SLC25A46 solute carrier family 25 member 46 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SLC25A46provided by HGNC
Official Full Name: solute carrier family 25 member 46provided by HGNC
Primary source: HGNC:HGNC:25198
See related: Ensembl:ENSG00000164209 MIM:610826; AllianceGenome:HGNC:25198
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: PCH1E; HMSN6B
Summary: This gene encodes a mitochondrial solute carrier protein family member. It functions in promoting mitochondrial fission, and prevents the formation of hyperfilamentous mitochondria. Mutation of this gene results in neuropathy and optic atrophy. [provided by RefSeq, Aug 2016]
Expression: Ubiquitous expression in brain (RPKM 17.7), thyroid (RPKM 13.2) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 5q22.1

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	5	NC_000005.10 (110738145..110765157)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	5	NC_060929.1 (111248730..111275743)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	5	NC_000005.9 (110073846..110100857)

Chromosome 5 - NC_000005.10 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

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The role of the mitochondrial outer membrane protein SLC25A46 in mitochondrial fission and fusion.
Title: The role of the mitochondrial outer membrane protein SLC25A46 in mitochondrial fission and fusion.
SLC25A46 mutations in patients with Parkinson's Disease and optic atrophy.
Title: SLC25A46 mutations in patients with Parkinson's Disease and optic atrophy.
Using exome sequencing, we identified biallelic disease-segregating loss-of-function mutations in SLC25A46 in both families. Our study adds to the definition of the SLC25A46-associated phenotypic spectrum that includes neonatal fatalities due to pontocerebellar hypoplasia as the severe extreme.
Title: Extension of the phenotype of biallelic loss-of-function mutations in SLC25A46 to the severe form of pontocerebellar hypoplasia type I.
Mutations in SLC25A46 were linked to three children in a Dutch family with pontocerebellar hypoplasia with spinal muscular dystrophy.
Title: Pontocerebellar hypoplasia with spinal muscular atrophy (PCH1): identification of SLC25A46 mutations in the original Dutch PCH1 family.
Mutation in SLC25A46 (NM_001303249.2:c.775C>T;p.(Arg259Cys)) causes optic atrophy and progressive limb spasticity, with no cerebellar atrophy or axonal neuropathy.
Title: A novel mutation in SLC25A46 causes optic atrophy and progressive limb spasticity, with no cerebellar atrophy or axonal neuropathy.
This study reported a novel variant (p.Trp160Ser) in SLC25A46 and we broaden the phenotypic spectrum associated with mutations in SLC25A46.
Title: SLC25A46 Mutations Associated with Autosomal Recessive Cerebellar Ataxia in North African Families.
This study identified of a homozygous missense mutation c.1022T>C and a homozygous genomic deletion involving exon 1 in SLC25A46 encoding a mitochondrial protein leading to lethal pontocerebellar hypoplasia with apnoea and profound weakness.
Title: Loss of function of SLC25A46 causes lethal congenital pontocerebellar hypoplasia.
These results show that SLC25A46 plays a role in a mitochondrial/endoplasmic reticulum pathway that facilitates lipid transfer, and link altered mitochondrial dynamics to early-onset neurodegenerative disease and cell fate decisions.
Title: SLC25A46 is required for mitochondrial lipid homeostasis and cristae maintenance and is responsible for Leigh syndrome.
SLC25A46 is selectively degraded from the outer membrane independently of mitophagy and apoptosis, providing a framework for mechanistic studies in the proteolysis of outer membrane proteins
Title: Rapid degradation of mutant SLC25A46 by the ubiquitin-proteasome system results in MFN1/2-mediated hyperfusion of mitochondria.
Our mutant mice provide a valid model for understanding the mechanistic basis of the complex SLC25A46-mediated pathologies, as well as for screening potential therapeutic interventions.
Title: Novel insights into SLC25A46-related pathologies in a genetic mouse model.

