SLC26A2
solute carrier family 26 member 2, the group of Solute carrier family 26
Basic information
Region (hg38): 5:149960757-149993455
Previous symbols: [ "DTD" ]
Links
Phenotypes
GenCC
Source:
- achondrogenesis type IB (Definitive), mode of inheritance: AR
- multiple epiphyseal dysplasia type 4 (Definitive), mode of inheritance: AR
- multiple epiphyseal dysplasia type 4 (Moderate), mode of inheritance: AR
- diastrophic dysplasia (Strong), mode of inheritance: AR
- atelosteogenesis type II (Moderate), mode of inheritance: AR
- achondrogenesis type IB (Moderate), mode of inheritance: AR
- diastrophic dysplasia (Supportive), mode of inheritance: AR
- atelosteogenesis type II (Supportive), mode of inheritance: AR
- achondrogenesis type IB (Supportive), mode of inheritance: AR
- multiple epiphyseal dysplasia type 4 (Supportive), mode of inheritance: AR
- diastrophic dysplasia (Strong), mode of inheritance: AR
- diastrophic dysplasia (Definitive), mode of inheritance: AR
- achondrogenesis type IB (Definitive), mode of inheritance: AR
- multiple epiphyseal dysplasia (Definitive), mode of inheritance: AR
- atelosteogenesis type II (Definitive), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Achondrogenesis, type IB; Atelosteogenesis II; De la Chapelle dysplasia; Diastrophic dysplasia; Epiphyseal dysplasia, multiple, 4 | 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 | Craniofacial; Musculoskeletal | 13993535; 5703690; 3799721; 4644462; 4064368; 3562108; 8528239; 8571951; 8723083; 8931695; 8723100; 1345170; 7923357; 9108864; 10482955; 10466420; 10465113; 11734236; 11565064; 11303514; 12525546; 12966518; 12220459; 15316973; 18708426; 18925670; 20301483; 20301689; 20525296; 21077202; 21155763; 21922596; 22052783 |
ClinVar
This is a list of variants' phenotypes submitted to
- Achondrogenesis, type IB (258 variants)
- Multiple epiphyseal dysplasia type 4 (222 variants)
- Diastrophic dysplasia (202 variants)
- Atelosteogenesis type II (177 variants)
- Sulfate transporter-related osteochondrodysplasia (168 variants)
- Achondrogenesis, type IB;Atelosteogenesis type II;Diastrophic dysplasia;Multiple epiphyseal dysplasia type 4 (81 variants)
- not provided (78 variants)
- Multiple epiphyseal dysplasia type 4;Achondrogenesis, type IB;Diastrophic dysplasia;Atelosteogenesis type II (39 variants)
- Achondrogenesis, type IB;Multiple epiphyseal dysplasia type 4;Diastrophic dysplasia;Atelosteogenesis type II (38 variants)
- Diastrophic dysplasia;Multiple epiphyseal dysplasia type 4;Atelosteogenesis type II;Achondrogenesis, type IB (30 variants)
- Achondrogenesis, type IB;Diastrophic dysplasia;Atelosteogenesis type II;Multiple epiphyseal dysplasia type 4 (26 variants)
- Achondrogenesis, type IB;Atelosteogenesis type II;Multiple epiphyseal dysplasia type 4;Diastrophic dysplasia (25 variants)
- Multiple epiphyseal dysplasia type 4;Diastrophic dysplasia;Achondrogenesis, type IB;Atelosteogenesis type II (24 variants)
- Atelosteogenesis type II;Achondrogenesis, type IB;Multiple epiphyseal dysplasia type 4;Diastrophic dysplasia (23 variants)
- Atelosteogenesis type II;Achondrogenesis, type IB;Diastrophic dysplasia;Multiple epiphyseal dysplasia type 4 (22 variants)
- not specified (21 variants)
- Multiple epiphyseal dysplasia type 4;Achondrogenesis, type IB;Atelosteogenesis type II;Diastrophic dysplasia (20 variants)
- Achondrogenesis, type IB;Multiple epiphyseal dysplasia type 4;Atelosteogenesis type II;Diastrophic dysplasia (19 variants)
- Inborn genetic diseases (18 variants)
- Atelosteogenesis type II;Diastrophic dysplasia;Achondrogenesis, type IB;Multiple epiphyseal dysplasia type 4 (18 variants)
- Diastrophic dysplasia;Achondrogenesis, type IB;Multiple epiphyseal dysplasia type 4;Atelosteogenesis type II (17 variants)
- Connective tissue disorder (17 variants)
- Achondrogenesis, type IB;Diastrophic dysplasia;Multiple epiphyseal dysplasia type 4;Atelosteogenesis type II (11 variants)
- Atelosteogenesis (9 variants)
- Achondrogenesis (9 variants)
- Multiple epiphyseal dysplasia type 4;Atelosteogenesis type II;Diastrophic dysplasia;Achondrogenesis, type IB (8 variants)
- Diastrophic dysplasia;Achondrogenesis, type IB;Atelosteogenesis type II;Multiple epiphyseal dysplasia type 4 (7 variants)
- SLC26A2-Related Disorders (6 variants)
- Atelosteogenesis type II;Multiple epiphyseal dysplasia type 4;Achondrogenesis, type IB;Diastrophic dysplasia (5 variants)
- Atelosteogenesis type II;Multiple epiphyseal dysplasia type 4;Diastrophic dysplasia;Achondrogenesis, type IB (4 variants)
- Multiple epiphyseal dysplasia type 4;Diastrophic dysplasia;Atelosteogenesis type II;Achondrogenesis, type IB (4 variants)
- Diastrophic dysplasia;Atelosteogenesis type II;Multiple epiphyseal dysplasia type 4;Achondrogenesis, type IB (4 variants)
- Diastrophic dysplasia;Atelosteogenesis type II;Achondrogenesis, type IB;Multiple epiphyseal dysplasia type 4 (4 variants)
- 3MC syndrome 2 (4 variants)
- Osteochondrodysplasia (3 variants)
- SLC26A2-related condition (2 variants)
- Diastrophic dysplasia;Multiple epiphyseal dysplasia type 4;Achondrogenesis, type IB;Atelosteogenesis type II (2 variants)
- Atelosteogenesis type II;Diastrophic dysplasia;Multiple epiphyseal dysplasia type 4;Achondrogenesis, type IB (2 variants)
- De la Chapelle dysplasia (1 variants)
- Diastrophic dysplasia;Achondrogenesis, type IB;Atelosteogenesis type II (1 variants)
- Multiple epiphyseal dysplasia type 4;Atelosteogenesis type II;Achondrogenesis, type IB;Diastrophic dysplasia (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC26A2 gene is commonly pathogenic or not.
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.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 177 | 181 | ||||
| missense | 16 | 153 | 177 | |||
| nonsense | 10 | 26 | 37 | |||
| start loss | 1 | |||||
| frameshift | 29 | 68 | 98 | |||
| inframe indel | 10 | |||||
| splice donor/acceptor (+/-2bp) | 5 | |||||
| splice region ? | 1 | 1 | 2 | |||
| non coding ? | 80 | 15 | 15 | 110 | ||
| Total | 43 | 115 | 248 | 197 | 16 |
Highest pathogenic variant AF is 0.000541
Variants in SLC26A2
This is a list of pathogenic ClinVar variants found in the SLC26A2 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 5-149960767-G-A | Atelosteogenesis type II • Achondrogenesis, type IB • Sulfate transporter-related osteochondrodysplasia • Multiple epiphyseal dysplasia type 4 • Diastrophic dysplasia | Uncertain significance (Jan 13, 2018) | ||
| 5-149960770-T-C | Multiple epiphyseal dysplasia type 4 • Achondrogenesis, type IB • Atelosteogenesis type II • Sulfate transporter-related osteochondrodysplasia • Diastrophic dysplasia | Uncertain significance (Jan 12, 2018) | ||
| 5-149960774-C-T | Likely benign (Jun 05, 2019) | |||
| 5-149960776-T-C | Sulfate transporter-related osteochondrodysplasia • Achondrogenesis, type IB • Multiple epiphyseal dysplasia type 4 • Diastrophic dysplasia • Atelosteogenesis type II | Uncertain significance (Jan 13, 2018) | ||
| 5-149960782-A-G | Achondrogenesis, type IB • Multiple epiphyseal dysplasia type 4 • Atelosteogenesis type II • Diastrophic dysplasia • Sulfate transporter-related osteochondrodysplasia | Uncertain significance (Jan 13, 2018) | ||
| 5-149960799-T-A | Atelosteogenesis type II • Multiple epiphyseal dysplasia type 4 • Achondrogenesis, type IB • Diastrophic dysplasia • Sulfate transporter-related osteochondrodysplasia | Uncertain significance (Jan 13, 2018) | ||
| 5-149960822-G-C | Atelosteogenesis type II • Achondrogenesis, type IB • Multiple epiphyseal dysplasia type 4 • Sulfate transporter-related osteochondrodysplasia • Diastrophic dysplasia | Conflicting classifications of pathogenicity (Jan 13, 2018) | ||
| 5-149960842-T-C | Atelosteogenesis type II • Achondrogenesis, type IB • Multiple epiphyseal dysplasia type 4 • Diastrophic dysplasia • Sulfate transporter-related osteochondrodysplasia | Uncertain significance (Jan 12, 2018) | ||
| 5-149960843-T-C | Diastrophic dysplasia • Multiple epiphyseal dysplasia type 4 • Atelosteogenesis type II • Sulfate transporter-related osteochondrodysplasia • Achondrogenesis, type IB | Uncertain significance (Jan 13, 2018) | ||
| 5-149960965-G-A | Diastrophic dysplasia • Atelosteogenesis type II • Sulfate transporter-related osteochondrodysplasia • Multiple epiphyseal dysplasia type 4 • Achondrogenesis, type IB | Uncertain significance (Jan 12, 2018) | ||
| 5-149960980-G-A | Achondrogenesis, type IB | Likely pathogenic (May 25, 2020) | ||
| 5-149960981-T-C | Diastrophic dysplasia • Multiple epiphyseal dysplasia type 4 • Multiple epiphyseal dysplasia type 4;Atelosteogenesis type II;Diastrophic dysplasia;Achondrogenesis, type IB • SLC26A2-related disorder • Sulfate transporter-related osteochondrodysplasia • Atelosteogenesis type II • 3MC syndrome 2 • Achondrogenesis, type IB | Pathogenic (Jan 05, 2024) | ||
| 5-149977400-G-A | Benign (Jun 14, 2018) | |||
| 5-149977497-A-G | Benign (Jun 14, 2018) | |||
| 5-149977655-G-T | Multiple epiphyseal dysplasia type 4 | Likely pathogenic (Mar 22, 2017) | ||
| 5-149977662-GAAAGT-G | Multiple epiphyseal dysplasia type 4;Atelosteogenesis type II;Diastrophic dysplasia;Achondrogenesis, type IB • Diastrophic dysplasia | Pathogenic/Likely pathogenic (Apr 01, 2022) | ||
| 5-149977664-A-G | Achondrogenesis, type IB;Diastrophic dysplasia;Atelosteogenesis type II;Multiple epiphyseal dysplasia type 4 | Likely benign (Jan 17, 2020) | ||
| 5-149977667-T-C | Achondrogenesis, type IB;Atelosteogenesis type II;Diastrophic dysplasia;Multiple epiphyseal dysplasia type 4 | Likely benign (Jan 05, 2024) | ||
| 5-149977673-G-A | Achondrogenesis, type IB;Diastrophic dysplasia;Multiple epiphyseal dysplasia type 4;Atelosteogenesis type II • Achondrogenesis, type IB | Likely benign (Nov 16, 2018) | ||
| 5-149977676-A-G | Achondrogenesis, type IB;Multiple epiphyseal dysplasia type 4;Diastrophic dysplasia;Atelosteogenesis type II | Conflicting classifications of pathogenicity (Dec 25, 2023) | ||
| 5-149977677-C-G | Diastrophic dysplasia;Multiple epiphyseal dysplasia type 4;Achondrogenesis, type IB;Atelosteogenesis type II • Inborn genetic diseases | Uncertain significance (Feb 10, 2022) | ||
| 5-149977682-C-T | Achondrogenesis, type IB;Diastrophic dysplasia;Atelosteogenesis type II;Multiple epiphyseal dysplasia type 4 | Likely benign (Jul 19, 2023) | ||
| 5-149977683-G-A | Uncertain significance (Nov 13, 2020) | |||
| 5-149977699-C-G | Diastrophic dysplasia • Achondrogenesis, type IB | Likely pathogenic (Jun 06, 2023) | ||
| 5-149977703-T-C | Achondrogenesis, type IB;Multiple epiphyseal dysplasia type 4;Atelosteogenesis type II;Diastrophic dysplasia | Likely benign (Jan 11, 2024) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| SLC26A2 | protein_coding | protein_coding | ENST00000286298 | 2 | 32719 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 7.50e-7 | 0.735 | 125692 | 0 | 53 | 125745 | 0.000211 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.0314 | 370 | 372 | 0.995 | 0.0000184 | 4837 |
| Missense in Polyphen | 147 | 141.64 | 1.0378 | 1857 | ||
| Synonymous | 0.419 | 130 | 136 | 0.954 | 0.00000657 | 1509 |
| Loss of Function | 1.23 | 12 | 17.6 | 0.683 | 8.48e-7 | 272 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000483 | 0.000478 |
| Ashkenazi Jewish | 0.0000993 | 0.0000992 |
| East Asian | 0.000217 | 0.000217 |
| Finnish | 0.0000924 | 0.0000924 |
| European (Non-Finnish) | 0.000203 | 0.000202 |
| Middle Eastern | 0.000217 | 0.000217 |
| South Asian | 0.000327 | 0.000327 |
| Other | 0.000164 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: Sulfate transporter. May play a role in endochondral bone formation. {ECO:0000269|PubMed:7923357}.;
- Disease
- DISEASE: Achondrogenesis 1B (ACG1B) [MIM:600972]: A form of achondrogenesis type 1, a lethal form of chondrodysplasia characterized by deficient ossification in the lumbar vertebrae and absent ossification in the sacral, pubic and ischial bones and clinically by stillbirth or early death. In addition to severe micromelia, there is a disproportionately large cranium due to marked edema of soft tissues. ACG1B is an autosomal recessive disease. {ECO:0000269|PubMed:8528239}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Atelosteogenesis 2 (AO2) [MIM:256050]: A perinatal dysplasia characterized by shortening of the limbs, a dysmorphic syndrome and radiographic skeletal features. Patients are stillborn or die soon after birth. {ECO:0000269|PubMed:8571951}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Multiple epiphyseal dysplasia 4 (EDM4) [MIM:226900]: A generalized skeletal dysplasia associated with significant morbidity. Joint pain, joint deformity, waddling gait, and short stature are the main clinical signs and symptoms. Radiological examination of the skeleton shows delayed, irregular mineralization of the epiphyseal ossification centers and of the centers of the carpal and tarsal bones. Multiple epiphyseal dysplasia is broadly categorized into the more severe Fairbank and the milder Ribbing types. The Fairbank type is characterized by shortness of stature, short and stubby fingers, small epiphyses in several joints, including the knee, ankle, hand, and hip. The Ribbing type is confined predominantly to the hip joints and is characterized by hands that are normal and stature that is normal or near-normal. Multiple epiphyseal dysplasia type 4 is a recessively inherited form, characterized by early childhood-onset hip dysplasia and recurrent patella dislocation. Short stature is not frequent. {ECO:0000269|PubMed:12966518, ECO:0000269|PubMed:21922596}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Glucocorticoid Receptor Pathway;Nuclear Receptors Meta-Pathway;Transport and synthesis of PAPS;Metabolism of carbohydrates;Phase II - Conjugation of compounds;Glycosaminoglycan metabolism;Biological oxidations;Metabolism;Transport of inorganic cations/anions and amino acids/oligopeptides;SLC-mediated transmembrane transport;Transport of small molecules;Cytosolic sulfonation of small molecules;Methionine and cysteine metabolism;Multifunctional anion exchangers
(Consensus)
Recessive Scores
- pRec
- 0.194
Intolerance Scores
- loftool
- 0.202
- rvis_EVS
- 0.18
- rvis_percentile_EVS
- 66.17
Haploinsufficiency Scores
- pHI
- 0.0942
- hipred
- N
- hipred_score
- 0.197
- ghis
- 0.374
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.152
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Slc26a2
- Phenotype
- growth/size/body region phenotype; cellular phenotype; craniofacial phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); skeleton phenotype; limbs/digits/tail phenotype;
Zebrafish Information Network
- Gene name
- slc26a2
- Affected structure
- neuromast hair cell
- Phenotype tag
- abnormal
- Phenotype quality
- decreased amount
Gene ontology
- Biological process
- ossification;ion transport;bicarbonate transport;oxalate transport;3'-phosphoadenosine 5'-phosphosulfate biosynthetic process;sulfate transmembrane transport;chloride transmembrane transport
- Cellular component
- plasma membrane;integral component of plasma membrane;membrane;apical plasma membrane;microvillus membrane;extracellular exosome
- Molecular function
- secondary active sulfate transmembrane transporter activity;bicarbonate transmembrane transporter activity;chloride transmembrane transporter activity;sulfate transmembrane transporter activity;anion:anion antiporter activity;oxalate transmembrane transporter activity