SPG7

Summary

SPG7 (SPG7 matrix AAA peptidase subunit, paraplegin, HGNC:11237) is a protein-coding gene on chromosome 16q24.3, encoding Mitochondrial inner membrane m-AAA protease component paraplegin (Q9UQ90). Catalytic component of the m-AAA protease, a protease that plays a key role in proteostasis of inner mitochondrial membrane proteins, and which is essential for axonal and neuron development.

This gene encodes a mitochondrial metalloprotease protein that is a member of the AAA family. Members of this protein family share an ATPase domain and have roles in diverse cellular processes including membrane trafficking, intracellular motility, organelle biogenesis, protein folding, and proteolysis. Mutations in this gene cause autosomal recessive spastic paraplegia 7. Two transcript variants encoding distinct isoforms have been identified.

Source: NCBI Gene 6687 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mitochondrial disease (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 5
• Clinical variants (ClinVar): 1,200 total — 94 pathogenic, 65 likely-pathogenic
• Phenotypes (HPO): 79
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_003119

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11237
Approved symbol	SPG7
Name	SPG7 matrix AAA peptidase subunit, paraplegin
Location	16q24.3
Locus type	gene with protein product
Status	Approved
Aliases	CAR, SPG5C
Ensembl gene	ENSG00000197912
Ensembl biotype	protein_coding
OMIM	602783
Entrez	6687

Gene structure

Transcript identifiers

Ensembl transcripts: 106 — 33 retained_intron, 31 nonsense_mediated_decay, 27 protein_coding, 15 protein_coding_CDS_not_defined

ENST00000268704, ENST00000341316, ENST00000561702, ENST00000561911, ENST00000561945, ENST00000562775, ENST00000563218, ENST00000563783, ENST00000564047, ENST00000564409, ENST00000565370, ENST00000565891, ENST00000566221, ENST00000566371, ENST00000566682, ENST00000567138, ENST00000568151, ENST00000568205, ENST00000568509, ENST00000569363, ENST00000569720, ENST00000569820, ENST00000611189, ENST00000642226, ENST00000642263, ENST00000642334, ENST00000642371, ENST00000642427, ENST00000642436, ENST00000642814, ENST00000642984, ENST00000643105, ENST00000643178, ENST00000643307, ENST00000643345, ENST00000643350, ENST00000643370, ENST00000643409, ENST00000643496, ENST00000643649, ENST00000643668, ENST00000643724, ENST00000643734, ENST00000643954, ENST00000643957, ENST00000644044, ENST00000644061, ENST00000644171, ENST00000644210, ENST00000644225, ENST00000644281, ENST00000644464, ENST00000644498, ENST00000644556, ENST00000644671, ENST00000644748, ENST00000644751, ENST00000644781, ENST00000644901, ENST00000644930, ENST00000645042, ENST00000645063, ENST00000645258, ENST00000645354, ENST00000645392, ENST00000645533, ENST00000645742, ENST00000645818, ENST00000645842, ENST00000645886, ENST00000645897, ENST00000645944, ENST00000645952, ENST00000645977, ENST00000646005, ENST00000646263, ENST00000646303, ENST00000646399, ENST00000646445, ENST00000646454, ENST00000646531, ENST00000646543, ENST00000646589, ENST00000646707, ENST00000646716, ENST00000646826, ENST00000646930, ENST00000646958, ENST00000647032, ENST00000647079, ENST00000647123, ENST00000647227, ENST00000647239, ENST00000647302, ENST00000647476, ENST00000647491, ENST00000892261, ENST00000892262, ENST00000918771, ENST00000918772, ENST00000918773, ENST00000965630, ENST00000965631, ENST00000965632, ENST00000965633, ENST00000965634

RefSeq mRNA: 3 — MANE Select: NM_003119 NM_001363850, NM_003119, NM_199367

CCDS: CCDS10977, CCDS10978, CCDS92212

Canonical transcript exons

ENST00000645818 — 17 exons

Exon	Start	End
ENSE00001408619	89524006	89524247
ENSE00002437745	89529477	89529579
ENSE00002626779	89556887	89557766
ENSE00003482291	89548003	89548113
ENSE00003518269	89554486	89554563
ENSE00003531524	89544648	89544772
ENSE00003537923	89530683	89530808
ENSE00003574138	89552979	89553135
ENSE00003591010	89532463	89532636
ENSE00003611853	89553794	89553960
ENSE00003614940	89510490	89510592
ENSE00003626965	89512948	89513037
ENSE00003646129	89531904	89532066
ENSE00003676489	89546658	89546760
ENSE00003681322	89526329	89526468
ENSE00003687410	89550494	89550609
ENSE00003904146	89508403	89508600

Expression profiles

Bgee: expression breadth ubiquitous, 302 present calls, max score 99.55.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 54.9186 / max 302.5122, expressed in 1823 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
155596	52.5382	1823
155595	2.1870	901
155599	0.1934	81

Top tissues by expression

303 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	99.55	gold quality
sural nerve	UBERON:0015488	98.44	gold quality
left lobe of thyroid gland	UBERON:0001120	97.77	gold quality
apex of heart	UBERON:0002098	97.63	gold quality
right lobe of thyroid gland	UBERON:0001119	97.55	gold quality
thyroid gland	UBERON:0002046	97.43	gold quality
mucosa of stomach	UBERON:0001199	97.41	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.35	gold quality
cerebellar hemisphere	UBERON:0002245	97.25	gold quality
cerebellar cortex	UBERON:0002129	97.21	gold quality
metanephros cortex	UBERON:0010533	97.17	gold quality
adenohypophysis	UBERON:0002196	97.09	gold quality
left ovary	UBERON:0002119	97.01	gold quality
cerebellum	UBERON:0002037	96.82	gold quality
right ovary	UBERON:0002118	96.78	gold quality
pituitary gland	UBERON:0000007	96.77	gold quality
right uterine tube	UBERON:0001302	96.77	gold quality
ventricular zone	UBERON:0003053	96.73	gold quality
endometrium epithelium	UBERON:0004811	96.69	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.68	gold quality
adrenal tissue	UBERON:0018303	96.62	gold quality
stromal cell of endometrium	CL:0002255	96.57	gold quality
skin of leg	UBERON:0001511	96.53	gold quality
right frontal lobe	UBERON:0002810	96.50	gold quality
right adrenal gland cortex	UBERON:0035827	96.44	gold quality
right testis	UBERON:0004534	96.37	gold quality
left testis	UBERON:0004533	96.36	gold quality
right adrenal gland	UBERON:0001233	96.33	gold quality
left adrenal gland cortex	UBERON:0035825	96.32	gold quality
adrenal cortex	UBERON:0001235	96.26	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.53
E-MTAB-10596	no	137.37

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): IRF1

miRNA regulators (miRDB)

20 targeting SPG7, 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-4487	99.96	64.58	1252
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-421	98.90	67.04	1883
HSA-MIR-6882-3P	98.23	67.01	1119
HSA-MIR-4691-3P	98.11	66.83	1204
HSA-MIR-4294	97.86	65.72	1110
HSA-MIR-6793-3P	97.66	65.78	1084
HSA-MIR-874-5P	96.93	63.92	1014
HSA-MIR-1292-5P	96.74	62.14	238
HSA-MIR-1178-5P	95.83	64.12	504
HSA-MIR-4330	95.44	66.39	993
HSA-MIR-4304	90.01	61.07	99

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 38)

• mutation in spastin and paraplegin genes does not appear to cause motor neuron disease (PMID:14506940)
• Adenoassociated virus-mediated intramuscular delivery of paraplegin halted the progression of neuropathological changes and rescued mitochondrial morphology in the peripheral nerves of paraplegin-deficient mice. (PMID:16357941)
• Cerebellar signs or cerebellar atrophy on brain imaging were the most frequent additional features in patients with SPG7 hereditary spastic paraplegia. (PMID:16534102)
• The new SPG7 gene mutation leads to a novel complicated autosomal recessive hereditary spastic paraparesis phenotype that widens the spectrum of different brain systems that are optionally affected in hereditary spastic paraplegia. (PMID:17646629)
• identification of six novel point mutations and one large intragenic deletion in hereditary spastic paraplegia (PMID:18200586)
• This study identified a novel paraplegin mutation, c.1047insC, in a non-consanguineous Norwegian family with ARHSP. (PMID:18563470)
• Results suggest that paraplegin mutations are a frequent cause of sporadic spastic paraparesis. (PMID:18799786)
• An intersubunit signaling network coordinates ATP hydrolysis by m-AAA protease paraplegin. (PMID:19748354)
• structural analysis of the ATPase domain of the human AAA+ protein paraplegin/SPG7 (PMID:19841671)
• The novel mutation is the first splice site mutation found in the SPG7 gene. It removes part of the AAA domain of paraplegin protein, probably leading to a loss-of-function of the paraplegin-AFG3L2 complex in the mitochondrial inner membrane. (PMID:20108356)
• Studies indicate that both mouse and human SPG7 ESTs containing alternative first exons. (PMID:22563492)
• Data suggest a pathogenic role for this SPG7 p.A510V variant. (PMID:22571692)
• SPG7 mutations correlate with spastic paraplegia phenotypes. (PMID:22964162)
• SPG7 mutations are a frequent cause of middle-aged onset of spastic gait when strict inclusion criteria are applied and should, therefore, be tested in autosomal recessive or sporadic hereditary spastic paraplegia. (PMID:23065789)
• This study showed that the p.Ala510Val mutation is prevalent amongst severe hereditary spastic paraparesis patients of UK. (PMID:23269439)
• A Japanese patient is reported with an SPG7 mutation for a slowly progressive form of autosomal recessive cerebellar ataxia and spastic paraplegia. (PMID:23857099)
• Using an unbiased exome sequencing approach we identified pathogenic compound heterozygous SPG7 mutations in patients with PEO and multiple mitochondrial DNA deletions in skeletal muscle (PMID:24727571)
• The SPG7 Q866 variant is efficiently processed independent of phosphorylation of AFG3L2 at Y179, which inhibits processing of SPG7. (PMID:24767997)
• In unexplained ataxia, there was a significant number of patients with SPG7 mutations. (PMID:25681447)
• a novel homozygous frameshift deletion in the SPG7 gene was identifies as the genetic cause of hereditary spastic paraplegia in a Greek family. (PMID:26260707)
• Data indicates that SPG7 is essential for the mitochondrial permeability transition pore (PTP) complex formation, interacts with CypD and VDAC and determines C terminus of SPG7 and CsA-binding region of CypD as necessary for PTP formation. (PMID:26387735)
• this case shows that the spectrum of pathologies in SPG7 can include neuron loss of the dentate nucleus and the inferior olivary nucleus as well as neuritic pathology. (PMID:26506339)
• Compound heterozygous variants in SPG7 identified in 22 French Canadian patients with spastic ataxia. (PMID:26626314)
• A Norwegian founder mutation p.H701P is a major cause of SPG7 in Norway. (PMID:26756429)
• The results of this study showed that the most frequently detected variant in this cohort was the SPG7 p.Leu78. (PMID:27084228)
• CACNA1A and SPG7 are major ataxia genes. (PMID:28444220)
• SPG7 mutants accounted for 2.3% of cerebellar ataxia cases in Italy, suggesting that this variant should be considered as a priority test in the presence of late-onset pure ataxia (PMID:30098094)
• Data report here co-occurrence of a heterozygous de novo AFG3L2 missense mutation (p.R468C) and a maternally inherited heterozygous intragenic deletion of SPG7 in a patient with a complex ataxic and extrapyramidal phenotype with early-onset optic atrophy. (PMID:30252181)
• we identified novel variants of SPG7 in two patients with late onset hereditary spastic paraplegias (PMID:30747022)
• study provides evidence for two novel candidate genes, SPG7 and RASGEF1B, associating with white coat effect (PMID:31044621)
• This is the largest spastic paraplegia 7 cohort study to date and shows a spasticity-predominant phenotype of loss-of-function variants and more frequent cerebellar ataxia and later onset in patients carrying at least 1 Ala510Val variant. (PMID:31068484)
• This finding of a missense mutation of SPG7 gene in a primary lateral sclerosis family expands the spectrum of known SPG7 mutations (PMID:31117107)
• Novel homozygous SPG7 missense mutation in a Chinese hereditary spastic paraplegia family. (PMID:32002796)
• SPG7 mutations in amyotrophic lateral sclerosis: a genetic link to hereditary spastic paraplegia. (PMID:32447552)
• Impaired flickering of the permeability transition pore causes SPG7 spastic paraplegia. (PMID:33045469)
• Neurophysiological and ophthalmological findings of SPG7-related spastic ataxia: a phenotype study in an Irish cohort. (PMID:33774748)
• Clinical and genetic characteristics of 21 Spanish patients with biallelic pathogenic SPG7 mutations. (PMID:34500365)
• A novel compound heterozygous SPG7 variant is associated with progressive spastic ataxia and persecutory delusions found in Chinese patients: two case reports. (PMID:35637455)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	spg7	ENSDARG00000068187
mus_musculus	Spg7	ENSMUSG00000000738
rattus_norvegicus	Spg7	ENSRNOG00000015150
drosophila_melanogaster	Spg7	FBGN0024992
caenorhabditis_elegans		WBGENE00021425
caenorhabditis_elegans		WBGENE00021615

Paralogs (2): YME1L1 (ENSG00000136758), AFG3L2 (ENSG00000141385)

Protein

Protein identifiers

Mitochondrial inner membrane m-AAA protease component paraplegin — Q9UQ90 (reviewed: Q9UQ90)

Alternative names: Cell matrix adhesion regulator, Paraplegin, Spastic paraplegia 7 protein

All UniProt accessions (43): A0A087X0F5, A0A2R8Y3M4, A0A2R8Y4L0, A0A2R8Y4L7, A0A2R8Y4M0, A0A2R8Y4M8, A0A2R8Y4Y7, A0A2R8Y4Z7, A0A2R8Y530, A0A2R8Y617, A0A2R8Y632, A0A2R8Y6E8, A0A2R8Y6K2, A0A2R8Y6Z7, A0A2R8Y726, A0A2R8Y729, A0A2R8Y7B8, A0A2R8Y7E2, A0A2R8Y7N2, A0A2R8Y856, A0A2R8YCU3, A0A2R8YDM8, A0A2R8YDQ1, A0A2R8YDS3, A0A2R8YDU1, Q9UQ90, A0A2R8YDW8, A0A2R8YEH4, A0A2R8YFF4, A0A2R8YFJ7, A0A2R8YFN9, A0A2R8YFQ9, A0A2R8YFW4, A0A2R8YG79, A0A2R8YG90, A0A2R8YGV4, A0A2R8YGZ0, A0A2U3TZH1, H3BMP1, H3BNE4, H3BTR8, H3BTY6, J3KRF6

UniProt curated annotations — full annotation on UniProt →

Function. Catalytic component of the m-AAA protease, a protease that plays a key role in proteostasis of inner mitochondrial membrane proteins, and which is essential for axonal and neuron development. SPG7 possesses both ATPase and protease activities: the ATPase activity is required to unfold substrates, threading them into the internal proteolytic cavity for hydrolysis into small peptide fragments. The m-AAA protease exerts a dual role in the mitochondrial inner membrane: it mediates the processing of specific regulatory proteins and ensures protein quality control by degrading misfolded polypeptides. Mediates protein maturation of the mitochondrial ribosomal subunit MRPL32/bL32m by catalyzing the cleavage of the presequence of MRPL32/bL32m prior to assembly into the mitochondrial ribosome. Acts as a regulator of calcium in neurons by mediating degradation of SMDT1/EMRE before its assembly with the uniporter complex, limiting the availability of SMDT1/EMRE for MCU assembly and promoting efficient assembly of gatekeeper subunits with MCU. Also regulates mitochondrial calcium by catalyzing degradation of MCU. Plays a role in the formation and regulation of the mitochondrial permeability transition pore (mPTP) and its proteolytic activity is dispensable for this function.

