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

Summary

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

Location:: 16q24.3

Exon count:: 22

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	16	NC_000016.10 (89508388..89557768)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	16	NC_060940.1 (95589029..95638316)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	16	NC_000016.9 (89574796..89624176)

Chromosome 16 - NC_000016.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: 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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
Impaired flickering of the permeability transition pore causes SPG7 spastic paraplegia.
Title: Impaired flickering of the permeability transition pore causes SPG7 spastic paraplegia.
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.
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.
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.
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.
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	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-61034 (e-PCR)
- UniSTS:49937

SHGC-148983 (e-PCR)
- UniSTS:176720

D16S2548E (e-PCR)
- UniSTS:151637

PMC25060P1 (e-PCR)
- UniSTS:272279

RH65258 (e-PCR)
- UniSTS:85735

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
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 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
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	TAS Traceable Author Statement more info	PubMed

General protein information

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Preferred Names: 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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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

NG_008082.1 RefSeqGene

Range

5007..54370

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001363850.1 → NP_001350779.1 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
NM_003119.4 → NP_003110.1 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
NM_199367.3 → NP_955399.1 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_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000016.10 Reference GRCh38.p14 Primary Assembly

Range

89508388..89557768

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017023598.2 → XP_016879087.1 paraplegin isoform X1

UniProtKB/TrEMBL

A0A2R8Y6E8
XM_047434538.1 → XP_047290494.1 paraplegin isoform X3

UniProtKB/TrEMBL

A0A2R8YFJ7

Related

ENSP00000493908.1, ENST00000645042.1
XM_005256321.5 → XP_005256378.1 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
XM_047434539.1 → XP_047290495.1 paraplegin isoform X4
XM_047434537.1 → XP_047290493.1 paraplegin isoform X2
XM_047434540.1 → XP_047290496.1 paraplegin isoform X6

Related

ENSP00000496434.1, ENST00000646445.1