ISCA2

Summary

ISCA2 (iron-sulfur cluster assembly 2, HGNC:19857) is a protein-coding gene on chromosome 14q24.3, encoding Iron-sulfur cluster assembly 2 homolog, mitochondrial (Q86U28). 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: 72.9% of cell lines).

The protein encoded by this gene is an A-type iron-sulfur cluster (ISC) protein found in mitochondria. The encoded protein appears to be involved in the maturation of mitochondrial iron-sulfur proteins. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 122961 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mitochondrial disease (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 98 total — 1 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 16
• Cancer dependency (DepMap): dependent in 72.9% of screened cell lines
• MANE Select transcript: NM_194279

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19857
Approved symbol	ISCA2
Name	iron-sulfur cluster assembly 2
Location	14q24.3
Locus type	gene with protein product
Status	Approved
Aliases	ISA2
Ensembl gene	ENSG00000165898
Ensembl biotype	protein_coding
OMIM	615317
Entrez	122961

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 retained_intron

ENST00000298818, ENST00000554924, ENST00000555139, ENST00000556816, ENST00000857193

RefSeq mRNA: 2 — MANE Select: NM_194279 NM_001272007, NM_194279

CCDS: CCDS32122, CCDS61504

Canonical transcript exons

ENST00000556816 — 4 exons

Exon	Start	End
ENSE00001506659	74494275	74494390
ENSE00002482443	74493765	74493845
ENSE00002495717	74494826	74497106
ENSE00003492181	74494050	74494152

Expression profiles

Bgee: expression breadth ubiquitous, 257 present calls, max score 95.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.6691 / max 110.6103, expressed in 1817 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
140575	23.6691	1817

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ventricle myocardium	UBERON:0006566	95.93	gold quality
deltoid	UBERON:0001476	94.78	gold quality
cardiac muscle of right atrium	UBERON:0003379	94.16	gold quality
tibialis anterior	UBERON:0001385	93.69	gold quality
myocardium	UBERON:0002349	93.63	gold quality
corpus epididymis	UBERON:0004359	93.43	gold quality
quadriceps femoris	UBERON:0001377	93.33	gold quality
vastus lateralis	UBERON:0001379	93.10	gold quality
kidney epithelium	UBERON:0004819	92.81	gold quality
bronchial epithelial cell	CL:0002328	92.80	gold quality
right adrenal gland	UBERON:0001233	92.70	gold quality
right adrenal gland cortex	UBERON:0035827	92.57	gold quality
bronchus	UBERON:0002185	92.46	gold quality
ileal mucosa	UBERON:0000331	92.34	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.91	gold quality
biceps brachii	UBERON:0001507	91.89	gold quality
skeletal muscle tissue	UBERON:0001134	91.63	gold quality
left adrenal gland	UBERON:0001234	91.49	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.45	gold quality
heart left ventricle	UBERON:0002084	91.39	gold quality
upper arm skin	UBERON:0004263	91.37	silver quality
cardiac ventricle	UBERON:0002082	91.30	gold quality
mucosa of transverse colon	UBERON:0004991	91.28	gold quality
left adrenal gland cortex	UBERON:0035825	91.22	gold quality
adrenal cortex	UBERON:0001235	91.18	gold quality
muscle tissue	UBERON:0002385	91.07	gold quality
heart right ventricle	UBERON:0002080	90.85	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	90.79	gold quality
adult mammalian kidney	UBERON:0000082	90.69	gold quality
ventricular zone	UBERON:0003053	90.45	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.39

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

35 targeting ISCA2, 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-3662	99.99	73.82	5684
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-7162-3P	99.89	68.16	1682
HSA-MIR-10393-5P	99.65	68.01	1368
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-150-3P	99.43	70.51	920
HSA-MIR-208A-5P	99.42	70.83	1913
HSA-MIR-208B-5P	99.42	70.83	1952
HSA-MIR-548B-3P	99.38	67.26	1000
HSA-MIR-3688-5P	99.12	69.67	1091
HSA-MIR-4795-5P	99.11	66.90	876
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-6868-5P	99.06	65.69	1284
HSA-MIR-153-3P	98.96	72.51	1644
HSA-MIR-4725-5P	98.67	65.42	628
HSA-MIR-504-5P	98.67	65.40	631
HSA-MIR-1248	98.47	67.54	1314
HSA-MIR-6870-3P	98.08	65.10	692
HSA-MIR-891A-3P	98.05	67.99	970
HSA-MIR-4443	98.02	66.25	1928
HSA-MIR-4660	97.79	67.44	1328
HSA-MIR-5196-3P	97.57	65.98	979
HSA-MIR-6515-5P	97.08	65.48	1219
HSA-MIR-3126-5P	96.87	65.83	912
HSA-MIR-6875-5P	96.87	65.49	958

