MIEF1

Summary

MIEF1 (mitochondrial elongation factor 1, HGNC:25979) is a protein-coding gene on chromosome 22q13.1, encoding Mitochondrial ribosome and complex I assembly factor AltMIEF1 (L0R8F8). Assembly factor involved in the biogenesis of the mitochondrial-specific ribosomes (mitoribosomes).

Enables identical protein binding activity; mitochondrial large ribosomal subunit binding activity; and purine ribonucleotide binding activity. Involved in several processes, including mitochondrial large ribosomal subunit assembly; mitochondrion organization; and regulation of mitochondrion organization. Located in mitochondrial matrix and mitochondrial outer membrane. Implicated in optic atrophy.

Source: NCBI Gene 54471 — RefSeq curated summary.

At a glance

• Gene–disease (curated): optic atrophy 14 (Limited, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 82 total — 2 pathogenic
• Phenotypes (HPO): 5
• MANE Select transcript: NM_019008

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25979
Approved symbol	MIEF1
Name	mitochondrial elongation factor 1
Location	22q13.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20232, MiD51, L0R8F8, D3A
Ensembl gene	ENSG00000100335
Ensembl biotype	protein_coding
OMIM	615497
Entrez	54471

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 7 protein_coding_CDS_not_defined, 5 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000325301, ENST00000402881, ENST00000404569, ENST00000428069, ENST00000433117, ENST00000434364, ENST00000464629, ENST00000465564, ENST00000467866, ENST00000478342, ENST00000479514, ENST00000481746, ENST00000489792, ENST00000494219, ENST00000962962

RefSeq mRNA: 2 — MANE Select: NM_019008 NM_001304564, NM_019008

CCDS: CCDS13995, CCDS77678

Canonical transcript exons

ENST00000325301 — 6 exons

Exon	Start	End
ENSE00000654738	39511849	39512026
ENSE00001048238	39504203	39504534
ENSE00001121296	39512232	39512494
ENSE00001351445	39513517	39518132
ENSE00001917461	39502290	39502437
ENSE00002245658	39511288	39511438

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 98.38.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.6470 / max 100.5920, expressed in 1815 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
192362	12.2576	1805
192361	3.0987	1533
192363	2.6495	1404
192360	0.6412	348

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	98.38	gold quality
secondary oocyte	CL:0000655	96.91	gold quality
male germ cell	CL:0000015	95.65	gold quality
right testis	UBERON:0004534	90.96	gold quality
left testis	UBERON:0004533	90.79	gold quality
testis	UBERON:0000473	89.54	gold quality
esophagus squamous epithelium	UBERON:0006920	88.80	gold quality
vena cava	UBERON:0004087	88.45	gold quality
endothelial cell	CL:0000115	87.96	gold quality
squamous epithelium	UBERON:0006914	87.62	gold quality
body of tongue	UBERON:0011876	87.39	gold quality
oocyte	CL:0000023	87.21	gold quality
pancreatic ductal cell	CL:0002079	87.04	silver quality
cerebellar vermis	UBERON:0004720	87.02	gold quality
epithelium of esophagus	UBERON:0001976	86.97	gold quality
ventricular zone	UBERON:0003053	86.92	gold quality
nephron tubule	UBERON:0001231	86.83	gold quality
tongue squamous epithelium	UBERON:0006919	86.82	silver quality
ganglionic eminence	UBERON:0004023	86.58	gold quality
myocardium	UBERON:0002349	86.39	silver quality
nipple	UBERON:0002030	86.34	gold quality
tendon of biceps brachii	UBERON:0008188	86.28	silver quality
pons	UBERON:0000988	86.27	gold quality
kidney epithelium	UBERON:0004819	86.27	gold quality
cervix squamous epithelium	UBERON:0006922	86.16	silver quality
cortical plate	UBERON:0005343	85.98	gold quality
cranial nerve II	UBERON:0000941	85.96	gold quality
islet of Langerhans	UBERON:0000006	85.92	gold quality
stromal cell of endometrium	CL:0002255	85.83	gold quality
left ventricle myocardium	UBERON:0006566	85.72	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.75

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

134 targeting MIEF1, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-6077	99.99	68.04	2299
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-3617-3P	99.98	67.86	918
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-LET-7D-5P	99.96	71.76	1632

Literature-anchored findings (GeneRIF, showing 17)

• MiD49/51 are new mediators of mitochondrial division affecting Drp1 action at mitochondria. (PMID:21508961)
• Mitochondrial outer membrane protein that recruits fission mediator Drp1 to the mitochondrial surface. (PMID:21508961)
• elevated MIEF1 levels induce mitochondrial fusion; depletion of MIEF1 causes mitochondrial fragmentation; MIEF1 interacts with and recruits Drp1 to mitochondria but inhibits Drp1 activity, executing a negative effect on mitochondrial fission (PMID:21701560)
• we find that either MiD49 or MiD51 can mediate Drp1 recruitment and mitochondrial fission in the absence of Fis1 and Mff (PMID:23283981)
• MIEF1 and MIEF2 are differentially expressed in human tissues during development (PMID:23880462)
• MiD49 and MiD51 can act independently of Mff and Fis1 in Drp1 recruitment and suggest that they provide specificity to the division of mitochondria. (PMID:23921378)
• The cytoplasmic domain of MiD51 was overexpressed, purified and crystallized. (PMID:24817717)
• The results indicate that Drp1-dependent mitochondrial fission through MiD49/MiD51 regulates cristae remodeling during intrinsic apoptosis. (PMID:26903540)
• MiD51 inhibits Drp1, whereas ADP promotes MiD51-mediated fission. [review] (PMID:27660309)
• In health, MiD51 regulate Drp1-mediated fission, whereas in disease, epigenetic upregulation of MiD51 increases mitotic fission, which drives pathological proliferation and apoptosis resistance (PMID:29431643)
• Loss of mitochondrial elongation factor 1 microprotein (MIEF1-MP) decreases the mitochondrial translation rate, while an elevated level of MIEF1-MP increases the translation rate (PMID:30215512)
• The study uncovers a bridging role of MIEF1 integrating cell death and mitophagy, unlikely dependent on mitochondrial dynamics, implying new insights to mechanisms determining cellular fate. (PMID:30894073)
• We found that the receptors mitochondrial fission factor (Mff) and mitochondrial elongation factor 1/2 (MIEF1/2) interact with and recruit Drp1(pS637) to mitochondria and that elevated Mff or MIEF levels promote Drp1(pS637) accumulation on mitochondria. We also noted that protein kinase A (PKA), which mediates phosphorylation of Drp1 on Ser-637, is partially present on mitochondria and interacts with both MIEFs and Mff (PMID:31533986)
• An epigenetic increase in mitochondrial fission by MiD49 and MiD51 regulates the cell cycle in cancer: Diagnostic and therapeutic implications. (PMID:32068312)
• Dominant mutations in MIEF1 affect mitochondrial dynamics and cause a singular late onset optic neuropathy. (PMID:33632269)
• Mid51/Fis1 mitochondrial oligomerization complex drives lysosomal untethering and network dynamics. (PMID:36044022)
• Ischemia/reperfusion-induced MiD51 upregulation recruits Drp1 to mitochondria and contributes to myocardial injury. (PMID:37149986)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	mief1	ENSDARG00000060991
mus_musculus	Mief1	ENSMUSG00000022412
rattus_norvegicus	Mief1	ENSRNOG00000017553

Paralogs (1): MIEF2 (ENSG00000177427)

Protein

Protein identifiers

Mitochondrial ribosome and complex I assembly factor AltMIEF1 — L0R8F8 (reviewed: L0R8F8, Q9NQG6)

Alternative names: Alternative MIEF1 protein, MIEF1 microprotein, alternative transcript upstream of MiD51

All UniProt accessions (3): Q9NQG6, B0QY94, B0QY95

UniProt curated annotations — full annotation on UniProt →

Function. Assembly factor involved in the biogenesis of the mitochondrial-specific ribosomes (mitoribosomes). Specifically associates with intermediates of the mitochondrial ribosome large subunit (mt-LSU) and is required for proper ribosome assembly, possibly preventing premature association of the large and small ribosomal subunits. Thereby, indirectly regulates mitochondrial translation. It is also required for complete assembly of the mitochondrial respiratory chain complex I. May also function in DNM1L-mediated mitochondrial fission.

Subunit / interactions. Interacts with intermediates of the mitochondrial ribosome large subunit (mt-LSU) (via MALSU1 as part of a complex that also contains NDUFAB1); regulates mitochondrial ribosomes assembly. Interacts with MRPL4. Interacts with MRPS27.

Subcellular location. Mitochondrion matrix.

Domain organisation. The LYR motif mediates interaction with NDUFAB1 and is required for the function in mitochondrial fission.

Miscellaneous. Product of an upstream open reading frame of the MIEF1 bicistronic gene.

Similarity. Belongs to the complex I LYR family.

Isoforms (3)

UniProt ID	Names	Canonical?
L0R8F8-1	3, uORF, AltMIEF1, AltMiD51	yes
Q9NQG6-1	1, MID51
Q9NQG6-2	2

RefSeq proteins (2): NP_001291493, NP_061881* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008011	Complex1_LYR_dom	Domain
IPR045300	Complex1_LYR_MIEF1-MP	Domain
IPR024810	MAB21L/cGLR	Family
IPR045909	MID49/MID51	Family
IPR046906	Mab-21_HhH/H2TH-like	Domain
IPR049097	MID51-like_C	Domain

Pfam: PF05347, PF20266, PF21297

UniProt features (76 total): helix 19, strand 14, mutagenesis site 8, binding site 6, sequence variant 6, turn 5, region of interest 5, modified residue 4, chain 2, topological domain 2, splice variant 2, short sequence motif 1, transmembrane region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

37 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
5X9C	X-RAY DIFFRACTION	1.85
4NXT	X-RAY DIFFRACTION	2.12
7OF0	ELECTRON MICROSCOPY	2.2
4NXU	X-RAY DIFFRACTION	2.3
4NXV	X-RAY DIFFRACTION	2.3
8QU5	ELECTRON MICROSCOPY	2.42
7OF7	ELECTRON MICROSCOPY	2.5
4NXW	X-RAY DIFFRACTION	2.55
4NXX	X-RAY DIFFRACTION	2.55
7PO4	ELECTRON MICROSCOPY	2.56
7O9M	ELECTRON MICROSCOPY	2.6
7OF2	ELECTRON MICROSCOPY	2.7
7OF3	ELECTRON MICROSCOPY	2.7
5X9B	X-RAY DIFFRACTION	2.7
9PRA	ELECTRON MICROSCOPY	2.83
7QH7	ELECTRON MICROSCOPY	2.89
7ODR	ELECTRON MICROSCOPY	2.9
7OF5	ELECTRON MICROSCOPY	2.9
8QSJ	ELECTRON MICROSCOPY	3
5OOM	ELECTRON MICROSCOPY	3.03
8PK0	ELECTRON MICROSCOPY	3.03
5OOL	ELECTRON MICROSCOPY	3.06
7QH6	ELECTRON MICROSCOPY	3.08
7A5J	ELECTRON MICROSCOPY	3.1
7O9K	ELECTRON MICROSCOPY	3.1
7ODS	ELECTRON MICROSCOPY	3.1
7ODT	ELECTRON MICROSCOPY	3.1
7OIC	ELECTRON MICROSCOPY	3.1
7A5H	ELECTRON MICROSCOPY	3.3
7OI9	ELECTRON MICROSCOPY	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-L0R8F8-F1	86.48	0.59
AF-Q9NQG6-F1	78.60	0.65

Functional residue map

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

L0R8F8 (canonical)

Mutagenesis-validated functional residues (2):

Position	Phenotype
12–14	decreased function in mitochondrial fission. unable to convert the mitochondrial morphology from tubular to fragmented.
39	abolishes interaction with ndufab1; when associated with 12-a–a-14.

Q9NQG6

Ligand- & substrate-binding residues (6): 187; 189; 201; 340; 342; 368

Post-translational modifications (4): 55, 59, 79, 94

Mutagenesis-validated functional residues (6):

Position	Phenotype
201	abolishes nucleotide-binding, but not dnm1l recruitment; when associated with e-342; e-368 and e-372.
235	no effect on mitochondrial localization. impairs dnm1l recruitment.
238–242	no effect on mitochondrial localization. impairs dnm1l recruitment.
342	abolishes nucleotide-binding, but not dnm1l recruitment; when associated with d-201; e-368 and e-372.
368	abolishes nucleotide-binding, but not dnm1l recruitment; when associated with d-201; e-342 and e-372.
372	abolishes nucleotide-binding, but not dnm1l recruitment; when associated with d-201; e-342 and e-368.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9937383	Mitochondrial ribosome-associated quality control

MSigDB gene sets: 163 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, ACTACCT_MIR196A_MIR196B, GOBP_POSITIVE_REGULATION_OF_MITOCHONDRIAL_FISSION, GOBP_PROTEIN_TARGETING, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_REGULATION_OF_PROTEIN_TARGETING_TO_MEMBRANE, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, COUP_01, PUJANA_CHEK2_PCC_NETWORK, GCM_PRKCG, GOBP_REGULATION_OF_MITOCHONDRION_ORGANIZATION, GCM_RING1, GOBP_PROTEIN_TARGETING_TO_MEMBRANE, GOBP_ORGANELLE_FISSION, GOBP_MITOCHONDRIAL_FISSION

GO Biological Process (8): mitochondrial fission (GO:0000266), mitochondrial respiratory chain complex I assembly (GO:0032981), positive regulation of mitochondrial translation (GO:0070131), mitochondrial large ribosomal subunit assembly (GO:1902775), positive regulation of mitochondrial fusion (GO:0010636), positive regulation of mitochondrial fission (GO:0090141), positive regulation of protein targeting to membrane (GO:0090314), mitochondrion organization (GO:0007005)

GO Molecular Function (6): mitochondrial large ribosomal subunit binding (GO:0140978), GDP binding (GO:0019003), identical protein binding (GO:0042802), ADP binding (GO:0043531), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (4): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), mitochondrial outer membrane (GO:0005741), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Mitochondrial translation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
positive regulation of organelle organization	2
positive regulation of developmental process	2
anion binding	2
mitochondrion organization	1
organelle fission	1
NADH dehydrogenase complex assembly	1
mitochondrial respiratory chain complex assembly	1
mitochondrial translation	1
positive regulation of translation	1
regulation of mitochondrial translation	1
ribosomal large subunit assembly	1
mitochondrial ribosome assembly	1
mitochondrial fusion	1
regulation of mitochondrial fusion	1
mitochondrial fission	1
regulation of mitochondrial fission	1
protein targeting to membrane	1
positive regulation of cellular process	1
regulation of protein targeting to membrane	1
positive regulation of establishment of protein localization	1
organelle organization	1
ribosomal large subunit binding	1
mitochondrial ribosome binding	1
guanyl ribonucleotide binding	1
protein binding	1
adenyl ribonucleotide binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1
mitochondrial membrane	1
organelle outer membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

248 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MIEF1	Q6ZT62	Q6ZT62	580
MIEF1	ASDURF	L0R819	575
MIEF1	SPAAR	A0A1B0GVQ0	475
MIEF1	LYRM1	O43325	432
MIEF1	PUSL1	Q8N0Z8	431
MIEF1	MYMX	A0A1B0GTQ4	419
MIEF1	RBFA	Q8N0V3	418
MIEF1	ETFRF1	Q6IPR1	418
MIEF1	GTPBP10	A4D1E9	403
MIEF1	NBDY	A0A0U1RRE5	399
MIEF1	CEACAM19	Q7Z692	397
MIEF1	MRLN	P0DMT0	397
MIEF1	MALSU1	Q96EH3	392
MIEF1	SLC35A4	Q96G79	376

IntAct

4 interactions, top by confidence:

A	B	Type	Score
NDUFAB1	MIEF1	psi-mi:“MI:0915”(physical association)	0.490
FHIP2B	VWA8	psi-mi:“MI:2364”(proximity)	0.270

ESM2 similar proteins: A3KNJ8, A3LNG8, A5D7J1, A5DH70, A5DY61, A7S1A4, A8MSI8, A9SNJ1, A9UMQ3, B2RYU8, B2RZD7, B3DFV0, B4F6X2, B5FXA0, B5FYC7, B5FZA8, B5X5U9, B5XCZ6, B6NK32, B8JLQ0, B9WD12, C4R7H7, C4Y4R9, C5DEI4, C5DR94, C9SBR9, D1Z4E1, L0R8F8, O43325, O60068, P42114, P82116, Q0UIG9, Q0VCG0, Q0VCR0, Q3UN90, Q503U1, Q5A7N3, Q6BQH4, Q6CTI7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	72
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
2626805	NM_019008.6(MIEF1):c.718T>A (p.Tyr240Asn)	Pathogenic
2626806	NM_019008.6(MIEF1):c.436C>T (p.Arg146Trp)	Pathogenic

SpliceAI

1359 predictions. Top by Δscore:

Variant	Effect	Δscore
22:39504201:A:AG	acceptor_gain	1.0000
22:39504202:G:GA	acceptor_gain	1.0000
22:39504202:GT:G	acceptor_gain	1.0000
22:39504369:G:GT	donor_gain	1.0000
22:39511280:A:AG	acceptor_gain	1.0000
22:39511281:T:G	acceptor_gain	1.0000
22:39511284:TCA:T	acceptor_loss	1.0000
22:39511286:A:AG	acceptor_gain	1.0000
22:39511286:AGA:A	acceptor_loss	1.0000
22:39511286:AGAT:A	acceptor_gain	1.0000
22:39511286:AGATG:A	acceptor_gain	1.0000
22:39511287:G:GT	acceptor_gain	1.0000
22:39511287:GA:G	acceptor_gain	1.0000
22:39511287:GAT:G	acceptor_gain	1.0000
22:39511287:GATG:G	acceptor_gain	1.0000
22:39511287:GATGA:G	acceptor_gain	1.0000
22:39511434:AGCGG:A	donor_gain	1.0000
22:39511435:GCGG:G	donor_gain	1.0000
22:39511435:GCGGG:G	donor_gain	1.0000
22:39511436:CGG:C	donor_gain	1.0000
22:39511437:GG:G	donor_gain	1.0000
22:39511437:GGG:G	donor_gain	1.0000
22:39511438:GG:G	donor_gain	1.0000
22:39511438:GGT:G	donor_loss	1.0000
22:39511439:G:GG	donor_gain	1.0000
22:39511440:T:G	donor_loss	1.0000
22:39511838:T:TA	acceptor_gain	1.0000
22:39511842:A:AG	acceptor_gain	1.0000
22:39511843:T:G	acceptor_gain	1.0000
22:39511846:CAGAT:C	acceptor_loss	1.0000

AlphaMissense

2975 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:39511404:C:A	A37D	1.000
22:39511410:T:A	L39Q	1.000
22:39511419:C:A	A42D	1.000
22:39511374:C:A	A27D	0.999
22:39511389:G:A	G32E	0.999
22:39511397:G:A	G35R	0.999
22:39511397:G:C	G35R	0.999
22:39511398:G:A	G35E	0.999
22:39511410:T:C	L39P	0.999
22:39511410:T:G	L39R	0.999
22:39511412:G:C	G40R	0.999
22:39511413:G:A	G40D	0.999
22:39511416:T:A	I41N	0.999
22:39511418:G:C	A42P	0.999
22:39511431:T:A	V46D	0.999
22:39511435:G:C	K47N	0.999
22:39511435:G:T	K47N	0.999
22:39512391:C:A	A161D	0.999
22:39512400:T:A	I164K	0.999
22:39513574:T:A	W215R	0.999
22:39513574:T:C	W215R	0.999
22:39513673:T:A	W248R	0.999
22:39513673:T:C	W248R	0.999
22:39513757:T:A	W276R	0.999
22:39513757:T:C	W276R	0.999
22:39513759:G:C	W276C	0.999
22:39513759:G:T	W276C	0.999
22:39513940:T:A	W337R	0.999
22:39513940:T:C	W337R	0.999
22:39511383:T:A	V30E	0.998

dbSNP variants (sampled 300 via entrez): RS1000210994 (22:39507039 G>C), RS1000347907 (22:39504031 A>G), RS1000480615 (22:39509301 C>T), RS1000545325 (22:39507624 G>A), RS1000713812 (22:39509574 G>A,C), RS1000923909 (22:39505308 C>A), RS1001489652 (22:39514552 T>A,C), RS1001602882 (22:39508753 G>C), RS1001685599 (22:39500160 G>A), RS1001698047 (22:39498979 C>T), RS1002040168 (22:39505630 C>T), RS1002080827 (22:39500546 T>A), RS1002150049 (22:39499276 T>A,C,G), RS1002202290 (22:39515497 C>G,T), RS1002431831 (22:39500178 G>A,C)

Disease associations

OMIM: gene MIM:615497 | disease phenotypes: MIM:620550

GenCC curated gene-disease

Disease	Classification	Inheritance
optic atrophy 14	Limited	Autosomal dominant

Mondo (3): optic atrophy 14 (MONDO:0957824), inherited retinal dystrophy (MONDO:0019118), optic atrophy (MONDO:0003608)

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

HPO phenotypes

5 total (6 of 5 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000543	Optic disc pallor
HP:0001133	Constriction of peripheral visual field
HP:0003596	Middle age onset
HP:0007663	Reduced visual acuity
HP:0000556	Retinal dystrophy

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST90002390_330	Mean corpuscular hemoglobin	3.000000e-10
GCST90013406_215	Liver enzyme levels (alkaline phosphatase)	2.000000e-28

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004527	mean corpuscular hemoglobin
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
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

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

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression	3
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	increases expression	1
butyraldehyde	increases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
epigallocatechin gallate	affects cotreatment, increases expression	1
pentanal	increases expression	1
di-n-butylphosphoric acid	affects expression	1
4-phenylbutyric acid	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
2-palmitoylglycerol	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Asbestos	affects expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	increases abundance, increases expression	1
Estradiol	increases expression	1
Methotrexate	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Ozone	increases oxidation, increases abundance, affects cotreatment	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Antirheumatic Agents	decreases expression	1
Palmitic Acid	decreases phosphorylation	1

Clinical trials (associated diseases)

49 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)
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
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)