OPA3

Summary

OPA3 (outer mitochondrial membrane lipid metabolism regulator OPA3, HGNC:8142) is a protein-coding gene on chromosome 19q13.32, encoding Optic atrophy 3 protein (Q9H6K4). May play some role in mitochondrial processes.

The mouse ortholog of this protein co-purifies with the mitochondrial inner membrane. Mutations in this gene have been shown to result in 3-methylglutaconic aciduria type III and autosomal dominant optic atrophy and cataract. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 80207 — RefSeq curated summary.

At a glance

• Gene–disease (curated): 3-methylglutaconic aciduria type 3 (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 599 total — 11 pathogenic, 26 likely-pathogenic
• Phenotypes (HPO): 54
• MANE Select transcript: NM_025136

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8142
Approved symbol	OPA3
Name	outer mitochondrial membrane lipid metabolism regulator OPA3
Location	19q13.32
Locus type	gene with protein product
Status	Approved
Aliases	FLJ22187, MGA3
Ensembl gene	ENSG00000125741
Ensembl biotype	protein_coding
OMIM	606580
Entrez	80207

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000263275, ENST00000323060, ENST00000544371

RefSeq mRNA: 2 — MANE Select: NM_025136 NM_001017989, NM_025136

CCDS: CCDS12668, CCDS33052

Canonical transcript exons

ENST00000263275 — 2 exons

Exon	Start	End
ENSE00001209050	45546281	45553911
ENSE00002312767	45584623	45584802

Expression profiles

Bgee: expression breadth ubiquitous, 213 present calls, max score 87.18.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.5807 / max 54.5813, expressed in 1798 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
181533	12.7795	1794
181537	3.7852	506
181534	1.8011	1341

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	87.18	gold quality
hindlimb stylopod muscle	UBERON:0004252	82.15	gold quality
apex of heart	UBERON:0002098	81.45	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.72	gold quality
gastrocnemius	UBERON:0001388	80.57	gold quality
heart left ventricle	UBERON:0002084	80.22	gold quality
gingival epithelium	UBERON:0001949	80.12	silver quality
cardiac ventricle	UBERON:0002082	79.95	gold quality
muscle of leg	UBERON:0001383	79.87	gold quality
stromal cell of endometrium	CL:0002255	78.97	gold quality
gingiva	UBERON:0001828	78.64	silver quality
right atrium auricular region	UBERON:0006631	77.57	gold quality
heart	UBERON:0000948	77.21	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.14	gold quality
buccal mucosa cell	CL:0002336	77.14	gold quality
left adrenal gland	UBERON:0001234	77.05	gold quality
left adrenal gland cortex	UBERON:0035825	76.85	gold quality
islet of Langerhans	UBERON:0000006	76.81	gold quality
granulocyte	CL:0000094	76.50	gold quality
right adrenal gland cortex	UBERON:0035827	76.40	gold quality
right adrenal gland	UBERON:0001233	76.22	gold quality
adrenal cortex	UBERON:0001235	76.17	gold quality
adrenal gland	UBERON:0002369	76.14	gold quality
muscle organ	UBERON:0001630	76.08	gold quality
blood	UBERON:0000178	76.00	gold quality
cardiac atrium	UBERON:0002081	75.91	gold quality
monocyte	CL:0000576	75.75	gold quality
amniotic fluid	UBERON:0000173	75.74	silver quality
leukocyte	CL:0000738	75.70	gold quality
mononuclear cell	CL:0000842	75.51	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ENAD-17	no	36.16
E-ANND-3	no	4.04

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

59 targeting OPA3, 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-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4500	99.99	72.72	2367
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-4458	99.96	71.64	1650
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-1179	99.71	68.70	1040
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084

Literature-anchored findings (GeneRIF, showing 14)

• type III 3-methylglutaconic aciduria (optic atrophy plus syndrome, or Costeff optic atrophy syndrome): identification of the OPA3 gene and its founder mutation in Iraqi Jews (PMID:11668429)
• The mouse ortholog of OPA3 purifies with mitochondrial inner membranes. (PMID:12865426)
• two missense mutations in OPA3 in two families affected by autosomal dominant optic atrophy and cataract (ADOAC) (PMID:15342707)
• patient with Costeff syndrome presenting the characteristics of this syndrome and the single-nucleotide polymorphic gene that causes this disease. (PMID:16838891)
• The mouse ortholog of OPA3 purifies with mitochondria (PMID:18614015)
• OPA1 mutations, mtDNA mutations, and OPA3 mutations in 980 patients Leber’s hereditary optic neuropathy and autosomal dominant optic atrophy (PMID:19319978)
• findings thus place the cellular metabolic defect of 3-methylglutaconic aciduria type III in the mitochondrion rather than the peroxisome and implicate loss of OPA3A rather than gain of OPA3B in disease etiology. (PMID:20350831)
• OPA3, as an integral mitochondrial outer membane perotein, has a crucial role in mitochondrial fission, and provides a direct link between mitochondrial morphology and optic atrophy. (PMID:20372962)
• OPA1 mutations are the most common genetic defects identified in patients with suspected Autosomal-dominant optic atrophy (DOA), whereas OPA3 mutations are very rare in isolated optic atrophy cases. (PMID:21036400)
• A novel missense mutation identifies OPA3 as the cause of a complex neurological disorder with marked lower limb dystonia. (PMID:23700088)
• Report the results of a comprehensive study on OPA3 mutations, including the mutation spectrum and its prevalence in a large cohort of ADOA patients, the associated clinical phenotype and the functional characterisation of a newly identified OPA3 mutant. (PMID:24136862)
• Mutations of the OPA3 gene can cause either autosomal dominant or autosomal recessive optic atrophy. (PMID:25205859)
• Low OPA3 expression is associated with squamous cell carcinoma in Paranasal Sinus Neoplasms. (PMID:30991875)
• Homozygous OPA3 mutation is associated with 3-methylglutaconic aciduria type III and optic atrophy. (PMID:31928268)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	opa3	ENSDARG00000061761
mus_musculus	Opa3	ENSMUSG00000052214
rattus_norvegicus	Opa3	ENSRNOG00000064373
drosophila_melanogaster	CG13601	FBGN0039126
drosophila_melanogaster	CG43998	FBGN0264740
drosophila_melanogaster	CG43999	FBGN0264741
caenorhabditis_elegans		WBGENE00019274

Protein

Protein identifiers

Optic atrophy 3 protein — Q9H6K4 (reviewed: Q9H6K4)

All UniProt accessions (2): Q9H6K4, B4DK77

UniProt curated annotations — full annotation on UniProt →

Function. May play some role in mitochondrial processes.

Subcellular location. Mitochondrion.

Tissue specificity. Ubiquitous. Most prominent expression in skeletal muscle and kidney.

Disease relevance. 3-methylglutaconic aciduria 3 (MGCA3) [MIM:258501] An autosomal recessive metabolic disorder that causes a neuro-ophthalmologic syndrome consisting of early-onset bilateral optic atrophy, spasticity, extrapyramidal dysfunction and cognitive deficit. Urinary excretion of 3-methylglutaconic acid and 3-methylglutaric acid is increased. MGCA3 can be distinguished from MGCA1 by the absence of increase of 3-hydroxyisovaleric acid levels. The disease is caused by variants affecting the gene represented in this entry. Optic atrophy 3 (OPA3) [MIM:165300] A condition that features progressive visual loss in association with optic atrophy. Atrophy of the optic disk indicates a deficiency in the number of nerve fibers which arise in the retina and converge to form the optic disk, optic nerve, optic chiasm and optic tracts. OPA3 is associated with cataract and a neurologic disorder characterized by extrapyramidal signs and ataxia. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the OPA3 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H6K4-1	1	yes
Q9H6K4-2	2

RefSeq proteins (2): NP_001017989, NP_079412* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010754	OPA3-like	Family

Pfam: PF07047

UniProt features (8 total): sequence variant 3, initiator methionine 1, chain 1, coiled-coil region 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H6K4-F1	83.13	0.24

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 243 (showing top): AHRARNT_01, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_GROWTH, FOXO1_01, GOBP_REGULATION_OF_LIPID_METABOLIC_PROCESS, GOBP_BONE_DEVELOPMENT, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, HFH8_01, GRE_C, GOBP_LIPID_METABOLIC_PROCESS, GOBP_FAT_CELL_DIFFERENTIATION, HFH1_01, GOBP_SENSORY_PERCEPTION

GO Biological Process (7): mitochondrion organization (GO:0007005), visual perception (GO:0007601), regulation of lipid metabolic process (GO:0019216), regulation of growth (GO:0040008), fat cell differentiation (GO:0045444), neuromuscular process (GO:0050905), bone development (GO:0060348)

GO Molecular Function (0):

GO Cellular Component (1): mitochondrion (GO:0005739)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
organelle organization	1
sensory perception of light stimulus	1
lipid metabolic process	1
regulation of primary metabolic process	1
growth	1
regulation of biological process	1
cell differentiation	1
nervous system process	1
skeletal system development	1
animal organ development	1
cytoplasm	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

36 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
TRDN	TMEM223	psi-mi:“MI:0914”(association)	0.640
TMEM9	ESYT2	psi-mi:“MI:0914”(association)	0.530
PCDHGB1	FAM171A2	psi-mi:“MI:0914”(association)	0.530
TNFRSF17	TSPAN6	psi-mi:“MI:0914”(association)	0.530
OPA3	H3C13	psi-mi:“MI:0915”(physical association)	0.400
PCDHGB6	OPA3	psi-mi:“MI:0915”(physical association)	0.400
OPA3	SUV39H1	psi-mi:“MI:0915”(physical association)	0.370
OPA3	KDM1A	psi-mi:“MI:0915”(physical association)	0.370
PRMT6	OPA3	psi-mi:“MI:0915”(physical association)	0.370
OPA3	TIMM23	psi-mi:“MI:0914”(association)	0.350
PHYHIPL	GAPDH	psi-mi:“MI:0914”(association)	0.350
OPA3	NDUFS8	psi-mi:“MI:0914”(association)	0.350
PHYHIPL	ATP5F1B	psi-mi:“MI:0914”(association)	0.350
ATP5F1A	NDUFAB1	psi-mi:“MI:0914”(association)	0.350
OPA3	CS	psi-mi:“MI:0914”(association)	0.350
ATP5F1A	ACOT7	psi-mi:“MI:0914”(association)	0.350
OPA3	NDUFAB1	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
IMMP2L	ANKHD1-EIF4EBP3	psi-mi:“MI:0914”(association)	0.350
GYPA	HYKK	psi-mi:“MI:0914”(association)	0.350
PCDHGB2	C2CD2L	psi-mi:“MI:0914”(association)	0.350
NRG1	CHST10	psi-mi:“MI:0914”(association)	0.350
VSTM1	FADS1	psi-mi:“MI:0914”(association)	0.350
TMEM154	VPS26A	psi-mi:“MI:0914”(association)	0.350
ACP2	C6orf47	psi-mi:“MI:0914”(association)	0.350
TMEM154	RPSA2	psi-mi:“MI:0914”(association)	0.350

BioGRID (51): OPA3 (Affinity Capture-RNA), OPA3 (Affinity Capture-MS), OPA3 (Affinity Capture-MS), IDE (Affinity Capture-MS), STOML2 (Affinity Capture-MS), CLPB (Affinity Capture-MS), OPA3 (Affinity Capture-MS), OPA3 (Affinity Capture-MS), YME1L1 (Affinity Capture-MS), SCO2 (Affinity Capture-MS), ECH1 (Affinity Capture-MS), SCO1 (Affinity Capture-MS), TIMM23 (Affinity Capture-MS), C1QBP (Affinity Capture-MS), ATP5C1 (Affinity Capture-MS)

