DNAJC30

Summary

DNAJC30 (DnaJ heat shock protein family (Hsp40) member C30, HGNC:16410) is a protein-coding gene on chromosome 7q11.23, encoding DnaJ homolog subfamily C member 30, mitochondrial (Q96LL9). Mitochondrial protein enriched in neurons that acts as a regulator of mitochondrial respiration.

This intronless gene encodes a member of the DNAJ molecular chaperone homology domain-containing protein family. This gene is deleted in Williams syndrome, a multisystem developmental disorder caused by the deletion of contiguous genes at 7q11.23.

Source: NCBI Gene 84277 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Leber-like hereditary optic neuropathy, autosomal recessive 1 (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 55 total — 6 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 204
• MANE Select transcript: NM_032317

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16410
Approved symbol	DNAJC30
Name	DnaJ heat shock protein family (Hsp40) member C30
Location	7q11.23
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000176410
Ensembl biotype	protein_coding
OMIM	618202
Entrez	84277

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000395176

RefSeq mRNA: 1 — MANE Select: NM_032317 NM_032317

CCDS: CCDS5556

Canonical transcript exons

ENST00000395176 — 1 exons

Exon	Start	End
ENSE00001520810	73680918	73683453

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 94.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.4099 / max 113.3905, expressed in 1806 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
84318	25.4081	1806
84319	0.0019	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibialis anterior	UBERON:0001385	94.06	silver quality
pancreatic ductal cell	CL:0002079	92.96	gold quality
kidney epithelium	UBERON:0004819	90.53	gold quality
ileal mucosa	UBERON:0000331	89.75	gold quality
endothelial cell	CL:0000115	89.73	gold quality
left ventricle myocardium	UBERON:0006566	88.76	gold quality
upper arm skin	UBERON:0004263	86.84	silver quality
pons	UBERON:0000988	85.60	gold quality
deltoid	UBERON:0001476	85.57	silver quality
cardiac muscle of right atrium	UBERON:0003379	85.56	silver quality
right adrenal gland	UBERON:0001233	85.33	gold quality
right adrenal gland cortex	UBERON:0035827	85.14	gold quality
nipple	UBERON:0002030	84.56	gold quality
left adrenal gland	UBERON:0001234	84.27	gold quality
adrenal cortex	UBERON:0001235	83.95	gold quality
secondary oocyte	CL:0000655	83.81	gold quality
left adrenal gland cortex	UBERON:0035825	83.67	gold quality
cerebellar vermis	UBERON:0004720	83.45	silver quality
apex of heart	UBERON:0002098	83.36	gold quality
prefrontal cortex	UBERON:0000451	83.24	gold quality
sperm	CL:0000019	83.19	gold quality
lateral nuclear group of thalamus	UBERON:0002736	82.75	gold quality
renal medulla	UBERON:0000362	82.60	gold quality
adrenal gland	UBERON:0002369	82.34	gold quality
cardiac atrium	UBERON:0002081	82.25	gold quality
substantia nigra pars compacta	UBERON:0001965	82.21	gold quality
ventral tegmental area	UBERON:0002691	82.20	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.04	gold quality
dorsal root ganglion	UBERON:0000044	82.00	gold quality
right atrium auricular region	UBERON:0006631	81.99	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.45
E-MTAB-6142	no	55.19

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

71 targeting DNAJC30, 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-4283	100.00	66.42	2097
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-10395-5P	99.86	67.35	676
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-370-5P	99.78	66.81	706
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-199A-3P	99.75	70.48	929
HSA-MIR-199B-3P	99.75	70.48	929
HSA-MIR-3129-5P	99.75	70.46	914
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-1290	99.59	69.90	2079

Literature-anchored findings (GeneRIF, showing 5)

• Impaired complex I repair causes recessive Leber’s hereditary optic neuropathy. (PMID:33465056)
• DNAJC30 disease-causing gene variants in a large Central European cohort of patients with suspected Leber’s hereditary optic neuropathy and optic atrophy. (PMID:35091433)
• Additive effect of DNAJC30 and NDUFA9 mutations causing Leigh syndrome. (PMID:36939934)
• Autosomal recessive Leber’s hereditary optic neuropathy caused by a homozygous variant in DNAJC30 gene. (PMID:37579815)
• DNAJC30 Gene Variants Are a Frequent Cause of a Rare Disease: Leber Hereditary Optic Neuropathy in Polish Patients. (PMID:38139324)

Cross-species orthologs

14 orthologs

Organism	Symbol	Gene ID
danio_rerio	dnajc30b	ENSDARG00000079415
mus_musculus	Dnajc30	ENSMUSG00000061118
rattus_norvegicus	Dnajc30	ENSRNOG00000031721
drosophila_melanogaster	CG2790	FBGN0027599
drosophila_melanogaster	Tpr2	FBGN0032586
drosophila_melanogaster	CG10565	FBGN0037051
drosophila_melanogaster	P58IPK	FBGN0037718
drosophila_melanogaster	l(3)80Fg	FBGN0287183
caenorhabditis_elegans		WBGENE00001020
caenorhabditis_elegans		WBGENE00001025
caenorhabditis_elegans		WBGENE00001026
caenorhabditis_elegans		WBGENE00001029
caenorhabditis_elegans	dnj-28	WBGENE00001046
caenorhabditis_elegans		WBGENE00008122

Paralogs (20): DNAJC11 (ENSG00000007923), DNAJC25 (ENSG00000059769), DNAJC10 (ENSG00000077232), DNAJC5 (ENSG00000101152), DNAJC3 (ENSG00000102580), DNAJC17 (ENSG00000104129), DNAJC2 (ENSG00000105821), DNAJC12 (ENSG00000108176), DNAJC4 (ENSG00000110011), DNAJC16 (ENSG00000116138), DNAJC14 (ENSG00000135392), DNAJC1 (ENSG00000136770), DNAJC13 (ENSG00000138246), DNAJC5B (ENSG00000147570), DNAJC5G (ENSG00000163793), DNAJC7 (ENSG00000168259), DNAJC21 (ENSG00000168724), DNAJC18 (ENSG00000170464), DNAJC24 (ENSG00000170946), DNAJC9 (ENSG00000213551)

Protein

Protein identifiers

DnaJ homolog subfamily C member 30, mitochondrial — Q96LL9 (reviewed: Q96LL9)

Alternative names: Williams-Beuren syndrome chromosomal region 18 protein

All UniProt accessions (1): Q96LL9

UniProt curated annotations — full annotation on UniProt →

Function. Mitochondrial protein enriched in neurons that acts as a regulator of mitochondrial respiration. Associates with the ATP synthase complex and facilitates ATP synthesis. May be a chaperone protein involved in the turnover of the subunits of mitochondrial complex I N-module. It facilitates the degradation of N-module subunits damaged by oxidative stress, and contributes to complex I functional efficiency.

Subunit / interactions. Associates with the ATP synthase complex. Interacts with MT-ATP6; interaction is direct. Interacts with ATP5MC2; interaction is direct.

Subcellular location. Mitochondrion inner membrane.

Tissue specificity. Expressed in brain, heart, kidney, liver, lung, spleen, stomach and testis. Highly expressed in the brain. In the neocortex, expressed in most, if not all, glutamatergic excitatory projection neurons (pyramidal) and many interneurons, with the strongest signal noticeably in large pyramidal neurons of layer 3C. Also present in pyramidal neurons of layer 3C PNs of the superior temporal cortex, as well as in pyramidal neurons (Betz cells) of the layer 5B primary motor cortex (at protein level).

