MSTO1

Summary

MSTO1 (misato mitochondrial distribution and morphology regulator 1, HGNC:29678) is a protein-coding gene on chromosome 1q22, encoding Protein misato homolog 1 (Q9BUK6). Involved in the regulation of mitochondrial distribution and morphology. It is a selective cancer dependency (DepMap: 80.6% of cell lines).

Involved in mitochondrion distribution; mitochondrion organization; and positive regulation of mitochondrial fusion. Located in mitochondrial outer membrane. Is active in cytosol.

Source: NCBI Gene 55154 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mitochondrial disease (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 19
• Clinical variants (ClinVar): 237 total — 9 pathogenic, 9 likely-pathogenic
• Phenotypes (HPO): 61
• Cancer dependency (DepMap): dependent in 80.6% of screened cell lines
• MANE Select transcript: NM_018116

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29678
Approved symbol	MSTO1
Name	misato mitochondrial distribution and morphology regulator 1
Location	1q22
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10504, LST005, MST, misato
Ensembl gene	ENSG00000125459
Ensembl biotype	protein_coding
OMIM	617619
Entrez	55154

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 20 protein_coding, 9 protein_coding_CDS_not_defined, 5 retained_intron, 1 nonsense_mediated_decay

ENST00000245564, ENST00000368341, ENST00000460199, ENST00000462250, ENST00000465137, ENST00000466815, ENST00000471209, ENST00000473327, ENST00000475253, ENST00000478756, ENST00000482284, ENST00000483734, ENST00000483832, ENST00000488901, ENST00000490642, ENST00000490743, ENST00000491308, ENST00000494995, ENST00000649846, ENST00000697770, ENST00000863883, ENST00000863884, ENST00000863885, ENST00000863886, ENST00000863887, ENST00000863888, ENST00000863889, ENST00000933227, ENST00000933228, ENST00000933229, ENST00000941775, ENST00000941776, ENST00000941777, ENST00000941778, ENST00000941779

RefSeq mRNA: 21 — MANE Select: NM_018116 NM_001256532, NM_001256533, NM_001350772, NM_001350773, NM_001350774, NM_001350775, NM_001350776, NM_001350777, NM_001350778, NM_001350779, NM_001350780, NM_001350781, NM_001350782, NM_001350783, NM_001350784, NM_001350785, NM_001350786, NM_001350787, NM_001350788, NM_001350789, NM_018116

CCDS: CCDS1114, CCDS91070

Canonical transcript exons

ENST00000245564 — 14 exons

Exon	Start	End
ENSE00003528340	155612844	155612975
ENSE00003576102	155612182	155612316
ENSE00003576235	155613049	155613233
ENSE00003633353	155612418	155612570
ENSE00003639910	155611983	155612100
ENSE00003704311	155610425	155610560
ENSE00003710620	155613462	155613566
ENSE00003901664	155610218	155610332
ENSE00003971634	155611549	155611603
ENSE00003971635	155611689	155611827
ENSE00003971636	155613657	155613766
ENSE00003971637	155611216	155611291
ENSE00003971638	155614059	155614951
ENSE00003971640	155611039	155611108

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 97.80.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0395 / max 37.8911, expressed in 3 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
5629	0.0395	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	97.80	gold quality
right testis	UBERON:0004534	97.75	gold quality
testis	UBERON:0000473	96.70	gold quality
pituitary gland	UBERON:0000007	96.41	gold quality
right ovary	UBERON:0002118	96.13	gold quality
adenohypophysis	UBERON:0002196	96.05	gold quality
left ovary	UBERON:0002119	95.98	gold quality
tibial nerve	UBERON:0001323	95.92	gold quality
right uterine tube	UBERON:0001302	95.69	gold quality
body of uterus	UBERON:0009853	95.68	gold quality
ovary	UBERON:0000992	95.56	gold quality
right lobe of thyroid gland	UBERON:0001119	95.46	gold quality
left uterine tube	UBERON:0001303	95.38	gold quality
endocervix	UBERON:0000458	95.27	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.02	gold quality
body of pancreas	UBERON:0001150	94.94	gold quality
thoracic mammary gland	UBERON:0005200	94.82	gold quality
sural nerve	UBERON:0015488	94.68	gold quality
left lobe of thyroid gland	UBERON:0001120	94.61	gold quality
prostate gland	UBERON:0002367	94.59	gold quality
metanephros cortex	UBERON:0010533	94.58	gold quality
thyroid gland	UBERON:0002046	94.46	gold quality
cerebellar cortex	UBERON:0002129	94.29	gold quality
cerebellar hemisphere	UBERON:0002245	94.28	gold quality
cerebellum	UBERON:0002037	94.26	gold quality
spleen	UBERON:0002106	94.21	gold quality
subcutaneous adipose tissue	UBERON:0002190	94.10	gold quality
ectocervix	UBERON:0012249	94.07	gold quality
myometrium	UBERON:0001296	93.97	gold quality
fallopian tube	UBERON:0003889	93.60	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.30

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

39 targeting MSTO1, 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-3120-5P	100.00	65.56	965
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-519A-3P	99.67	71.67	1868
HSA-MIR-519B-3P	99.67	71.67	1868
HSA-MIR-519C-3P	99.67	71.67	1870
HSA-MIR-1260A	99.61	66.67	1098
HSA-MIR-1260B	99.61	66.67	1098
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-532-3P	99.34	65.76	1195
HSA-MIR-190B-3P	99.33	68.29	1382
HSA-MIR-183-5P	99.31	72.27	1164

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 80.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 8)

• These results indicated that human Misato has a role(s) in mitochondrial distribution and morphology and that its unregulated expression leads to cell death. (PMID:17349998)
• Recessive mutations in MSTO1 cause mitochondrial dynamics impairment, leading to myopathy and ataxia (PMID:28544275)
• Thus, an MSTO1 loss-of-function mutation is associated with a human disorder showing mitochondrial involvement. MSTO1 likely has a physiologically relevant role in mitochondrial morphogenesis by supporting mitochondrial fusion. (PMID:28554942)
• we have described two unrelated patients with biallelic MSTO1 mutations. Our report provides valuable information on the consequences of MSTO1 mutations for human phenotypes. (PMID:29339779)
• Whole-exome sequencing identifies rare compound heterozygous mutations in the MSTO1 gene associated with cerebellar ataxia and myopathy. (PMID:30684668)
• MSTO1 mutations cause mtDNA depletion, manifesting as muscular dystrophy with cerebellar involvement. (PMID:31463572)
• Evidence of motor axon or motor neuron damage in a Chinese patient with compound heterozygous MSTO1 variants. (PMID:33222031)
• Autosomal recessive pathogenic MSTO1 variants in hereditary optic atrophy. (PMID:37431816)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	msto1	ENSDARG00000024381
mus_musculus	Msto1	ENSMUSG00000068922
rattus_norvegicus	Msto1	ENSRNOG00000020357
drosophila_melanogaster	mst	FBGN0020272

Protein

Protein identifiers

Protein misato homolog 1 — Q9BUK6 (reviewed: Q9BUK6)

All UniProt accessions (4): Q9BUK6, A0A3B3IUD2, A0A8V8TLP0, V9GYF2

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the regulation of mitochondrial distribution and morphology. Required for mitochondrial fusion and mitochondrial network formation.

Subcellular location. Mitochondrion outer membrane. Cytoplasm.

Tissue specificity. Present in all cell lines tested (at protein level). Widely expressed.

Disease relevance. Myopathy, mitochondrial, and ataxia (MMYAT) [MIM:617675] A neuromuscular disorder characterized by muscle weakness and atrophy, ataxia, poor growth, delayed motor development, dysdiadochokinesia, dysmetria and additional neurologic features. Some patients show skeletal and endocrine anomalies, as well as behavioral psychiatric manifestations. MMYAT transmission pattern is consistent with autosomal dominant inheritance in some families, and autosomal recessive inheritance in others. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the misato family.

Isoforms (7)

UniProt ID	Names	Canonical?
Q9BUK6-1	1	yes
Q9BUK6-2	2
Q9BUK6-3	3
Q9BUK6-4	4
Q9BUK6-5	5
Q9BUK6-6	6
Q9BUK6-7	7

RefSeq proteins (21): NP_001243461, NP_001243462, NP_001337701, NP_001337702, NP_001337703, NP_001337704, NP_001337705, NP_001337706, NP_001337707, NP_001337708, NP_001337709, NP_001337710, NP_001337711, NP_001337712, NP_001337713, NP_001337714, NP_001337715, NP_001337716, NP_001337717, NP_001337718, NP_060586* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019605	Misato_II_tubulin-like	Domain
IPR029209	DML1/Misato_tubulin	Domain
IPR036525	Tubulin/FtsZ_GTPase_sf	Homologous_superfamily
IPR049942	DML1/Misato	Family

Pfam: PF10644, PF14881

UniProt features (17 total): splice variant 8, sequence variant 4, sequence conflict 3, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BUK6-F1	83.83	0.58

Functional residue map

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

Post-translational modifications (1): 495

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 200 (showing top): HORIUCHI_WTAP_TARGETS_DN, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, PATIL_LIVER_CANCER, GOBP_REGULATION_OF_MITOCHONDRION_ORGANIZATION, GOCC_MITOCHONDRIAL_ENVELOPE, chr1q22, GOBP_MITOCHONDRIAL_FUSION, GOBP_POSITIVE_REGULATION_OF_DEVELOPMENTAL_PROCESS, GOBP_MITOCHONDRION_LOCALIZATION, MODULE_207, GOBP_ORGANELLE_LOCALIZATION, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, GOBP_MITOCHONDRION_DISTRIBUTION, GOBP_ORGANELLE_FUSION, SENESE_HDAC3_TARGETS_DN

GO Biological Process (3): mitochondrion organization (GO:0007005), positive regulation of mitochondrial fusion (GO:0010636), mitochondrion distribution (GO:0048311)

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

GO Cellular Component (5): cytoplasm (GO:0005737), mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), cytosol (GO:0005829), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cytoplasm	2
organelle organization	1
mitochondrial fusion	1
regulation of mitochondrial fusion	1
positive regulation of organelle organization	1
positive regulation of developmental process	1
mitochondrion localization	1
binding	1
intracellular anatomical structure	1
intracellular membrane-bounded organelle	1
mitochondrial membrane	1
organelle outer membrane	1

Protein interactions and networks

STRING

896 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MSTO1	SLC25A37	Q9NYZ2	565
MSTO1	TIMM10B	Q9Y5J6	541
MSTO1	TIMM8B	Q9Y5J9	521
MSTO1	GRPEL1	Q9HAV7	504
MSTO1	TIMM22	Q9Y584	501
MSTO1	ATP13A1	Q9HD20	459
MSTO1	TIMM17B	O60830	457
MSTO1	SLC25A19	Q9HC21	447
MSTO1	TIMM50	Q3ZCQ8	445
MSTO1	SLC25A22	Q9H936	445
MSTO1	MIEF2	Q96C03	429
MSTO1	TIMM17A	Q99595	429
MSTO1	MFF	Q9GZY8	417
MSTO1	TMCO4	Q5TGY1	412
MSTO1	MFN2	O95140	392

IntAct

50 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
PDCL3	PEX7	psi-mi:“MI:0914”(association)	0.640
HDDC3	MSTO1	psi-mi:“MI:0915”(physical association)	0.560
CCT3	PDCD5	psi-mi:“MI:0914”(association)	0.530
CCT6A	TXNDC9	psi-mi:“MI:0914”(association)	0.530
CCNJL	PIK3C2A	psi-mi:“MI:0914”(association)	0.530
COMTD1	IFRD1	psi-mi:“MI:0914”(association)	0.530
LPCAT1	SLC27A2	psi-mi:“MI:0914”(association)	0.530
UBE2DNL	MSTO1	psi-mi:“MI:0915”(physical association)	0.370
CASP9	MSTO1	psi-mi:“MI:0915”(physical association)	0.370
NR1H3	MSTO1	psi-mi:“MI:0915”(physical association)	0.370
EP300	MSTO1	psi-mi:“MI:0915”(physical association)	0.370
Nedd1		psi-mi:“MI:0914”(association)	0.350
Tor1aip1	PEX10	psi-mi:“MI:0914”(association)	0.350
Ufl1	PRSS1	psi-mi:“MI:0914”(association)	0.350
Fign	MAP3K4	psi-mi:“MI:0914”(association)	0.350
RBCK1	UMAD1	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
ENG	IGKV2-28	psi-mi:“MI:0914”(association)	0.350
IMMP1L	EIF1AY	psi-mi:“MI:0914”(association)	0.350
IMMP2L	ANKHD1-EIF4EBP3	psi-mi:“MI:0914”(association)	0.350
CCT4	PDCD5	psi-mi:“MI:0914”(association)	0.350
CCT8	PDCD5	psi-mi:“MI:0914”(association)	0.350
ARHGAP25	UBA6	psi-mi:“MI:0914”(association)	0.350
GPR17	TMEM120B	psi-mi:“MI:0914”(association)	0.350
DNA2	TARS3	psi-mi:“MI:0914”(association)	0.350
CFAP184	TARS3	psi-mi:“MI:0914”(association)	0.350

BioGRID (79): MSTO1 (Affinity Capture-MS), MSTO1 (Affinity Capture-MS), MSTO1 (Affinity Capture-MS), MSTO1 (Affinity Capture-MS), MSTO1 (Affinity Capture-MS), MSTO1 (Affinity Capture-MS), MSTO1 (Affinity Capture-MS), MSTO1 (Affinity Capture-MS), MSTO1 (Affinity Capture-MS), MSTO1 (Affinity Capture-MS), MSTO1 (Affinity Capture-MS), MSTO1 (Affinity Capture-MS), MSTO1 (Affinity Capture-MS), MSTO1 (Affinity Capture-MS), MSTO1 (Affinity Capture-MS)

ESM2 similar proteins: A5D9D4, B2RUP2, D3ZI76, D4ACE5, F1MLB4, O08983, O35828, O75161, P56201, P58742, P59240, Q0VG06, Q13144, Q16586, Q17RQ9, Q1L908, Q27J81, Q28CX0, Q2TBP8, Q2YDW2, Q499N3, Q4FZX0, Q4R681, Q4VBE8, Q5RF82, Q64350, Q6IUP3, Q6NUI2, Q6V7V2, Q70J99, Q80YR2, Q86V87, Q8BGW4, Q8C0R7, Q8CHW4, Q8N0W3, Q8N9W5, Q8TE02, Q95K25, Q96EP0

Diamond homologs: A5D9D4, Q1L908, Q2YDW2, Q4R681, Q5RF82, Q7S2Y8, Q9BUK6, P87066, Q752Y2, A1CNV1, A2QAY5, Q4IBL8, Q0V254

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 75 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
Formation of tubulin folding intermediates by CCT/TriC	5	51.6×	4e-06
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	5	49.7×	4e-06
Prefoldin mediated transfer of substrate to CCT/TriC	5	48.0×	4e-06
Chaperonin-mediated protein folding	5	36.6×	1e-05
Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding	5	36.6×	1e-05
Association of TriC/CCT with target proteins during biosynthesis	5	35.7×	1e-05
Protein folding	5	31.6×	2e-05

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of telomere maintenance via telomerase	5	60.1×	3e-06
protein folding	6	10.2×	2e-03
protein stabilization	8	8.8×	4e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	9
Uncertain significance	138
Likely benign	44
Benign	18

Top pathogenic / likely-pathogenic (18)

Variant ID	HGVS	Classification
2426441	NC_000001.10:g.(?155581953)(155583377_?)del	Pathogenic
2571791	NM_018116.4(MSTO1):c.100C>T (p.Arg34Ter)	Pathogenic
3248009	NC_000001.10:g.(?155581953)(155582381_?)del	Pathogenic
3336212	NM_018116.4(MSTO1):c.1190G>A (p.Trp397Ter)	Pathogenic
4293810	NM_018116.4(MSTO1):c.595del (p.Glu199fs)	Pathogenic
438832	NM_018116.4(MSTO1):c.1128C>A (p.Phe376Leu)	Pathogenic
504109	NM_018116.4(MSTO1):c.1259del (p.Gly420fs)	Pathogenic
987949	NM_018116.4(MSTO1):c.1099-1G>A	Pathogenic
987950	NM_018116.4(MSTO1):c.79C>T (p.Gln27Ter)	Pathogenic
1693163	NM_018116.4(MSTO1):c.65C>A (p.Ala22Glu)	Likely pathogenic
2142931	NM_018116.4(MSTO1):c.366+1G>C	Likely pathogenic
2229213	NM_018116.4(MSTO1):c.1A>C (p.Met1Leu)	Likely pathogenic
2426443	NC_000001.10:g.(?155581953)(155583377_?)dup	Likely pathogenic
2426444	NC_000001.10:g.(?155582189)(155583377_?)dup	Likely pathogenic
3383325	NM_018116.4(MSTO1):c.1350G>C (p.Leu450Phe)	Likely pathogenic
438831	NM_018116.4(MSTO1):c.1033C>T (p.Arg345Cys)	Likely pathogenic
438834	NM_018116.4(MSTO1):c.966+1G>A	Likely pathogenic
522862	NM_018116.4(MSTO1):c.676C>T (p.Gln226Ter)	Likely pathogenic

SpliceAI

2349 predictions. Top by Δscore:

Variant	Effect	Δscore
1:155610559:GG:G	donor_gain	1.0000
1:155610560:GG:G	donor_gain	1.0000
1:155611038:GGTA:G	acceptor_gain	1.0000
1:155612084:A:T	donor_gain	1.0000
1:155612175:C:A	acceptor_gain	1.0000
1:155612180:A:AG	acceptor_gain	1.0000
1:155612180:AG:A	acceptor_gain	1.0000
1:155612180:AGG:A	acceptor_gain	1.0000
1:155612181:G:GG	acceptor_gain	1.0000
1:155612181:GG:G	acceptor_gain	1.0000
1:155612181:GGG:G	acceptor_gain	1.0000
1:155612181:GGGC:G	acceptor_gain	1.0000
1:155612181:GGGCT:G	acceptor_gain	1.0000
1:155612255:A:G	donor_gain	1.0000
1:155612312:GTGGG:G	donor_gain	1.0000
1:155612313:TGGG:T	donor_gain	1.0000
1:155612314:GGG:G	donor_gain	1.0000
1:155612314:GGGG:G	donor_gain	1.0000
1:155612315:GG:G	donor_gain	1.0000
1:155612315:GGG:G	donor_gain	1.0000
1:155612315:GGGT:G	donor_loss	1.0000
1:155612316:GG:G	donor_gain	1.0000
1:155612317:G:GG	donor_gain	1.0000
1:155612317:GTG:G	donor_loss	1.0000
1:155612318:T:A	donor_loss	1.0000
1:155612414:C:G	acceptor_gain	1.0000
1:155612415:CAG:C	acceptor_loss	1.0000
1:155612416:A:AG	acceptor_gain	1.0000
1:155612416:A:C	acceptor_loss	1.0000
1:155612417:G:GC	acceptor_loss	1.0000

AlphaMissense

3669 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:155610321:T:A	W25R	0.996
1:155610321:T:C	W25R	0.996
1:155611793:A:C	S176R	0.996
1:155611795:C:A	S176R	0.996
1:155611795:C:G	S176R	0.996
1:155610289:G:T	G14V	0.995
1:155610540:T:C	L67P	0.995
1:155611757:T:A	W164R	0.995
1:155611757:T:C	W164R	0.995
1:155610289:G:A	G14E	0.994
1:155612215:T:C	F238L	0.994
1:155612217:C:A	F238L	0.994
1:155612217:C:G	F238L	0.994
1:155610288:G:A	G14R	0.993
1:155610288:G:C	G14R	0.993
1:155612182:G:C	G227R	0.993
1:155612005:T:C	F195L	0.992
1:155612007:T:A	F195L	0.992
1:155612007:T:G	F195L	0.992
1:155612186:T:C	F228S	0.992
1:155612014:G:T	G198W	0.989
1:155612066:T:C	L215P	0.989
1:155612081:A:T	E220V	0.989
1:155612911:G:C	R345P	0.989
1:155612014:G:A	G198R	0.988
1:155612014:G:C	G198R	0.988
1:155612450:C:A	N282K	0.988
1:155612450:C:G	N282K	0.988
1:155610495:G:C	R52P	0.987
1:155612088:T:G	C222W	0.987

dbSNP variants (sampled 300 via entrez): RS1000128315 (1:155575224 A>G), RS1000159718 (1:155581087 G>A), RS1000192235 (1:155574889 G>T), RS1000219555 (1:155600597 G>A), RS1000252832 (1:155593704 C>T), RS1000314403 (1:155574613 C>G), RS1000345210 (1:155574311 A>G), RS1000400255 (1:155607136 C>A), RS1000424714 (1:155568258 T>G), RS1000495618 (1:155588364 C>G,T), RS1000547197 (1:155572917 T>C), RS1000647165 (1:155573132 G>A), RS1000782775 (1:155611221 G>A), RS1000880356 (1:155578529 G>T), RS1000938273 (1:155579800 G>A,T)

Disease associations

OMIM: gene MIM:617619 | disease phenotypes: MIM:617675, MIM:213000

GenCC curated gene-disease

Disease	Classification	Inheritance
mitochondrial myopathy-cerebellar ataxia-pigmentary retinopathy syndrome	Definitive	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): mitochondrial myopathy-cerebellar ataxia-pigmentary retinopathy syndrome (MONDO:0044714), isolated cerebellar hypoplasia/agenesis (MONDO:0008939), neuromuscular disease (MONDO:0019056), myopathy (MONDO:0005336), inborn mitochondrial myopathy (MONDO:0009637)

Orphanet (5): Mitochondrial myopathy-cerebellar ataxia-pigmentary retinopathy syndrome (Orphanet:502423), Isolated cerebellar agenesis (Orphanet:1398), Cerebellar hypoplasia-tapetoretinal degeneration syndrome (Orphanet:2246), Neuromuscular disease (Orphanet:68381), Mitochondrial myopathy (Orphanet:206966)

HPO phenotypes

61 total (30 of 61 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000218	High palate
HP:0000276	Long face
HP:0000303	Mandibular prognathia
HP:0000347	Micrognathia
HP:0000365	Hearing impairment
HP:0000543	Optic disc pallor
HP:0000580	Pigmentary retinopathy
HP:0000601	Hypotelorism
HP:0000716	Depression
HP:0000729	Autistic behavior
HP:0000739	Anxiety
HP:0000750	Delayed speech and language development
HP:0000767	Pectus excavatum
HP:0000786	Primary amenorrhea
HP:0000836	Hyperthyroidism
HP:0000870	Increased circulating prolactin concentration
HP:0000980	Pallor
HP:0001012	Multiple lipomas
HP:0001251	Ataxia
HP:0001256	Mild intellectual disability
HP:0001265	Hyporeflexia
HP:0001270	Motor delay
HP:0001288	Gait disturbance
HP:0001290	Generalized hypotonia
HP:0001310	Dysmetria
HP:0001321	Cerebellar hypoplasia
HP:0001324	Muscle weakness
HP:0001337	Tremor

GWAS associations

19 associations (top):

Study	Trait	p-value
GCST001725_35	Inflammatory bowel disease	6.000000e-11
GCST004131_70	Inflammatory bowel disease	6.000000e-08
GCST004132_44	Crohn’s disease	2.000000e-07
GCST007294_124	Body fat distribution (trunk fat ratio)	8.000000e-35
GCST007294_3	Body fat distribution (trunk fat ratio)	6.000000e-21
GCST007294_50	Body fat distribution (trunk fat ratio)	1.000000e-15
GCST007295_17	Body fat distribution (leg fat ratio)	3.000000e-13
GCST007295_37	Body fat distribution (leg fat ratio)	7.000000e-17
GCST007295_72	Body fat distribution (leg fat ratio)	1.000000e-28
GCST009640_6	Urinary albumin-to-creatinine ratio	1.000000e-08
GCST009649_5	Serum cancer antigen 15.3 levels	1.000000e-11
GCST010696_19	Cortical thickness (min-P)	2.000000e-10
GCST010697_10	Cortical surface area (min-P)	3.000000e-10
GCST010698_59	Subcortical volume (min-P)	9.000000e-10
GCST010699_20	Brain morphology (min-P)	7.000000e-10
GCST010700_5	Cortical thickness (MOSTest)	8.000000e-17
GCST010701_66	Cortical surface area (MOSTest)	1.000000e-09
GCST010702_43	Subcortical volume (MOSTest)	3.000000e-10
GCST010703_253	Brain morphology (MOSTest)	4.000000e-14

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004341	body fat distribution
EFO:0007778	urinary albumin to creatinine ratio
EFO:0010585	cancer antigen 15.3 measurement
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D017240	Mitochondrial Myopathies	C05.651.460; C10.668.491.500; C18.452.660.560
D009468	Neuromuscular Diseases	C10.668
C562568	Cerebellar Hypoplasia (supp.)

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
bisphenol A	decreases expression	2
GSK-J4	decreases expression	1
beta-lapachone	increases expression	1
sodium arsenite	decreases expression	1
avobenzone	decreases expression	1
CGP 52608	affects binding, increases reaction	1
nutlin 3	affects cotreatment, increases secretion	1
14-deoxy-11,12-didehydroandrographolide	decreases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	decreases expression	1
bisphenol S	affects cotreatment, decreases expression	1
jinfukang	increases expression	1
Acetaminophen	decreases expression	1
Caffeine	increases phosphorylation	1
Dactinomycin	increases secretion, affects cotreatment	1
Dexamethasone	decreases expression, affects cotreatment	1
Estradiol	increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Hydrogen Peroxide	affects expression	1
Indomethacin	affects cotreatment, decreases expression	1
Methotrexate	decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Aflatoxin B1	increases methylation	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00331656	PHASE4	UNKNOWN	Comparative Study of Non-Invasive Mask Ventilation vs Cuirass Ventilation in Patients With Acute Respiratory Failure.
NCT00994552	PHASE4	UNKNOWN	Comparison of Pressure Support and Pressure Control Ventilation in Chronic Respiratory Failure
NCT00120055	PHASE4	COMPLETED	Association Between Systemic Exposure of Atorvastatin and Metabolites and Atorvastatin-induced Myotoxicity
NCT03633565	PHASE4	UNKNOWN	Comparative Study of Strategies for Management of Duchenne Myopathy (DM)
NCT00839033	PHASE3	TERMINATED	Evaluation of a Mechanical Device During Acute Respiratory Failure in Patients With Neuromuscular Disorders
NCT00942227	PHASE3	COMPLETED	The Value of Traction in Treatment of Lumbar Radiculopathy
NCT00979108	PHASE3	COMPLETED	The Value of Traction in the Treatment of Cervical Radiculopathy
NCT01826487	PHASE3	COMPLETED	Phase 3 Study of Ataluren in Participants With Nonsense Mutation Duchenne Muscular Dystrophy (nmDMD)
NCT02090959	PHASE3	TERMINATED	An Extension Study of Ataluren (PTC124) in Participants With Nonsense Mutation Dystrophinopathy
NCT02436096	PHASE3	COMPLETED	A Study to Evaluate eFFIcacy and Safety of Sublingual TNX-102 SL Tablet Taken at Bedtime in Patients With fibRoMyalgia
NCT02829814	PHASE3	TERMINATED	Repeat of: A Study to Evaluate Efficacy and Safety of Sublingual TNX-102 SL Tablet Taken at Bedtime in Patients With Fibromyalgia
NCT03179631	PHASE3	COMPLETED	Long-Term Outcomes of Ataluren in Duchenne Muscular Dystrophy
NCT05126758	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Deramiocel (CAP-1002) in Ambulatory and Non-Ambulatory Patients With Duchenne Muscular Dystrophy
NCT05156320	PHASE3	COMPLETED	Efficacy and Safety of Apitegromab in Patients With Later-Onset Spinal Muscular Atrophy Treated With Nusinersen or Risdiplam
NCT05337553	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Efficacy and Safety of Taldefgrobep Alfa in Participants With Spinal Muscular Atrophy
NCT05626855	PHASE3	ACTIVE_NOT_RECRUITING	Long-Term Safety & Efficacy of Apitegromab in Patients With SMA Who Completed Previous Trials of Apitegromab
NCT06672237	PHASE3	RECRUITING	A Phase 3 Study of NTLA-2001 in ATTRv-PN
NCT01225614	PHASE3	UNKNOWN	Efficacy and Tolerance of Early Launching of Nocturnal Non Invasive
NCT03323749	PHASE3	TERMINATED	A Trial to Evaluate Safety and Efficacy of Elamipretide Primary Mitochondrial Myopathy Followed by Open-Label Extension
NCT05162768	PHASE3	COMPLETED	Study to Evaluate Efficacy and Safety of Elamipretide in Subjects With Primary Mitochondrial Disease From Nuclear DNA Mutations (nPMD)
NCT01074359	PHASE2	TERMINATED	Safety and Efficacy Study of A0001 in Patients With the A3243G Mitochondrial DNA Point Mutation
NCT01371149	PHASE2	COMPLETED	Patient -Ventilator Interaction in Chronic Respiratory Failure
NCT02022072	PHASE2	TERMINATED	Evaluation of Vital Capacity
NCT03127514	PHASE2	COMPLETED	AMX0035 in Patients With Amyotrophic Lateral Sclerosis (ALS)
NCT03406780	PHASE2	COMPLETED	A Study of CAP-1002 in Ambulatory and Non-Ambulatory Patients With Duchenne Muscular Dystrophy
NCT03921528	PHASE2	COMPLETED	An Active Treatment Study of SRK-015 in Patients With Type 2 or Type 3 Spinal Muscular Atrophy
NCT05479981	PHASE2	COMPLETED	Extension of AOC 1001-CS1 (MARINA) Study in Adult Myotonic Dystrophy Type 1 (DM1) Patients
NCT06339580	PHASE2	RECRUITING	Assessment of Volume-targeted Ventilation in Patients With Neuromuscular Disease
NCT07071935	PHASE2	NOT_YET_RECRUITING	A Clinical Trial of Early Ventilation in Amyotrophic Lateral Sclerosis (EVENT ALS)
NCT07287189	PHASE2	RECRUITING	Phase 2 Study of SAT-3247 in Pediatric Ambulatory Patients
NCT00457314	PHASE2	UNKNOWN	The Effects of Exercise Versus Inactivity on People With Mitochondrial Muscle Disease
NCT02255422	PHASE2	COMPLETED	RTA 408 Capsules in Patients With Mitochondrial Myopathy - MOTOR
NCT02909400	PHASE2	COMPLETED	The KHENERGY Study
NCT04165239	PHASE2	COMPLETED	The KHENERGYZE Study
NCT04535609	PHASE2	COMPLETED	An Efficacy and Safety Study of 24 Week Treatment With Mavodelpar (REN001) in Primary Mitochondrial Myopathy Patients
NCT04641962	PHASE2	TERMINATED	A Study to Evaluate ASP0367 in Participants With Primary Mitochondrial Myopathy
NCT05590468	PHASE2	ACTIVE_NOT_RECRUITING	A Study to Evaluate Vitamin B3 Derivative to Treat Mitochondrial Myopathy
NCT05962333	PHASE2	UNKNOWN	Effect and Safety MABs Administration m.3243A>G Mutation Carriers
NCT06754098	PHASE2	RECRUITING	Doxecitin and Doxribthymine in Adult Subjects With Thymidine Kinase 2 (TK2) Deficiency
NCT00252252	PHASE1	COMPLETED	AutoVPAP Versus VPAP; Assessment of Sleep and Ventilation