ESM2 similar proteins: A0PJW6, A1L1J9, A4FV45, A8MXQ7, F1MX48, O00411, P70606, Q05B52, Q05B66, Q0VCA3, Q16611, Q1JQC5, Q1L9A2, Q2VPK5, Q3B8B2, Q3SX05, Q3SYU1, Q3TYL0, Q3URS9, Q4R5Q4, Q505D7, Q5E9Q3, Q5PPN7, Q5R6Z1, Q5RAS8, Q5RJV0, Q5T1A1, Q641S2, Q643R3, Q66LN0, Q6NUQ4, Q6NVG1, Q6P6S4, Q86VI3, Q8BKF1, Q8BWM0, Q8C3X8, Q8N0W3, Q92843, Q92952

Diamond homologs: Q05B66, Q1L9A2, Q505D7, Q54NW1, Q641S2, Q9H6K4, Q9P7W0, Q9VCG2, Q9VCG3

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
OPA3	up-regulates	Mitochondrial_fission

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	11
Likely pathogenic	26
Uncertain significance	296
Likely benign	148
Benign	34

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1727235	NM_025136.4(OPA3):c.143-1G>A	Pathogenic
2128878	NM_025136.4(OPA3):c.103G>T (p.Glu35Ter)	Pathogenic
3248433	NC_000019.9:g.(?46056772)(46088022_?)del	Pathogenic
3775723	NM_025136.4(OPA3):c.55del (p.Val19fs)	Pathogenic
4239	NM_025136.4(OPA3):c.143-1G>C	Pathogenic
4240	NM_025136.4(OPA3):c.277G>A (p.Gly93Ser)	Pathogenic
4241	NM_025136.4(OPA3):c.313C>G (p.Gln105Glu)	Pathogenic
4242	NM_025136.4(OPA3):c.322_339del (p.Gln108_Glu113del)	Pathogenic
831267	NC_000019.10:g.(?45584613)(45584774_?)del	Pathogenic
918005	NM_025136.4(OPA3):c.32T>A (p.Leu11Gln)	Pathogenic
952107	NM_025136.4(OPA3):c.143-2_143-1delinsCC	Pathogenic
1067581	NM_025136.4(OPA3):c.1A>G (p.Met1Val)	Likely pathogenic
1324830	NM_025136.4(OPA3):c.194del (p.Gly65fs)	Likely pathogenic
1723421	NC_000019.9:g.(46057170_46087880)(46088123?)del	Likely pathogenic
2190228	NM_025136.4(OPA3):c.152G>A (p.Trp51Ter)	Likely pathogenic
225178	NM_025136.4(OPA3):c.235C>G (p.Leu79Val)	Likely pathogenic
2677419	NM_025136.4(OPA3):c.217G>T (p.Glu73Ter)	Likely pathogenic
2677421	NM_025136.4(OPA3):c.97C>T (p.Arg33Ter)	Likely pathogenic
2677422	NM_025136.4(OPA3):c.227dup (p.Ala77fs)	Likely pathogenic
2677423	NM_025136.4(OPA3):c.287del (p.Cys96fs)	Likely pathogenic
3239998	NM_025136.4(OPA3):c.82_84delinsT (p.Ile27_Lys28insTer)	Likely pathogenic
3239999	NM_025136.4(OPA3):c.411_422delinsC (p.Gln137fs)	Likely pathogenic
3248434	NC_000019.9:g.(?46056772)(46057189_?)del	Likely pathogenic
3583954	NM_025136.4(OPA3):c.308_312del (p.Arg103fs)	Likely pathogenic
370448	NM_025136.4(OPA3):c.539A>G (p.Ter180Trp)	Likely pathogenic
3760447	NM_025136.4(OPA3):c.140A>G (p.Gln47Arg)	Likely pathogenic
4816243	NM_025136.4(OPA3):c.13_20del (p.Ala5fs)	Likely pathogenic
4816244	NM_025136.4(OPA3):c.318_319dup (p.Gln107fs)	Likely pathogenic
4816245	NM_025136.4(OPA3):c.458_459del (p.Arg153fs)	Likely pathogenic
4816246	NM_025136.4(OPA3):c.472_494del (p.Glu158fs)	Likely pathogenic

SpliceAI

837 predictions. Top by Δscore:

Variant	Effect	Δscore
19:45553907:ATACA:A	acceptor_gain	1.0000
19:45553908:TACA:T	acceptor_gain	1.0000
19:45553909:ACA:A	acceptor_gain	1.0000
19:45553910:CA:C	acceptor_gain	1.0000
19:45553910:CAC:C	acceptor_gain	1.0000
19:45553911:ACTG:A	acceptor_loss	1.0000
19:45553912:C:A	acceptor_loss	1.0000
19:45553912:C:CC	acceptor_gain	1.0000
19:45553913:T:G	acceptor_loss	1.0000
19:45584619:TCA:T	donor_loss	1.0000
19:45584620:CA:C	donor_loss	1.0000
19:45584621:A:AC	donor_gain	1.0000
19:45584622:C:CA	donor_gain	1.0000
19:45584622:CG:C	donor_gain	1.0000
19:45584622:CGT:C	donor_gain	1.0000
19:45602091:TTA:T	donor_loss	1.0000
19:45602093:A:AC	donor_gain	1.0000
19:45602093:AC:A	donor_gain	1.0000
19:45602093:ACCTG:A	donor_gain	1.0000
19:45602094:C:CG	donor_gain	1.0000
19:45602094:CC:C	donor_gain	1.0000
19:45602094:CCT:C	donor_gain	1.0000
19:45602094:CCTG:C	donor_gain	1.0000
19:45602094:CCTGC:C	donor_gain	1.0000
19:45553915:C:CT	acceptor_gain	0.9900
19:45561410:T:TA	donor_gain	0.9900
19:45584622:CGTT:C	donor_gain	0.9900
19:45584622:CGTTG:C	donor_gain	0.9900
19:45584617:A:AC	donor_gain	0.9800
19:45584618:C:CC	donor_gain	0.9800

AlphaMissense

1142 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:45553768:A:G	C96R	0.997
19:45584673:G:T	A31D	0.997
19:45553806:A:G	L83P	0.996
19:45584628:G:T	A46D	0.996
19:45584705:G:C	S20R	0.996
19:45584705:G:T	S20R	0.996
19:45584707:T:G	S20R	0.996
19:45584721:C:T	G15D	0.996
19:45584722:C:G	G15R	0.996
19:45584681:C:A	K28N	0.995
19:45584681:C:G	K28N	0.995
19:45584694:G:T	A24D	0.995
19:45553813:C:G	A81P	0.994
19:45553883:C:A	K57N	0.994
19:45553883:C:G	K57N	0.994
19:45553906:G:C	H50D	0.994
19:45584702:C:A	K21N	0.994
19:45584702:C:G	K21N	0.994
19:45584735:C:A	K10N	0.994
19:45584735:C:G	K10N	0.994
19:45584748:A:C	F6C	0.994
19:45553776:C:T	G93D	0.993
19:45553800:C:T	G85D	0.993
19:45584641:A:G	C42R	0.993
19:45553795:C:G	A87P	0.992
19:45584639:G:C	C42W	0.992
19:45584709:A:T	V19D	0.992
19:45584747:G:C	F6L	0.992
19:45584747:G:T	F6L	0.992
19:45584748:A:G	F6S	0.992

dbSNP variants (sampled 300 via entrez): RS1000028864 (19:45563647 C>A), RS1000068542 (19:45557618 G>A), RS1000119120 (19:45538654 C>A,T), RS1000176341 (19:45583049 G>C), RS1000199912 (19:45541608 A>C), RS1000217028 (19:45579989 C>T), RS1000277660 (19:45569305 A>T), RS1000278265 (19:45585452 G>A), RS1000335583 (19:45574845 C>G), RS1000362886 (19:45570633 G>A), RS1000383587 (19:45555375 G>A,T), RS1000440286 (19:45574489 G>A), RS1000475296 (19:45534918 A>G), RS1000512828 (19:45560859 G>A), RS1000525932 (19:45553040 G>A)

