SLC26A2

Summary

SLC26A2 (solute carrier family 26 member 2, HGNC:10994) is a protein-coding gene on chromosome 5q32, encoding Sulfate transporter (P50443). Sulfate transporter which mediates sulfate uptake into chondrocytes in order to maintain adequate sulfation of proteoglycans which is needed for cartilage development.

The diastrophic dysplasia sulfate transporter is a transmembrane glycoprotein implicated in the pathogenesis of several human chondrodysplasias. It apparently is critical in cartilage for sulfation of proteoglycans and matrix organization.

Source: NCBI Gene 1836 — RefSeq curated summary.

At a glance

• Gene–disease (curated): SLC26A2-related skeletal dysplasia (Definitive, ClinGen) — +5 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 945 total — 75 pathogenic, 98 likely-pathogenic
• Phenotypes (HPO): 202
• MANE Select transcript: NM_000112

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10994
Approved symbol	SLC26A2
Name	solute carrier family 26 member 2
Location	5q32
Locus type	gene with protein product
Status	Approved
Aliases	DTDST
Ensembl gene	ENSG00000155850
Ensembl biotype	protein_coding
OMIM	606718
Entrez	1836

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 11 protein_coding, 1 retained_intron

ENST00000286298, ENST00000433184, ENST00000503336, ENST00000690410, ENST00000862081, ENST00000862082, ENST00000862083, ENST00000862084, ENST00000862085, ENST00000862086, ENST00000862087, ENST00000862088

RefSeq mRNA: 1 — MANE Select: NM_000112 NM_000112

CCDS: CCDS4300

Canonical transcript exons

ENST00000286298 — 3 exons

Exon	Start	End
ENSE00001023063	149980293	149987400
ENSE00001023064	149977628	149978351
ENSE00001407868	149960758	149960979

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 99.66.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.3482 / max 900.4095, expressed in 1789 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
59402	9.7458	1744
59405	5.4949	681
59403	4.4994	1532
59404	0.5959	281
203738	0.0122	4

Top tissues by expression

298 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
colonic mucosa	UBERON:0000317	99.66	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.63	gold quality
mucosa of transverse colon	UBERON:0004991	98.94	gold quality
rectum	UBERON:0001052	98.70	gold quality
seminal vesicle	UBERON:0000998	97.49	gold quality
mucosa of paranasal sinus	UBERON:0005030	97.47	gold quality
trigeminal ganglion	UBERON:0001675	97.40	gold quality
adrenal tissue	UBERON:0018303	96.84	gold quality
ileal mucosa	UBERON:0000331	96.51	gold quality
upper leg skin	UBERON:0004262	95.86	gold quality
corpus epididymis	UBERON:0004359	95.76	gold quality
oral cavity	UBERON:0000167	95.28	gold quality
cauda epididymis	UBERON:0004360	94.71	gold quality
nasal cavity epithelium	UBERON:0005384	94.58	gold quality
jejunal mucosa	UBERON:0000399	94.43	gold quality
tibia	UBERON:0000979	94.36	gold quality
lower lobe of lung	UBERON:0008949	94.16	gold quality
placenta	UBERON:0001987	94.00	gold quality
nasal cavity mucosa	UBERON:0001826	93.85	gold quality
endometrium	UBERON:0001295	93.43	gold quality
trachea	UBERON:0003126	93.27	gold quality
epithelium of nasopharynx	UBERON:0001951	92.38	gold quality
nasopharynx	UBERON:0001728	92.37	gold quality
esophagus squamous epithelium	UBERON:0006920	92.37	gold quality
transverse colon	UBERON:0001157	92.13	gold quality
skin of hip	UBERON:0001554	91.71	gold quality
gingiva	UBERON:0001828	91.12	gold quality
gingival epithelium	UBERON:0001949	91.01	gold quality
visceral pleura	UBERON:0002401	90.97	gold quality
superior surface of tongue	UBERON:0007371	90.85	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	2531.29
E-MTAB-6701	yes	122.23
E-MTAB-7249	yes	11.38
E-CURD-46	yes	9.17
E-HCAD-1	yes	8.95
E-MTAB-8410	yes	8.30
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1

miRNA regulators (miRDB)

175 targeting SLC26A2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-9-3P	99.96	70.88	2068

Literature-anchored findings (GeneRIF, showing 30)

• Functional characterization of three novel tissue-specific anion exchangers SLC26A7, -A8, and -A9. (SLC26A7).(SLC26A8).(SLC26A9) three entries (PMID:11834742)
• DTDST function is crucial for the uptake of extracellular sulfate required for proteoglycan sulfation. (PMID:14692227)
• The effects of sulfur availablility on proteoglycan sulfation in mice transgenic for a mutation of this gene are reported. (PMID:16719839)
• This study found an association between single nucleotide polymorphisms of the SLC26A2 gene and juvenile idiopathic arthritis. (PMID:17393463)
• DTDST is upregulated by dexamethasone stimulation of HT1080 fibrosarcoma cells and is required for fibronectin (FN) extracellular matrix deposition by these cells. (PMID:18056413)
• A novel SLC26A2 mutation was found in all subjects, inserted by site-directed mutagenesis in a vector harbouring the SLC26A2 cDNA, and expressed in sulfate transport deficient Chinese hamster ovary (CHO) cells to measure sulfate uptake activity (PMID:18708426)
• Characterize transport of oxalate and sulfate by human SLC26A2 and mouse Slc26a2 expressed in Xenopus oocytes. (PMID:20219950)
• Diminished DTDST expression through epigenetic silencing is associated with colon cancer. (PMID:20460514)
• Analysis suggests that, while the DTDST family of disorders contains at least seven different conditions, gene mutations appear to cause a phenotypic continuum. DTDST genotype alone is an imperfect predictor of clinical severity along this continuum. (PMID:21077202)
• New intermediate phenotype between MED and DD caused by compound heterozygous mutations in the DTDST gene is reported. (PMID:21077204)
• Mutations in the SLC26A2 gene causes diastrophic dysplasia. (PMID:21155763)
• 73% of autosomal-recessive multiple epiphyseal dysplasia patients were either homozygous, or compound heterozygous, for SLC26A2 mutations. (PMID:21922596)
• Solute carrier family 26 member a2 (Slc26a2) protein functions as an electroneutral SOFormula/OH-/Cl- exchanger regulated b (PMID:22190686)
• SLC13A4 and SLC26A2 were the most abundant sulfate transporter mRNAs, which localized to syncytiotrophoblast and cytotrophoblast cells, respectively. (PMID:23453247)
• A compound heterozygote SLC26A2 mutation is associated with robin sequence, mild limbs shortness, accelerated carpal ossification, and multiple epiphysial dysplasia (PMID:23840040)
• Up-regulation of SLC26A2 is associated with colorectal cancer. (PMID:24222123)
• Diastrophic dysplasia sulfate transporter (SLC26A2) is expressed in the adrenal cortex and regulates aldosterone secretion. (PMID:24591336)
• findings provide the first identification of autosomal dominant SLC26A2 mutations in patients with dysplastic spondylolysis, suggesting a new clinical entity in the pathogenesis of chondrodysplasia involving lumbosacral spine (PMID:26077908)
• slc26a2 is to be a critical otic gene whose dysfunction may induce hearing impairment (PMID:26375458)
• Results show that SLC26A2 expression is high in numerous tumor types and, provide evidence that it downregulates the TRAIL receptors, DR4 and DR5 which confers resistance to TRAIL. (PMID:28108622)
• Molecular analysis of human solute carrier SLC26A2, SLC26A3, and SLC26A4 anion transporter disease-causing mutations using 3-dimensional homology modeling has been presented. (PMID:28941661)
• Two heterozygous mutations in SLC26A2 mutations occur in a three-generational family with cases of multiple epiphyseal dysplasias. (PMID:29024831)
• Data identified two novel mutations in SLC26A2 gene: c.824 T > C and c.1198C > T in two siblings multiple epiphyseal dysplasia 4 within a Chinese family. Both mutations were inherited from both parents, one mutation from each. (PMID:29724173)
• Molecular analysis revealed that patient I is heterozygous for two known pathogenic variants in SLC26A2, a splice site variant c.-26+2T > C and a missense variant c.1957T > A (p.Cys653Ser), while patient II is compound heterozygous for missense variants c.835C > T (p.Arg279Trp) and c.1535C > A (p.Thr512Lys) (PMID:30423444)
• N-glycosylation plays three roles in the functional expression of SLC26 proteins: (1) to retain misfolded proteins in the endoplamic reticulum, (2) to stabilize the protein at the cell surface, and (3) to maintain the transport protein in a functional state. (PMID:30462520)
• Two unrelated pedigrees with achondrogenesis type 1b carrying a Japan-specific pathogenic variant in SLC26A2. (PMID:31880411)
• Computational biology insights into genotype-clinical phenotype-protein phenotype relationships between novel SLC26A2 variants identified in inherited skeletal dysplasias. (PMID:36007841)
• Clinical and Genetic Characteristics of Multiple Epiphyseal Dysplasia Type 4. (PMID:36140680)
• [Analysis of genetic variants and molecular pathogenesis in a Chinese pedigree affected with Multiple epiphyseal dysplasia]. (PMID:38946362)
• Biallelic variants in SLC26A2 cause multiple epiphyseal dysplasia-4 by disturbing chondrocyte homeostasis. (PMID:38956600)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc26a2	ENSDARG00000011618
mus_musculus	Slc26a2	ENSMUSG00000034320
rattus_norvegicus	Slc26a2	ENSRNOG00000018082

Paralogs (9): SLC26A4 (ENSG00000091137), SLC26A3 (ENSG00000091138), SLC26A8 (ENSG00000112053), SLC26A1 (ENSG00000145217), SLC26A7 (ENSG00000147606), SLC26A5 (ENSG00000170615), SLC26A9 (ENSG00000174502), SLC26A11 (ENSG00000181045), SLC26A6 (ENSG00000225697)

Protein

Protein identifiers

Sulfate transporter — P50443 (reviewed: P50443)

Alternative names: Diastrophic dysplasia protein, Solute carrier family 26 member 2

All UniProt accessions (3): P50443, C9JAN6, H0YA38

UniProt curated annotations — full annotation on UniProt →

Function. Sulfate transporter which mediates sulfate uptake into chondrocytes in order to maintain adequate sulfation of proteoglycans which is needed for cartilage development. Mediates electroneutral anion exchange of sulfate ions for oxalate ions and of sulfate and oxalate ions for chloride ions. Mediates exchange of sulfate and oxalate ions for hydroxyl ions and of chloride ions for bromide, iodide and nitrate ions. The coupling of sulfate transport to both hydroxyl and chloride ions likely serves to ensure transport at both acidic pH when most sulfate uptake is mediated by sulfate-hydroxide exchange and alkaline pH when most sulfate uptake is mediated by sulfate-chloride exchange. Essential for chondrocyte proliferation, differentiation and cell size expansion.

Subcellular location. Cell membrane. Apical cell membrane.

Tissue specificity. Ubiquitously expressed.

Post-translational modifications. N-glycosylated.

Disease relevance. Diastrophic dysplasia (DTD) [MIM:222600] An autosomal recessive disease characterized by osteochondrodysplasia with clinical features including dwarfism, spinal deformation, and specific joint abnormalities. The disease is caused by variants affecting the gene represented in this entry. 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. The disease is caused by variants affecting the gene represented in this entry. 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. The disease is caused by variants affecting the gene represented in this entry. 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. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. An extracellular acidic pH inhibits chloride-sulfate and chloride-oxalate exchange activity whereas an intracellular acidic pH activates chloride-sulfate exchange with no effect on chloride-oxalate exchange activity.

Similarity. Belongs to the SLC26A/SulP transporter (TC 2.A.53) family.