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 72.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 11)

• 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 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)
• We identified a homoallelic missense founder mutation in ISCA2 leading to mitochondrial depletion and reduced complex I activity as well as decreased ISCA2, ISCA1 and IBA57 expression in fibroblasts. (PMID:25539947)
• these data indicate loss of ISCA2 impaired function of 4Fe-4S proteins resulting in a fatal encephalopathy accompanied by a relatively unusual combination of features including mtDNA depletion alongside complex II deficiency and hyperglycinemia that may facilitate diagnosis of ISCA2 deficiency patients. (PMID:29297947)
• Structural properties of [2Fe-2S] ISCA2-IBA57: a complex of the mitochondrial iron-sulfur cluster assembly machinery. (PMID:31831856)
• Expanding the genotype-phenotype spectrum of ISCA2-related multiple mitochondrial dysfunction syndrome-cavitating leukoencephalopathy and prolonged survival. (PMID:32424628)
• Characterization and Reconstitution of Human Lipoyl Synthase (LIAS) Supports ISCA2 and ISCU as Primary Cluster Donors and an Ordered Mechanism of Cluster Assembly. (PMID:33562493)
• ISCA1 Orchestrates ISCA2 and NFU1 in the Maturation of Human Mitochondrial [4Fe-4S] Proteins. (PMID:33711344)
• ISCA2 deficiency leads to heme synthesis defects and impaired erythroid differentiation in K562 cells by indirect ROS-mediated IRP1 activation. (PMID:35714932)
• ISCA2 inhibition decreases HIF and induces ferroptosis in clear cell renal carcinoma. (PMID:36097192)
• 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	isca2	ENSDARG00000038154
mus_musculus	Isca2	ENSMUSG00000021241
rattus_norvegicus	Isca2-ps1	ENSRNOG00000005077
rattus_norvegicus	Isca2	ENSRNOG00000012085
drosophila_melanogaster	CG13623	FBGN0039205
caenorhabditis_elegans		WBGENE00013218

Paralogs (1): ISCA1 (ENSG00000135070)

Protein

Protein identifiers

Iron-sulfur cluster assembly 2 homolog, mitochondrial — Q86U28 (reviewed: Q86U28)

Alternative names: HESB-like domain-containing protein 1

All UniProt accessions (2): J3QSS7, Q86U28

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. May be involved in the binding of an intermediate of Fe/S cluster assembly.

Subunit / interactions. Heterotetramer; forms a dimer of dimers with IBA57. Interacts with [2Fe-2S]-ISCA2 forming the heterodimer [2Fe- 2S]-ISCA2-IBA57 complex; [2Fe-2S] cluster binding is absolutely required to promote the complex formation.

Subcellular location. Mitochondrion.

Disease relevance. Multiple mitochondrial dysfunctions syndrome 4 (MMDS4) [MIM:616370] A severe disorder of systemic energy metabolism, resulting in weakness, respiratory failure, lack of neurologic development, lactic acidosis, hyperglycinemia and early death. 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?
Q86U28-1	1	yes
Q86U28-2	2

RefSeq proteins (2): NP_001258936, NP_919255* (*=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

Pfam: PF01521

UniProt features (15 total): mutagenesis site 3, binding site 3, sequence conflict 2, splice variant 2, transit peptide 1, chain 1, region of interest 1, compositionally biased region 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86U28-F1	77.98	0.43

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): 79; 144; 146

Mutagenesis-validated functional residues (3):

Position	Phenotype
79	abolishes the formation of the [2fe-2s] isca2-iba57 complex formation.
144	abolishes the formation of the [2fe-2s] isca2-iba57 complex formation.
146	abolishes the formation of the [2fe-2s] isca2-iba57 complex formation.

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: 124 (showing top): LFA1_Q6, GOBP_PROTEIN_MATURATION, chr14q24, AACTTT_UNKNOWN, BURTON_ADIPOGENESIS_5, NUYTTEN_EZH2_TARGETS_DN, GOCC_MITOCHONDRIAL_MATRIX, GOCC_MITOCHONDRIAL_PROTEIN_CONTAINING_COMPLEX, GOMF_METAL_CLUSTER_BINDING, GOMF_IRON_ION_BINDING, GOMF_2_IRON_2_SULFUR_CLUSTER_BINDING, GOMF_4_IRON_4_SULFUR_CLUSTER_BINDING, BOUDOUKHA_BOUND_BY_IGF2BP2, REACTOME_MITOCHONDRIAL_IRON_SULFUR_CLUSTER_BIOGENESIS, ASH1L_TARGET_GENES

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

GO Molecular Function (7): iron ion binding (GO:0005506), identical protein binding (GO:0042802), 2 iron, 2 sulfur cluster binding (GO:0051537), 4 iron, 4 sulfur cluster binding (GO:0051539), protein binding (GO:0005515), metal ion binding (GO:0046872), iron-sulfur cluster binding (GO:0051536)

GO Cellular Component (3): 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
iron-sulfur cluster binding	2
metallo-sulfur cluster assembly	1
gene expression	1
protein metabolic process	1
transition metal ion binding	1
protein binding	1
binding	1
cation binding	1
metal cluster binding	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

1264 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ISCA2	IBA57	Q5T440	995
ISCA2	GLRX5	Q86SX6	947
ISCA2	ISCA1	Q9BUE6	935
ISCA2	NFU1	Q9UMS0	892
ISCA2	ISCU	Q9H1K1	879
ISCA2	LIAS	O43766	840
ISCA2	BOLA3	Q53S33	822
ISCA2	LYRM4	Q9HD34	806
ISCA2	FDX2	Q6P4F2	798
ISCA2	NFS1	Q9Y697	795
ISCA2	FXN	Q16595	787
ISCA2	BOLA1	Q9Y3E2	775
ISCA2	NUBPL	Q8TB37	758
ISCA2	ABCB7	O75027	714
ISCA2	ACO2	Q99798	691

IntAct

102 interactions, top by confidence:

A	B	Type	Score
ISCA2	IBA57	psi-mi:“MI:0407”(direct interaction)	0.860
IBA57	ISCA2	psi-mi:“MI:0407”(direct interaction)	0.860
	ISCA2	psi-mi:“MI:0407”(direct interaction)	0.820
ISCA2	RNF41	psi-mi:“MI:0915”(physical association)	0.780
RNF41	ISCA2	psi-mi:“MI:0915”(physical association)	0.780
NHERF2	PODXL	psi-mi:“MI:0914”(association)	0.770
ISCA2	ISCA1	psi-mi:“MI:0407”(direct interaction)	0.740
ISCA1	ISCA2	psi-mi:“MI:0407”(direct interaction)	0.740
TEPSIN	AP4M1	psi-mi:“MI:0914”(association)	0.700
CDA	LIN7A	psi-mi:“MI:0914”(association)	0.640
ISCA2	ISCA2	psi-mi:“MI:0407”(direct interaction)	0.620
	ISCA2	psi-mi:“MI:0407”(direct interaction)	0.620

BioGRID (78): ISCA2 (Two-hybrid), ISCA2 (Affinity Capture-MS), ISCA2 (Affinity Capture-MS), ISCA2 (Affinity Capture-MS), ISCA2 (Affinity Capture-MS), ISCA2 (PCA), ISCA2 (Synthetic Lethality), COA7 (Co-fractionation), ISCA2 (Co-fractionation), ISCA2 (Co-fractionation), ISCA2 (Co-fractionation), ISCA2 (Co-fractionation), ISCA2 (Co-fractionation), ISCA2 (Co-fractionation), ISCA2 (Co-fractionation)

ESM2 similar proteins: A6QLY4, A8MPP1, A9NAW9, B5X5B4, D3ZBP4, D3ZX08, F1MH07, O00746, O35952, O43542, O75879, P0DN75, P85094, P87355, Q05B51, Q14CH7, Q2KHV5, Q2TBG7, Q501S4, Q502I6, Q5JTZ9, Q5R788, Q5ZJ74, Q60HD0, Q641W2, Q6AXC6, Q6I7R3, Q6PAY6, Q83AK7, Q86U28, Q8CGK3, Q8K3A0, Q8LBM4, Q8LCY2, Q8NFF5, Q8R035, Q8R086, Q8T3X9, Q8TB37, Q8TDZ2

Diamond homologs: A0K4K7, A0KNY6, A0KZS2, A0Q5J0, A1JJQ3, A1K969, A1RMG3, A1S3U4, A1V053, A2S583, A3D1R9, A3MP61, A3N2B0, A3NZ78, A3QBP0, A4IZA5, A4JBK6, A4SJ82, A4T031, A4Y4G8, A5F947, A5UFF5, A6SUP2, A6WKM0, A7MUU6, A7NDP2, A8H175, A9AH79, A9I246, A9L5J9, B0BR51, B0TIR0, B0TZ08, B0UU19, B1JVU6, B1YTD3, B2AH60, B2JGV0, B2SDK6, B2SYK8

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
ISCA2	“form complex”	“ISCA2-IBA57 mitochondrial iron-sulfur protein assembly complex”	binding
ISCA2	“form complex”	“ISCA1-ISCA2 mitochondrial iron-sulfur protein assembly complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	2
Uncertain significance	50
Likely benign	34
Benign	4

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
2288035	NM_194279.4(ISCA2):c.139G>T (p.Glu47Ter)	Pathogenic
1215027	NM_194279.4(ISCA2):c.116C>A (p.Ser39Ter)	Likely pathogenic
2581360	NM_194279.4(ISCA2):c.313A>G (p.Arg105Gly)	Likely pathogenic

SpliceAI

456 predictions. Top by Δscore:

Variant	Effect	Δscore
14:74493875:GGTGT:G	donor_gain	0.9900
14:74493907:GAAAC:G	donor_gain	0.9900
14:74494045:CGCA:C	acceptor_loss	0.9900
14:74494047:CA:C	acceptor_loss	0.9900
14:74494049:G:A	acceptor_loss	0.9900
14:74494396:G:GT	donor_gain	0.9900
14:74494399:G:GT	donor_gain	0.9900
14:74494824:AG:A	acceptor_gain	0.9900
14:74494825:GG:G	acceptor_gain	0.9900
14:74494825:GGGT:G	acceptor_gain	0.9900
14:74493843:CAGG:C	donor_loss	0.9800
14:74493844:AG:A	donor_loss	0.9800
14:74493845:GGT:G	donor_loss	0.9800
14:74493847:T:G	donor_loss	0.9800
14:74494048:A:AG	acceptor_gain	0.9800
14:74494049:G:GG	acceptor_gain	0.9800
14:74494148:TCCAG:T	donor_loss	0.9800
14:74494149:CCAG:C	donor_loss	0.9800
14:74494150:CAGG:C	donor_loss	0.9800
14:74494151:AGG:A	donor_loss	0.9800
14:74494152:GGTA:G	donor_loss	0.9800
14:74494153:G:GA	donor_loss	0.9800
14:74494154:T:A	donor_loss	0.9800
14:74494327:G:T	donor_gain	0.9800
14:74494419:G:GT	donor_gain	0.9800
14:74493843:C:T	donor_gain	0.9700
14:74493864:C:T	donor_gain	0.9700
14:74494048:AG:A	acceptor_gain	0.9700
14:74494049:GG:G	acceptor_gain	0.9700
14:74494825:GGGTA:G	acceptor_gain	0.9700

AlphaMissense

983 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:74494930:T:C	F132S	0.999
14:74494983:T:C	F150L	0.999
14:74494985:C:A	F150L	0.999
14:74494985:C:G	F150L	0.999
14:74494335:T:C	C79R	0.998
14:74494342:G:A	G81E	0.998
14:74494858:T:A	V108D	0.998
14:74494869:A:C	S112R	0.998
14:74494871:C:A	S112R	0.998
14:74494871:C:G	S112R	0.998
14:74494902:T:C	F123L	0.998
14:74494904:C:A	F123L	0.998
14:74494904:C:G	F123L	0.998
14:74494929:T:C	F132L	0.998
14:74494930:T:G	F132C	0.998
14:74494931:T:A	F132L	0.998
14:74494931:T:G	F132L	0.998
14:74494312:G:T	R71M	0.997
14:74494335:T:A	C79S	0.997
14:74494336:G:C	C79S	0.997
14:74494345:T:C	F82S	0.997
14:74494984:T:C	F150S	0.997
14:74494984:T:G	F150C	0.997
14:74494146:C:G	C56W	0.996
14:74494312:G:C	R71T	0.996
14:74494336:G:A	C79Y	0.996
14:74494965:T:C	C144R	0.996
14:74494145:G:A	C56Y	0.995
14:74494309:T:C	L70P	0.995
14:74494313:G:C	R71S	0.995

