SLC5A12
protein-codingsolute carrier family 5 member 12, the group of Solute carrier family 5
Gene summary
Normal blood lactate is maintained at about 1.5 mM, and little filtered lactate is excreted in urine. Reabsorption of lactate is mediated by the low-affinity Na(+)-coupled lactate transporter SLC5A12 in the initial part of the proximal tubule and by the high-affinity Na(+)-coupled lactate transporter SLC5A8 (MIM 608044) in the distal proximal tubule (Gopal et al., 2007 [PubMed 17692818]).[supplied by OMIM, Dec 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~56.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SLC5A12 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_178498.4. 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 | 2 | 3 | |||
| missense | 77 | 2 | 79 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 79 | 4 | 0 | 83 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_848593.2 | 15 | MANE Select | |
| Ensembl | ENSP00000379326.3 | 15 | MANE Select | |
| Ensembl | ENSP00000280467.6 | 9 | Standard | |
| Ensembl | ENSP00000280467.6 | 9 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Nuclear Receptors Meta-Pathway
- NRF2 pathway
- Transport of inorganic cations/anions and amino acids/oligopeptides
- SLC-mediated transmembrane transport
- Transport of small molecules
Biological Process
- ion transport
- sodium ion transport
- lactate transmembrane transport
Molecular Function
- organic acid:sodium symporter activity
- lactate transmembrane transporter activity
Cellular Component
- plasma membrane
- integral component of membrane
- apical plasma membrane
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000396005
- Coding exons
- 15
- Length
- 56409
- Individuals with no LoFs
- 125702
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 46
- Defined
- 125748
- p
- 0.000183
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.15 | 267 | 326 | 0.820 | 0.0000158 | 3963 |
| Missense (PolyPhen) | 95 | 136.72 | 0.69487 | 1640 | ||
| Synonymous | -0.0941 | 119 | 118 | 1.01 | 0.00000571 | 1243 |
| Loss of Function | 2.95 | 16 | 34.8 | 0.460 | 0.00000189 | 390 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00018 | 0.00018 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0.00033 | 0.00032 | rare |
| European (Non-Finnish) | 0.00025 | 0.00025 | rare |
| South Asian | 0.000098 | 0.000098 | rare |
| Other | 0.00018 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Acts as an electroneutral and low-affinity sodium (Na(+))-dependent sodium-coupled solute transporter. Catalyzes the transport across the plasma membrane of many monocarboxylates such as lactate, pyruvate, nicotinate, propionate, butyrate and beta-D- hydroxybutyrate. May be responsible for the first step of reabsorption of monocarboxylates from the lumen of the proximal tubule of the kidney and the small intestine. May play also a role in monocarboxylates transport in the retina (By similarity). Mediates electroneutral uptake of lactate, with a stoichiometry of 2 Na(+) for each lactate (By similarity). {ECO:0000250, ECO:0000269|PubMed:17692818}.;
Recessive Scores
- pRec
- 0.0863
Intolerance Scores
- LoFtool
- 0.278
- RVIS EVS
- -0.07
- RVIS percentile EVS
- 48.69
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.160
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |