SLC25A46

solute carrier family 25 member 46, the group of Solute carrier family 25

Basic information

Region (hg38): 5:110738136-110765161

Links

ENSG00000164209 ∙ NCBI:91137 ∙ OMIM:610826 ∙ HGNC:25198 ∙ Uniprot:Q96AG3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neuropathy, hereditary motor and sensory, type 6B (Moderate), mode of inheritance: AR
• pontocerebellar hypoplasia type 1 (Supportive), mode of inheritance: AR
• hereditary motor and sensory neuropathy type 6 (Supportive), mode of inheritance: AD
• neuropathy, hereditary motor and sensory, type 6B (Definitive), mode of inheritance: AR
• neuropathy, hereditary motor and sensory, type 6B (Strong), mode of inheritance: AR
• pontocerebellar hypoplasia, type 1E (Strong), mode of inheritance: AR
• Leigh syndrome (Limited), mode of inheritance: AR
• neuropathy, hereditary motor and sensory, type 6B (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neuropathy, hereditary motor and sensory, type VIB with optic atrophy; Pontocerebellar hypoplasia, type 1E	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic; Ophthalmologic	26168012; 27390132; 27543974; 28637197; 28653766

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC25A46 gene.

• Neuropathy,_hereditary_motor_and_sensory,_type_6B (319 variants)
• Inborn_genetic_diseases (89 variants)
• not_provided (64 variants)
• Pontocerebellar_hypoplasia,_type_1E (15 variants)
• SLC25A46-related_disorder (11 variants)
• not_specified (7 variants)
• Optic_atrophy (2 variants)
• SLC25A46-associated_optic_atrophy_spectrum_disorder (2 variants)
• Retinal_dystrophy (1 variants)
• Spastic_ataxia (1 variants)
• Intellectual_disability (1 variants)
• Charcot-Marie-Tooth_disease (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC25A46 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000138773.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous	1		1	81	2	85
missense	6	7	174	9	1	197
nonsense	3	4	1			8
start loss	1		1			2
frameshift	7	4	1			12
splice donor/acceptor (+/-2bp)	4	3	1			8
Total	22	18	179	90	3

Highest pathogenic variant AF is 0.000033734712

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC25A46	protein_coding	protein_coding	ENST00000355943	8	27021

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000131	0.959	125706	0	26	125732	0.000103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.160	219	226	0.970	0.0000110	2710
Missense in Polyphen		40	64.128	0.62375		725
Synonymous	0.0169	81	81.2	0.998	0.00000397	834
Loss of Function	1.88	11	20.1	0.547	0.00000111	219

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000217	0.000210
Ashkenazi Jewish	0.00	0.00
East Asian	0.000116	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.000107	0.000106
Middle Eastern	0.000116	0.000109
South Asian	0.000180	0.000163
Other	0.000331	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May play a role in mitochondrial dynamics by controlling mitochondrial membrane fission. {ECO:0000269|PubMed:26168012}.
• Disease: DISEASE: Neuropathy, hereditary motor and sensory, 6B (HMSN6B) [MIM:616505]: An autosomal recessive neurologic disorder characterized by 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. Charcot-Marie-Tooth disease is a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. It is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies and primary peripheral axonal neuropathies. Peripheral axonal neuropathies are characterized by signs of axonal regeneration in the absence of obvious myelin alterations, and normal or slightly reduced nerve conduction velocities. {ECO:0000269|PubMed:26168012}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.107

Intolerance Scores

• loftool: 0.373
• rvis_EVS: 0.84
• rvis_percentile_EVS: 88.3

Haploinsufficiency Scores

• pHI: 0.184
• hipred: N
• hipred_score: 0.333
• ghis: 0.454

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.424

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Slc25a46

Zebrafish Information Network

• Gene name: slc25a46
• Affected structure: retinal ganglion cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: mitochondrial membrane fission
• Cellular component: mitochondrion;mitochondrial outer membrane;integral component of membrane
• Molecular function: protein binding