SLC19A2
protein-codingsolute carrier family 19 member 2, the group of Solute carrier family 19
Gene summary
This gene encodes the thiamin transporter protein. Mutations in this gene cause thiamin-responsive megaloblastic anemia syndrome (TRMA), which is an autosomal recessive disorder characterized by diabetes mellitus, megaloblastic anemia and sensorineural deafness. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2016]
- TRMA
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~22.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0009575
Submitter: Genomics England PanelApp
Inheritance Pattern: AR
Disease ID:MONDO:0009575
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0009575
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0009575
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0009575
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0009575
Submitter: Natera
Clinical Genomic Database (CGD)
Manifestation: Audiologic/Otolaryngologic; Endocrine; Hematologic
Intervention: Endocrine; Hematologic
Rationale: High-dose thiamine can improve anemia and may ameliorate diabetes; Individuals may also have sensorineural hearing loss, but prelingual onset appears to have not been reported
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SLC19A2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006996.3. 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 | 4 | 153 | 1 | 158 | ||
| missense | 2 | 10 | 159 | 12 | 2 | 185 |
| nonsense | 18 | 2 | 2 | 22 | ||
| start loss | 0 | |||||
| frameshift | 21 | 3 | 2 | 26 | ||
| splice donor/acceptor (+/-2bp) | 3 | 4 | 7 | |||
| Total | 44 | 19 | 167 | 165 | 3 | 398 |
Highest pathogenic variant AF is 0.000038418828
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_008927.1 | 6 | MANE Select | |
| Ensembl | ENSP00000236137.5 | 6 | MANE Select | |
| RefSeq | NP_001306596.1 | 5 | Standard | |
| Ensembl | ENSP00000356778.3 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Vitamin digestion and absorption - Homo sapiens (human)
- Thiamine Metabolism
- Glucocorticoid Receptor Pathway
- Nuclear Receptors Meta-Pathway
- Vitamin B1 (thiamin) metabolism
Biological Process
- folic acid transport
- thiamine transport
- thiamine-containing compound metabolic process
- transmembrane transport
- thiamine transmembrane transport
Molecular Function
- protein binding
- folic acid transmembrane transporter activity
- thiamine transmembrane transporter activity
Cellular Component
- plasma membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000236137
- Coding exons
- 6
- Length
- 22095
- Individuals with no LoFs
- 125710
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 38
- Defined
- 125748
- p
- 0.000151
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.192 | 263 | 272 | 0.967 | 0.0000136 | 3165 |
| Missense (PolyPhen) | 123 | 117.07 | 1.0507 | 1440 | ||
| Synonymous | 0.302 | 104 | 108 | 0.963 | 0.00000539 | 1061 |
| Loss of Function | 2.36 | 9 | 20.6 | 0.438 | 0.00000105 | 221 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00019 | 0.00018 | rare |
| South Asian | 0.00026 | 0.00026 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: High-affinity transporter for the intake of thiamine. {ECO:0000269|PubMed:10391222, ECO:0000269|PubMed:10542220}.;
Recessive Scores
- pRec
- 0.159
Intolerance Scores
- LoFtool
- 0.258
- RVIS EVS
- -0.27
- RVIS percentile EVS
- 34.6
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.323
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |