bgee: expression breadth ubiquitous, 259 present calls, max score 99.53.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 45.2359 / max 576.1547, expressed in 1819 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
38107	38.6705	1814
38108	3.4843	1573
38109	2.2147	1193
38110	0.8664	499

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ventricle myocardium	UBERON:0006566	99.53	gold quality
cardiac muscle of right atrium	UBERON:0003379	99.07	gold quality
myocardium	UBERON:0002349	98.89	gold quality
kidney epithelium	UBERON:0004819	98.73	gold quality
deltoid	UBERON:0001476	98.41	gold quality
tibialis anterior	UBERON:0001385	98.40	gold quality
quadriceps femoris	UBERON:0001377	98.38	gold quality
vastus lateralis	UBERON:0001379	98.33	gold quality
heart right ventricle	UBERON:0002080	98.32	gold quality
upper arm skin	UBERON:0004263	98.13	gold quality
heart left ventricle	UBERON:0002084	98.09	gold quality
cardiac ventricle	UBERON:0002082	98.08	gold quality
apex of heart	UBERON:0002098	97.80	gold quality
biceps brachii	UBERON:0001507	97.75	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.74	gold quality
skeletal muscle tissue	UBERON:0001134	97.69	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	97.63	gold quality
heart	UBERON:0000948	97.62	gold quality
cardiac atrium	UBERON:0002081	97.57	gold quality
right atrium auricular region	UBERON:0006631	97.51	gold quality
muscle of leg	UBERON:0001383	97.43	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.42	gold quality
corpus callosum	UBERON:0002336	97.41	gold quality
muscle tissue	UBERON:0002385	97.40	gold quality
gastrocnemius	UBERON:0001388	97.37	gold quality
body of tongue	UBERON:0011876	97.31	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.11	gold quality
ileal mucosa	UBERON:0000331	97.08	gold quality
spinal cord	UBERON:0002240	96.89	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	96.79	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-5	no	2.21
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1

miRNA regulators (miRDB)

19 targeting TIMMDC1, 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-1297	99.91	73.41	3162
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-6513-3P	99.59	69.77	1102
HSA-MIR-653-5P	99.46	67.35	1300
HSA-MIR-363-5P	99.46	64.51	1015
HSA-MIR-4477B	99.23	70.49	1733
HSA-MIR-6074	98.89	69.64	2187
HSA-MIR-2115-5P	98.66	68.07	1191
HSA-MIR-634	97.74	67.11	818
HSA-MIR-711	96.60	65.75	528
HSA-MIR-675-3P	95.77	69.27	675
HSA-MIR-6816-3P	95.05	66.08	459
HSA-MIR-450A-5P	93.89	64.57	50
HSA-LET-7D-3P	89.01	66.89	93

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 13.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 7)

• Quantitative proteomics demonstrated a role for TIMMDC1 in assembly of membrane-embedded and soluble arms of the complex. (PMID:24344204)
• Cell-cycle arrest genes such as CCNG2 and PTEN as well as genes involved in cell migration inhibition, such as TIMP3 and COL3A1, were upregulated after C3orf1 depletion in 95D cells. (PMID:25391042)
• Findings suggest that TIMMDC1 may play an important role in human gastric cancer development, and its underlying mechanism is not only associated with mitochondrial complex I inhibition and reduced mitochondrial respiration, but is also associated with reduced glycolysis activity and the AKT/GSK3beta/beta-catenin signaling pathways. (PMID:30123074)
• Whole exome sequencing of a patient with Leigh-like syndrome identified homozygous protein-truncating variants in TIMMDC1 which was predicted to truncate 61 amino acids at the C-terminus. Functional studies demonstrated a hypomorphic impact of the variant on CI assembly. However, the mutant protein could still rescue CI assembly in TIMMDC1 knockout cells. (PMID:30981218)
• Data suggest that the hub genes NADH:ubiquinone oxidoreductase subunit B5 (NDUFB5), translocase of inner mitochondrial membrane domain containing 1 (TIMMDC1), and voltage-dependent anion channel 3 (VDAC3) might serve as potential biomarkers for diagnosis and/or therapeutic targets for precise treatment of septic cardiomyopathy (SC) . (PMID:31794266)
• Deep intronic TIMMDC1 variant delays diagnosis of rapidly progressive complex I deficiency. (PMID:33278652)
• A membrane arm of mitochondrial complex I sufficient to promote respirasome formation. (PMID:33852835)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	timmdc1	ENSDARG00000053466
mus_musculus	Timmdc1	ENSMUSG00000002846
rattus_norvegicus	Timmdc1	ENSRNOG00000002999
drosophila_melanogaster	140up	FBGN0010340
caenorhabditis_elegans		WBGENE00021421

Protein

Protein identifiers

Complex I assembly factor TIMMDC1, mitochondrial — Q9NPL8 (reviewed: Q9NPL8)

Alternative names: Protein M5-14, Translocase of inner mitochondrial membrane domain-containing protein 1

All UniProt accessions (8): Q9NPL8, C9JR82, C9JU35, F8WAU6, F8WB00, F8WC42, G3XA94, H7C5U1

UniProt curated annotations — full annotation on UniProt →

Function. Chaperone protein involved in the assembly of the mitochondrial NADH:ubiquinone oxidoreductase complex (complex I). Participates in constructing the membrane arm of complex I.

Subunit / interactions. Associates with the intermediate 315 kDa subcomplex of incompletely assembled complex I. Interacts with TMEM70.

Subcellular location. Mitochondrion membrane.

Tissue specificity. Generalized expression enhanced in heart and skeletal muscle.

Disease relevance. Mitochondrial complex I deficiency, nuclear type 31 (MC1DN31) [MIM:618251] 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. MC1DN31 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 Tim17/Tim22/Tim23 family.

RefSeq proteins (1): NP_057673* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR055299	TIMMDC1	Family

Pfam: PF02466

UniProt features (11 total): transmembrane region 4, sequence conflict 3, sequence variant 2, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NPL8-F1	72.08	0.13

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): 277

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: 173 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, MODULE_522, GOBP_MITOCHONDRIAL_RESPIRATORY_CHAIN_COMPLEX_ASSEMBLY, MARTINEZ_RB1_TARGETS_DN, GOCC_MITOCHONDRIAL_ENVELOPE, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, DODD_NASOPHARYNGEAL_CARCINOMA_UP, ELK1_01, BREDEMEYER_RAG_SIGNALING_NOT_VIA_ATM_UP, MODULE_114, GOCC_ORGANELLE_INNER_MEMBRANE, SCGGAAGY_ELK1_02, GOCC_ORGANELLE_ENVELOPE, GOBP_NADH_DEHYDROGENASE_COMPLEX_ASSEMBLY, KASLER_HDAC7_TARGETS_1_UP

GO Biological Process (1): mitochondrial respiratory chain complex I assembly (GO:0032981)

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

GO Cellular Component (5): nucleoplasm (GO:0005654), 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
cellular anatomical structure	2
NADH dehydrogenase complex assembly	1
mitochondrial respiratory chain complex assembly	1
binding	1
nuclear lumen	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
mitochondrion	1
mitochondrial envelope	1
organelle membrane	1

Protein interactions and networks

STRING

1016 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TIMMDC1	TMEM126B	Q8IUX1	896
TIMMDC1	NDUFAF1	Q9Y375	815
TIMMDC1	ECSIT	Q9BQ95	807
TIMMDC1	ACAD9	Q9H845	765
TIMMDC1	FOXRED1	Q96CU9	761
TIMMDC1	NDUFA8	P51970	719
TIMMDC1	NDUFA13	Q9P0J0	692
TIMMDC1	NDUFA3	O95167	679
TIMMDC1	TMEM186	Q96B77	670
TIMMDC1	NDUFAF4	Q9P032	655
TIMMDC1	NDUFAF5	Q5TEU4	652
TIMMDC1	TMEM70	Q9BUB7	625
TIMMDC1	NDUFAF3	Q9BU61	599
TIMMDC1	NDUFA1	O15239	556
TIMMDC1	DMAC2	Q9NW81	550

IntAct

280 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
FATE1	TIMMDC1	psi-mi:“MI:0915”(physical association)	0.670
TIMMDC1	FATE1	psi-mi:“MI:0915”(physical association)	0.670
TIMMDC1	NDUFB11	psi-mi:“MI:0915”(physical association)	0.670
NDUFAF4	NDUFS8	psi-mi:“MI:0914”(association)	0.640
YIPF1	TIMMDC1	psi-mi:“MI:0915”(physical association)	0.560
SERF1A	TIMMDC1	psi-mi:“MI:0915”(physical association)	0.560
SCD	TIMMDC1	psi-mi:“MI:0915”(physical association)	0.560
VMA12	TIMMDC1	psi-mi:“MI:0915”(physical association)	0.560
DCBLD2	TIMMDC1	psi-mi:“MI:0915”(physical association)	0.560
SERP2	TIMMDC1	psi-mi:“MI:0915”(physical association)	0.560
ATP6AP2	TIMMDC1	psi-mi:“MI:0915”(physical association)	0.560
TIMMDC1	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
PIGF	TIMMDC1	psi-mi:“MI:0915”(physical association)	0.560
CYP4F12	TIMMDC1	psi-mi:“MI:0915”(physical association)	0.560
ANKRD46	TIMMDC1	psi-mi:“MI:0915”(physical association)	0.560
STX12	TIMMDC1	psi-mi:“MI:0915”(physical association)	0.560
CDS2	TIMMDC1	psi-mi:“MI:0915”(physical association)	0.560
ARLN	TIMMDC1	psi-mi:“MI:0915”(physical association)	0.560
IFNA2	TIMMDC1	psi-mi:“MI:0915”(physical association)	0.560
DIABLO	TIMMDC1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (273): FATE1 (Two-hybrid), TIMMDC1 (Affinity Capture-MS), ARL5B (Affinity Capture-MS), NDUFAF1 (Affinity Capture-MS), ECSIT (Affinity Capture-MS), ACAD9 (Affinity Capture-MS), NDUFC2 (Affinity Capture-MS), TMEM126B (Affinity Capture-MS), TIMMDC1 (Affinity Capture-MS), TIMMDC1 (Affinity Capture-MS), TIMMDC1 (Affinity Capture-MS), TIMMDC1 (Affinity Capture-MS), TIMMDC1 (Affinity Capture-MS), TIMMDC1 (Affinity Capture-MS), ECSIT (Affinity Capture-MS)

ESM2 similar proteins: A1D3P4, A2QPL8, A4IIC3, A5DAI1, B0XPV4, B2WFD4, C0NLX2, C0RZV6, C1G565, C1GZK1, C4JDF8, C5GN10, C5JCV0, C6H4B5, D4AT37, D4DGR3, D6WMX4, E0W1I1, O14681, O94502, P0C0R5, Q03327, Q08DE5, Q0V3D6, Q1E4N0, Q20799, Q21153, Q2UBI2, Q4KM77, Q4WJ38, Q568N3, Q5EB62, Q5H9E4, Q5IRJ6, Q5PQZ3, Q5R9I3, Q5ZIG3, Q61070, Q63ZR7, Q6DCE3

Diamond homologs: P81928, Q568N3, Q5XK94, Q6AY94, Q8BUY5, Q9NPL8

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 97 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	12	40.5×	1e-14
Respiratory electron transport	12	23.3×	7e-12
Aerobic respiration and respiratory electron transport	11	19.9×	3e-10

GO biological processes:

GO term	Partners	Fold	FDR
mitochondrial respiratory chain complex I assembly	11	58.7×	1e-14
mitochondrial electron transport, NADH to ubiquinone	7	32.6×	4e-07
proton motive force-driven mitochondrial ATP synthesis	7	23.9×	3e-06
aerobic respiration	7	22.5×	3e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	5
Uncertain significance	81
Likely benign	30
Benign	12

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
429020	NM_016589.4(TIMMDC1):c.597-1340A>G	Pathogenic
4848998	NM_016589.4(TIMMDC1):c.631_635delinsTAGTT (p.Lys211_Tyr212delinsTer)	Pathogenic
1709036	NM_016589.4(TIMMDC1):c.596+1del	Likely pathogenic
2498078	NM_016589.4(TIMMDC1):c.191_192del (p.Lys64fs)	Likely pathogenic
2501222	NM_016589.4(TIMMDC1):c.194+2T>C	Likely pathogenic
3391305	NM_016589.4(TIMMDC1):c.414G>A (p.Trp138Ter)	Likely pathogenic
3678295	NM_016589.4(TIMMDC1):c.361-2A>T	Likely pathogenic

SpliceAI

1607 predictions. Top by Δscore:

Variant	Effect	Δscore
3:119498926:GA:G	donor_gain	1.0000
3:119498928:G:GG	donor_gain	1.0000
3:119500693:A:AG	acceptor_gain	1.0000
3:119500694:G:GG	acceptor_gain	1.0000
3:119513640:GCT:G	acceptor_gain	1.0000
3:119517203:A:AG	acceptor_gain	1.0000
3:119517204:G:GA	acceptor_gain	1.0000
3:119517204:GC:G	acceptor_gain	1.0000
3:119517204:GCA:G	acceptor_gain	1.0000
3:119517311:GAGTG:G	donor_gain	1.0000
3:119517313:GTG:G	donor_gain	1.0000
3:119523605:GGAAA:G	acceptor_gain	1.0000
3:119498830:G:GT	donor_gain	0.9900
3:119498843:A:T	donor_gain	0.9900
3:119498894:G:GT	donor_gain	0.9900
3:119498910:G:GT	donor_gain	0.9900
3:119498922:C:T	donor_gain	0.9900
3:119498934:G:GG	donor_gain	0.9900
3:119500694:GT:G	acceptor_gain	0.9900
3:119501797:G:GT	donor_gain	0.9900
3:119503530:A:AG	acceptor_gain	0.9900
3:119503531:G:GG	acceptor_gain	0.9900
3:119503953:GCACA:G	acceptor_gain	0.9900
3:119513639:A:AG	acceptor_gain	0.9900
3:119513640:G:GG	acceptor_gain	0.9900
3:119513717:GGG:G	donor_gain	0.9900
3:119513718:GGG:G	donor_gain	0.9900
3:119515858:AGTT:A	acceptor_gain	0.9900
3:119515859:GTTG:G	acceptor_gain	0.9900
3:119517202:CAGC:C	acceptor_loss	0.9900

AlphaMissense

1844 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:119513652:A:C	S177R	0.984
3:119513654:T:A	S177R	0.984
3:119513654:T:G	S177R	0.984
3:119503575:G:A	G135D	0.981
3:119503589:T:A	W140R	0.976
3:119503589:T:C	W140R	0.976
3:119500763:G:A	G88D	0.974
3:119500765:T:A	W89R	0.966
3:119500765:T:C	W89R	0.966
3:119503577:T:A	W136R	0.965
3:119503577:T:C	W136R	0.965
3:119503586:G:C	G139R	0.963
3:119503967:A:C	S155R	0.963
3:119503969:T:A	S155R	0.963
3:119503969:T:G	S155R	0.963
3:119503583:T:A	W138R	0.960
3:119503583:T:C	W138R	0.960
3:119500778:G:A	G93E	0.957
3:119503594:A:C	R141S	0.957
3:119503594:A:T	R141S	0.957
3:119503616:T:C	F149L	0.957
3:119503618:C:A	F149L	0.957
3:119503618:C:G	F149L	0.957
3:119504016:C:A	A171E	0.956
3:119500798:G:C	A100P	0.955
3:119513658:T:C	F179L	0.953
3:119513660:T:A	F179L	0.953
3:119513660:T:G	F179L	0.953
3:119500775:G:A	G92E	0.952
3:119503550:G:C	A127P	0.952

dbSNP variants (sampled 300 via entrez): RS1000053038 (3:119517574 T>G), RS1000098664 (3:119521263 G>A), RS1000127134 (3:119508152 T>A), RS1000134773 (3:119521036 C>G,T), RS1000193972 (3:119502527 C>T), RS1000354956 (3:119508083 A>G), RS1000359751 (3:119514648 C>T), RS1000450439 (3:119504288 G>A), RS1000661514 (3:119496925 C>A,T), RS1000711995 (3:119496596 T>C), RS1000784424 (3:119516795 C>G), RS1000795578 (3:119511267 C>G), RS1000968082 (3:119512952 G>A,C), RS1001185981 (3:119508735 T>G), RS1001260949 (3:119509160 C>G,T)

Disease associations

OMIM: gene MIM:615534 | disease phenotypes: MIM:618251, MIM:252010

GenCC curated gene-disease

Disease	Classification	Inheritance
mitochondrial complex I deficiency, nuclear type 31	Strong	Autosomal recessive
mitochondrial complex I deficiency	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
Leigh syndrome	Limited	AR
mitochondrial disease	Definitive	AR

Mondo (3): mitochondrial complex I deficiency, nuclear type 31 (MONDO:0032634), mitochondrial complex I deficiency, nuclear type 1 (MONDO:0100224), mitochondrial complex I deficiency (MONDO:0100133)

Orphanet (0):

HPO phenotypes

50 total (30 of 50 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:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001254	Lethargy
HP:0001263	Global developmental delay
HP:0001298	Encephalopathy
HP:0001310	Dysmetria
HP:0001324	Muscle weakness
HP:0001336	Myoclonus
HP:0001508	Failure to thrive
HP:0001511	Intrauterine growth retardation
HP:0001639	Hypertrophic cardiomyopathy
HP:0001943	Hypoglycemia
HP:0002013	Vomiting
HP:0002093	Respiratory insufficiency
HP:0002119	Ventriculomegaly
HP:0002205	Recurrent respiratory infections
HP:0002240	Hepatomegaly

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST001198_7	Multiple sclerosis	3.000000e-09
GCST001417_2	Arthritis (juvenile idiopathic)	1.000000e-07
GCST004145_1	Primary biliary cholangitis	1.000000e-06
GCST005528_1	Juvenile idiopathic arthritis (oligoarticular or rheumatoid factor-negative polyarticular)	4.000000e-07
GCST005531_110	Multiple sclerosis	1.000000e-23
GCST005581_44	Primary biliary cirrhosis	7.000000e-16
GCST005752_152	Systemic lupus erythematosus	1.000000e-11
GCST007036_1	Primary biliary cholangitis	6.000000e-09
GCST007400_1	Systemic lupus erythematosus	1.000000e-09
GCST007932_8	Medication use (thyroid preparations)	6.000000e-13
GCST009131_7	Systemic sclerosis	2.000000e-10
GCST009597_291	Multiple sclerosis	4.000000e-30
GCST010571_21	Autoimmune thyroid disease	3.000000e-11
GCST011956_76	Systemic lupus erythematosus	2.000000e-30

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009933	Thyroid preparation use 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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression, increases methylation	3
Acetaminophen	increases expression	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
dicrotophos	decreases expression	1
bisphenol A	affects cotreatment, increases expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	affects binding, increases reaction	1
di-n-butylphosphoric acid	affects expression	1
azoxystrobin	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
picoxystrobin	increases expression	1
bisphenol AF	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Air Pollutants, Occupational	decreases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Catechin	affects cotreatment, increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Nickel	decreases expression	1
Rotenone	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Cyclosporine	decreases expression	1
Thapsigargin	increases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E2LV	HAP1 TIMMDC1 (-) 1	Cancer cell line	Male
CVCL_E2LW	HAP1 TIMMDC1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

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