Subunit / interactions. Forms heterooligomers with AFG3L2; the m-AAA protease is composed of heterohexamers of AFG3L2 and SPG7. Component of the mitochondrial permeability transition pore complex (mPTPC), at least composed of SPG7, VDAC1 and PPIF. Interacts with MAIP1.

Subcellular location. Mitochondrion inner membrane.

Tissue specificity. Ubiquitous.

Post-translational modifications. Upon import into the mitochondrion, the N-terminal transit peptide is cleaved by the mitochondrial-processing peptidase (MPP) to generate an intermediate form which undergoes a second proteolytic cleavage mediated by proteases AFG3L2 removing an additional N-terminal fragment to generate the proteolytically active mature form.

Disease relevance. Spastic paraplegia 7, autosomal recessive (SPG7) [MIM:607259] A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG7 is a complex form. Additional clinical features are cerebellar syndrome, supranuclear palsy, and cognitive impairment, particularly disturbance of attention and executive functions. The disease is caused by variants affecting the gene represented in this entry. Defects in SPG7 may cause autosomal recessive osteogenesis imperfecta (OI). Osteogenesis imperfecta defines a group of connective tissue disorders characterized by bone fragility and low bone mass. Clinical features of SPG7-related osteogenesis imperfecta include recurrent fractures, mild bone deformities, delayed tooth eruption, normal hearing and white sclera.

Cofactor. Binds 1 zinc ion per subunit.

Similarity. In the N-terminal section; belongs to the AAA ATPase family. In the C-terminal section; belongs to the peptidase M41 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UQ90-1	1	yes
Q9UQ90-2	2

RefSeq proteins (3): NP_001350779, NP_003110, NP_955399 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000642	Peptidase_M41	Domain
IPR003593	AAA+_ATPase	Domain
IPR003959	ATPase_AAA_core	Domain
IPR005936	FtsH	Family
IPR011546	Pept_M41_FtsH_extracell	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR037219	Peptidase_M41-like	Homologous_superfamily
IPR041569	AAA_lid_3	Domain
IPR050928	ATP-dep_Zn_Metalloprotease	Family

Pfam: PF00004, PF01434, PF06480, PF17862

Enzyme classification (BRENDA):

• EC 3.4.24.B18 — (BRENDA: organisms, substrates, inhibitors, Km, kcat entries)

Catalyzed reactions (Rhea), 1 shown:

• ATP + H2O = ADP + phosphate + H(+) (RHEA:13065)

UniProt features (68 total): sequence variant 19, binding site 10, helix 10, strand 6, mutagenesis site 4, region of interest 3, topological domain 3, splice variant 2, transmembrane region 2, sequence conflict 2, transit peptide 1, propeptide 1, compositionally biased region 1, active site 1, chain 1, modified residue 1, turn 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2QZ4	X-RAY DIFFRACTION	2.22

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UQ90-F1	74.10	0.29

Functional residue map

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

Catalytic / active sites (1): 575

Ligand- & substrate-binding residues (10): 312; 352; 353; 354; 355; 356; 357; 574; 578; 650

Post-translational modifications (1): 505

Mutagenesis-validated functional residues (4):

Position	Phenotype
574–577	abolished metalloprotease activity.
574	loss of proteolytic activity but no loss of interaction with ppif; when associated with g-575 and s-577.
575	loss of proteolytic activity but no loss of interaction with ppif; when associated with g-574 and s-577.
577	no loss of interaction with ppif. loss of proteolytic activity but no loss of interaction with ppif; when associated wit

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-8949664	Processing of SMDT1
R-HSA-9837999	Mitochondrial protein degradation
R-HSA-382551	Transport of small molecules
R-HSA-392499	Metabolism of proteins
R-HSA-8949215	Mitochondrial calcium ion transport

MSigDB gene sets: 315 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, MULLIGHAN_NPM1_SIGNATURE_3_UP, WANG_CLIM2_TARGETS_UP, GOBP_AXO_DENDRITIC_TRANSPORT, GOMF_METALLOPEPTIDASE_ACTIVITY, GOBP_MITOCHONDRIAL_TRANSPORT, RODRIGUES_NTN1_TARGETS_DN, GOBP_MONOATOMIC_CATION_TRANSPORT, BROWNE_HCMV_INFECTION_48HR_DN, NIKOLSKY_BREAST_CANCER_16Q24_AMPLICON, GOBP_PROTEIN_MATURATION, GOBP_REGULATION_OF_CALCIUM_ION_TRANSMEMBRANE_TRANSPORT, GOCC_MITOCHONDRIAL_ENVELOPE, TIEN_INTESTINE_PROBIOTICS_24HR_UP