Disease associations

OMIM: gene MIM:606580 | disease phenotypes: MIM:165300, MIM:258501, MIM:250950

GenCC curated gene-disease

Disease	Classification	Inheritance
optic atrophy 3	Definitive	Autosomal dominant
3-methylglutaconic aciduria type 3	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
optic atrophy 3	Moderate	AD

Mondo (4): optic atrophy 3 (MONDO:0008133), 3-methylglutaconic aciduria type 3 (MONDO:0009787), achromatopsia (MONDO:0018852), 3-methylglutaconic aciduria (MONDO:0017359)

Orphanet (4): Autosomal dominant optic atrophy and cataract (Orphanet:67036), 3-methylglutaconic aciduria type 3 (Orphanet:67047), Achromatopsia (Orphanet:49382), 3-methylglutaconic aciduria (Orphanet:289902)

HPO phenotypes

54 total (30 of 54 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000365	Hearing impairment
HP:0000505	Visual impairment
HP:0000518	Cataract
HP:0000543	Optic disc pallor
HP:0000552	Tritanomaly
HP:0000575	Scotoma
HP:0000603	Central scotoma
HP:0000618	Blindness
HP:0000639	Nystagmus
HP:0000642	Red-green dyschromatopsia
HP:0000648	Optic atrophy
HP:0001172	Abnormal thumb morphology
HP:0001249	Intellectual disability
HP:0001251	Ataxia
HP:0001257	Spasticity
HP:0001260	Dysarthria
HP:0001266	Choreoathetosis
HP:0001272	Cerebellar atrophy
HP:0001284	Areflexia
HP:0001288	Gait disturbance
HP:0001315	Reduced tendon reflexes
HP:0001337	Tremor
HP:0001347	Hyperreflexia
HP:0001377	Limited elbow extension
HP:0001761	Pes cavus
HP:0002071	Abnormality of extrapyramidal motor function
HP:0002072	Chorea
HP:0002174	Postural tremor

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001313_4	Depression and alcohol dependence	4.000000e-06
GCST007827_3	Alzheimer’s disease or HDL levels (pleiotropy)	1.000000e-97

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
C579867	3-Methylglutaconic Aciduria (supp.)
C535311	Costeff optic atrophy syndrome (supp.)
C537128	Optic atrophy and cataract, autosomal dominant (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases methylation	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
corosolic acid	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Sunitinib	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Doxorubicin	decreases expression	1
Estradiol	affects expression	1
Ethyl Methanesulfonate	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Smoke	decreases expression	1
Testosterone	increases expression	1
Tobacco Smoke Pollution	decreases methylation	1
Urethane	decreases expression	1
Sodium Selenite	increases expression	1
Antirheumatic Agents	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01648452	PHASE1/PHASE2	COMPLETED	CNTF Implants for CNGB3 Achromatopsia
NCT02599922	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Safety and Efficacy Trial of AAV Gene Therapy in Patients With CNGB3 Achromatopsia (A Clarity Clinical Trial)
NCT02610582	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Safety and Efficacy of rAAV.hCNGA3 Gene Therapy in Patients With CNGA3-linked Achromatopsia
NCT02935517	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Safety and Efficacy Trial of AAV Gene Therapy in Patients With CNGA3 Achromatopsia (A Clarity Clinical Trial)
NCT03001310	PHASE1/PHASE2	COMPLETED	Gene Therapy for Achromatopsia (CNGB3)
NCT03758404	PHASE1/PHASE2	COMPLETED	Gene Therapy for Achromatopsia (CNGA3)
NCT04041232	EARLY_PHASE1	SUSPENDED	PBA Use for Treatment of ATF6-/- Patients
NCT01846052	Not specified	COMPLETED	Clinical and Genetic Characterization of Individuals With Achromatopsia
NCT02435940	Not specified	RECRUITING	Inherited Retinal Degenerative Disease Registry
NCT03278873	Not specified	TERMINATED	Long-Term Follow-Up Gene Therapy Study for Achromatopsia CNGB3 and CNGA3
NCT04124185	Not specified	COMPLETED	Natural History Study for Achromatopsia
NCT07085533	Not specified	RECRUITING	Natural History Study of Inherited Retinal Diseases