MCAT

Summary

MCAT (malonyl-CoA-acyl carrier protein transacylase, HGNC:29622) is a protein-coding gene on chromosome 22q13.2, encoding Malonyl-CoA-acyl carrier protein transacylase, mitochondrial (Q8IVS2). Catalyzes the transfer of a malonyl moiety from malonyl-CoA to the free thiol group of the phosphopantetheine arm of the mitochondrial ACP protein (NDUFAB1).

The protein encoded by this gene is found exclusively in the mitochondrion, where it catalyzes the transfer of a malonyl group from malonyl-CoA to the mitochondrial acyl carrier protein. The encoded protein may be part of a fatty acid synthase complex that is more like the type II prokaryotic and plastid complexes rather than the type I human cytosolic complex. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 27349 — RefSeq curated summary.

At a glance

• Gene–disease (curated): optic atrophy 15 (Moderate, GenCC) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 57 total — 2 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 11
• MANE Select transcript: NM_173467

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29622
Approved symbol	MCAT
Name	malonyl-CoA-acyl carrier protein transacylase
Location	22q13.2
Locus type	gene with protein product
Status	Approved
Aliases	MT, MCT, fabD, FASN2C, NET62, MCT1
Ensembl gene	ENSG00000100294
Ensembl biotype	protein_coding
OMIM	614479
Entrez	27349

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000290429, ENST00000327555, ENST00000464244, ENST00000608052, ENST00000891956, ENST00000891957, ENST00000891958, ENST00000972440

RefSeq mRNA: 2 — MANE Select: NM_173467 NM_014507, NM_173467

CCDS: CCDS14045, CCDS33660

Canonical transcript exons

ENST00000290429 — 4 exons

Exon	Start	End
ENSE00000656759	43137081	43137298
ENSE00000656760	43141162	43141249
ENSE00001321011	43142926	43143398
ENSE00001671837	43132209	43133486

Expression profiles

Bgee: expression breadth ubiquitous, 260 present calls, max score 88.78.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.8200 / max 148.3446, expressed in 1804 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
194504	16.8200	1804

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	88.78	gold quality
right uterine tube	UBERON:0001302	88.17	gold quality
right adrenal gland	UBERON:0001233	87.53	gold quality
right adrenal gland cortex	UBERON:0035827	87.35	gold quality
epithelium of bronchus	UBERON:0002031	87.02	gold quality
left adrenal gland	UBERON:0001234	86.98	gold quality
prefrontal cortex	UBERON:0000451	86.67	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.55	gold quality
left adrenal gland cortex	UBERON:0035825	86.51	gold quality
bronchial epithelial cell	CL:0002328	86.50	gold quality
bronchus	UBERON:0002185	86.50	gold quality
adult mammalian kidney	UBERON:0000082	86.42	gold quality
gastrocnemius	UBERON:0001388	86.16	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.92	gold quality
adrenal cortex	UBERON:0001235	85.78	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	85.78	gold quality
muscle of leg	UBERON:0001383	85.32	gold quality
hindlimb stylopod muscle	UBERON:0004252	85.14	gold quality
right frontal lobe	UBERON:0002810	85.01	gold quality
adrenal gland	UBERON:0002369	84.87	gold quality
cortical plate	UBERON:0005343	84.73	gold quality
metanephros cortex	UBERON:0010533	84.71	gold quality
heart left ventricle	UBERON:0002084	84.67	gold quality
anterior cingulate cortex	UBERON:0009835	84.63	gold quality
right lobe of liver	UBERON:0001114	84.60	gold quality
cingulate cortex	UBERON:0003027	84.58	gold quality
adenohypophysis	UBERON:0002196	84.44	gold quality
cardiac ventricle	UBERON:0002082	84.34	gold quality
Brodmann (1909) area 9	UBERON:0013540	84.06	gold quality
endometrium epithelium	UBERON:0004811	83.84	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.28

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, CEBPB, DNMT1, FOS, JUN, KDM5B, LITAF, MTF1, MTF2, NFKB1, PITX1, PURB, SNAI1, STAT3, YBX1

miRNA regulators (miRDB)

29 targeting MCAT, 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-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-3162-3P	100.00	65.37	363
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-6516-3P	99.65	68.57	1238
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-4753-5P	99.54	68.51	1356
HSA-MIR-330-3P	99.41	69.95	2521
HSA-MIR-3064-5P	99.26	66.13	1497
HSA-MIR-3085-3P	99.26	66.16	1490
HSA-MIR-6504-5P	99.26	65.95	1487
HSA-MIR-4326	98.97	67.63	962
HSA-MIR-1-5P	98.70	68.66	1017
HSA-MIR-3158-3P	98.45	64.25	560
HSA-MIR-758-3P	98.42	68.60	1122
HSA-MIR-6747-3P	97.73	64.84	1596
HSA-MIR-1226-3P	97.51	66.32	1063
HSA-MIR-505-5P	97.01	65.54	778
HSA-MIR-6736-3P	96.98	65.22	1342
HSA-MIR-2909	96.36	67.30	562
HSA-MIR-1251-5P	95.78	64.10	374
HSA-MIR-4515	95.70	65.73	716

Literature-anchored findings (GeneRIF, showing 2)

• Novel mutations in malonyl-CoA-acyl carrier protein transacylase provoke autosomal recessive optic neuropathy. (PMID:31915829)
• MCAT Mutations Cause Nuclear LHON-like Optic Neuropathy. (PMID:33918393)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mcat	ENSDARG00000016613
mus_musculus	Mcat	ENSMUSG00000048755
rattus_norvegicus	Mcat	ENSRNOG00000010539
drosophila_melanogaster	beg	FBGN0036691
caenorhabditis_elegans		WBGENE00016812

Protein

Protein identifiers

Malonyl-CoA-acyl carrier protein transacylase, mitochondrial — Q8IVS2 (reviewed: Q8IVS2)

Alternative names: Mitochondrial malonyl CoA:ACP acyltransferase, Mitochondrial malonyltransferase, [Acyl-carrier-protein] malonyltransferase

All UniProt accessions (2): Q8IVS2, V9GYY6

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the transfer of a malonyl moiety from malonyl-CoA to the free thiol group of the phosphopantetheine arm of the mitochondrial ACP protein (NDUFAB1). This suggests the existence of the biosynthesis of fatty acids in mitochondria. Also acts as a mitochondrial small ribosomal subunit (mt-SSU) assembly factor.

Subcellular location. Mitochondrion.

Disease relevance. Optic atrophy 15 (OPA15) [MIM:620583] A disease characterized by visual impairment 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. OPA15 is an autosomal recessive form. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Lipid metabolism; fatty acid biosynthesis.

Similarity. Belongs to the type II malonyltransferase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8IVS2-1	1	yes
Q8IVS2-2	2

RefSeq proteins (2): NP_055322, NP_775738* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001227	Ac_transferase_dom_sf	Homologous_superfamily
IPR014043	Acyl_transferase_dom	Domain
IPR016035	Acyl_Trfase/lysoPLipase	Homologous_superfamily
IPR016036	Malonyl_transacylase_ACP-bd	Homologous_superfamily
IPR052760	Mitochondrial_malonyltrans	Family

Pfam: PF00698

Enzyme classification (BRENDA):

• EC 2.3.1.39 — [acyl-carrier-protein] S-malonyltransferase (BRENDA: 37 organisms, 73 substrates, 50 inhibitors, 77 Km, 35 kcat entries)

Substrate kinetics (BRENDA)

11 substrates with measured Km, best-characterized 11. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
MALONYL-COA	0.0013–1.4	43
[ACYL-CARRIER PROTEIN]	0.075–3.5	10
ACYL-CARRIER PROTEIN	0.042–1.3	7
AN [ACYL-CARRIER PROTEIN]	0.011–0.04	6
METHYLMALONYL-COA	0.016–0.58	4
MALONYL COA	0.0094–0.015	2
ACETOACETYL-COA	0.11	1
ACETYL-COA	0.2	1
HOLO-ACYL-CARRIER PROTEIN	0.0141	1
PANTETHEINE	0.0013	1
N-ACETYLCYSTEAMINE	—	0

Catalyzed reactions (Rhea), 1 shown:

• holo-[ACP] + malonyl-CoA = malonyl-[ACP] + CoA (RHEA:41792)

UniProt features (42 total): helix 17, strand 10, sequence variant 4, turn 3, active site 2, splice variant 2, transit peptide 1, chain 1, mutagenesis site 1, modified residue 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
2C2N	X-RAY DIFFRACTION	1.55
8CSS	ELECTRON MICROSCOPY	2.36
8CSQ	ELECTRON MICROSCOPY	2.54
8CSR	ELECTRON MICROSCOPY	2.54
8CSP	ELECTRON MICROSCOPY	2.66

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IVS2-F1	87.19	0.79

Functional residue map

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

Catalytic / active sites (2): 153; 270

Post-translational modifications (1): 314

Mutagenesis-validated functional residues (1):

Position	Phenotype
178	strongly decreased affinity for malonyl-coa.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-77289	Mitochondrial Fatty Acid Beta-Oxidation

MSigDB gene sets: 143 (showing top): GOBP_LIPID_MODIFICATION, GOBP_RIBOSOME_BIOGENESIS, GOBP_FATTY_ACID_CATABOLIC_PROCESS, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_RIBOSOME_ASSEMBLY, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, GOBP_RIBOSOMAL_SMALL_SUBUNIT_BIOGENESIS, GOBP_ORGANIC_ACID_CATABOLIC_PROCESS, VANHARANTA_UTERINE_FIBROID_WITH_7Q_DELETION_DN, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION, GOBP_FATTY_ACID_BIOSYNTHETIC_PROCESS, GOBP_ORGANELLE_ASSEMBLY, GOBP_MONOCARBOXYLIC_ACID_BIOSYNTHETIC_PROCESS

GO Biological Process (6): fatty acid biosynthetic process (GO:0006633), fatty acid beta-oxidation (GO:0006635), mitochondrial small ribosomal subunit assembly (GO:0180026), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631), monocarboxylic acid metabolic process (GO:0032787)

GO Molecular Function (4): RNA binding (GO:0003723), [acyl-carrier-protein] S-malonyltransferase activity (GO:0004314), RNA folding chaperone (GO:0140691), transferase activity (GO:0016740)

GO Cellular Component (2): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Fatty acid metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
fatty acid metabolic process	1
lipid biosynthetic process	1
monocarboxylic acid biosynthetic process	1
fatty acid catabolic process	1
fatty acid ligase activity	1
fatty acid oxidation	1
ribosomal small subunit assembly	1
mitochondrial ribosome assembly	1
primary metabolic process	1
lipid metabolic process	1
monocarboxylic acid metabolic process	1
carboxylic acid metabolic process	1
nucleic acid binding	1
S-malonyltransferase activity	1
molecular_function	1
RNA folding	1
catalytic activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

2566 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MCAT	TEAD1	P28347	891
MCAT	TEAD4	Q15561	885
MCAT	OXSM	Q9NWU1	711
MCAT	HSD17B8	Q92506	706
MCAT	ACACA	Q13085	679
MCAT	MECR	Q9BV79	666
MCAT	AASDHPPT	Q9NRN7	647
MCAT	ACACB	O00763	597
MCAT	FASN	P49327	559
MCAT	ACSL3	O95573	558
MCAT	ACSL1	P33121	527
MCAT	F5H3C5	F5H3C5	512
MCAT	SOD2	P04179	512
MCAT	PISD	Q9UG56	511
MCAT	CBR4	Q8N4T8	499

IntAct

60 interactions, top by confidence:

A	B	Type	Score
ZNF324B	ZNF316	psi-mi:“MI:0914”(association)	0.530
RBM3	PRMT5	psi-mi:“MI:0914”(association)	0.530
MRPS15	MRPS14	psi-mi:“MI:0914”(association)	0.530
DDX28	PTCD1	psi-mi:“MI:0914”(association)	0.530
MCAT	ALAS1	psi-mi:“MI:0914”(association)	0.530
MRPS34	ZZEF1	psi-mi:“MI:0914”(association)	0.530
MRPS18C	MRPS14	psi-mi:“MI:0914”(association)	0.530
ZFC3H1	HNRNPCL1	psi-mi:“MI:0914”(association)	0.530
HNRNPA1	PTCD1	psi-mi:“MI:0914”(association)	0.530
RBMX	PTCD1	psi-mi:“MI:0914”(association)	0.530
METTL17	HSPD1	psi-mi:“MI:0914”(association)	0.530
MRPS15	PRKACG	psi-mi:“MI:0914”(association)	0.530
RBM3	AARS2	psi-mi:“MI:0914”(association)	0.530
CIRBP	PRMT5	psi-mi:“MI:0914”(association)	0.530
HNRNPU	MRPS11	psi-mi:“MI:0914”(association)	0.530
PRR3	MRPS14	psi-mi:“MI:0914”(association)	0.530
DOCK5	DOCK1	psi-mi:“MI:0914”(association)	0.500
NDUFAB1	MIEF1	psi-mi:“MI:0915”(physical association)	0.490
MYC	TARS3	psi-mi:“MI:0914”(association)	0.350
Chmp3	DTL	psi-mi:“MI:0914”(association)	0.350
KIE-1	GTPBP10	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
MRPS34	CIBAR1	psi-mi:“MI:0914”(association)	0.350
MRPL4	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
HNRNPA1	HNRNPR	psi-mi:“MI:0914”(association)	0.350

BioGRID (156): MCAT (Affinity Capture-MS), MCAT (Affinity Capture-MS), MCAT (Affinity Capture-MS), MCAT (Affinity Capture-MS), MCAT (Affinity Capture-MS), MCAT (Affinity Capture-MS), MCAT (Affinity Capture-MS), RPUSD2 (Co-fractionation), MCAT (Affinity Capture-MS), MCAT (Affinity Capture-MS), MCAT (Affinity Capture-MS), MCAT (Affinity Capture-MS), MCAT (Affinity Capture-MS), MCAT (Affinity Capture-MS), MCAT (Affinity Capture-MS)

ESM2 similar proteins: A2Y3Q5, A4QEC1, B1MC29, O04921, O42479, O48902, O54820, O57478, O59786, O88637, P15719, P16622, P22315, P22600, P22830, P34913, P42043, P42044, P42045, Q05145, Q0BWA5, Q0DIV0, Q13057, Q3YA36, Q5EA75, Q5L283, Q69TB1, Q6AHF2, Q6JQN1, Q6NH66, Q71XF4, Q73C08, Q7UFZ7, Q81TU9, Q83FJ2, Q83H94, Q8BTW8, Q8FTB1, Q8IVS2, Q8K370

Diamond homologs: A0A067XNI2, A0A0D2YG10, A0A142C799, A0A1B3PEI6, A7Z4X8, A7Z4Y0, B2HIL7, B4ER96, B8MYS6, E0D202, E0D204, E9F8M3, I6XD69, O34787, O34825, O85140, P0AAI9, P0AAJ0, P43712, P71019, P73242, P96285, P9WES1, P9WES2, P9WET5, Q2T4N0, Q5AXA9, Q5HGK3, Q6G9Y3, Q6GHK5, Q7A124, Q7A5Z3, Q7TXK8, Q8IVS2, Q8R3F5, Q8T3L6, Q8X8I7, Q93QD4, Q99UN8, Q9R9J2

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MTF1	“up-regulates quantity by expression”	MCAT	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 73 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
Mitochondrial ribosome-associated quality control	17	40.9×	2e-21
Mitochondrial translation	14	37.8×	2e-17
Mitochondrial translation initiation	15	37.3×	2e-18
Mitochondrial translation elongation	15	37.3×	2e-18
Mitochondrial translation termination	15	32.3×	2e-17
Translation	15	18.2×	7e-14

GO biological processes:

GO term	Partners	Fold	FDR
mitochondrial translation	16	42.1×	1e-19
regulation of alternative mRNA splicing, via spliceosome	5	18.5×	6e-04
RNA processing	5	16.6×	8e-04
translation	10	15.6×	2e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	41
Likely benign	7
Benign	4

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
2628319	NM_173467.5(MCAT):c.424-2A>G	Pathogenic
2628320	NM_173467.5(MCAT):c.823G>A (p.Glu275Lys)	Pathogenic
4823521	NM_173467.5(MCAT):c.423+1G>A	Likely pathogenic

SpliceAI

808 predictions. Top by Δscore:

Variant	Effect	Δscore
22:43137165:G:A	donor_gain	1.0000
22:43137181:T:TA	donor_gain	1.0000
22:43141154:T:TA	donor_gain	1.0000
22:43141156:CTGTA:C	donor_loss	1.0000
22:43141157:TGTA:T	donor_loss	1.0000
22:43141159:TA:T	donor_loss	1.0000
22:43141160:A:AT	donor_loss	1.0000
22:43135955:T:TA	donor_gain	0.9900
22:43137097:A:C	donor_gain	0.9900
22:43138145:TGTG:T	donor_gain	0.9900
22:43141246:TCACC:T	acceptor_loss	0.9900
22:43141248:ACCT:A	acceptor_loss	0.9900
22:43141250:CTGT:C	acceptor_loss	0.9900
22:43141251:T:C	acceptor_loss	0.9900
22:43137139:A:AC	donor_gain	0.9800
22:43137140:C:CC	donor_gain	0.9800
22:43141247:CAC:C	acceptor_gain	0.9800
22:43141259:CAGA:C	acceptor_loss	0.9700
22:43137133:T:TA	donor_gain	0.9600
22:43137133:TC:T	donor_gain	0.9600
22:43141246:TCAC:T	acceptor_gain	0.9600
22:43141247:CACC:C	acceptor_gain	0.9600
22:43142924:A:AC	donor_gain	0.9600
22:43142925:C:CC	donor_gain	0.9600
22:43133485:GCC:G	acceptor_loss	0.9500
22:43142919:GCCTC:G	donor_loss	0.9500
22:43142920:CCT:C	donor_loss	0.9500
22:43142921:CTCAC:C	donor_loss	0.9500
22:43142922:TCA:T	donor_loss	0.9500
22:43142923:C:CG	donor_loss	0.9500

AlphaMissense

2517 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:43133240:A:G	W326R	0.997
22:43133240:A:T	W326R	0.997
22:43133238:C:A	W326C	0.994
22:43133238:C:G	W326C	0.994
22:43133409:G:C	F269L	0.994
22:43133409:G:T	F269L	0.994
22:43133411:A:G	F269L	0.994
22:43141214:A:C	S153R	0.994
22:43141214:A:T	S153R	0.994
22:43141216:T:G	S153R	0.994
22:43133408:G:C	H270D	0.993
22:43141215:C:A	S153I	0.992
22:43137091:C:T	G240E	0.991
22:43137275:C:G	A179P	0.991
22:43143148:G:C	F67L	0.991
22:43143148:G:T	F67L	0.991
22:43143150:A:G	F67L	0.991
22:43137137:A:G	C225R	0.990
22:43141197:G:T	A159D	0.990
22:43143149:A:G	F67S	0.990
22:43141209:C:A	G155V	0.989
22:43141224:G:T	A150D	0.989
22:43142958:C:G	A131P	0.989
22:43142960:G:T	A130D	0.989
22:43141221:C:T	G151E	0.987
22:43141225:C:G	A150P	0.987
22:43133170:C:T	G349D	0.986
22:43142945:A:G	L135P	0.986
22:43143031:G:C	S106R	0.986
22:43143031:G:T	S106R	0.986

dbSNP variants (sampled 300 via entrez): RS1000118989 (22:43132658 A>G), RS1000158514 (22:43137820 G>A,C), RS1000493498 (22:43135439 G>A), RS1000594470 (22:43140557 C>T), RS1000842684 (22:43135643 C>T), RS1001120539 (22:43132811 T>C), RS1001252394 (22:43137630 A>G), RS1001254558 (22:43138190 T>G), RS1001724712 (22:43137808 C>T), RS1002094978 (22:43133721 A>C), RS1002106876 (22:43134613 G>A), RS1002260280 (22:43139261 G>A), RS1002312513 (22:43138966 G>A), RS1002325936 (22:43138891 G>T), RS1002401805 (22:43144587 C>G,T)

Disease associations

OMIM: gene MIM:614479 | disease phenotypes: MIM:620583

GenCC curated gene-disease

Disease	Classification	Inheritance
optic atrophy 15	Moderate	Autosomal recessive
autosomal recessive optic atrophy	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
optic atrophy 15	Limited	AR

Mondo (3): inherited retinal dystrophy (MONDO:0019118), optic atrophy 15 (MONDO:0957935), (MONDO:0014753)

Orphanet (1): OBSOLETE: Inherited retinal disorder (Orphanet:71862)

HPO phenotypes

11 total (12 of 11 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000543	Optic disc pallor
HP:0000603	Central scotoma
HP:0000613	Photophobia
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0002315	Headache
HP:0003621	Juvenile onset
HP:0007641	Dyschromatopsia
HP:0007663	Reduced visual acuity
HP:0011462	Young adult onset
HP:0000556	Retinal dystrophy

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001370_51	Prostate cancer (SNP x SNP interaction)	2.000000e-06

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D058499	Retinal Dystrophies	C11.768.585.658

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression	3
Acetaminophen	decreases expression	2
Air Pollutants	increases abundance, increases expression, decreases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
triphenyl phosphate	affects expression	1
glycidyl methacrylate	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
GW 4064	affects cotreatment, decreases expression	1
6-(4-chlorophenyl)imidazo(2,1-b)(1,3)thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime	affects cotreatment, decreases expression	1
Cadmium	increases abundance, increases expression	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Ribonucleotides	affects binding	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Isotretinoin	decreases expression	1
Oleic Acid	affects cotreatment, decreases expression	1
Okadaic Acid	increases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT05902962	PHASE1	COMPLETED	SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects
NCT06319872	PHASE1	RECRUITING	The Effects of Disulfiram (Antabuse®) on Visual Acuity in Patients With Retinal Degeneration
NCT06455826	PHASE1	COMPLETED	MAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects (Wallaby)
NCT04855045	PHASE2/PHASE3	UNKNOWN	An Open-label, Dose Escalation and Double-masked, Randomized, Controlled Trial Evaluating Safety and Tolerability of Sepofarsen in Children (<8 Years of Age) With LCA10 Caused by Mutations in the CEP290 Gene.
NCT03872479	PHASE1/PHASE2	UNKNOWN	Single Ascending Dose Study in Participants With LCA10
NCT04123626	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Safety and Tolerability of QR-1123 in Subjects With Autosomal Dominant Retinitis Pigmentosa Due to the P23H Mutation in the RHO Gene
NCT04545736	PHASE1/PHASE2	RECRUITING	Oral Metformin for Treatment of ABCA4 Retinopathy
NCT06212297	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Fellow-eye Study (FE) of LX101 in Subjects With Inherited Retinal Dystrophy
NCT06852963	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Repeat-Dose, Open-Label, Two Arm Safety and Efficacy Study of Two Doses of VP-001 Administered Intravitreally in Participants With Confirmed PRPF31 Mutation-Associated Retinal Dystrophy, Including Participants Previously Treated With VP001
NCT07177196	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Personalized Antisense Oligonucleotide Therapy for a Single Participant With PRPH2 Mutation Associated With Retinal Dystrophy
NCT07063030	EARLY_PHASE1	RECRUITING	A Study of LX107 Gene Therapy in AIPL1-IRD Patients
NCT01546181	Not specified	COMPLETED	Retinal Imaging by Adaptive Optics in Healthy Eyes and During Retinal and General Diseases
NCT01876147	Not specified	COMPLETED	Visual and Functional Assessment in Low Vision Patients
NCT01920867	Not specified	UNKNOWN	Stem Cell Ophthalmology Treatment Study
NCT02014389	Not specified	RECRUITING	Evaluation of Objective Perimetry Using Chromatic Multifocal Pupillometer
NCT02983305	Not specified	COMPLETED	Optical Head-Mounted Display Technology for Low Vision Rehabilitation
NCT03592017	Not specified	COMPLETED	Performance of Long-wavelength Autofluorescence Imaging
NCT03662386	Not specified	TERMINATED	Prospective Analysis of Genotype-phenotype Correlations Observed in a Large Cohort of Patients With Hereditary Retinal Dystrophies - GEPHIRD
NCT03691168	Not specified	UNKNOWN	Multi-center Observation of the Natural Course of Inherited Retinal Dystrophies
NCT03843840	Not specified	COMPLETED	Dual Wavelength OCT
NCT03853252	Not specified	COMPLETED	iPS Cells of Patients for Models of Retinal Dystrophies
NCT05130385	Not specified	UNKNOWN	High Resolution Optical Coherence Tomography
NCT05294978	Not specified	RECRUITING	EyeConic: Qualification for Cone-Optogenetics
NCT05573984	Not specified	ACTIVE_NOT_RECRUITING	Natural History of PRPF31 Mutation-Associated Retinal Dystrophy
NCT05793515	Not specified	COMPLETED	Mechanisms of Inherited Retinal Dystrophies Using Whole Genome Sequencing and in Vitro and in Vivo Models
NCT05820100	Not specified	COMPLETED	Observational Study to Assess the Reliability and Validity of the MLYMT and MLSDT
NCT05976139	Not specified	RECRUITING	Micropulsed Laser in Patients With Macular Oedema in Retinal Dystrophies
NCT06162585	Not specified	ACTIVE_NOT_RECRUITING	Non-Interventional Long Term Follow-up Study of Participants Previously Enrolled in the RESTORE Study
NCT06177977	Not specified	RECRUITING	SS-HH-OCT as a Novel Diagnostic Modality for Early-Onset Retinal Dystrophies (EORDs)
NCT06375239	Not specified	RECRUITING	Observational Study to Assess Endpoint Operational Feasibility & Measurement Properties in Patients with Retinal Degeneration
NCT06908161	Not specified	NOT_YET_RECRUITING	Functional Assessments in Vision Impairment
NCT07085533	Not specified	RECRUITING	Natural History Study of Inherited Retinal Diseases
NCT07502664	Not specified	RECRUITING	Development and Evaluation of Functional Visual Field and Navigation Endpoints in Moderate to Profound Inherited Retinal Disease (DEFINE-IRD)
NCT07529041	Not specified	ENROLLING_BY_INVITATION	Real-time Acoustic Biofeedback for Enhancing Fixation Stability: A Proof-of-concept Study to Improve Ophthalmic Imaging Diagnostic Quality