RMND1

Summary

RMND1 (required for meiotic nuclear division 1 homolog, HGNC:21176) is a protein-coding gene on chromosome 6q25.1, encoding Required for meiotic nuclear division protein 1 homolog (Q9NWS8). Required for mitochondrial translation, possibly by coordinating the assembly or maintenance of the mitochondrial ribosome.

The protein encoded by this gene belongs to the evolutionary conserved sif2 family of proteins that share the DUF155 domain in common. This protein is thought to be localized in the mitochondria and involved in mitochondrial translation. Mutations in this gene are associated with combined oxidative phosphorylation deficiency-11. Alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 55005 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mitochondrial disease (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 382 total — 31 pathogenic, 20 likely-pathogenic
• Phenotypes (HPO): 39
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_017909

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21176
Approved symbol	RMND1
Name	required for meiotic nuclear division 1 homolog
Location	6q25.1
Locus type	gene with protein product
Status	Approved
Aliases	bA351K16.3, FLJ20627, RMD1
Ensembl gene	ENSG00000155906
Ensembl biotype	protein_coding
OMIM	614917
Entrez	55005

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 12 retained_intron, 11 protein_coding, 7 nonsense_mediated_decay

ENST00000336451, ENST00000444024, ENST00000491268, ENST00000622845, ENST00000643550, ENST00000643564, ENST00000644054, ENST00000644711, ENST00000645367, ENST00000645895, ENST00000645917, ENST00000646926, ENST00000682004, ENST00000682299, ENST00000682392, ENST00000682641, ENST00000682760, ENST00000683439, ENST00000683724, ENST00000683740, ENST00000684301, ENST00000684605, ENST00000684658, ENST00000684715, ENST00000684765, ENST00000904151, ENST00000938883, ENST00000938884, ENST00000949374, ENST00000949375

RefSeq mRNA: 2 — MANE Select: NM_017909 NM_001271937, NM_017909

CCDS: CCDS5232, CCDS75539

Canonical transcript exons

ENST00000444024 — 12 exons

Exon	Start	End
ENSE00001023343	151417279	151417399
ENSE00001023347	151421245	151421321
ENSE00001023348	151422541	151422605
ENSE00001128585	151405720	151405836
ENSE00001949103	151452016	151452126
ENSE00002456727	151423525	151423631
ENSE00002522212	151430138	151430177
ENSE00002526084	151427482	151427582
ENSE00003562221	151445308	151445825
ENSE00003562589	151436446	151436554
ENSE00003665220	151433155	151433230
ENSE00003743774	151404762	151405267

Expression profiles

Bgee: expression breadth ubiquitous, 273 present calls, max score 90.99.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.7291 / max 113.4517, expressed in 1778 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
76193	5.4744	1665
76192	5.2115	1533
76191	1.9934	1104
76189	0.0497	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.99	gold quality
ganglionic eminence	UBERON:0004023	89.78	gold quality
calcaneal tendon	UBERON:0003701	89.18	gold quality
adrenal tissue	UBERON:0018303	88.49	gold quality
right lobe of liver	UBERON:0001114	88.37	gold quality
tendon	UBERON:0000043	88.13	gold quality
cortical plate	UBERON:0005343	88.03	gold quality
ventricular zone	UBERON:0003053	87.81	gold quality
tendon of biceps brachii	UBERON:0008188	87.02	silver quality
buccal mucosa cell	CL:0002336	86.64	gold quality
right adrenal gland cortex	UBERON:0035827	86.18	gold quality
adult mammalian kidney	UBERON:0000082	85.96	gold quality
right lobe of thyroid gland	UBERON:0001119	85.78	gold quality
right adrenal gland	UBERON:0001233	85.75	gold quality
left ovary	UBERON:0002119	85.68	gold quality
left lobe of thyroid gland	UBERON:0001120	85.58	gold quality
liver	UBERON:0002107	85.57	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.51	gold quality
thyroid gland	UBERON:0002046	85.51	gold quality
mucosa of transverse colon	UBERON:0004991	85.44	gold quality
hindlimb stylopod muscle	UBERON:0004252	85.38	gold quality
left adrenal gland	UBERON:0001234	85.36	gold quality
metanephros cortex	UBERON:0010533	85.23	gold quality
left adrenal gland cortex	UBERON:0035825	85.18	gold quality
rectum	UBERON:0001052	85.17	gold quality
right ovary	UBERON:0002118	85.10	gold quality
popliteal artery	UBERON:0002250	85.01	gold quality
tibial artery	UBERON:0007610	85.01	gold quality
adrenal gland	UBERON:0002369	84.94	gold quality
ovary	UBERON:0000992	84.91	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-9388	yes	11.86
E-ANND-3	yes	5.52

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

18 targeting RMND1, 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-4775	99.98	75.00	6394
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-6073	99.60	70.36	793
HSA-MIR-143-3P	99.49	69.05	1457
HSA-MIR-4770	99.49	69.09	1451
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-6878-3P	99.24	64.23	920
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-4656	98.79	66.22	1306
HSA-MIR-508-3P	98.66	69.62	887
HSA-MIR-1304-3P	98.29	66.44	1207
HSA-MIR-3652	97.71	65.43	1890
HSA-MIR-4430	97.47	65.61	1813
HSA-MIR-3620-5P	97.42	63.95	792
HSA-MIR-1587	96.95	64.03	932
HSA-MIR-500B-3P	96.49	65.40	1087

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 9)

• Results demonstrate that the RMND1 complex is necessary for mitochondrial translation, possibly by coordinating the assembly or maintenance of the mitochondrial ribosome. (PMID:23022098)
• The RMND1 mutation caused haploinsufficiency that was rescued by overexpression of the wild-type transcript in mutant fibroblasts; this overexpression increased the levels and activities of mitochondrial respiratory-chain proteins. (PMID:23022099)
• Hearing impairment and renal failure are associated with RMND1 mutations. (PMID:26395190)
• Expression of ESR1, RMND1 and CCDC170 associated with variants in separate enhancer elements predisposing breast cancer. [meta-analysis] (PMID:26928228)
• We suggest that patients with Perrault syndrome are screened for variants in RMND1 along side the known Perrault syndrome genes.Renal phenotypes in women with Perrault syndrome features may indicate the causative variant is in RMND1 but the absence of renal dysfunction should not preclude RMND1 screening (PMID:29671881)
• The study shows that an association of theRMND1/CCDC170-ESR1 single nucleotide polymorphisms can exist with osteopenia, osteoporosis, or fragility fracture. (PMID:30601066)
• RFX3 plays a role in RMND1 expression. (PMID:31237926)
• Two Novel Pathogenic Variants Confirm RMND1 Causative Role in Perrault Syndrome with Renal Involvement. (PMID:32911714)
• Hyporeninemic hypoaldosteronism in RMND1-related mitochondrial disease. (PMID:37450011)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rmnd1	ENSDARG00000027465
mus_musculus	Rmnd1	ENSMUSG00000019763
rattus_norvegicus	Rmnd1	ENSRNOG00000019501
drosophila_melanogaster	CG11679	FBGN0030678
caenorhabditis_elegans		WBGENE00014176

Protein

Protein identifiers

Required for meiotic nuclear division protein 1 homolog — Q9NWS8 (reviewed: Q9NWS8)

All UniProt accessions (10): Q9NWS8, A0A087WXU0, A0A2R8Y4J4, A0A2R8Y4P5, A0A2R8YFC3, A0A2U3TZJ1, A0A804HHW6, A0A804HHY2, A0A804HKF8, A0A804HLE1

UniProt curated annotations — full annotation on UniProt →

Function. Required for mitochondrial translation, possibly by coordinating the assembly or maintenance of the mitochondrial ribosome.

Subunit / interactions. Homooligomer.

Subcellular location. Mitochondrion.

Disease relevance. Combined oxidative phosphorylation deficiency 11 (COXPD11) [MIM:614922] A severe, multisystemic, autosomal recessive, disorder characterized by deficiencies of multiple mitochondrial respiratory enzymes leading to neonatal hypotonia and lactic acidosis. Affected individuals may have respiratory insufficiency, foot deformities, or seizures. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the RMD1/sif2 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9NWS8-1	1	yes
Q9NWS8-2	2
Q9NWS8-3	3

RefSeq proteins (2): NP_001258866, NP_060379* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003734	DUF155	Domain
IPR051624	RMD1/Sad1-interacting	Family

Pfam: PF02582

UniProt features (10 total): sequence variant 4, splice variant 3, transit peptide 1, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NWS8-F1	70.28	0.52

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 259 (showing top): GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, GOBP_MITOCHONDRIAL_TRANSLATION, GOBP_TRANSLATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, chr6q25, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, USF_01, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, AACTTT_UNKNOWN, FISCHER_DREAM_TARGETS, USF_02, GOBP_POSITIVE_REGULATION_OF_TRANSLATION, GOBP_REGULATION_OF_TRANSLATION, GOBP_POSITIVE_REGULATION_OF_PROTEIN_METABOLIC_PROCESS

GO Biological Process (2): translation (GO:0006412), positive regulation of mitochondrial translation (GO:0070131)

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

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
peptidyltransferase activity	1
translational initiation	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
mitochondrial translation	1
positive regulation of translation	1
regulation of mitochondrial translation	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

972 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RMND1	DCPH1	Q9H993	788
RMND1	CCDC170	Q8IYT3	754
RMND1	ZBTB2	Q8N680	655
RMND1	TWNK	Q96RR1	551
RMND1	TRMT5	Q32P41	513
RMND1	MTRF1L	Q9UGC7	513
RMND1	TMEM70	Q9BUB7	479
RMND1	MTRFR	Q9H3J6	477
RMND1	MTHFD1L	Q6UB35	476
RMND1	UTP15	Q8TED0	451
RMND1	ERAL1	O75616	434
RMND1	PDAP1	Q13442	427
RMND1	PLEKHG1	Q9ULL1	418
RMND1	PUS1	Q9Y606	406
RMND1	MRPS16	Q9Y3D3	400

IntAct

134 interactions, top by confidence:

A	B	Type	Score
RIN1	NRAS	psi-mi:“MI:0914”(association)	0.840
GPC1	HADHB	psi-mi:“MI:0914”(association)	0.740
RXYLT1	FKTN	psi-mi:“MI:0914”(association)	0.710
DDRGK1	UFL1	psi-mi:“MI:0914”(association)	0.710
RETREG3	PLSCR1	psi-mi:“MI:0914”(association)	0.640
GALNT6	RMND1	psi-mi:“MI:0915”(physical association)	0.620
FAM9B	RMND1	psi-mi:“MI:0915”(physical association)	0.560
DNAJC1	RMND1	psi-mi:“MI:0915”(physical association)	0.560
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
IPPK	TMEM223	psi-mi:“MI:0914”(association)	0.530
C3AR1	TMEM120B	psi-mi:“MI:0914”(association)	0.530
HTR2C	KLRG2	psi-mi:“MI:0914”(association)	0.530
SPPL2B	UQCRQ	psi-mi:“MI:0914”(association)	0.530
GALNT6	NDUFS4	psi-mi:“MI:0914”(association)	0.530
SLC39A9	B4GALT5	psi-mi:“MI:0914”(association)	0.530
RXFP4	SC5D	psi-mi:“MI:0914”(association)	0.530
TRARG1	SGPL1	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM120B	psi-mi:“MI:0914”(association)	0.530
RIC3	ATP9A	psi-mi:“MI:0914”(association)	0.530
SRPRB	CTDNEP1	psi-mi:“MI:0914”(association)	0.530
DEFB104A	IFI30	psi-mi:“MI:0914”(association)	0.530
TMEM43	ENDOD1	psi-mi:“MI:0914”(association)	0.530

BioGRID (248): FAM9B (Two-hybrid), RMND1 (Affinity Capture-MS), RMND1 (Affinity Capture-MS), RMND1 (Affinity Capture-MS), RMND1 (Affinity Capture-MS), RMND1 (Affinity Capture-MS), RMND1 (Affinity Capture-MS), RMND1 (Affinity Capture-MS), RMND1 (Affinity Capture-MS), RMND1 (Affinity Capture-MS), RMND1 (Affinity Capture-MS), RMND1 (Affinity Capture-MS), RMND1 (Affinity Capture-MS), RMND1 (Affinity Capture-MS), RMND1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0K9RDW0, A2WY50, A2Z9W7, A3BV82, B8APK3, C3VEQ2, F4I4B6, O49931, O81360, P93236, Q058N4, Q0DVX2, Q0JCU7, Q4I298, Q4R4M1, Q4WCV3, Q53NI2, Q56X76, Q5E9N5, Q5NCE8, Q5R447, Q5RAR5, Q5VRY0, Q60649, Q6ATB4, Q6YSY5, Q7SFQ9, Q7X6P3, Q7XAP4, Q7Y1B6, Q84W55, Q8CI78, Q8L4S2, Q8S4W7, Q8VZF6, Q93YU2, Q93ZD7, Q9AUK4, Q9ET09, Q9FGC7

Diamond homologs: O74446, P43620, Q03441, Q09877, Q9NWS8, Q5RAR5, Q8CI78

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 169 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
Glycosaminoglycan metabolism	6	11.1×	2e-03
O-linked glycosylation of mucins	7	10.8×	1e-03
Metabolism of carbohydrates and carbohydrate derivatives	8	8.1×	1e-03
Class A/1 (Rhodopsin-like receptors)	10	6.2×	1e-03
GPCR ligand binding	10	5.4×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
chondroitin sulfate proteoglycan biosynthetic process	6	24.2×	4e-05
protein O-linked glycosylation via N-acetylgalactosamine	8	22.3×	2e-06
protein O-linked glycosylation	9	13.1×	1e-05
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	7	9.9×	1e-03
positive regulation of cytosolic calcium ion concentration	10	7.5×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	31
Likely pathogenic	20
Uncertain significance	141
Likely benign	106
Benign	50

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1366404	NM_017909.4(RMND1):c.834del (p.Gln279fs)	Pathogenic
1456606	NC_000006.11:g.(?151766423)(151766946_?)del	Pathogenic
1951855	NM_017909.4(RMND1):c.850_851del (p.Arg284fs)	Pathogenic
1974729	NM_017909.4(RMND1):c.1094_1095insA (p.Ser366fs)	Pathogenic
2002772	NM_017909.4(RMND1):c.221dup (p.Ser75fs)	Pathogenic
2028797	NM_017909.4(RMND1):c.1254dup (p.His419fs)	Pathogenic
2032705	NM_017909.4(RMND1):c.735del (p.Lys245fs)	Pathogenic
2113509	NM_017909.4(RMND1):c.525del (p.Phe176fs)	Pathogenic
2136483	NM_017909.4(RMND1):c.533C>T (p.Thr178Met)	Pathogenic
225255	NM_017909.4(RMND1):c.713A>G (p.Asn238Ser)	Pathogenic
225256	NM_017909.4(RMND1):c.1303C>T (p.Leu435Phe)	Pathogenic
225257	NM_017909.4(RMND1):c.565C>T (p.Gln189Ter)	Pathogenic
225258	NM_017909.4(RMND1):c.533C>A (p.Thr178Lys)	Pathogenic
225259	NM_017909.4(RMND1):c.1317+1G>T	Pathogenic
225261	NM_017909.4(RMND1):c.830+1G>A	Pathogenic
2426411	NC_000006.11:g.(?151751253)(151757709_?)del	Pathogenic
2498152	NM_017909.4(RMND1):c.108del (p.Phe36fs)	Pathogenic
280833	NM_017909.4(RMND1):c.485del (p.Pro162fs)	Pathogenic
3622504	NM_017909.4(RMND1):c.990del (p.Gln330fs)	Pathogenic
3655326	NM_017909.4(RMND1):c.111_129del (p.Glu37fs)	Pathogenic
374907	NC_000006.12:g.151421322del	Pathogenic
3899958	NM_017909.4(RMND1):c.818A>C (p.Tyr273Ser)	Pathogenic
3899971	NM_017909.4(RMND1):c.80A>G (p.His27Arg)	Pathogenic
39765	NM_017909.4(RMND1):c.1250G>A (p.Arg417Gln)	Pathogenic
4525798	NC_000006.11:g.(?151725896)(151773262_?)del	Pathogenic
4718525	NM_017909.4(RMND1):c.533del (p.Thr178fs)	Pathogenic
4818888	NM_017909.4(RMND1):c.463C>T (p.Gln155Ter)	Pathogenic
916005	GRCh37/hg19 6q25.1(chr6:151757398-151757691)	Pathogenic
981951	NM_017909.4(RMND1):c.856del (p.Glu286fs)	Pathogenic
988229	NM_017909.4(RMND1):c.829_830+2del	Pathogenic

SpliceAI

1754 predictions. Top by Δscore:

Variant	Effect	Δscore
6:151405714:TCTTA:T	donor_loss	1.0000
6:151405715:CTTA:C	donor_loss	1.0000
6:151405716:TTAC:T	donor_loss	1.0000
6:151405717:TAC:T	donor_loss	1.0000
6:151405718:A:AC	donor_gain	1.0000
6:151405718:A:AG	donor_loss	1.0000
6:151405719:C:CC	donor_gain	1.0000
6:151405719:C:CT	donor_loss	1.0000
6:151405719:CCT:C	donor_gain	1.0000
6:151405833:TGAC:T	acceptor_gain	1.0000
6:151405834:GAC:G	acceptor_gain	1.0000
6:151405834:GACC:G	acceptor_loss	1.0000
6:151405836:CC:C	acceptor_loss	1.0000
6:151405836:CCTA:C	acceptor_gain	1.0000
6:151405837:C:CC	acceptor_gain	1.0000
6:151405839:A:AC	acceptor_gain	1.0000
6:151405839:A:C	acceptor_gain	1.0000
6:151405841:G:C	acceptor_gain	1.0000
6:151417274:CGTA:C	donor_loss	1.0000
6:151417275:GTA:G	donor_loss	1.0000
6:151417276:TACCT:T	donor_loss	1.0000
6:151417277:A:AC	donor_gain	1.0000
6:151417277:ACC:A	donor_loss	1.0000
6:151417278:C:CC	donor_gain	1.0000
6:151417399:CCT:C	acceptor_loss	1.0000
6:151417399:CCTT:C	acceptor_gain	1.0000
6:151417400:C:CC	acceptor_gain	1.0000
6:151417400:C:CG	acceptor_loss	1.0000
6:151417401:T:C	acceptor_gain	1.0000
6:151417402:T:C	acceptor_gain	1.0000

AlphaMissense

2975 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:151417348:C:A	W377C	1.000
6:151417348:C:G	W377C	1.000
6:151405820:A:G	L406P	0.999
6:151417350:A:G	W377R	0.999
6:151417350:A:T	W377R	0.999
6:151422578:A:G	L322P	0.999
6:151422599:A:G	L315P	0.999
6:151423545:G:A	S306F	0.999
6:151423546:A:G	S306P	0.999
6:151423551:G:T	A304D	0.999
6:151430158:A:G	W237R	0.999
6:151430158:A:T	W237R	0.999
6:151436524:C:G	A179P	0.999
6:151405793:A:G	L415P	0.998
6:151405802:A:G	L412P	0.998
6:151417285:T:A	R398S	0.998
6:151417285:T:G	R398S	0.998
6:151417286:C:G	R398T	0.998
6:151417301:A:G	L393P	0.998
6:151421257:A:G	L356P	0.998
6:151423536:A:G	L309P	0.998
6:151423539:G:T	A308D	0.998
6:151423545:G:T	S306Y	0.998
6:151430172:C:T	G232E	0.998
6:151430173:C:G	G232R	0.998
6:151430173:C:T	G232R	0.998
6:151436523:G:T	A179E	0.998
6:151436535:G:T	A175E	0.998
6:151405733:A:T	L435H	0.997
6:151417286:C:A	R398I	0.997

dbSNP variants (sampled 300 via entrez): RS1000047185 (6:151410842 G>A), RS1000071938 (6:151424039 T>TA), RS1000073366 (6:151408469 A>T), RS1000286355 (6:151452337 T>C,G), RS1000298143 (6:151450887 A>G), RS1000334305 (6:151452481 C>A,T), RS1000349656 (6:151411773 C>A), RS1000371778 (6:151406058 G>C), RS1000427186 (6:151420584 T>C), RS1000444151 (6:151447952 T>C), RS1000445378 (6:151406223 C>T), RS1000497537 (6:151432761 G>T), RS1000620560 (6:151451571 C>T), RS1000641915 (6:151441779 C>T), RS1000672835 (6:151451783 A>G,T)

Disease associations

OMIM: gene MIM:614917 | disease phenotypes: MIM:614922, MIM:256100

GenCC curated gene-disease

Disease	Classification	Inheritance
combined oxidative phosphorylation defect type 11	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
mitochondrial disease	Definitive	AR

Mondo (5): combined oxidative phosphorylation defect type 11 (MONDO:0013969), mitochondrial disease (MONDO:0044970), mitochondrial oxidative phosphorylation disorder (MONDO:0016387), nephronophthisis (MONDO:0019005), congenital nervous system disorder (MONDO:0002320)

Orphanet (4): Combined oxidative phosphorylation defect type 11 (Orphanet:324535), Mitochondrial disease (Orphanet:68380), Mitochondrial oxidative phosphorylation disorder (Orphanet:223713), Nephronophthisis (Orphanet:655)

HPO phenotypes

39 total (30 of 39 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000083	Renal insufficiency
HP:0000089	Renal hypoplasia
HP:0000107	Renal cyst
HP:0000110	Renal dysplasia
HP:0000365	Hearing impairment
HP:0001250	Seizure
HP:0001254	Lethargy
HP:0001263	Global developmental delay
HP:0001265	Hyporeflexia
HP:0001284	Areflexia
HP:0001290	Generalized hypotonia
HP:0001302	Pachygyria
HP:0001308	Tongue fasciculations
HP:0001336	Myoclonus
HP:0001344	Absent speech
HP:0001397	Hepatic steatosis
HP:0001410	Decreased liver function
HP:0001522	Death in infancy
HP:0001561	Polyhydramnios
HP:0001638	Cardiomyopathy
HP:0001947	Renal tubular acidosis
HP:0002079	Hypoplasia of the corpus callosum
HP:0002120	Cerebral cortical atrophy
HP:0002151	Increased circulating lactate concentration
HP:0002240	Hepatomegaly
HP:0002490	Increased CSF lactate
HP:0002878	Respiratory failure
HP:0003128	Lactic acidosis
HP:0003198	Myopathy

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001063_1	Chronic myeloid leukemia	2.000000e-06

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
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	4
Valproic Acid	affects expression, decreases methylation, increases expression	4
dicrotophos	decreases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	increases expression, affects cotreatment	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1
Vorinostat	increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Atrazine	decreases expression	1
Hydrogen Peroxide	increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Quercetin	decreases expression	1
Rotenone	increases expression	1
Tetrachlorodibenzodioxin	increases expression, affects cotreatment	1
Tretinoin	decreases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03351998	PHASE4	COMPLETED	Impact of Statin Therapy on Muscle Mitochondrial Function and Aerobic Capacity
NCT00432744	PHASE3	COMPLETED	Phase III Trial of Coenzyme Q10 in Mitochondrial Disease
NCT05162768	PHASE3	COMPLETED	Study to Evaluate Efficacy and Safety of Elamipretide in Subjects With Primary Mitochondrial Disease From Nuclear DNA Mutations (nPMD)
NCT06451757	PHASE3	RECRUITING	KHENERFIN Study: A Trial to Evaluate the Efficacy and Safety of Sonlicromanol in Primary Mitochondrial Diseases
NCT02398201	PHASE2	COMPLETED	A Study of Bezafibrate in Mitochondrial Myopathy
NCT02473445	PHASE2	TERMINATED	A Long-term Extension of Study RP103-MITO-001 (NCT02023866) to Assess Cysteamine Bitartrate Delayed-release Capsules (RP103) in Children With Inherited Mitochondrial Disease
NCT02500628	PHASE2	COMPLETED	Heart Rate Variability in Response to Metformin Challenge
NCT02805790	PHASE2	COMPLETED	Safety, Tolerability, Efficacy of MTP-131 for Treatment of Mitochondrial Disease in Subjects From the MMPOWER Study
NCT02909400	PHASE2	COMPLETED	The KHENERGY Study
NCT02976038	PHASE2	TERMINATED	Open-Label Extension Trial to Characterize the Long-term Safety and Tolerability of Elamipretide in Subjects With Genetically Confirmed Primary Mitochondrial Myopathy (PMM)
NCT03177798	PHASE2	COMPLETED	Mitochondria and Chronic Kidney Disease
NCT03866954	PHASE2	WITHDRAWN	Trial of Erythrocyte Encapsulated Thymidine Phosphorylase In Mitochondrial Neurogastrointestinal Encephalomyopathy
NCT04165239	PHASE2	COMPLETED	The KHENERGYZE Study
NCT04604548	PHASE2	COMPLETED	The KHENEREXT Study
NCT04802707	PHASE2	RECRUITING	Deoxynucleosides Pyrimidines as Treatment for Mitochondrial Depletion Syndrome
NCT04846036	PHASE2	SUSPENDED	The KHENERGYC Study
NCT05650229	PHASE2	RECRUITING	Efficacy of KL1333 in Adult Patients With Primary Mitochondrial Disease
NCT05972954	PHASE2	COMPLETED	OMT-28 in Patients With Primary Mitochondrial Disease (PMD) (PMD-OPTION)
NCT06017869	PHASE2	RECRUITING	Evaluate the Safety and Therapeutic Effects of a Single Intravenous Infusion (IV) of Autologous CD34+ Cells Enriched With Allogenic Placenta-derived Mitochondria in Patients With a Diagnosis of Pearson Syndrome (PS)
NCT07514338	PHASE2	NOT_YET_RECRUITING	Open Label Extension to Assess Long Term Safety and Efficacy of KL1333 in Patients With Primary Mitochondrial Disease
NCT00060515	PHASE1	TERMINATED	RG2133 (2’,3’,5’-Tri-O-Acetyluridine) in Mitochondrial Disease
NCT02348125	PHASE1	UNKNOWN	Does Clinical Treatment of Mitochondrial Dysfunction Impact Autism Spectrum Disorder (ASD)?
NCT02544217	PHASE1	COMPLETED	A Dose-escalating Clinical Trial With KH176
NCT03888716	PHASE1	COMPLETED	A Phase Ia/Ib, SAD and MAD Study of of KL1333 in Healthy Subjects and Patients With Primary Mitochondrial Disease
NCT04086329	PHASE1	RECRUITING	Validation of Oxygen Nanosensor in Mitochondrial Myopathy
NCT04643249	PHASE1	COMPLETED	Drug-drug Interaction Study of KL1333 in Healthy Subjects
NCT05241262	PHASE1	RECRUITING	Study of N-acetylcysteine in the Treatment of Patients With the m.3243A>G Mutation and Low Brain Glutathione Levels
NCT05569122	PHASE1	RECRUITING	Applying pGz in Mitochondrial Disease
NCT06819683	PHASE1	RECRUITING	Validation of Nanosensor Oxygen Measurement
NCT07258667	PHASE1	NOT_YET_RECRUITING	Pilot Study of the Efficacy of Nicotinamide (Vitamin B3) in Leber’s Hereditary Optic Neuropathy
NCT04378075	PHASE2/PHASE3	TERMINATED	A Study to Evaluate Efficacy and Safety of Vatiquinone for Treating Mitochondrial Disease in Participants With Refractory Epilepsy
NCT01642056	PHASE1/PHASE2	COMPLETED	EPI-743 for Metabolism or Mitochondrial Disorders
NCT03384420	PHASE1/PHASE2	COMPLETED	A Study to Evaluate the Safety and Therapeutic Effects of Transplantation of MNV-BM-BLD in Pediatric Patients With Pearson Syndrome
NCT06051448	PHASE1/PHASE2	COMPLETED	Promoting Resilience in Stress Management (PRISM) and Clinical-focused Narrative (CFN) Pilot in Adults With Primary Mitochondrial Disease (PMD).
NCT01252979	EARLY_PHASE1	COMPLETED	Ketones & Mitochondrial Heteroplasmy
NCT00786539	Not specified	COMPLETED	Mitochondria Inborn Errors of Metabolism and ANT Defects in Mitochondria Diseases
NCT00829270	Not specified	COMPLETED	Economic and Medical Evaluation of the Whole Mitochondrial DNA Screening by Surveyor and Mitochips Techniques
NCT00831948	Not specified	UNKNOWN	Identification of Large-Scale Mutations of POLG Gene by QMPSF in Patients With Mitochondrial DNA Instability.
NCT01001585	Not specified	TERMINATED	Anesthetic Effects in Mitochondrial Disease
NCT01148550	Not specified	SUSPENDED	Longitudinal Study of Mitochondrial Hepatopathies