GO Biological Process (9): proteolysis (GO:0006508), nervous system development (GO:0007399), anterograde axonal transport (GO:0008089), mitochondrial protein processing (GO:0034982), regulation of mitochondrial membrane permeability (GO:0046902), regulation of calcium import into the mitochondrion (GO:0110097), mitochondrial outer membrane permeabilization involved in programmed cell death (GO:1902686), mitochondrion organization (GO:0007005), calcium import into the mitochondrion (GO:0036444)

GO Molecular Function (12): ATP-dependent peptidase activity (GO:0004176), metalloendopeptidase activity (GO:0004222), ATP binding (GO:0005524), peptidase activity (GO:0008233), zinc ion binding (GO:0008270), ATP hydrolysis activity (GO:0016887), obsolete unfolded protein binding (GO:0051082), nucleotide binding (GO:0000166), protein binding (GO:0005515), metallopeptidase activity (GO:0008237), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (6): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), m-AAA complex (GO:0005745), mitochondrial permeability transition pore complex (GO:0005757), axon cytoplasm (GO:1904115), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Mitochondrial calcium ion transport	1
Metabolism of proteins	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
peptidase activity	2
ATP-dependent activity	2
protein metabolic process	1
system development	1
axonal transport	1
axon cytoplasm	1
mitochondrion	1
protein processing	1
regulation of membrane permeability	1
calcium import into the mitochondrion	1
regulation of calcium ion transmembrane transport	1
programmed cell death	1
positive regulation of mitochondrial membrane permeability	1
organelle organization	1
mitochondrial calcium ion transmembrane transport	1
intercellular transport	1
endopeptidase activity	1
metallopeptidase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
transition metal ion binding	1
ribonucleoside triphosphate phosphatase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
cation binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
inner mitochondrial membrane protein complex	1
peptidase complex	1
mitochondrial envelope	1
pore complex	1
mitochondrial protein-containing complex	1
axon	1
neuron projection cytoplasm	1

Protein interactions and networks

STRING

3629 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPG7	SPG11	Q96JI7	957
SPG7	PPIF	P30405	931
SPG7	AFG3L2	Q9Y4W6	927
SPG7	VDAC1	P21796	910
SPG7	SPG21	Q9NZD8	905
SPG7	PNPLA6	Q8IY17	866
SPG7	SPART	Q8N0X7	823
SPG7	AP5Z1	O43299	820
SPG7	GJC2	Q5T442	786
SPG7	HSPE1	P61604	783
SPG7	ZNF276	Q8N554	738
SPG7	HSPD1	P10809	733
SPG7	CLPP	Q16740	707
SPG7	OMA1	Q96E52	702
SPG7	CDK10	Q15131	695

IntAct

195 interactions, top by confidence:

A	B	Type	Score
PNMA1	SPG7	psi-mi:“MI:0915”(physical association)	0.780
SPG7	MDFI	psi-mi:“MI:0915”(physical association)	0.780
SPG7	PNMA1	psi-mi:“MI:0915”(physical association)	0.780
MDFI	SPG7	psi-mi:“MI:0915”(physical association)	0.780
TUBA1C	TXNDC9	psi-mi:“MI:0914”(association)	0.730
SPG7	MTUS2	psi-mi:“MI:0915”(physical association)	0.670
B3GNT3	PGRMC1	psi-mi:“MI:0914”(association)	0.670
SLC1A1	AGPAT2	psi-mi:“MI:0914”(association)	0.640
SPG7	NDUFB9	psi-mi:“MI:0915”(physical association)	0.590
SPG7	PSTPIP1	psi-mi:“MI:0915”(physical association)	0.560
CCNDBP1	SPG7	psi-mi:“MI:0915”(physical association)	0.560
SPG7	KRTAP10-7	psi-mi:“MI:0915”(physical association)	0.560
SPG7	KRTAP10-9	psi-mi:“MI:0915”(physical association)	0.560
SPG7	PSME3	psi-mi:“MI:0915”(physical association)	0.560
SPG7	HNRNPK	psi-mi:“MI:0915”(physical association)	0.560
SPG7	KHDRBS2	psi-mi:“MI:0915”(physical association)	0.560
KRT40	SPG7	psi-mi:“MI:0915”(physical association)	0.560
NOTCH2NLA	SPG7	psi-mi:“MI:0915”(physical association)	0.560
RBPMS	SPG7	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (146): SPG7 (Two-hybrid), SPG7 (Two-hybrid), PSTPIP1 (Two-hybrid), PNMA1 (Two-hybrid), PSME3 (Two-hybrid), RBPMS (Two-hybrid), MTUS2 (Two-hybrid), CCNDBP1 (Two-hybrid), LZTS2 (Two-hybrid), KRT40 (Two-hybrid), KHDRBS2 (Two-hybrid), KRTAP10-7 (Two-hybrid), KRTAP10-9 (Two-hybrid), KRTAP10-3 (Two-hybrid), NOTCH2NL (Two-hybrid)