dbSNP variants (sampled 300 via entrez): RS1000030169 (14:74494298 G>A), RS1000046958 (14:74492214 T>C,G), RS1000498103 (14:74497025 C>G), RS1001728150 (14:74494688 A>G), RS1002340489 (14:74493662 T>C), RS1002389680 (14:74493494 G>A,C,T), RS1003052603 (14:74496417 G>A,C), RS1003345507 (14:74495232 G>T), RS1003397804 (14:74494934 A>G), RS1003671581 (14:74496352 C>G,T), RS1003940857 (14:74496539 A>G), RS1004062569 (14:74497137 C>G,T), RS1005542001 (14:74493689 T>A,C), RS1005573226 (14:74493809 C>G,T), RS1005601150 (14:74493549 C>G,T)

Disease associations

OMIM: gene MIM:615317 | disease phenotypes: MIM:616370, MIM:603513, MIM:612900, MIM:605711

GenCC curated gene-disease

Disease	Classification	Inheritance
multiple mitochondrial dysfunctions syndrome 4	Strong	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): multiple mitochondrial dysfunctions syndrome 4 (MONDO:0014611), optic atrophy (MONDO:0003608), neurodegenerative disease (MONDO:0005559), spastic quadriplegic cerebral palsy (MONDO:0016215), fatal multiple mitochondrial dysfunctions syndrome (MONDO:0017338)

Orphanet (3): Multiple mitochondrial dysfunctions syndrome type 4 (Orphanet:457406), Inherited congenital spastic tetraplegia (Orphanet:210141), Multiple mitochondrial dysfunctions syndrome (Orphanet:289573)

HPO phenotypes

16 total (16 of 16 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000505	Visual impairment
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0001257	Spasticity
HP:0001290	Generalized hypotonia
HP:0001344	Absent speech
HP:0001347	Hyperreflexia
HP:0002376	Developmental regression
HP:0002415	Leukodystrophy
HP:0002518	Abnormal periventricular white matter morphology
HP:0003593	Infantile onset
HP:0003676	Progressive
HP:0011923	Decreased activity of mitochondrial complex I
HP:0012736	Profound global developmental delay
HP:0031358	Vegetative state

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST003457_3	Soluble receptor for advanced glycation end-product levels	3.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007819	advanced glycation end-product measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D019636	Neurodegenerative Diseases	C10.574
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
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

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases methylation	3
Particulate Matter	decreases expression, increases abundance	2
GSK-J4	decreases expression	1
glycidyl methacrylate	increases expression	1
arsenite	increases reaction, affects binding	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Doxorubicin	decreases expression	1
Estradiol	decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Rotenone	decreases expression	1
Testosterone	increases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
Cyclosporine	decreases expression	1
Sodium Selenite	increases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01662414	PHASE4	COMPLETED	Effect of Undenatured Cysteine-Rich Whey Protein Isolate (HMS 90®) in Patients With Parkinson’s Disease
NCT04871464	PHASE4	UNKNOWN	Role and Mechanism of Probiotics in Improving Motor Symptoms in Mild to Moderate Parkinson’s Disease
NCT05357612	PHASE4	RECRUITING	Characterization of the Serotonin 2A Receptor Selective PET Tracer [18F]MH.MZ in Patients With Neurodegenerative Diseases
NCT05508789	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Donanemab (LY3002813) in Participants With Early Symptomatic Alzheimer’s Disease (TRAILBLAZER-ALZ 5)
NCT05738486	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Different Donanemab (LY3002813) Dosing Regimens in Adults With Early Alzheimer’s Disease (TRAILBLAZER-ALZ 6)
NCT06111014	PHASE3	TERMINATED	Continuation Study for Latozinemab
NCT06672237	PHASE3	RECRUITING	A Phase 3 Study of NTLA-2001 in ATTRv-PN
NCT00001365	PHASE2	COMPLETED	Dextromethorphan for the Treatment of Parkinson’s Disease and Similar Conditions of the Nervous System
NCT00406029	PHASE2	COMPLETED	Dyskinesia in Parkinson’s Disease (Study P04501)
NCT00537017	PHASE2	COMPLETED	Follow Up Safety Study of SCH 420814 in Subjects With Parkinson’s Disease (P05175)
NCT00907283	PHASE2	UNKNOWN	Ferrochelating Treatment in Patients Affected by Neurodegeneration With Brain Iron Accumulation (NBIA)
NCT01518374	PHASE2	COMPLETED	Clinical Evaluation of Florbetapir F 18 (18F-AV-45)
NCT02656498	PHASE2	COMPLETED	[18F]THK-5351 Positron Emission Computed Tomography Study of Normal, Mild Cognitive Impairment, Alzheimer’s Disease and Other Neurodegenerative Disease
NCT03127514	PHASE2	COMPLETED	AMX0035 in Patients With Amyotrophic Lateral Sclerosis (ALS)
NCT03538522	PHASE2	COMPLETED	A Double-Blind, Placebo-Controlled Safety and Efficacy Study of NA-831
NCT04838301	PHASE2	RECRUITING	Allopregnanolone Regenerative Therapeutic for Mild Alzheimer’s Disease
NCT04937452	PHASE2	COMPLETED	Dopaminergic Therapy for Frontotemporal Dementia Patients
NCT05318976	PHASE2	COMPLETED	A Study of XPro1595 in Patients With Early Alzheimer’s Disease With Biomarkers of Inflammation
NCT05321498	PHASE2	WITHDRAWN	Study to Assess the Efficacy of XPro1595 in Patients With Mild Cognitive Impairment With Biomarkers of Inflammation
NCT05479981	PHASE2	COMPLETED	Extension of AOC 1001-CS1 (MARINA) Study in Adult Myotonic Dystrophy Type 1 (DM1) Patients
NCT05522387	PHASE2	TERMINATED	An Open-Label Extension of XPro1595 in Patients With Alzheimer’s Disease
NCT01064505	PHASE1	COMPLETED	Safety Study of a Single IVT Injection of QPI-1007 in Chronic Optic Nerve Atrophy and Recent Onset NAION Patients
NCT05147701	PHASE1	RECRUITING	Safety of Cultured Allogeneic Adult Umbilical Cord Derived Mesenchymal Stem Cells for NAION
NCT00316797	PHASE1	COMPLETED	Biodistribution and Safety of a Radiopharmaceutical in Healthy Subjects
NCT01758510	PHASE1	COMPLETED	Safety Study of HLA-haplo Matched Allogenic Bone Marrow Derived Stem Cell Treatment in Amyotrophic Lateral Sclerosis
NCT02267434	PHASE1	COMPLETED	Study Assessing Tolerability and Safety of AFFITOPE® PD03A in Patients With Early Parkinson’s Disease
NCT02270489	PHASE1	COMPLETED	Study Assessing Safety and Therapeutic Activity of AFFITOPE® PD01A and PD03A in Patients With Early MSA
NCT03065192	PHASE1	COMPLETED	Safety and Efficacy Study of VY-AADC01 for Advanced Parkinson’s Disease
NCT04578028	PHASE1	COMPLETED	A First in Human Study to Assess the Safety, Tolerability and Pharmacokinetics of ONO-2808-01 in Healthy Participants
NCT05143463	PHASE1	COMPLETED	A FIH Study to Assess the Safety and Tolerability of NS Intravenous NS101 Infusion
NCT05490576	PHASE1	UNKNOWN	Tau And Connectomics In TES Study
NCT05792163	PHASE1	COMPLETED	A First Time in Human Study of SNP318 as a Treatment for Neurodegenerative Diseases Including Alzheimer’s Disease
NCT07232147	PHASE1	NOT_YET_RECRUITING	Clinical Research on Stem Cell Therapy for Parkinson’s Disease
NCT02882477	PHASE2/PHASE3	UNKNOWN	Treatment of Wolfram Syndrome Type 2 With the Chelator Deferiprone and Incretin Based Therapy
NCT01834079	PHASE1/PHASE2	UNKNOWN	Study the Safety and Efficacy of Bone Marrow Derived Autologous Cells for the Treatment of Optic Nerve Disease
NCT04680143	PHASE1/PHASE2	COMPLETED	Systemic Erythropoietin Injection in Patients Having Optic Atrophy
NCT03011541	Not specified	RECRUITING	Stem Cell Ophthalmology Treatment Study II
NCT04580979	Not specified	COMPLETED	Natural History Study of FDXR Mutation-related Mitochondriopathy
NCT04594590	Not specified	COMPLETED	Natural History Study of SLC25A46 Mutation-related Mitochondriopathy
NCT04723160	Not specified	COMPLETED	Computer Aided Diagnosis of Multiple Eye Fundus Diseases From Color Fundus Photograph