RefSeq proteins (1): NP_000103* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001902	SLC26A/SulP_fam	Family
IPR002645	STAS_dom	Domain
IPR011547	SLC26A/SulP_dom	Domain
IPR018045	S04_transporter_CS	Conserved_site
IPR036513	STAS_dom_sf	Homologous_superfamily

Pfam: PF00916, PF01740

Catalyzed reactions (Rhea), 6 shown:

• oxalate(in) + sulfate(out) = oxalate(out) + sulfate(in) (RHEA:72275)
• iodide(in) + chloride(out) = iodide(out) + chloride(in) (RHEA:72379)
• sulfate(out) + 2 chloride(in) = sulfate(in) + 2 chloride(out) (RHEA:75091)
• oxalate(out) + 2 chloride(in) = oxalate(in) + 2 chloride(out) (RHEA:75095)
• bromide(in) + chloride(out) = bromide(out) + chloride(in) (RHEA:75335)
• nitrate(in) + chloride(out) = nitrate(out) + chloride(in) (RHEA:75339)

UniProt features (29 total): sequence variant 11, transmembrane region 8, glycosylation site 3, modified residue 2, sequence conflict 2, chain 1, region of interest 1, domain 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
8TNX	ELECTRON MICROSCOPY	3.03
8TNW	ELECTRON MICROSCOPY	3.17
8TNY	ELECTRON MICROSCOPY	3.55
7XLM	ELECTRON MICROSCOPY	3.73

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P50443-F1	80.97	0.51

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 12, 16

Glycosylation sites (3): 199, 205, 357

Function

Pathways and Gene Ontology

Reactome pathways

18 pathways

ID	Pathway
R-HSA-174362	Transport and metabolism of PAPS
R-HSA-3560792	Defective SLC26A2 causes chondrodysplasias
R-HSA-427601	Inorganic anion exchange by SLC26 transporters
R-HSA-1430728	Metabolism
R-HSA-156580	Phase II - Conjugation of compounds
R-HSA-156584	Cytosolic sulfonation of small molecules
R-HSA-1630316	Glycosaminoglycan metabolism
R-HSA-1643685	Disease
R-HSA-211859	Biological oxidations
R-HSA-3560782	Diseases associated with glycosaminoglycan metabolism
R-HSA-3781865	Diseases of glycosylation
R-HSA-382551	Transport of small molecules
R-HSA-425393
R-HSA-425407	SLC-mediated transmembrane transport
R-HSA-5619102	SLC transporter disorders
R-HSA-5619115	Disorders of transmembrane transporters
R-HSA-5668914	Diseases of metabolism
R-HSA-71387	Metabolism of carbohydrates and carbohydrate derivatives

MSigDB gene sets: 601 (showing top): WANG_CLIM2_TARGETS_UP, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_CARTILAGE_DEVELOPMENT, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, XU_GH1_AUTOCRINE_TARGETS_UP, GOBP_INORGANIC_ANION_TRANSPORT, FOXO1_01, USF_C, GOBP_ORGANIC_ACID_TRANSPORT, PATIL_LIVER_CANCER, SENESE_HDAC1_AND_HDAC2_TARGETS_DN, WANG_ESOPHAGUS_CANCER_VS_NORMAL_DN, TRAYNOR_RETT_SYNDROM_DN, MODULE_205, GOBP_CHLORIDE_TRANSPORT

GO Biological Process (6): chondrocyte differentiation (GO:0002062), oxalate transport (GO:0019532), chondrocyte proliferation (GO:0035988), sulfate transmembrane transport (GO:1902358), chloride transmembrane transport (GO:1902476), transmembrane transport (GO:0055085)

GO Molecular Function (5): solute:inorganic anion antiporter activity (GO:0005452), secondary active sulfate transmembrane transporter activity (GO:0008271), sulfate transmembrane transporter activity (GO:0015116), oxalate transmembrane transporter activity (GO:0019531), chloride:bicarbonate antiporter activity (GO:0140900)