ESM2 similar proteins: A1A4J8, A6H784, D3ZS74, D4A6D7, E9QBI7, O42899, O43819, O60341, O75880, P00258, P10109, P23833, P24483, P30048, P38072, Q05B51, Q0VCH8, Q12931, Q2KHU5, Q2NKY8, Q2TBI4, Q3ULF4, Q4VAE3, Q5EA41, Q5REY3, Q5RH02, Q5SUC9, Q69ZP3, Q6DKK2, Q6PI78, Q6ZQ88, Q7ZUC7, Q8BMS4, Q8JZQ2, Q8LAL0, Q8N490, Q8VCL2, Q920A7, Q95N00, Q96HS1

Diamond homologs: A0B6D7, A1RSA2, A1RSA3, A1RV38, A1RWU6, A1RWU7, A2BL93, A2BTJ7, A2SQR6, A3CTR4, A3DNV8, A3DNV9, A3MS27, A3MS28, A4FZL6, A4WGV2, A4WGV3, A4WLY0, A5EXH6, A5UMF4, A6URV8, A6UWR5, A6VIW1, A7I781, A8AC24, A8XFM8, A9A6N2, B0R601, B1GZK7, B1YC69, B1ZMG6, B5Y8Q8, B6YXR2, B7PXE3, B9LPV1, C3MQ13, C3MVD2, C3N5N1, C3NE95, C3NHF4

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 183 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.

GO biological processes:

GO term	Partners	Fold	FDR
G protein-coupled receptor signaling pathway	16	3.7×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

1200 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	94
Likely pathogenic	65
Uncertain significance	488
Likely benign	327
Benign	66

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1076752	NC_000016.9:g.(?89595875)(89595997_?)del	Pathogenic
1076753	NC_000016.9:g.(?89614405)(89617023_?)del	Pathogenic
1323644	NM_003119.4(SPG7):c.711del (p.Lys238fs)	Pathogenic
1323646	NM_003119.4(SPG7):c.1704_1705del (p.Lys569fs)	Pathogenic
1338869	NM_003119.4(SPG7):c.2166_2167insCAACAACCTG (p.Asp723fs)	Pathogenic
1417486	NM_003119.4(SPG7):c.861del (p.Phe287fs)	Pathogenic
1452161	NM_003119.4(SPG7):c.749del (p.Phe250fs)	Pathogenic
1455682	NC_000016.9:g.(?89576878)(89579465_?)del	Pathogenic
1456367	NM_003119.4(SPG7):c.1124del (p.Gly375fs)	Pathogenic
1459618	NC_000016.9:g.(?89574826)(89597236_?)del	Pathogenic
1459620	NC_000016.9:g.(?89619467)(89620817_?)del	Pathogenic
1459932	NC_000016.9:g.(?89574826)(89579465_?)del	Pathogenic
1459933	NC_000016.9:g.(?89613046)(89617037_?)del	Pathogenic
1900732	NM_003119.4(SPG7):c.2140_2141del (p.Thr714fs)	Pathogenic
1904633	NM_003119.4(SPG7):c.1170del (p.Arg391fs)	Pathogenic
2033743	NM_003119.4(SPG7):c.1477dup (p.Leu493fs)	Pathogenic
2112862	NM_003119.4(SPG7):c.960del (p.Val321fs)	Pathogenic
212294	NM_003119.4(SPG7):c.861dup (p.Asn288Ter)	Pathogenic
215221	NM_003119.4(SPG7):c.2189del (p.Asn730fs)	Pathogenic
217269	NM_003119.4(SPG7):c.1715C>T (p.Ala572Val)	Pathogenic
217270	NM_003119.4(SPG7):c.988-1G>A	Pathogenic
217272	NM_003119.4(SPG7):c.473_474del (p.Leu158fs)	Pathogenic
2500208	NM_003119.4(SPG7):c.2195T>C (p.Leu732Pro)	Pathogenic
2500209	NM_003119.4(SPG7):c.286+853A>G	Pathogenic
254070	NM_003119.3(SPG7):c.1553-?_1779+?del	Pathogenic
2571599	NM_003119.4(SPG7):c.808del (p.Tyr270fs)	Pathogenic
2572387	NM_003119.4(SPG7):c.1303C>T (p.Gln435Ter)	Pathogenic
265420	NM_003119.4(SPG7):c.1617del (p.Val540fs)	Pathogenic
2664724	NM_003119.4(SPG7):c.1151-1G>C	Pathogenic
2682507	NC_000016.9:g.(89595988_89597090)_(89620972_89623294)del	Pathogenic

SpliceAI

4031 predictions. Top by Δscore:

Variant	Effect	Δscore
16:89508596:TGCAG:T	donor_loss	1.0000
16:89508598:CAG:C	donor_loss	1.0000
16:89508599:AG:A	donor_loss	1.0000
16:89508600:GGTAA:G	donor_loss	1.0000
16:89508601:GTAA:G	donor_loss	1.0000
16:89508602:T:G	donor_loss	1.0000
16:89510485:TTCAG:T	acceptor_gain	1.0000
16:89510486:TCAG:T	acceptor_gain	1.0000
16:89510487:CAG:C	acceptor_gain	1.0000
16:89510488:A:AG	acceptor_gain	1.0000
16:89510488:A:C	acceptor_loss	1.0000
16:89510488:AGA:A	acceptor_gain	1.0000
16:89510489:G:GA	acceptor_gain	1.0000
16:89510489:GA:G	acceptor_gain	1.0000
16:89510489:GAG:G	acceptor_gain	1.0000
16:89510489:GAGC:G	acceptor_gain	1.0000
16:89510489:GAGCT:G	acceptor_gain	1.0000
16:89510589:TTAGG:T	donor_loss	1.0000
16:89510590:TAGG:T	donor_loss	1.0000
16:89510591:AGG:A	donor_loss	1.0000
16:89510592:GGTA:G	donor_loss	1.0000
16:89510593:G:GG	donor_gain	1.0000
16:89510593:GTAT:G	donor_loss	1.0000
16:89510594:T:A	donor_loss	1.0000
16:89512946:A:AT	acceptor_loss	1.0000
16:89512946:AGGT:A	acceptor_gain	1.0000
16:89512947:G:GA	acceptor_loss	1.0000
16:89512947:GGTG:G	acceptor_gain	1.0000
16:89513035:AAG:A	donor_loss	1.0000
16:89513036:AGGT:A	donor_loss	1.0000

AlphaMissense

5175 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:89526387:T:C	L226P	1.000
16:89532526:T:A	V405D	1.000
16:89524130:G:C	W167C	0.999
16:89524130:G:T	W167C	0.999
16:89524138:T:C	F170S	0.999
16:89524177:T:A	V183D	0.999
16:89526438:T:A	V243D	0.999
16:89531953:T:C	L346P	0.999
16:89531956:T:C	L347P	0.999
16:89531961:G:C	G349R	0.999
16:89531962:G:A	G349D	0.999
16:89531971:G:A	G352D	0.999
16:89531976:G:T	G354W	0.999
16:89531977:G:A	G354E	0.999
16:89531977:G:T	G354V	0.999
16:89531992:C:A	A359D	0.999
16:89531997:G:C	A361P	0.999
16:89532004:C:A	A363D	0.999
16:89532012:G:C	A366P	0.999
16:89532024:T:C	F370L	0.999
16:89532026:C:A	F370L	0.999
16:89532026:C:G	F370L	0.999
16:89532048:T:C	F378L	0.999
16:89532049:T:C	F378S	0.999
16:89532050:C:A	F378L	0.999
16:89532050:C:G	F378L	0.999
16:89532490:T:C	L393P	0.999
16:89532521:C:G	C403W	0.999
16:89532532:T:A	I407N	0.999
16:89532535:A:T	D408V	0.999

dbSNP variants (sampled 300 via entrez): RS1000029997 (16:89509249 G>A,T), RS1000039255 (16:89537385 G>A), RS1000065948 (16:89541098 A>G), RS1000119548 (16:89546073 C>G), RS1000231353 (16:89526818 C>T), RS1000246454 (16:89552390 G>A,C), RS1000290416 (16:89516490 G>T), RS1000299200 (16:89513445 G>A), RS1000370218 (16:89539255 G>A,C), RS1000406749 (16:89544636 C>A,G,T), RS1000415398 (16:89537253 C>A,G,T), RS1000452171 (16:89548751 G>A,C), RS1000477922 (16:89549971 T>G), RS1000486238 (16:89539406 G>A), RS1000501601 (16:89546945 C>G,T)

Disease associations

OMIM: gene MIM:602783 | disease phenotypes: MIM:607259, MIM:603896, MIM:303350, MIM:108600, MIM:615491, MIM:615911, MIM:167800

GenCC curated gene-disease

Disease	Classification	Inheritance
hereditary spastic paraplegia 7	Definitive	Autosomal recessive
autosomal dominant optic atrophy	Strong	Autosomal dominant
lateral sclerosis	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
mitochondrial disease	Disputed	AD
mitochondrial disease	Definitive	AR

Mondo (17): hereditary spastic paraplegia 7 (MONDO:0011803), inherited retinal dystrophy (MONDO:0019118), leukoencephalopathy with vanishing white matter 1 (MONDO:0020507), hereditary spastic paraplegia (MONDO:0019064), spastic ataxia (MONDO:0017845), mitochondrial disease (MONDO:0044970), hereditary ataxia (MONDO:0100309), optic atrophy (MONDO:0003608), distal hereditary motor neuropathy (MONDO:0018894), early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome (MONDO:0014209), intellectual disability (MONDO:0001071), optic nerve disorder (MONDO:0002135), frontotemporal dementia and/or amyotrophic lateral sclerosis 2 (MONDO:0014395), hereditary chronic pancreatitis (MONDO:0008185), proximal spinal muscular atrophy (MONDO:0019079)

Orphanet (13): Spastic paraplegia type 7 (Orphanet:99013), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Cree leukoencephalopathy (Orphanet:99854), Hereditary spastic paraplegia (Orphanet:685), Spastic ataxia (Orphanet:316226), Hereditary ataxia (Orphanet:183518), Mitochondrial disease (Orphanet:68380), Distal hereditary motor neuropathy (Orphanet:53739), Early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome (Orphanet:352654), Frontotemporal dementia with motor neuron disease (Orphanet:275872), Autosomal dominant hereditary chronic pancreatitis (Orphanet:676), Proximal spinal muscular atrophy (Orphanet:70), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

79 total (30 of 79 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000012	Urinary urgency
HP:0000020	Urinary incontinence
HP:0000365	Hearing impairment
HP:0000511	Vertical supranuclear gaze palsy
HP:0000543	Optic disc pallor
HP:0000605	Supranuclear gaze palsy
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0001257	Spasticity
HP:0001258	Spastic paraplegia
HP:0001260	Dysarthria
HP:0001272	Cerebellar atrophy
HP:0001288	Gait disturbance
HP:0001310	Dysmetria
HP:0001324	Muscle weakness
HP:0001328	Specific learning disability
HP:0001347	Hyperreflexia
HP:0001350	Slurred speech
HP:0001611	Hypernasal speech
HP:0001761	Pes cavus
HP:0002015	Dysphagia
HP:0002061	Lower limb spasticity
HP:0002064	Spastic gait
HP:0002066	Gait ataxia
HP:0002070	Limb ataxia
HP:0002071	Abnormality of extrapyramidal motor function
HP:0002075	Dysdiadochokinesis
HP:0002120	Cerebral cortical atrophy

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST006979_644	Heel bone mineral density	3.000000e-10
GCST007486_17	Hair morphology traits	8.000000e-11
GCST008968_2	White coat effect (clinic systolic blood pressure minus ambulatory systolic blood pressure)	2.000000e-06
GCST009379_173	Type 2 diabetes	3.000000e-09
GCST90000025_112	Appendicular lean mass	3.000000e-20

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density
EFO:0006944	systolic blood pressure change measurement
EFO:0004980	appendicular lean mass

MeSH disease descriptors (10)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
D029241	Optic Atrophy, Autosomal Dominant	C10.292.700.225.500.100; C10.574.500.662.100; C11.270.564.100; C11.640.451.451.100; C16.320.290.564.100; C16.320.400.630.100; C18.452.660.665
D009901	Optic Nerve Diseases	C10.292.700; C11.640
D058499	Retinal Dystrophies	C11.768.585.658
D015419	Spastic Paraplegia, Hereditary	C10.500.300.820; C10.574.500.495.820; C10.668.829.800.300.820; C16.131.666.300.820; C16.320.400.375.820
C537262	Hereditary pancreatitis (supp.)
C531684	Hereditary spinal ataxia (supp.)
C564815	Spastic Ataxia (supp.)
C564599	Spastic Paraplegia 7, Autosomal Recessive (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

3 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs12960	Toxicity	3	docetaxel;thalidomide	Prostatic Neoplasms
rs2019604	Toxicity	4	anthracyclines and related substances	Neoplasms
rs2292954	Toxicity	3	docetaxel;thalidomide	Prostatic Neoplasms

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs12960	RPL13, SNORD68, SPG7	3	2.00	1	docetaxel;thalidomide
rs2019604	RPL13, SPG7	4	-1.25	1	anthracyclines and related substances
rs2292954	RPL13, SPG7	3	2.00	1	docetaxel;thalidomide

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation, increases mutagenesis	2
bisphenol F	affects cotreatment, decreases expression	1
alpha-pinene	affects cotreatment, affects expression, affects oxidation, increases abundance	1
bisphenol A	decreases expression	1
sodium arsenate	decreases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	decreases expression	1
manganese chloride	increases abundance, decreases expression	1
nickel sulfate	increases expression	1
methacrylaldehyde	affects expression, affects oxidation, increases abundance, affects cotreatment	1
beta-methylcholine	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
2-palmitoylglycerol	increases expression	1
perfluorohexanesulfonic acid	decreases expression	1
bisphenol S	affects cotreatment, decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Acetaminophen	increases expression	1
Acrolein	affects oxidation, increases abundance, affects cotreatment, affects expression	1
Air Pollutants	affects cotreatment, affects expression, affects oxidation, increases abundance	1
Arsenic	affects methylation	1
Atrazine	decreases expression	1
Cocaine	decreases expression	1
Copper	increases expression, affects binding	1
Dexamethasone	affects cotreatment, decreases expression	1
Disulfiram	affects binding, increases expression	1

Cellosaurus cell lines

1 cell lines: 1 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B0FN	ZZUi030-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT07542548	PHASE4	COMPLETED	D-Cycloserine for Serine Palmitoyltransferase Inhibition
NCT03351998	PHASE4	COMPLETED	Impact of Statin Therapy on Muscle Mitochondrial Function and Aerobic Capacity
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
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
NCT00324454	PHASE2	COMPLETED	Levetiracetam for Cramps, Spasticity and Neuroprotection in Motor Neuron Disease
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]
NCT03961906	PHASE2	COMPLETED	Physiotherapy in Hereditary Spastic Paraplegia
NCT04768166	PHASE2	COMPLETED	Testing Miglustat Administration in Subjects With Spastic Paraplegia 11
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
NCT00202397	PHASE2	COMPLETED	Effect of Riluzole as a Symptomatic Approach in Patients With Chronic Cerebellar Ataxia
NCT06461286	PHASE1	ACTIVE_NOT_RECRUITING	SAD of IVT PYC-001 in OPA1 Mutation-Associated Autosomal Dominant Optic Atrophy (Sundew)
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)
NCT06117020	PHASE1	COMPLETED	Single and Multiple Ascending Dose Study of MTR-601 in Healthy Individuals
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