Submit: New GeneRIF Correction See all GeneRIFs (17)

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
Neuropathy, hereditary motor and sensory, type 6B MedGen: C4225302 OMIM: 616505 GeneReviews: Not available	Compare labs
Pontocerebellar hypoplasia, type 1E MedGen: C5543328 OMIM: 619303 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Genetic variants associated with cardiac structure and function: a meta-analysis and replication of genome-wide association data. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association analysis identifies 11 risk variants associated with the asthma with hay fever phenotype. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis of genome-wide association studies identifies ten loci influencing allergic sensitization. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D5S2563 (e-PCR)
- UniSTS:34305

RH17735 (e-PCR)
- UniSTS:73231

SLC25A46 (e-PCR)
- UniSTS:504930

D5S2477 (e-PCR)
- UniSTS:79863

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-containing complex binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in autophagy of mitochondrion	IEA Inferred from Electronic Annotation more info
involved_in axon development	IBA Inferred from Biological aspect of Ancestor more info
involved_in cerebellar Purkinje cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in cristae formation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in dendrite development	IEA Inferred from Electronic Annotation more info
involved_in establishment of localization in cell	IEA Inferred from Electronic Annotation more info
involved_in locomotion involved in locomotory behavior	IEA Inferred from Electronic Annotation more info
involved_in mitochondrial fission	IBA Inferred from Biological aspect of Ancestor more info
involved_in mitochondrial fission	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within mitochondrial fission	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in mitochondrial fission	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in mitochondrial membrane fission	IEA Inferred from Electronic Annotation more info
involved_in mitochondrial transport	IEA Inferred from Electronic Annotation more info
involved_in myelination in peripheral nervous system	IEA Inferred from Electronic Annotation more info
involved_in optic nerve development	IEA Inferred from Electronic Annotation more info
involved_in peripheral nervous system neuron axonogenesis	IEA Inferred from Electronic Annotation more info
involved_in phospholipid homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein-containing complex assembly	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within respiratory chain complex IV assembly	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in synapse assembly	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
is_active_in mitochondrial outer membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in mitochondrial outer membrane	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrial outer membrane	IMP Inferred from Mutant Phenotype more info	PubMed
located_in mitochondrion	HTP more info	PubMed
located_in mitochondrion	IDA Inferred from Direct Assay more info

General protein information

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Preferred Names: mitochondrial outer membrane protein SLC25A46

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_051334.1 RefSeqGene

Range

5872..32022

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_1091

mRNA and Protein(s)

NM_001303249.3 → NP_001290178.1 mitochondrial outer membrane protein SLC25A46 isoform 2

See identical proteins and their annotated locations for NP_001290178.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 3' coding region, compared to variant 1. The encoded isoform (2) is shorter than isoform 1.

Source sequence(s)

AC008650, AK300123, BC017169, DA713164

Consensus CDS

CCDS78045.1

UniProtKB/Swiss-Prot

Q96AG3

Related

ENSP00000399717.2, ENST00000447245.6

Conserved Domains (1) summary

pfam00153
Location:236 → 321

Mito_carr; Mitochondrial carrier protein
NM_001303250.3 → NP_001290179.1 mitochondrial outer membrane protein SLC25A46 isoform 3 precursor

See identical proteins and their annotated locations for NP_001290179.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (3) has a distinct and shorter N-terminus than isoform 1.

Source sequence(s)

AC008650, AK302326, BC017169, DB051498

UniProtKB/TrEMBL

B4DY98, D6RBG9

Conserved Domains (1) summary

pfam00153
Location:226 → 311

Mito_carr; Mitochondrial carrier protein
NM_138773.4 → NP_620128.1 mitochondrial outer membrane protein SLC25A46 isoform 1

See identical proteins and their annotated locations for NP_620128.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

AC008650, AK290217, BC017169, DA713164

Consensus CDS

CCDS4100.1

UniProtKB/Swiss-Prot

A8K2F2, B3KRE6, B4DTA3, D3DSZ6, D6R9W7, Q04197, Q96AG3

Related

ENSP00000348211.3, ENST00000355943.8

Conserved Domains (1) summary

pfam00153
Location:317 → 402

Mito_carr; Mitochondrial carrier protein

RNA

NR_138151.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (4) contains an alternate internal exon compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AC008650