SLC25A11
protein-codingsolute carrier family 25 member 11, the group of Solute carrier family 25
Gene summary
The oxoglutarate/malate carrier transports 2-oxoglutarate across the inner membranes of mitochondria in an electroneutral exchange for malate or other dicarboxylic acids (summary by Iacobazzi et al., 1992 [PubMed 1457818]).[supplied by OMIM, Jan 2011]
- SLC20A4
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~2.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0017366
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0032767
Submitter: Ambry Genetics
Inheritance Pattern: Unknown
Disease ID:MONDO:0032767
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Oncologic
Intervention: Oncologic
Rationale: The condition can involve increased risk of the development of ceratain types of neoplasms, and awareness may allow early diagnosis and management
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SLC25A11 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003562.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 4 | 19 | 24 | ||
| missense | 3 | 42 | 2 | 47 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 5 | 0 | 48 | 21 | 0 | 74 |
Highest pathogenic variant AF is 0.0000020534105
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003553.2 | 8 | MANE Select | |
| Ensembl | ENSP00000225665.7 | 8 | MANE Select | |
| RefSeq | NP_001158889.1 | 8 | Standard | |
| RefSeq | NP_001158890.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Transfer of Acetyl Groups into Mitochondria
- Malate-Aspartate Shuttle
- Gluconeogenesis
- Glycogenosis, Type IA. Von gierke disease
- Glycogenosis, Type IC
Biological Process
- gluconeogenesis
- alpha-ketoglutarate transport
- transmembrane transport
Molecular Function
- RNA binding
- oxoglutarate:malate antiporter activity
Cellular Component
- nucleus
- mitochondrion
- mitochondrial inner membrane
- integral component of plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000225665
- Coding exons
- 8
- Length
- 3122
- Individuals with no LoFs
- 125716
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 7
- Defined
- 125723
- p
- 0.0000278
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.49 | 105 | 205 | 0.511 | 0.0000134 | 2008 |
| Missense (PolyPhen) | 20 | 72.57 | 0.27559 | 608 | ||
| Synonymous | -0.516 | 88 | 82.1 | 1.07 | 0.00000516 | 666 |
| Loss of Function | 2.89 | 3 | 15.2 | 0.198 | 8.47e-7 | 159 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000047 | 0.000046 | rare |
| European (Non-Finnish) | 0.000035 | 0.000035 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Catalyzes the transport of 2-oxoglutarate across the inner mitochondrial membrane in an electroneutral exchange for malate or other dicarboxylic acids, and plays an important role in several metabolic processes, including the malate-aspartate shuttle, the oxoglutarate/isocitrate shuttle, in gluconeogenesis from lactate, and in nitrogen metabolism (By similarity). Maintains mitochondrial fusion and fission events, and the organization and morphology of cristae (PubMed:21448454). Involved in the regulation of apoptosis (By similarity). {ECO:0000250|UniProtKB:P97700, ECO:0000250|UniProtKB:Q9CR62, ECO:0000269|PubMed:21448454}.;
Recessive Scores
- pRec
- 0.318
Intolerance Scores
- LoFtool
- 0.129
- RVIS EVS
- -0.34
- RVIS percentile EVS
- 30.07
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.973
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |