SLC2A10
protein-codingsolute carrier family 2 member 10, the group of Solute carrier family 2
Gene summary
This gene encodes a member of the class III facilitative glucose transporter family. The encoded protein plays a role in regulation of glucose homeostasis. Mutations in this gene have been associated with arterial tortuosity syndrome.[provided by RefSeq, Dec 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~26.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0008818
Submitter: ClinGen
*SLC2A10* has been reported in association with autosomal recessive arterial tortuosity syndrome (ATS) in at least 106 individuals (Callewaert B, De Paepe A, Coucke P, GeneReviews, 2023). Clinical phenotypes of ATS include aortic tortuosity, tortuosity of large and mid-sized arteries, pulmonary artery stenosis, joint hypermobility, ocular abnormalities, and characteristic facial features. Phenotype severity ranges from neonatal lethality to adults with isolated phenotypes. Aortic aneurysms varied from very slowly progressive to rapid dilation and dissection. 14 variants (missense, nonsense, deletion, and frameshift) reported in 10 probands in 4 publications (PMIDs: 17935213, 18818946, 37619836, 29323665) are included in this curation. The mechanism of pathogenicity is loss of function. This gene-disease association is also supported by experimental evidence including protein expression in the aorta (PMID:23715323) and a mouse model double knock out for both SLC2A10 and Gulo that recapitulated isolated phenotypes of ATS including decreases in diameter in the descending aorta and compromised extracellular matrix formation (PMID:32307537). Finally the curation is supported by the biochemical function of *SLC2A10*, which encodes GLUT10, a glucose transporting protein that transports dehydroascorbic acid (DHA). Phenotypes from variants in *SLC2A10* may be a result of impaired vitamin C cellular compartmentalization, increases in ROS/oxidative stress, and defective TGF-B signaling. In summary, *SLC2A10* is definitively associated with autosomal recessive arterial tortuosity syndrome. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. The evidence summary was approved by the Heritable Thoracic Aortic Aneurysm and Dissection subgroup of the Hereditary Cardiovascular Disease Gene Curation Expert Panel on 9/6/2024.
Inheritance Pattern: AR
Disease ID:MONDO:0008818
Submitter: Genomics England PanelApp
Inheritance Pattern: AR
Disease ID:MONDO:0008818
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0008818
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0008818
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0008818
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0008818
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Cardiovascular; Dermatologic; Genitourinary; Musculoskeletal; Renal
Intervention: Cardiovascular
Rationale: Individuals appear to be at increased risk of cradiovascular manifestations, such as ischemic events, arterial aneurysm, and other findings, and preventive measures and prompt treatment may be beneficial
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SLC2A10 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_030777.4. 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 | 192 | 4 | 197 | ||
| missense | 4 | 20 | 298 | 43 | 4 | 369 |
| nonsense | 7 | 4 | 11 | |||
| start loss | 1 | 2 | 3 | |||
| frameshift | 14 | 6 | 1 | 21 | ||
| splice donor/acceptor (+/-2bp) | 4 | 9 | 13 | |||
| Total | 26 | 36 | 309 | 235 | 8 | 614 |
Highest pathogenic variant AF is 0.0001716167
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_110404.1 | 5 | MANE Select | |
| Ensembl | ENSP00000352216.2 | 5 | MANE Select | |
| Ensembl | ENSP00000478679.1 | 2 | Standard | |
| Ensembl | ENSP00000478679.1 | 2 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| slc2a10 | Danio rerio | Structure: vasculature Quality: irregular spatial pattern abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Nuclear Receptors Meta-Pathway
- NRF2 pathway
- SLC-mediated transmembrane transport
- Transport of small molecules
- Fructose and mannose metabolism
Biological Process
- hexose transmembrane transport
- proton transmembrane transport
- glucose transmembrane transport
Molecular Function
- carbohydrate:proton symporter activity
- D-glucose transmembrane transporter activity
Cellular Component
- plasma membrane
- integral component of plasma membrane
- endomembrane system
- integral component of membrane
- perinuclear region of cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000359271
- Coding exons
- 5
- Length
- 26840
- Individuals with no LoFs
- 125694
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 54
- Defined
- 125748
- p
- 0.000215
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.755 | 338 | 301 | 1.12 | 0.0000191 | 3399 |
| Missense (PolyPhen) | 115 | 112.48 | 1.0224 | 1316 | ||
| Synonymous | -1.53 | 162 | 139 | 1.17 | 0.00000886 | 1295 |
| Loss of Function | 0.435 | 13 | 14.8 | 0.878 | 8.37e-7 | 160 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00049 | 0.00049 | rare |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00028 | 0.00028 | rare |
| South Asian | 0.00016 | 0.00016 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Facilitative glucose transporter.;
Recessive Scores
- pRec
- 0.180
Intolerance Scores
- LoFtool
- 0.217
- RVIS EVS
- 0.23
- RVIS percentile EVS
- 68.52
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.561
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |