SPG7

SPG7 matrix AAA peptidase subunit, paraplegin, the group of AAA ATPases

Basic information

Region (hg38): 16:89490719-89557766

Previous symbols: [ "CMAR" ]

Links

ENSG00000197912NCBI:6687OMIM:602783HGNC:11237Uniprot:Q9UQ90AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • hereditary spastic paraplegia 7 (Definitive), mode of inheritance: AR
  • lateral sclerosis (Supportive), mode of inheritance: AD
  • hereditary spastic paraplegia 7 (Supportive), mode of inheritance: AD
  • hereditary spastic paraplegia 7 (Strong), mode of inheritance: AR
  • hereditary spastic paraplegia 7 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Spastic paraplegia 7, autosomal recessiveARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingNeurologic9635427; 9634528; 16534102; 18200586; 18799786; 20108356; 21623769; 22571692; 22964162
Heterozygotes may demonstrate manifestations

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SPG7 gene.

  • Hereditary_spastic_paraplegia_7 (772 variants)
  • not_provided (392 variants)
  • Inborn_genetic_diseases (108 variants)
  • not_specified (106 variants)
  • Hereditary_spastic_paraplegia (69 variants)
  • SPG7-related_disorder (41 variants)
  • Retinal_dystrophy (10 variants)
  • Spastic_ataxia (5 variants)
  • Leukoencephalopathy_with_vanishing_white_matter_1 (4 variants)
  • Hereditary_ataxia (3 variants)
  • Spastic_paraplegia (2 variants)
  • Spastic_paraparesis (2 variants)
  • Intellectual_disability (2 variants)
  • Spastic_Paraplegia,_Recessive (2 variants)
  • Mitochondrial_disease (2 variants)
  • Sensorimotor_neuropathy (2 variants)
  • Optic_atrophy (2 variants)
  • Cerebral_cortical_atrophy (2 variants)
  • Dysarthria (2 variants)
  • Gait_ataxia (2 variants)
  • Hereditary_pancreatitis (1 variants)
  • Optic_nerve_hypoplasia (1 variants)
  • Polyneuropathy (1 variants)
  • Proximal_spinal_muscular_atrophy (1 variants)
  • Frontotemporal_dementia_and/or_amyotrophic_lateral_sclerosis_2 (1 variants)
  • Seizure (1 variants)
  • Memory_impairment (1 variants)
  • Spastic_tetraparesis (1 variants)
  • Distal_spinal_muscular_atrophy (1 variants)
  • Early-onset_progressive_neurodegeneration-blindness-ataxia-spasticity_syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SPG7 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000003119.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
1
clinvar
16
clinvar
166
clinvar
5
clinvar
188
missense
9
clinvar
48
clinvar
414
clinvar
17
clinvar
2
clinvar
490
nonsense
15
clinvar
23
clinvar
4
clinvar
42
start loss
1
6
7
frameshift
37
clinvar
32
clinvar
3
clinvar
72
splice donor/acceptor (+/-2bp)
10
clinvar
18
clinvar
28
Total 73 127 437 183 7

Highest pathogenic variant AF is 0.0057954653

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
SPG7protein_codingprotein_codingENST00000268704 1766852
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
1.97e-368.36e-812532224241257480.00170
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-0.8725284751.110.00003425129
Missense in Polyphen205215.610.950792137
Synonymous-4.222792031.380.00001631632
Loss of Function-1.694836.91.300.00000225416

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.002120.00212
Ashkenazi Jewish0.0004970.000496
East Asian0.0009790.000979
Finnish0.001070.00106
European (Non-Finnish)0.001950.00191
Middle Eastern0.0009790.000979
South Asian0.003570.00350
Other0.001640.00163

dbNSFP

Source: dbNSFP

Function
FUNCTION: ATP-dependent zinc metalloprotease. Plays a role in the formation and regulation of the mitochondrial permeability transition pore (mPTP) and its proteolytic activity is dispensable for this function (PubMed:26387735). {ECO:0000269|PubMed:26387735, ECO:0000305}.;
Disease
DISEASE: 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. {ECO:0000269|PubMed:16534102, ECO:0000269|PubMed:17646629, ECO:0000269|PubMed:20186691, ECO:0000269|PubMed:27217339, ECO:0000269|PubMed:9635427}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=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. {ECO:0000269|PubMed:20579626}.;
Pathway
Transport of small molecules;Mitochondrial calcium ion transport;Processing of SMDT1 (Consensus)

Intolerance Scores

loftool
0.103
rvis_EVS
-1.05
rvis_percentile_EVS
7.62

Haploinsufficiency Scores

pHI
0.140
hipred
N
hipred_score
0.294
ghis
0.624

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.975

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Spg7
Phenotype
growth/size/body region phenotype; skeleton phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan);

Gene ontology

Biological process
proteolysis;mitochondrial calcium ion transmembrane transport;mitochondrion organization;nervous system development;anterograde axonal transport;regulation of mitochondrial membrane permeability;mitochondrial outer membrane permeabilization involved in programmed cell death
Cellular component
mitochondrion;mitochondrial inner membrane;m-AAA complex;mitochondrial permeability transition pore complex;axon cytoplasm
Molecular function
metalloendopeptidase activity;protein binding;ATP binding;peptidase activity;zinc ion binding;unfolded protein binding