GO Cellular Component (5): plasma membrane (GO:0005886), membrane (GO:0016020), apical plasma membrane (GO:0016324), microvillus membrane (GO:0031528), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
Metabolism	2
Disease	2
Glycosaminoglycan metabolism	1
Diseases associated with glycosaminoglycan metabolism	1
SLC transporter disorders	1
SLC-mediated transport of inorganic anions	1
Biological oxidations	1
Phase II - Conjugation of compounds	1
Metabolism of carbohydrates and carbohydrate derivatives	1
Diseases of glycosylation	1
Diseases of metabolism	1
Transport of small molecules	1
Disorders of transmembrane transporters	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell differentiation	1
cartilage development	1
dicarboxylic acid transport	1
cell population proliferation	1
inorganic anion transport	1
transmembrane transport	1
sulfur compound transport	1
chloride transport	1
monoatomic anion transmembrane transport	1
transport	1
cellular process	1
antiporter activity	1
sulfate transmembrane transporter activity	1
secondary active transmembrane transporter activity	1
sulfur compound transmembrane transporter activity	1
sulfate transmembrane transport	1
dicarboxylic acid transmembrane transporter activity	1
oxalate transport	1
solute:inorganic anion antiporter activity	1
chloride transmembrane transporter activity	1
bicarbonate:monoatomic anion antiporter activity	1
membrane	1
cell periphery	1
cellular anatomical structure	1
apical part of cell	1
plasma membrane region	1
microvillus	1
cell projection membrane	1
extracellular vesicle	1

Protein interactions and networks

STRING

1636 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC26A2	PAPSS2	O95340	919
SLC26A2	PAPSS1	O43252	918
SLC26A2	MATN3	O15232	906
SLC26A2	SLC13A1	Q9BZW2	903
SLC26A2	SLC13A4	Q9UKG4	879
SLC26A2	COL9A2	Q14055	871
SLC26A2	SLC13A2	Q13183	855
SLC26A2	COL9A1	P20849	831
SLC26A2	COL9A3	Q14050	822
SLC26A2	CANT1	Q8WVQ1	806
SLC26A2	TRIP11	Q15643	788
SLC26A2	SLC13A3	Q8WWT9	788
SLC26A2	COL2A1	P02458	650
SLC26A2	CFTR	P13569	647
SLC26A2	TCOF1	Q13428	636

IntAct

61 interactions, top by confidence:

A	B	Type	Score
ENTREP1	WWP2	psi-mi:“MI:0914”(association)	0.850
VAPB	FAM83G	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
SLC20A1	LIN7A	psi-mi:“MI:0914”(association)	0.640
LYPD3	SCAMP1	psi-mi:“MI:0914”(association)	0.640
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
LGALS3	PODXL	psi-mi:“MI:0914”(association)	0.530
SLC22A16	APBA3	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
Lgals3bp	CS	psi-mi:“MI:0914”(association)	0.350
TNFAIP3	FZD7	psi-mi:“MI:0914”(association)	0.350
ERGIC3	TMEM223	psi-mi:“MI:0914”(association)	0.350
LGALS8	SLC22A23	psi-mi:“MI:0914”(association)	0.350
LGALS3	PODXL	psi-mi:“MI:0914”(association)	0.350
SLC22A9	GPR89A	psi-mi:“MI:0914”(association)	0.350
TMEM52B	PIK3R2	psi-mi:“MI:0914”(association)	0.350
SLC22A16	AGPAT2	psi-mi:“MI:0914”(association)	0.350
PMEL	MAN1A2	psi-mi:“MI:0914”(association)	0.350
SLC22A6	GK	psi-mi:“MI:0914”(association)	0.350
	SHTN1	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
CANX	HLA-A	psi-mi:“MI:0914”(association)	0.350
TTMP	TMEM223	psi-mi:“MI:0914”(association)	0.350
CLEC12B	GXYLT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (96): SLC26A2 (Affinity Capture-MS), SLC26A2 (Affinity Capture-MS), SLC26A2 (Affinity Capture-MS), SLC26A2 (Affinity Capture-MS), SLC26A2 (Affinity Capture-MS), SLC26A2 (Affinity Capture-MS), SLC26A2 (Affinity Capture-MS), SLC26A2 (Affinity Capture-MS), SLC26A2 (Affinity Capture-MS), SLC26A2 (Affinity Capture-MS), SLC26A2 (Affinity Capture-MS), SLC26A2 (Affinity Capture-MS), SLC26A2 (Affinity Capture-MS), SLC26A2 (Affinity Capture-MS), SLC26A2 (Affinity Capture-MS)

