AFG3L2 AFG3 like matrix AAA peptidase subunit 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: AFG3L2provided by HGNC
Official Full Name: AFG3 like matrix AAA peptidase subunit 2provided by HGNC
Primary source: HGNC:HGNC:315
See related: Ensembl:ENSG00000141385 MIM:604581; AllianceGenome:HGNC:315
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: OPA12; SCA28; SPAX5
Summary: This gene encodes a protein localized in mitochondria and closely related to paraplegin. The paraplegin gene is responsible for an autosomal recessive form of hereditary spastic paraplegia. This gene is a candidate gene for other hereditary spastic paraplegias or neurodegenerative disorders. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in duodenum (RPKM 38.9), heart (RPKM 35.3) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 18p11.21

Exon count:: 17

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	18	NC_000018.10 (12328944..12377227, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	18	NC_060942.1 (12491960..12540204, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	18	NC_000018.9 (12328943..12377226, complement)

Chromosome 18 - NC_000018.10 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 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?

AFG3L2 and ACO2-Linked Dominant Optic Atrophy: Genotype-Phenotype Characterization Compared to OPA1 Patients.
Title: AFG3L2 and ACO2-Linked Dominant Optic Atrophy: Genotype-Phenotype Characterization Compared to OPA1 Patients.
Dual regulation of SLC25A39 by AFG3L2 and iron controls mitochondrial glutathione homeostasis.
Title: Dual regulation of SLC25A39 by AFG3L2 and iron controls mitochondrial glutathione homeostasis.
Autoregulatory control of mitochondrial glutathione homeostasis.
Title: Autoregulatory control of mitochondrial glutathione homeostasis.
AFG3L2 Biallelic Mutation: Clinical Heterogeneity in Two Italian Patients.
Title: AFG3L2 Biallelic Mutation: Clinical Heterogeneity in Two Italian Patients.
Expanding the phenotype of AFG3L2 mutations: Late-onset autosomal recessive spinocerebellar ataxia.
Title: Expanding the phenotype of AFG3L2 mutations: Late-onset autosomal recessive spinocerebellar ataxia.
A novel AFG3L2 mutation close to AAA domain leads to aberrant OMA1 and OPA1 processing in a family with optic atrophy.
Title: A novel AFG3L2 mutation close to AAA domain leads to aberrant OMA1 and OPA1 processing in a family with optic atrophy.
Spastic ataxia with eye-of-the-tiger-like sign in 4 siblings due to novel compound heterozygous AFG3L2 mutation.
Title: Spastic ataxia with eye-of-the-tiger-like sign in 4 siblings due to novel compound heterozygous AFG3L2 mutation.
Inactivation of the mitochondrial protease Afg3l2 results in severely diminished respiratory chain activity and widespread defects in mitochondrial gene expression.
Title: Inactivation of the mitochondrial protease Afg3l2 results in severely diminished respiratory chain activity and widespread defects in mitochondrial gene expression.
ATPase Domain AFG3L2 Mutations Alter OPA1 Processing and Cause Optic Neuropathy.
Title: ATPase Domain AFG3L2 Mutations Alter OPA1 Processing and Cause Optic Neuropathy.
Our data identify the earliest events in SCA28 pathogenesis and open new perspectives for therapy. By identifying similar mitochondrial phenotypes between SCA28 cells and AFG3L2(+/-) cells, our results support haploinsufficiency as the mechanism for the studied pathogenic variants.
Title: Pathogenic variants in the AFG3L2 proteolytic domain cause SCA28 through haploinsufficiency and proteostatic stress-driven OMA1 activation.

