ISCA1

Summary

ISCA1 (iron-sulfur cluster assembly 1, HGNC:28660) is a protein-coding gene on chromosome 9q21.33, encoding Iron-sulfur cluster assembly 1 homolog, mitochondrial (Q9BUE6). Involved in the maturation of mitochondrial 4Fe-4S proteins functioning late in the iron-sulfur cluster assembly pathway. It is a selective cancer dependency (DepMap: 20.5% of cell lines).

ISCA1 is a mitochondrial protein involved in the biogenesis and assembly of iron-sulfur clusters, which play a role in electron-transfer reactions (Cozar-Castellano et al., 2004 [PubMed 15262227]).

Source: NCBI Gene 81689 — RefSeq curated summary.

At a glance

• Gene–disease (curated): multiple mitochondrial dysfunctions syndrome 5 (Strong, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 41 total — 1 pathogenic
• Phenotypes (HPO): 19
• Cancer dependency (DepMap): dependent in 20.5% of screened cell lines
• MANE Select transcript: NM_030940

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28660
Approved symbol	ISCA1
Name	iron-sulfur cluster assembly 1
Location	9q21.33
Locus type	gene with protein product
Status	Approved
Aliases	MGC4276, ISA1, hIscA, hIscA1
Ensembl gene	ENSG00000135070
Ensembl biotype	protein_coding
OMIM	611006
Entrez	81689

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000311534, ENST00000326094, ENST00000375991, ENST00000637705

RefSeq mRNA: 1 — MANE Select: NM_030940 NM_030940

CCDS: CCDS35056

Canonical transcript exons

ENST00000375991 — 4 exons

Exon	Start	End
ENSE00001288143	86282378	86282538
ENSE00001889916	86264546	86266191
ENSE00003471704	86274189	86274242
ENSE00003583190	86272007	86272112

Expression profiles

Bgee: expression breadth ubiquitous, 296 present calls, max score 97.74.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.1498 / max 144.2379, expressed in 1799 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
101208	14.9261	1795
101206	1.0267	577
101207	0.1970	88

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	97.74	gold quality
biceps brachii	UBERON:0001507	97.27	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.12	gold quality
heart right ventricle	UBERON:0002080	96.85	gold quality
adult organism	UBERON:0007023	96.30	gold quality
trabecular bone tissue	UBERON:0002483	96.25	gold quality
nephron tubule	UBERON:0001231	95.93	gold quality
choroid plexus epithelium	UBERON:0003911	95.86	gold quality
pons	UBERON:0000988	95.84	gold quality
myocardium	UBERON:0002349	95.83	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.71	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.64	gold quality
vastus lateralis	UBERON:0001379	95.52	gold quality
prefrontal cortex	UBERON:0000451	95.39	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.25	gold quality
quadriceps femoris	UBERON:0001377	95.17	gold quality
muscle organ	UBERON:0001630	95.11	gold quality
skeletal muscle organ	UBERON:0014892	95.11	gold quality
muscle of leg	UBERON:0001383	95.08	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	95.07	gold quality
gastrocnemius	UBERON:0001388	95.06	gold quality
diaphragm	UBERON:0001103	94.98	gold quality
germinal epithelium of ovary	UBERON:0001304	94.97	gold quality
primary visual cortex	UBERON:0002436	94.95	gold quality
skeletal muscle tissue	UBERON:0001134	94.82	gold quality
cardiac muscle of right atrium	UBERON:0003379	94.68	gold quality
bone element	UBERON:0001474	94.64	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	94.59	gold quality
muscle tissue	UBERON:0002385	94.57	gold quality
superior frontal gyrus	UBERON:0002661	94.53	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-10042	yes	23.33
E-MTAB-9221	yes	16.35
E-HCAD-9	yes	7.48
E-MTAB-7606	no	999.35
E-CURD-85	no	117.72
E-HCAD-5	no	2.29
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

64 targeting ISCA1, 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-340-5P	100.00	72.50	4437
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-3156-3P	99.76	66.72	939
HSA-MIR-4645-3P	99.76	69.33	993
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-182-3P	99.57	67.57	825
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-486-5P	99.51	70.39	707
HSA-MIR-4452	99.50	68.45	1493
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-363-5P	99.46	64.51	1015

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 20.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 13)

• screening a human brain cDNA expression library with serum from a patient suffering from the autoimmune Sjogren’s syndrome yielded a gene product called hIscA implicated in iron-sulfur cluster biogenesis (PMID:15262227)
• Required for functional heme biosynthesis in erythroid cells. (PMID:19656490)
• human IscA1 plays an important role in both mitochondrial and cytosolic iron-sulfur cluster biogenesis, and a notable component of the latter is the interaction between IscA1 and IOP1. (PMID:19864422)
• Iron-binding activity of human iron-sulfur cluster assembly protein hIscA1 (PMID:20302570)
• ISCA1, ISCA2, and IBA57 were depleted by RNA interference. Depleted cells contained massively swollen and enlarged mitochondria that were virtually devoid of cristae membranes, demonstrating the importance of these proteins for mitochondrial biogenesis. (PMID:22323289)
• The data presented here show that the Isu1 suppressor mimics the frataxin effects on Nfs1, explaining the bypassing activity. (PMID:24217246)
• The structural plasticity of the dimeric state of the [2Fe-2S] bound form of human GRX5 is the crucial factor that allows an efficient cluster transfer to the partner proteins human ISCA1 and ISCA2 by a specific protein-protein recognition mechanism. (PMID:24733926)
• the phenotype observed in all affected subjects with the ISCA1 pathogenic variant is similar to that previously described in all four types of multiple mitochondrial dysfunctions syndromes. (PMID:28356563)
• hHmozygous p.(Glu87Lys) variant in ISCA1 is associated with a multiple mitochondrial dysfunctions syndrome (PMID:28615675)
• Expanding the phenotype of mitochondrial disease: Novel pathogenic variant in ISCA1 leading to instability of the iron-sulfur cluster in the protein. (PMID:32092383)
• ISCA1 Orchestrates ISCA2 and NFU1 in the Maturation of Human Mitochondrial [4Fe-4S] Proteins. (PMID:33711344)
• Identification of ISCA1 as novel immunological and prognostic biomarker for bladder cancer. (PMID:36072584)
• Copper exerts cytotoxicity through inhibition of iron-sulfur cluster biogenesis on ISCA1/ISCA2/ISCU assembly proteins. (PMID:37225108)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	isca1	ENSDARG00000051956
mus_musculus	Isca1	ENSMUSG00000044792
mus_musculus	AK157302	ENSMUSG00000078139
rattus_norvegicus	Isca1	ENSRNOG00000018343
drosophila_melanogaster	MagR	FBGN0026666
caenorhabditis_elegans		WBGENE00012666

Paralogs (1): ISCA2 (ENSG00000165898)

Protein

Protein identifiers

Iron-sulfur cluster assembly 1 homolog, mitochondrial — Q9BUE6 (reviewed: Q9BUE6)

Alternative names: HESB-like domain-containing protein 2, Iron-sulfur assembly protein IscA

All UniProt accessions (4): A0A1B0GTK6, Q9BUE6, Q5TBE2, Q5TBE9

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the maturation of mitochondrial 4Fe-4S proteins functioning late in the iron-sulfur cluster assembly pathway. Probably involved in the binding of an intermediate of Fe/S cluster assembly.

Subunit / interactions. Interacts with CRY2, but not with CRY1 (in vitro).

Subcellular location. Mitochondrion.

Tissue specificity. Detected in cerebellum, kidney and heart.

Disease relevance. Multiple mitochondrial dysfunctions syndrome 5 (MMDS5) [MIM:617613] An autosomal recessive, severe disorder characterized by early onset neurological deterioration, seizures, cerebral and cerebellar leukodystrophy, dysmyelination, cortical migrational abnormalities, lactic acidosis and early demise. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the HesB/IscA family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BUE6-1	1	yes
Q9BUE6-2	2

RefSeq proteins (1): NP_112202* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000361	ATAP_core_dom	Domain
IPR016092	ATAP	Family
IPR017870	FeS_cluster_insertion_CS	Conserved_site
IPR035903	HesB-like_dom_sf	Homologous_superfamily
IPR050322	Fe-S_cluster_asmbl/transfer	Family

Pfam: PF01521

UniProt features (7 total): binding site 3, transit peptide 1, chain 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BUE6-F1	90.18	0.71

Functional residue map

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

Ligand- & substrate-binding residues (3): 57; 121; 123

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-1362409	Mitochondrial iron-sulfur cluster biogenesis
R-HSA-9854311	Maturation of TCA enzymes and regulation of TCA cycle
R-HSA-1428517	Aerobic respiration and respiratory electron transport
R-HSA-1430728	Metabolism
R-HSA-71403	Citric acid cycle (TCA cycle)

MSigDB gene sets: 155 (showing top): GCM_GSPT1, GCM_ZNF198, RODWELL_AGING_KIDNEY_NO_BLOOD_DN, GCM_BCL2L1, LINDGREN_BLADDER_CANCER_CLUSTER_2A_DN, YGACNNYACAR_UNKNOWN, GOBP_PROTEIN_MATURATION, PETRETTO_HEART_MASS_QTL_CIS_DN, GNF2_SPTA1, PETRETTO_LEFT_VENTRICLE_MASS_QTL_CIS_DN, GARY_CD5_TARGETS_DN, GCM_SUFU, FLECHNER_BIOPSY_KIDNEY_TRANSPLANT_REJECTED_VS_OK_DN, GCM_NF2, ACEVEDO_LIVER_CANCER_UP

GO Biological Process (2): iron-sulfur cluster assembly (GO:0016226), protein maturation (GO:0051604)

GO Molecular Function (4): metal ion binding (GO:0046872), 2 iron, 2 sulfur cluster binding (GO:0051537), protein binding (GO:0005515), iron-sulfur cluster binding (GO:0051536)

GO Cellular Component (4): cytoplasm (GO:0005737), mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), mitochondrial [4Fe-4S] assembly complex (GO:0120510)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Metabolism	2
Citric acid cycle (TCA cycle)	1
Aerobic respiration and respiratory electron transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
metallo-sulfur cluster assembly	1
gene expression	1
protein metabolic process	1
cation binding	1
iron-sulfur cluster binding	1
binding	1
metal cluster binding	1
intracellular anatomical structure	1
cellular anatomical structure	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1
mitochondrial protein-containing complex	1
iron-sulfur cluster assembly complex	1

Protein interactions and networks

STRING

1472 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ISCA1	IBA57	Q5T440	992
ISCA1	ISCA2	Q86U28	935
ISCA1	GLRX5	Q86SX6	914
ISCA1	NFU1	Q9UMS0	877
ISCA1	ISCU	Q9H1K1	843
ISCA1	NFS1	Q9Y697	811
ISCA1	LIAS	O43766	811
ISCA1	LYRM4	Q9HD34	810
ISCA1	NUBPL	Q8TB37	807
ISCA1	BOLA3	Q53S33	803
ISCA1	CIAO3	Q9H6Q4	793
ISCA1	FDX2	Q6P4F2	793
ISCA1	BOLA1	Q9Y3E2	760
ISCA1	ACO2	Q99798	744
ISCA1	GLRX3	O76003	743

IntAct

81 interactions, top by confidence:

A	B	Type	Score
GORASP2	GOLGA2	psi-mi:“MI:0914”(association)	0.880
RIN1	ABL1	psi-mi:“MI:0914”(association)	0.790
ISCA2	ISCA1	psi-mi:“MI:0407”(direct interaction)	0.740
ISCA1	ISCA2	psi-mi:“MI:0407”(direct interaction)	0.740
PSMD2	PSMD11	psi-mi:“MI:0914”(association)	0.730
TEPSIN	AP4M1	psi-mi:“MI:0914”(association)	0.700
TRIB1	DET1	psi-mi:“MI:0914”(association)	0.640
SCGB1D1	FAM234B	psi-mi:“MI:0914”(association)	0.530
TRIB2	POTEF	psi-mi:“MI:0914”(association)	0.530
NUDT6	DENR	psi-mi:“MI:0914”(association)	0.530
HSPB9	USP12	psi-mi:“MI:0914”(association)	0.530
SPATA24	GGPS1	psi-mi:“MI:0914”(association)	0.530
RAB40B	RAB40AL	psi-mi:“MI:0914”(association)	0.530
RAB40A	RAB40AL	psi-mi:“MI:0914”(association)	0.530
RAB40AL	VSIG8	psi-mi:“MI:0914”(association)	0.530
TRIB1	UBE2E1	psi-mi:“MI:0914”(association)	0.530
GH2	METAP1	psi-mi:“MI:0914”(association)	0.530
ZMAT3	ACTA2	psi-mi:“MI:0914”(association)	0.530
WDR18	NOL9	psi-mi:“MI:0914”(association)	0.530

BioGRID (136): ISCA1 (Affinity Capture-MS), ISCA1 (Affinity Capture-MS), ISCA1 (Affinity Capture-MS), ISCA1 (Affinity Capture-MS), ISCA1 (Affinity Capture-MS), ISCA1 (Affinity Capture-MS), ISCA1 (Affinity Capture-MS), ISCA1 (Affinity Capture-MS), ISCA1 (Affinity Capture-MS), ISCA1 (Affinity Capture-MS), ISCA1 (Affinity Capture-MS), ISCA1 (Affinity Capture-MS), ISCA1 (Proximity Label-MS), ISCA1 (Affinity Capture-MS), ISCA1 (Affinity Capture-MS)

ESM2 similar proteins: A4WDA9, A9MHJ6, A9N1X7, B1IWD3, B1LNI4, B1XB03, B4EZU6, B4T0S0, B4TDB4, B4TRX3, B5BAW8, B5F1B8, B5FR83, B5R5A0, B5RD10, B5XNJ9, B6I5A0, B7LKB1, B7M7N1, B7MIL8, B7MYG2, B7N6B5, B7NRH7, B7UGX4, C0PYK9, C5BEU3, P0AAC8, P0AAC9, P0DN75, Q0TEV7, Q31XW2, Q3SZG8, Q3YZ24, Q4QRC6, Q4R5F0, Q54VS1, Q57LH1, Q5PNG5, Q5ZJ74, Q7CQ12

Diamond homologs: A1AE65, A1JKQ4, A1VMK3, A4T031, A4TMV2, A4WDA9, A6TCE9, A7FFX3, A7MGY0, A8GHY1, A9I246, A9MHJ6, A9N1X7, A9R816, B1IWD3, B1JRZ0, B1LNI4, B1XB03, B2FJT4, B2K9R5, B4EZU6, B4SLD1, B4T0S0, B4TDB4, B4TRX3, B5BAW8, B5F1B8, B5FR83, B5R5A0, B5RD10, B5XNJ9, B6I5A0, B7LDC0, B7LKB1, B7M7N1, B7MIL8, B7MYG2, B7N6B5, B7NRH7, B7UGX4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ISCA1	“form complex”	“ISCA1-ISCA2 mitochondrial iron-sulfur protein assembly complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 91 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.

GO biological processes:

GO term	Partners	Fold	FDR
glucose metabolic process	5	16.0×	5e-03
proteasome-mediated ubiquitin-dependent protein catabolic process	9	5.9×	5e-03
intracellular signal transduction	11	5.2×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	16
Likely benign	19
Benign	3

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
695121	NM_030940.4(ISCA1):c.29T>G (p.Val10Gly)	Pathogenic

SpliceAI

734 predictions. Top by Δscore:

Variant	Effect	Δscore
9:86272001:ACTC:A	donor_loss	1.0000
9:86272002:CTCA:C	donor_loss	1.0000
9:86272003:TCACC:T	donor_loss	1.0000
9:86272004:CACCA:C	donor_loss	1.0000
9:86272005:A:AC	donor_gain	1.0000
9:86272005:A:T	donor_loss	1.0000
9:86272005:AC:A	donor_gain	1.0000
9:86272005:ACCAT:A	donor_gain	1.0000
9:86272006:C:A	donor_loss	1.0000
9:86272006:C:CC	donor_gain	1.0000
9:86272006:CC:C	donor_gain	1.0000
9:86272006:CCAT:C	donor_gain	1.0000
9:86272006:CCATC:C	donor_gain	1.0000
9:86272109:CTAC:C	acceptor_gain	1.0000
9:86272110:TAC:T	acceptor_gain	1.0000
9:86274183:ACTT:A	donor_loss	1.0000
9:86274184:CT:C	donor_loss	1.0000
9:86274185:TTA:T	donor_loss	1.0000
9:86274186:TACA:T	donor_loss	1.0000
9:86274187:A:AC	donor_gain	1.0000
9:86274188:C:CC	donor_gain	1.0000
9:86274188:C:G	donor_loss	1.0000
9:86274188:CATG:C	donor_gain	1.0000
9:86274240:TGTC:T	acceptor_loss	1.0000
9:86274241:GTC:G	acceptor_loss	1.0000
9:86274243:C:CC	acceptor_gain	1.0000
9:86282374:TCA:T	donor_loss	1.0000
9:86282375:CA:C	donor_loss	1.0000
9:86282376:A:AC	donor_gain	1.0000
9:86282376:A:AT	donor_loss	1.0000

AlphaMissense

828 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:86266052:A:C	F127L	1.000
9:86266052:A:T	F127L	1.000
9:86266054:A:G	F127L	1.000
9:86266104:A:G	F110S	1.000
9:86272072:C:T	G59D	1.000
9:86272078:C:G	C57S	1.000
9:86272078:C:T	C57Y	1.000
9:86272079:A:G	C57R	1.000
9:86272079:A:T	C57S	1.000
9:86266055:G:C	S126R	0.999
9:86266055:G:T	S126R	0.999
9:86266057:T:G	S126R	0.999
9:86266062:C:A	G124V	0.999
9:86266065:C:G	C123S	0.999
9:86266065:C:T	C123Y	0.999
9:86266066:A:G	C123R	0.999
9:86266066:A:T	C123S	0.999
9:86266068:C:T	G122D	0.999
9:86266071:C:A	C121F	0.999
9:86266071:C:G	C121S	0.999
9:86266071:C:T	C121Y	0.999
9:86266072:A:G	C121R	0.999
9:86266072:A:T	C121S	0.999
9:86266091:G:C	N114K	0.999
9:86266091:G:T	N114K	0.999
9:86266097:G:C	F112L	0.999
9:86266097:G:T	F112L	0.999
9:86266098:A:C	F112C	0.999
9:86266098:A:G	F112S	0.999
9:86266099:A:G	F112L	0.999

dbSNP variants (sampled 300 via entrez): RS1000029020 (9:86278649 G>C), RS1000409192 (9:86275532 G>A), RS1000504617 (9:86270174 A>C), RS1000615380 (9:86267315 G>A), RS1000620636 (9:86270512 A>T), RS1000695136 (9:86281411 T>C), RS1000806080 (9:86265256 A>G), RS1000895680 (9:86282280 G>A,C), RS1001018904 (9:86276116 C>T), RS1001071647 (9:86267779 G>C), RS1001526266 (9:86282081 C>T), RS1001556534 (9:86276457 T>C,G), RS1001622401 (9:86275912 C>T), RS1001674601 (9:86276168 A>T), RS1001738086 (9:86280356 C>T)

Disease associations

OMIM: gene MIM:611006 | disease phenotypes: MIM:617613, MIM:605711

GenCC curated gene-disease

Disease	Classification	Inheritance
multiple mitochondrial dysfunctions syndrome 5	Strong	Autosomal recessive

Mondo (2): multiple mitochondrial dysfunctions syndrome 5 (MONDO:0033282), fatal multiple mitochondrial dysfunctions syndrome (MONDO:0017338)

Orphanet (2): Multiple mitochondrial dysfunctions syndrome type 5 (Orphanet:569274), Multiple mitochondrial dysfunctions syndrome (Orphanet:289573)

HPO phenotypes

19 total (19 of 19 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000486	Strabismus
HP:0000580	Pigmentary retinopathy
HP:0001250	Seizure
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001302	Pachygyria
HP:0001347	Hyperreflexia
HP:0001510	Growth delay
HP:0002119	Ventriculomegaly
HP:0002151	Increased circulating lactate concentration
HP:0002376	Developmental regression
HP:0002415	Leukodystrophy
HP:0003236	Elevated circulating creatine kinase concentration
HP:0003593	Infantile onset
HP:0003676	Progressive
HP:0011968	Feeding difficulties
HP:0012448	Delayed myelination

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002875_55	Diisocyanate-induced asthma	5.000000e-06
GCST006804_185	Red cell distribution width	4.000000e-08
GCST90002404_115	Red cell distribution width	1.000000e-12

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006995	response to diisocyanate
EFO:0009188	Red cell distribution width

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C565304	Multiple Mitochondrial Dysfunctions Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression	2
methylmercuric chloride	increases expression	1
fenofibric acid	affects binding, increases expression	1
bisphenol A	affects expression	1
glycidyl methacrylate	decreases expression	1
potassium chromate(VI)	increases expression	1
cylindrospermopsin	increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
bisphenol S	affects cotreatment, increases expression	1
PCI 5002	affects cotreatment, increases expression	1
Bortezomib	increases expression	1
Rosiglitazone	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects expression	1
Azacitidine	increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Diazinon	increases methylation	1
Doxorubicin	decreases expression	1
Folic Acid	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Silver	increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	affects expression	1
Vitamin E	decreases expression	1
Zinc	increases expression, affects cotreatment	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Isotretinoin	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01439854	Not specified	COMPLETED	Study of Dapagliflozin on Mitochondrial Dysfunction and Impaired Insulin Signaling/Action