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    SPG7 SPG7 matrix AAA peptidase subunit, paraplegin [ Homo sapiens (human) ]

    Gene ID: 6687, updated on 2-Nov-2024

    Summary

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    Official Symbol
    SPG7provided by HGNC
    Official Full Name
    SPG7 matrix AAA peptidase subunit, parapleginprovided by HGNC
    Primary source
    HGNC:HGNC:11237
    See related
    Ensembl:ENSG00000197912 MIM:602783; AllianceGenome:HGNC:11237
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    CAR; PGN; CMAR; SPG5C
    Summary
    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. [provided by RefSeq, Mar 2014]
    Expression
    Ubiquitous expression in thyroid (RPKM 11.5), skin (RPKM 10.1) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See SPG7 in Genome Data Viewer
    Location:
    16q24.3
    Exon count:
    22
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 16 NC_000016.10 (89508388..89557768)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 16 NC_060940.1 (95589029..95638316)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 16 NC_000016.9 (89574796..89624176)

    Chromosome 16 - NC_000016.10Genomic Context describing neighboring genes Neighboring gene ankyrin repeat domain containing 11 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:89524753-89525254 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:89525255-89525754 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:89529183-89530171 Neighboring gene CMPK1 pseudogene 2 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:89553656-89554156 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:89554157-89554657 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11413 Neighboring gene H3K27ac hESC enhancer GRCh37_chr16:89555515-89556028 Neighboring gene H3K27ac hESC enhancer GRCh37_chr16:89556029-89556543 Neighboring gene uncharacterized LOC101930112 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7907 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7906 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7908 Neighboring gene uncharacterized LOC101927863 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11414 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7909 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7910 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7911 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7912 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:89585576-89586076 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:89586077-89586577 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr16:89588494-89589051 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:89589052-89589608 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11415 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11416 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:89601956-89602646 Neighboring gene ReSE screen-validated silencer GRCh37_chr16:89625532-89625751 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11417 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7913 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7914 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:89630776-89631518 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:89631519-89632262 Neighboring gene ReSE screen-validated silencer GRCh37_chr16:89640372-89640629 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7915 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7916 Neighboring gene small nucleolar RNA, C/D box 68 Neighboring gene ribosomal protein L13 Neighboring gene copine 7

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Functional evaluation of paraplegin mutations by a yeast complementation assay. Bonn F, et al. Hum Mutat, 2010 May. PMID 20186691
    2. A founder mutation p.H701P identified as a major cause of SPG7 in Norway. Rydning SL, et al. Eur J Neurol, 2016 Apr. PMID 26756429
    3. SPG7 mutations explain a significant proportion of French Canadian spastic ataxia cases. Choquet K, et al. Eur J Hum Genet, 2016 Jul. PMID 26626314, Free PMC Article
    4. Abnormal Paraplegin Expression in Swollen Neurites, τ- and α-Synuclein Pathology in a Case of Hereditary Spastic Paraplegia SPG7 with an Ala510Val Mutation. Thal DR, et al. Int J Mol Sci, 2015 Oct 21. PMID 26506339, Free PMC Article
    5. Identification of a novel homozygous SPG7 mutation by whole exome sequencing in a Greek family with a complicated form of hereditary spastic paraplegia. Daoud H, et al. Eur J Med Genet, 2015 Nov. PMID 26260707

    See all (91) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. A novel compound heterozygous SPG7 variant is associated with progressive spastic ataxia and persecutory delusions found in Chinese patients: two case reports.
      Title: A novel compound heterozygous SPG7 variant is associated with progressive spastic ataxia and persecutory delusions found in Chinese patients: two case reports.
    2. Novel homozygous SPG7 missense mutation in a Chinese hereditary spastic paraplegia family.
      Title: Novel homozygous SPG7 missense mutation in a Chinese hereditary spastic paraplegia family.
    3. Clinical and genetic characteristics of 21 Spanish patients with biallelic pathogenic SPG7 mutations.
      Title: Clinical and genetic characteristics of 21 Spanish patients with biallelic pathogenic SPG7 mutations.
    4. Neurophysiological and ophthalmological findings of SPG7-related spastic ataxia: a phenotype study in an Irish cohort.
      Title: Neurophysiological and ophthalmological findings of SPG7-related spastic ataxia: a phenotype study in an Irish cohort.
    5. Impaired flickering of the permeability transition pore causes SPG7 spastic paraplegia.
      Title: Impaired flickering of the permeability transition pore causes SPG7 spastic paraplegia.
    6. SPG7 mutations in amyotrophic lateral sclerosis: a genetic link to hereditary spastic paraplegia.
      Title: SPG7 mutations in amyotrophic lateral sclerosis: a genetic link to hereditary spastic paraplegia.
    7. we identified novel variants of SPG7 in two patients with late onset hereditary spastic paraplegias
      Title: High diagnostic yield and novel variants in very late-onset spasticity.
    8. This finding of a missense mutation of SPG7 gene in a primary lateral sclerosis family expands the spectrum of known SPG7 mutations
      Title: Exome Sequencing Identifies a Mutation (Y740C) in Spastic Paraplegia 7 Gene Associated with Adult-Onset Primary Lateral Sclerosis in a Chinese Family.
    9. study provides evidence for two novel candidate genes, SPG7 and RASGEF1B, associating with white coat effect
      Title: Genome-wide association study of white-coat effect in hypertensive patients.
    10. 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.
      Title: Loss of paraplegin drives spasticity rather than ataxia in a cohort of 241 patients with SPG7.
    Submit: New GeneRIF Correction See all GeneRIFs (39)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Hereditary spastic paraplegia 7
    MedGen: C1846564 OMIM: 607259 GeneReviews: Spastic Paraplegia 7, Hereditary Ataxia Overview
    		not available

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    HIV-1 interactions

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    Replication interactions

    Interaction Pubs
    Knockdown of spastic paraplegia 7 (SPG7) by siRNA inhibits the early stages of HIV-1 replication in 293T cells infected with VSV-G pseudotyped HIV-1 PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ37308, MGC126331, MGC126332

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables ATP hydrolysis activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables ATP-dependent peptidase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables metalloendopeptidase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables metalloendopeptidase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables peptidase activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables unfolded protein binding TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables zinc ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in anterograde axonal transport IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in mitochondrial outer membrane permeabilization involved in programmed cell death IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in mitochondrial protein processing IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in nervous system development TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in proteolysis TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in regulation of calcium import into the mitochondrion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of mitochondrial membrane permeability IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in axon cytoplasm IEA
    Inferred from Electronic Annotation
    more info
    		  
    part_of m-AAA complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    part_of m-AAA complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in mitochondrial inner membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in mitochondrial inner membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in mitochondrial inner membrane TAS
    Traceable Author Statement
    more info
    		  
    part_of mitochondrial permeability transition pore complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in mitochondrion HTP PubMed 

    General protein information

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    Preferred Names
    mitochondrial inner membrane m-AAA protease component paraplegin
    Names
    SPG7, paraplegin matrix AAA peptidase subunit
    cell matrix adhesion regulator
    spastic paraplegia 7 (pure and complicated autosomal recessive)
    spastic paraplegia 7 protein

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_008082.1 RefSeqGene

      Range
      5007..54370
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001363850.1 → NP_001350779.1  mitochondrial inner membrane m-AAA protease component paraplegin isoform 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) represents the longest transcript and encodes the longest isoform (3).
      Source sequence(s)
      AC092123, BC036104, BC052587, HY006239, Y16610
      Consensus CDS
      CCDS92212.1
      UniProtKB/TrEMBL
      A0A2R8Y3M4, A0A2U3TZH1
      Related
      ENSP00000493590.1, ENST00000645063.1
      Conserved Domains (2) summary
      pfam06480
      Location:145 → 242
      FtsH_ext; FtsH Extracellular
      cl27568
      Location:265 → 729
      TIP49; TIP49 C-terminus

    2. NM_003119.4 → NP_003110.1  mitochondrial inner membrane m-AAA protease component paraplegin isoform 1 precursor

      See identical proteins and their annotated locations for NP_003110.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      BC036104, HY006239, Y16610
      Consensus CDS
      CCDS10977.1
      UniProtKB/Swiss-Prot
      O75756, Q2TB70, Q58F00, Q96IB0, Q9UQ90
      UniProtKB/TrEMBL
      A0A2U3TZH1
      Related
      ENSP00000495795.2, ENST00000645818.2
      Conserved Domains (5) summary
      TIGR01241
      Location:265 → 748
      FtsH_fam; ATP-dependent metalloprotease FtsH
      pfam00004
      Location:346 → 479
      AAA; ATPase family associated with various cellular activities (AAA)
      pfam01434
      Location:561 → 746
      Peptidase_M41; Peptidase family M41
      pfam06480
      Location:145 → 242
      FtsH_ext; FtsH Extracellular
      cl21455
      Location:308 → 364
      P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases

    3. NM_199367.3 → NP_955399.1  mitochondrial inner membrane m-AAA protease component paraplegin isoform 2 precursor

      See identical proteins and their annotated locations for NP_955399.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks multiple 3' coding exons and contains an alternate 3' terminal exon, resulting in a different 3' coding region and 3' UTR, compared to variant 1. The encoded isoform (2) contains a shorter and distinct C-terminus compared to isoform 1.
      Source sequence(s)
      BC007692, CA447374, HY006239, Y16610
      Consensus CDS
      CCDS10978.1
      UniProtKB/TrEMBL
      A0A2R8Y729
      Related
      ENSP00000341157.2, ENST00000341316.6
      Conserved Domains (3) summary
      pfam00004
      Location:346 → 447
      AAA; ATPase family associated with various cellular activities (AAA)
      pfam06480
      Location:145 → 242
      FtsH_ext; FtsH Extracellular
      cl21455
      Location:308 → 364
      P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000016.10 Reference GRCh38.p14 Primary Assembly

      Range
      89508388..89557768
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017023598.2 → XP_016879087.1  mitochondrial inner membrane m-AAA protease component paraplegin isoform X1

      UniProtKB/TrEMBL
      A0A2R8Y6E8

    2. XM_047434538.1 → XP_047290494.1  mitochondrial inner membrane m-AAA protease component paraplegin isoform X3

      UniProtKB/TrEMBL
      A0A2R8YFJ7
      Related
      ENSP00000493908.1, ENST00000645042.1

    3. XM_005256321.5 → XP_005256378.1  mitochondrial inner membrane m-AAA protease component paraplegin isoform X5

      UniProtKB/TrEMBL
      A0A2R8Y632, A0A2R8Y7N2
      Related
      ENSP00000495219.1, ENST00000646930.1
      Conserved Domains (3) summary
      pfam00004
      Location:346 → 441
      AAA; ATPase family associated with various cellular activities (AAA)
      pfam06480
      Location:145 → 242
      FtsH_ext; FtsH Extracellular
      cl21455
      Location:308 → 364
      P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases

    4. XM_047434539.1 → XP_047290495.1  mitochondrial inner membrane m-AAA protease component paraplegin isoform X4

    5. XM_047434537.1 → XP_047290493.1  mitochondrial inner membrane m-AAA protease component paraplegin isoform X2

    6. XM_047434540.1 → XP_047290496.1  mitochondrial inner membrane m-AAA protease component paraplegin isoform X6

      Related
      ENSP00000496434.1, ENST00000646445.1

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060940.1 Alternate T2T-CHM13v2.0

      Range
      95589029..95638316
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054313779.1 → XP_054169754.1  mitochondrial inner membrane m-AAA protease component paraplegin isoform X1

    2. XM_054313781.1 → XP_054169756.1  mitochondrial inner membrane m-AAA protease component paraplegin isoform X3

      UniProtKB/TrEMBL
      A0A2R8YFJ7

    3. XM_054313782.1 → XP_054169757.1  mitochondrial inner membrane m-AAA protease component paraplegin isoform X5

      UniProtKB/TrEMBL
      A0A2R8Y632

    4. XM_054313780.1 → XP_054169755.1  mitochondrial inner membrane m-AAA protease component paraplegin isoform X2

    5. XM_054313783.1 → XP_054169758.1  mitochondrial inner membrane m-AAA protease component paraplegin isoform X7

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9UQ90.2 GenPept UniProtKB/Swiss-Prot:Q9UQ90

    Gene LinkOut

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