Disease relevance. DNAJC30 is located in the Williams-Beuren syndrome (WBS) critical region. WBS results from a hemizygous deletion of several genes on chromosome 7q11.23 thought to arise as a consequence of unequal crossing over between highly homologous low-copy repeat sequences flanking the deleted region. WBS is an autosomal dominant disorder characterized by multiple clinical manifestations including neurologic features such as intellectual disability, cardiovascular, urogenital and skeletal features, and distinctive facies. Deletion of DNAJC30 is responsible for mitochondrial dysfunction underlyining certain neurodevelopmental abnormalities observed in WBS. Leber-like hereditary optic neuropathy, autosomal recessive 1 (LHONAR1) [MIM:619382] An autosomal recessive form of Leber hereditary optic neuropathy, a mitochondrial disease resulting in bilateral painless loss of central vision due to selective degeneration of the retinal ganglion cells and their axons. The disorder shows incomplete penetrance and male predominance. The disease is caused by variants affecting the gene represented in this entry.

RefSeq proteins (1): NP_115693* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001623	DnaJ_domain	Domain
IPR036869	J_dom_sf	Homologous_superfamily
IPR053025	Mito_ATP_Synthase-Asso	Family

Pfam: PF00226

UniProt features (17 total): sequence variant 5, helix 5, transit peptide 1, chain 1, turn 1, transmembrane region 1, domain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2YUA	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96LL9-F1	71.87	0.28

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 545 (showing top): GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GOBP_ATP_BIOSYNTHETIC_PROCESS, GOBP_OXIDATIVE_PHOSPHORYLATION, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_NUCLEOSIDE_TRIPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_TRIPHOSPHATE_BIOSYNTHETIC_PROCESS, GOCC_MITOCHONDRIAL_ENVELOPE, GOBP_HEAD_DEVELOPMENT, chr7q11, GOBP_CELLULAR_RESPIRATION

GO Biological Process (3): ATP biosynthetic process (GO:0006754), brain development (GO:0007420), regulation of mitochondrial ATP synthesis coupled proton transport (GO:1905706)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (3): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
purine ribonucleotide biosynthetic process	1
purine ribonucleoside triphosphate biosynthetic process	1
ATP metabolic process	1
central nervous system development	1
animal organ development	1
head development	1
proton motive force-driven mitochondrial ATP synthesis	1
regulation of ATP biosynthetic process	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1098 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DNAJC30	DNAJC11	Q9NVH1	573
DNAJC30	BUD23	O43709	544
DNAJC30	MT-ATP6	P00846	523
DNAJC30	ANKRD13B	Q86YJ7	517
DNAJC30	TMEM270	Q6UE05	507
DNAJC30	EXOSC6	Q5RKV6	500
DNAJC30	TBL2	Q9Y4P3	498
DNAJC30	WDR53	Q7Z5U6	482
DNAJC30	SYNDIG1L	A6NDD5	468
DNAJC30	SPATA22	Q8NHS9	456
DNAJC30	GTF2IRD1	Q9UHL9	451
DNAJC30	DNAJC19	Q96DA6	441
DNAJC30	CIMAP1C	Q8IXM7	440
DNAJC30	GTF2IRD2B	Q6EKJ0	431
DNAJC30	DNAJC28	Q9NX36	424

IntAct

131 interactions, top by confidence:

A	B	Type	Score
NDUFS6	NDUFS8	psi-mi:“MI:0914”(association)	0.640
TMED2	ATP9A	psi-mi:“MI:0914”(association)	0.640
DNAJC30	NDUFA7	psi-mi:“MI:0914”(association)	0.640
NDUFA9	NDUFS4	psi-mi:“MI:0914”(association)	0.640
FATE1	DNAJC30	psi-mi:“MI:0915”(physical association)	0.560
KASH5	DNAJC30	psi-mi:“MI:0915”(physical association)	0.560
	DNAJC30	psi-mi:“MI:0915”(physical association)	0.560
DNAJC30	CALN1	psi-mi:“MI:0915”(physical association)	0.560
FAM209A	DNAJC30	psi-mi:“MI:0915”(physical association)	0.560
DNAJC30	REEP4	psi-mi:“MI:0915”(physical association)	0.560
JAGN1	DNAJC30	psi-mi:“MI:0915”(physical association)	0.560
LRRC25	DNAJC30	psi-mi:“MI:0915”(physical association)	0.560
RNF170	DNAJC30	psi-mi:“MI:0915”(physical association)	0.560
DNAJC30	MGST2	psi-mi:“MI:0915”(physical association)	0.560
PEX12	DNAJC30	psi-mi:“MI:0915”(physical association)	0.560
EBP	DNAJC30	psi-mi:“MI:0915”(physical association)	0.560
DNAJC30	SIGLEC12	psi-mi:“MI:0915”(physical association)	0.560
SLC10A4	DNAJC30	psi-mi:“MI:0915”(physical association)	0.560
TMEM52B	DNAJC30	psi-mi:“MI:0915”(physical association)	0.560
MSMO1	DNAJC30	psi-mi:“MI:0915”(physical association)	0.560
MRM1	DNAJC30	psi-mi:“MI:0915”(physical association)	0.560
DNAJC30	SLC35C2	psi-mi:“MI:0915”(physical association)	0.560
AQP6	DNAJC30	psi-mi:“MI:0915”(physical association)	0.560
SLC51A	DNAJC30	psi-mi:“MI:0915”(physical association)	0.560
MFSD14B	DNAJC30	psi-mi:“MI:0915”(physical association)	0.560
GPX8	DNAJC30	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (255): NDUFV3 (Affinity Capture-MS), NDUFA7 (Affinity Capture-MS), NDUFS4 (Affinity Capture-MS), DNAJC30 (Affinity Capture-MS), DNAJC30 (Reconstituted Complex), DNAJC30 (Two-hybrid), DNAJC30 (Two-hybrid), DNAJC30 (Affinity Capture-MS), DNAJC30 (Affinity Capture-MS), DNAJC30 (Affinity Capture-MS), NDUFV3 (Affinity Capture-MS), DNAJC30 (Affinity Capture-MS), DNAJC30 (Affinity Capture-MS), DNAJC30 (Affinity Capture-MS), DNAJC30 (Affinity Capture-MS)

ESM2 similar proteins: A0JPP8, A1A4P4, A2ALW5, D3ZSC8, J9VP29, O43278, O75064, P59041, P92029, Q0WTI8, Q1ECT8, Q2KHT9, Q2KI83, Q2KIL7, Q3U1Y4, Q3UJV1, Q3UMT1, Q4G0I0, Q4VBF2, Q5BJW9, Q5BKU9, Q5HZT9, Q5R7Q6, Q5RFR4, Q5T124, Q5XJW2, Q5ZJ07, Q6DGF9, Q6IPM2, Q6RUT7, Q75BG6, Q8JZP9, Q8K1S6, Q8SPE7, Q8TAE8, Q8VD26, Q8WWL2, Q91WT4, Q96AN5, Q96D70

Diamond homologs: A0KMI5, A1WX30, A3MA88, A4IX29, A4W6D6, A4XKA5, A5FZ18, A5W9A2, A6VCL7, A7I2G3, A7MIK3, A7ZHA5, A9IGC5, A9W6R8, B0B7R0, B0BBX5, B0U3J7, B0U833, B0VA24, B0VQ00, B1LZ52, B1ZGR2, B1ZUS0, B2I2G6, B2I6F5, B2IBR5, B2RLJ0, B3EE31, B3QPW8, B4S9D0, B7GV08, B7I2B2, B7KSZ5, B7UI60, B7V1H2, B8IHL2, B9KH92, B9MJZ0, C4Z1J3, C6BYN5

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 88 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
Complex I biogenesis	13	35.3×	2e-15
Aerobic respiration and respiratory electron transport	16	23.2×	8e-16
Respiratory electron transport	13	20.3×	3e-12

GO biological processes:

GO term	Partners	Fold	FDR
mitochondrial electron transport, NADH to ubiquinone	12	55.2×	4e-16
proton motive force-driven mitochondrial ATP synthesis	15	50.6×	1e-19
aerobic respiration	13	41.3×	6e-16
mitochondrial respiratory chain complex I assembly	5	26.4×	1e-04
monoatomic ion transmembrane transport	5	13.3×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	3
Uncertain significance	37
Likely benign	7
Benign	1

Top pathogenic / likely-pathogenic (9)

Variant ID	HGVS	Classification
1171026	NM_032317.3(DNAJC30):c.232C>T (p.Pro78Ser)	Pathogenic
1171027	NM_032317.3(DNAJC30):c.302T>A (p.Leu101Gln)	Pathogenic
2628014	NM_032317.3(DNAJC30):c.130_131del (p.Ser44fs)	Pathogenic
2628015	NM_032317.3(DNAJC30):c.610G>T (p.Glu204Ter)	Pathogenic
2628016	NM_032317.3(DNAJC30):c.227ACC[1] (p.His77del)	Pathogenic
3062986	GRCh37/hg19 7q11.21-11.23(chr7:66776724-74629034)x3	Pathogenic
1299584	NM_032317.3(DNAJC30):c.293A>C (p.Tyr98Ser)	Likely pathogenic
2628724	NM_032317.3(DNAJC30):c.24G>A (p.Trp8Ter)	Likely pathogenic
3250184	NM_032317.3(DNAJC30):c.172dup (p.Ser58fs)	Likely pathogenic

SpliceAI

28 predictions. Top by Δscore:

Variant	Effect	Δscore
7:73682723:C:A	donor_gain	0.7400
7:73682728:C:A	donor_gain	0.5700
7:73682722:C:CA	donor_gain	0.5300
7:73683132:AGG:A	donor_gain	0.5000
7:73683099:TGCG:T	donor_gain	0.4200
7:73682738:T:A	donor_gain	0.4000
7:73683036:T:TA	donor_gain	0.3900
7:73682844:C:CA	donor_gain	0.3800
7:73683098:T:C	donor_gain	0.3400
7:73683378:T:TA	donor_gain	0.3300
7:73683096:A:AC	donor_gain	0.3200
7:73683097:C:CC	donor_gain	0.3200
7:73683100:G:A	donor_gain	0.3100
7:73682888:T:A	donor_gain	0.2600
7:73683068:T:TA	donor_gain	0.2600
7:73682727:T:TA	donor_gain	0.2400
7:73683092:T:TA	donor_gain	0.2200
7:73683397:C:CT	donor_gain	0.2200
7:73682405:A:C	acceptor_gain	0.2100
7:73682441:C:A	acceptor_gain	0.2100
7:73682841:ACT:A	donor_gain	0.2100
7:73682842:CTC:C	donor_gain	0.2100
7:73682917:C:CC	acceptor_gain	0.2100
7:73683191:G:T	acceptor_gain	0.2100
7:73683374:A:AT	donor_gain	0.2100
7:73682458:G:T	acceptor_gain	0.2000
7:73682879:AGGCG:A	donor_gain	0.2000
7:73683126:C:CT	donor_gain	0.2000

AlphaMissense

1434 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:73683226:C:A	K66N	0.995
7:73683226:C:G	K66N	0.995
7:73682923:G:C	F167L	0.994
7:73682923:G:T	F167L	0.994
7:73682925:A:G	F167L	0.994
7:73683151:G:C	F91L	0.994
7:73683151:G:T	F91L	0.994
7:73683153:A:G	F91L	0.994
7:73683195:G:C	H77D	0.994
7:73683105:G:T	R107S	0.991
7:73683193:G:C	H77Q	0.991
7:73683193:G:T	H77Q	0.991
7:73683222:C:G	A68P	0.989
7:73682938:G:C	F162L	0.985
7:73682938:G:T	F162L	0.985
7:73682940:A:G	F162L	0.985
7:73683096:A:C	Y110D	0.984
7:73683152:A:G	F91S	0.984
7:73683195:G:T	H77N	0.984
7:73683230:A:C	I65S	0.982
7:73683230:A:G	I65T	0.982
7:73683135:C:G	A97P	0.981
7:73683219:A:C	Y69D	0.981
7:73682932:A:C	F164L	0.980
7:73682932:A:T	F164L	0.980
7:73682934:A:G	F164L	0.980
7:73683095:T:G	Y110S	0.979
7:73683104:C:G	R107P	0.979
7:73683185:C:G	R80P	0.978
7:73683194:T:C	H77R	0.975

dbSNP variants (sampled 300 via entrez): RS1001446592 (7:73684536 C>A,G), RS1001907886 (7:73681216 C>T), RS1003468683 (7:73682807 G>A,C), RS1003583624 (7:73682550 C>T), RS1003884552 (7:73681198 C>T), RS1005891041 (7:73683662 C>A,T), RS1005969809 (7:73682504 T>G), RS1007534091 (7:73684952 A>G), RS1008084382 (7:73680779 G>A,T), RS1009706337 (7:73685110 C>G), RS1009802854 (7:73684786 C>G,T), RS1011066179 (7:73681893 G>C), RS1011752231 (7:73681534 G>T), RS1013077704 (7:73684223 G>A), RS1013761851 (7:73683973 C>G,T)

Disease associations

OMIM: gene MIM:618202 | disease phenotypes: MIM:619382, MIM:308905

GenCC curated gene-disease

Disease	Classification	Inheritance
Leber hereditary optic neuropathy, autosomal recessive	Strong	Autosomal recessive
Leber-like hereditary optic neuropathy, autosomal recessive 1	Strong	Autosomal recessive
Leber hereditary optic neuropathy	Supportive	Mitochondrial

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
Leber-like hereditary optic neuropathy, autosomal recessive 1	Definitive	AR

Mondo (6): Leber-like hereditary optic neuropathy, autosomal recessive 1 (MONDO:0958183), Leber hereditary optic neuropathy, autosomal recessive (MONDO:0030309), inherited retinal dystrophy (MONDO:0019118), optic atrophy (MONDO:0003608), Leber optic atrophy, susceptibility to (MONDO:0010640), Leber hereditary optic neuropathy (MONDO:0010788)

Orphanet (2): OBSOLETE: Inherited retinal disorder (Orphanet:71862), Leber hereditary optic neuropathy (Orphanet:104)

HPO phenotypes

204 total (30 of 204 shown, HPO-id order):

HPO	Term
HP:0000010	Recurrent urinary tract infections
HP:0000014	Abnormality of the bladder
HP:0000015	Bladder diverticulum
HP:0000023	Inguinal hernia
HP:0000025	Functional abnormality of male internal genitalia
HP:0000028	Cryptorchidism
HP:0000044	Hypogonadotropic hypogonadism
HP:0000075	Renal duplication
HP:0000076	Vesicoureteral reflux
HP:0000083	Renal insufficiency
HP:0000089	Renal hypoplasia
HP:0000093	Proteinuria
HP:0000121	Nephrocalcinosis
HP:0000125	Pelvic kidney
HP:0000147	Polycystic ovaries
HP:0000154	Wide mouth
HP:0000158	Macroglossia
HP:0000179	Thick lower lip vermilion
HP:0000212	Gingival overgrowth
HP:0000232	Everted lower lip vermilion
HP:0000252	Microcephaly
HP:0000275	Narrow face
HP:0000280	Coarse facial features
HP:0000286	Epicanthus
HP:0000307	Pointed chin
HP:0000337	Broad forehead
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000358	Posteriorly rotated ears

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST010725_13	Malaria	8.000000e-06
GCST010725_74	Malaria	6.000000e-06
GCST010725_91	Malaria	7.000000e-06

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
D029242	Optic Atrophy, Hereditary, Leber	C10.292.700.225.500.400; C10.574.500.662.400; C11.270.564.400; C11.640.451.451.400; C16.320.290.564.400; C16.320.400.630.400; C18.452.660.670
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

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
GSK-J4	decreases expression	1
FR900359	decreases phosphorylation	1
butyraldehyde	decreases expression	1
ferrous chloride	decreases expression	1
avobenzone	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
bisphenol B	increases expression	1
jinfukang	increases expression	1
bisphenol AF	increases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	increases expression	1
Lead	affects expression	1
Silicon Dioxide	increases expression	1
Thiram	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	increases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03293524	PHASE3	COMPLETED	Efficacy & Safety Study of Bilateral IVT Injection of GS010 in LHON Subjects Due to the ND4 Mutation for up to 1 Year
NCT03406104	PHASE3	COMPLETED	RESCUE and REVERSE Long-term Follow-up
NCT07406854	PHASE3	ACTIVE_NOT_RECRUITING	A Phase 3, Multicenter, Randomized, Double-Masked, Sham-Controlled Clinical Trial for Leber’s Hereditary Optic Neuropathy (LHON) Associated With ND4 Mutation
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
NCT02176733	PHASE2	UNKNOWN	Trial of Cyclosporine in the Acute Phase of Leber Hereditary Optic Neuropathy
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]
NCT02544217	PHASE1	COMPLETED	A Dose-escalating Clinical Trial With KH176
NCT07258667	PHASE1	NOT_YET_RECRUITING	Pilot Study of the Efficacy of Nicotinamide (Vitamin B3) in Leber’s Hereditary Optic Neuropathy
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
NCT03153293	PHASE2/PHASE3	UNKNOWN	A Single Intravitreal Injection of rAAV2-ND4 for the Treatment of Leber’s Hereditary Optic Neuropathy
NCT02064569	PHASE1/PHASE2	COMPLETED	Safety Evaluation of Gene Therapy in Leber Hereditary Optic Neuropathy (LHON) Patients
NCT05293626	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Gene Therapy Clinical Trial for the Treatment of Leber’s Hereditary Optic Neuropathy Associated With ND4 Mutations
NCT05820152	PHASE1/PHASE2	TERMINATED	Gene Therapy Clinical Trial for the Treatment of Leber’s Hereditary Optic Neuropathy Associated With ND1 Mutations
NCT01267422	Not specified	COMPLETED	Safety and Efficacy Study of rAAV2-ND4 Treatment of Leber Hereditary Optic Neuropathy (LHON)
NCT01803906	Not specified	ENROLLING_BY_INVITATION	Tissue Sample Study for Mitochondrial Disorders
NCT01892943	Not specified	COMPLETED	Leber Hereditary Optic Neuropathy (LHON) Historical Case Record Survey
NCT03011541	Not specified	RECRUITING	Stem Cell Ophthalmology Treatment Study II
NCT03295071	Not specified	COMPLETED	REALITY LHON Registry
NCT03428178	Not specified	UNKNOWN	Efficacy Study of Gene Therapy for The Treatment of Acute LHON Onset Within Three Months
NCT03475173	Not specified	RECRUITING	New Non-invasive Modalities for Assessing Retinal Structure and Function
NCT03672968	Not specified	NO_LONGER_AVAILABLE	EAP_GS010_single Patient
NCT05554835	Not specified	RECRUITING	Global Registry and Natural History Study for Mitochondrial Disorders
NCT06376279	Not specified	ENROLLING_BY_INVITATION	Genetic Diagnosis in Inborn Errors of Metabolism
NCT06682819	Not specified	RECRUITING	Metabolomics Analysis According to the Retinal Nerve Fiber Layer in Patients With NOHL Mutations (MétabOCT)
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