SLC25A46
Identifiers
Aliases	SLC25A46, HMSN6B, solute carrier family 25 member 46, PCH1E
External IDs	OMIM: 610826; MGI: 1914703; HomoloGene: 14518; GeneCards: SLC25A46; OMA:SLC25A46 - orthologs
Gene location (Human) Chr. Chromosome 5 (human)[1] Band 5q22.1 Start 110,738,136 bp[1] End 110,765,161 bp[1]
Gene location (Mouse) Chr. Chromosome 18 (mouse)[2] Band 18|18 B1 Start 31,689,164 bp[2] End 31,742,964 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in secondary oocyte sperm lateral nuclear group of thalamus right ventricle Achilles tendon pars compacta biceps brachii jejunal mucosa pons pars reticulata Top expressed in supraoptic nucleus Epithelium of choroid plexus Region I of hippocampus proper trigeminal ganglion pineal gland superior cervical ganglion interventricular septum medial dorsal nucleus substantia nigra extraocular muscle More reference expression data BioGPS n/a
Gene ontology Molecular function protein binding Cellular component integral component of membrane membrane mitochondrial outer membrane mitochondrion Biological process mitochondrial membrane fission Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 91137 67453 Ensembl ENSG00000164209 ENSMUSG00000024259 UniProt Q96AG3 Q9CQS4 RefSeq (mRNA) NM_001303249 NM_001303250 NM_138773 NM_026165 NM_001357461 RefSeq (protein) NP_001290178 NP_001290179 NP_620128 NP_080441 NP_001344390 Location (UCSC) Chr 5: 110.74 – 110.77 Mb Chr 18: 31.69 – 31.74 Mb PubMed search [3] [4]
Wikidata
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Solute carrier family 25 member 46 is a protein that in humans is encoded by the SLC25A46 gene. This protein is a member of the SLC25 mitochondrial solute carrier family. It is a transmembrane protein located in the mitochondrial outer membrane involved in lipid transfer from the endoplasmic reticulum (ER) to mitochondria.^[5][6] Mutations in this gene result in neuropathy and optic atrophy.^[7]

The SLC25A46 gene is located on the q arm of chromosome 5 in position 22.1 and spans 27,039 base pairs.^[7] The gene produces a 46.2 kDa protein composed of 418 amino acids.^[8][9] This gene has 8 exons and encodes a multi-pass integral membrane protein localized to the mitochondrial outer membrane.^[10][11][12]

The encoded protein is an orphan transporter involved in lipid transfer from the endoplasmic reticulum to mitochondria.^[13][6] It promotes mitochondrial fission and prevents the formation of hyperfilamentous mitochondria. This protein forms a complex with mitofilin (IMMT) on the inner mitochondrial membrane, independent of MFN2.^[5]

Mutations in the SLC25A46 gene, inherited in an autosomal recessive manner, cause type 6B hereditary motor and sensory neuropathy. Symptoms include early-onset optic atrophy, progressive visual loss, and peripheral sensorimotor neuropathy manifesting as axonal Charcot-Marie-Tooth disease, with variable age at onset and severity.^[11][12]

Overexpression of this protein causes mitochondrial fragmentation while knockdown of this protein causes mitochondrial hyperfusion and hyperfilamentous mitochondria due to decreased mitochondrial fission.^[5] Loss of this gene also has many other effects: premature cellular senescence, impaired cellular respiration, destabilization of the MICOS (mitochondrial contact site and cristae organizing system) complex, loss of and shortened cristae, altered ER morphology, impaired cell migration, and changes in mitochondrial phospholipid composition.^[6]

This protein interacts with IMMT, a component of the MICOS complex, along with other components of this complex and components of an ER membrane protein complex involved in transferring lipids to mitochondria.^[11][12][6] Additionally, this protein interacts with SLC7A8, SLC10A1, SLC10A6, FHL3, FUNDC1, linc01142, LEPROTL1, ODF4, VMA21, MFSD14B, PQLC1, HSD17B11, REEP2, REEP4, and TOMM22.^[14] This protein possibly interacts with OPA1 and MFN2.^[6]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.