Submit: New GeneRIF Correction See all GeneRIFs (30)

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
Optic atrophy 12 MedGen: C5436534 OMIM: 618977 GeneReviews: Not available	Compare labs
Spastic ataxia 5 MedGen: C3280977 OMIM: 614487 GeneReviews: Hereditary Ataxia Overview	Compare labs
Spinocerebellar ataxia type 28 MedGen: C1853249 OMIM: 610246 GeneReviews: Hereditary Ataxia Overview, Spinocerebellar Ataxia Type 28	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 AFG3 ATPase family gene 3-like 2 (AFG3L2) 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

RH104597 (e-PCR)
- UniSTS:99862

SHGC-36229 (e-PCR)
- UniSTS:66176

RH75493 (e-PCR)
- UniSTS:84173

RH65391 (e-PCR)
- UniSTS:25565

STS-N21031 (e-PCR)
- UniSTS:52708

D18S902E (e-PCR)
- UniSTS:150512

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables ATP hydrolysis activity	IDA Inferred from Direct Assay more info	PubMed
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 metallopeptidase activity	IMP Inferred from Mutant Phenotype 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 axonogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in calcium import into the mitochondrion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to glutathione	IDA Inferred from Direct Assay more info	PubMed
involved_in cristae formation	IEA Inferred from Electronic Annotation more info
involved_in membrane protein proteolysis	IDA Inferred from Direct Assay more info	PubMed
involved_in mitochondrial calcium ion homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in mitochondrial fusion	IEA Inferred from Electronic Annotation more info
involved_in mitochondrial protein processing	IBA Inferred from Biological aspect of Ancestor more info
involved_in mitochondrial protein quality control	IDA Inferred from Direct Assay more info	PubMed
involved_in muscle cell development	IEA Inferred from Electronic Annotation more info
involved_in myelination	IEA Inferred from Electronic Annotation more info
involved_in nerve development	IEA Inferred from Electronic Annotation more info
involved_in neuromuscular junction development	IEA Inferred from Electronic Annotation more info
involved_in protein autoprocessing	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in protein maturation	IDA Inferred from Direct Assay more info	PubMed
involved_in protein processing	ISS Inferred from Sequence or Structural Similarity more info
involved_in proteolysis	IDA Inferred from Direct Assay more info	PubMed
involved_in proteolysis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of calcium import into the mitochondrion	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of multicellular organism growth	IEA Inferred from Electronic Annotation more info
involved_in righting reflex	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
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
is_active_in mitochondrial inner membrane	TAS Traceable Author Statement more info	PubMed
located_in mitochondrial inner membrane	TAS Traceable Author Statement more info
located_in mitochondrion	HTP more info	PubMed
located_in mitochondrion	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: mitochondrial inner membrane m-AAA protease component AFG3L2

Names: AFG3 ATPase family gene 3-like 2; AFG3 ATPase family member 3-like 2; AFG3 like AAA ATPase 2; AFG3-like protein 2; ATPase family gene 3, yeast; paraplegin-like 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_023361.1 RefSeqGene

Range

5001..53333

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_666

mRNA and Protein(s)

NM_006796.3 → NP_006787.2 mitochondrial inner membrane m-AAA protease component AFG3L2

See identical proteins and their annotated locations for NP_006787.2

Status: REVIEWED

Source sequence(s)

BC024282, BU786821, BX091241, DN993083

Consensus CDS

CCDS11859.1

UniProtKB/Swiss-Prot

Q6P1L0, Q9Y4W6

UniProtKB/TrEMBL

A0A8I5KVV1

Related

ENSP00000269143.2, ENST00000269143.8

Conserved Domains (2) summary

pfam06480
Location:146 → 242

FtsH_ext; FtsH Extracellular

cl27568
Location:253 → 746

TIP49; TIP49 C-terminus

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

NC_000018.10 Reference GRCh38.p14 Primary Assembly

Range

12328944..12377227 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011525601.4 → XP_011523903.1 mitochondrial inner membrane m-AAA protease component AFG3L2 isoform X1

UniProtKB/TrEMBL

A0A8I5KVV1

Conserved Domains (4) summary

TIGR01241
Location:253 → 679

FtsH_fam; ATP-dependent metalloprotease FtsH

pfam00004
Location:345 → 476

AAA; ATPase family associated with various cellular activities (AAA)

pfam01434
Location:562 → 677

Peptidase_M41; Peptidase family M41

pfam06480
Location:146 → 242

FtsH_ext; FtsH Extracellular