ESM2 similar proteins: A0FKN5, D7PC76, O00341, O04289, O35874, O43511, O57321, O70531, P24942, P31597, P40879, P43003, P43005, P46411, P50443, P51906, P51907, P53391, P53392, P56564, P58743, Q62273, Q65AC2, Q69DJ1, Q7SYH5, Q7T2C4, Q8BYF6, Q8CIW6, Q8GYH8, Q8JZR4, Q8N695, Q924C9, Q94LW6, Q95135, Q99NH7, Q9BEG8, Q9BXS9, Q9EPH0, Q9FEP7, Q9FY46

Diamond homologs: A0FKN5, A4IIF2, A8J6J0, D7PC76, O43511, O70531, P40879, P45380, P50443, P53391, P53392, P58735, P58743, Q5EBI0, Q5RAL2, Q62273, Q65AC2, Q69DJ1, Q7LBE3, Q7T2C4, Q8BU91, Q8CIW6, Q8GYH8, Q8HY59, Q8NG04, Q8R2Z3, Q8TE54, Q924C9, Q99NH7, Q9BEG8, Q9BXS9, Q9EPH0, Q9FY46, Q9GJY3, Q9H2B4, Q9JKQ2, Q9R154, Q9R155, Q9SAY1, Q9WVC8

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 80 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
SLC-mediated transmembrane transport	6	7.4×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

945 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	75
Likely pathogenic	98
Uncertain significance	328
Likely benign	283
Benign	17

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1067905	NM_000112.4(SLC26A2):c.2065_2066del (p.Thr689fs)	Pathogenic
1323605	NM_000112.4(SLC26A2):c.1283del (p.Pro428fs)	Pathogenic
1326262	NM_000112.4(SLC26A2):c.796dup (p.Thr266fs)	Pathogenic
1374813	NM_000112.4(SLC26A2):c.1203_1204insTTTTTTTTTTTTTTTTTTTNNNNNNNNNNGACGGGGTTTCACCTTGTTAGCCAGGATGGTCTCGATCTCCTGACCTCATGATCCACCCGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCGCGCCCGGCCATTTTCT (p.Glu402delinsPhePhePhePhePhePheXaaXaaXaaXaaThrGlyPheHisLeuValSerGlnAspGlyLeuAspLeuLeuThrSerTer)	Pathogenic
1388388	NM_000112.4(SLC26A2):c.1810_1811del (p.Val604fs)	Pathogenic
1402115	NM_000112.4(SLC26A2):c.1393_1394del (p.Leu465fs)	Pathogenic
1412823	NM_000112.4(SLC26A2):c.1592del (p.Leu531fs)	Pathogenic
1419742	NM_000112.4(SLC26A2):c.2004_2007del (p.Glu669fs)	Pathogenic
1436633	NM_000112.4(SLC26A2):c.1155del (p.Asp385fs)	Pathogenic
1452842	NM_000112.4(SLC26A2):c.1147_1150del (p.Val382_Ala383insTer)	Pathogenic
1452846	NM_000112.4(SLC26A2):c.1772del (p.Asn591fs)	Pathogenic
1453452	NM_000112.4(SLC26A2):c.100del (p.Glu34fs)	Pathogenic
1453498	NM_000112.4(SLC26A2):c.58_62dup (p.Asp21fs)	Pathogenic
1453606	NM_000112.4(SLC26A2):c.218del (p.Lys73fs)	Pathogenic
1453912	NM_000112.4(SLC26A2):c.1720del (p.Ile574fs)	Pathogenic
1454165	NM_000112.4(SLC26A2):c.78_88dup (p.Glu30fs)	Pathogenic
1456395	NM_000112.4(SLC26A2):c.1272dup (p.Asn425Ter)	Pathogenic
1456546	NM_000112.4(SLC26A2):c.1306del (p.Thr436fs)	Pathogenic
1456961	NM_000112.4(SLC26A2):c.1064_1065insAAAAA (p.Asn355fs)	Pathogenic
1683434	NM_000112.4(SLC26A2):c.1114A>T (p.Lys372Ter)	Pathogenic
1999769	NM_000112.4(SLC26A2):c.2095del (p.Tyr699fs)	Pathogenic
2014463	NM_000112.4(SLC26A2):c.1343C>A (p.Ser448Ter)	Pathogenic
2027074	NM_000112.4(SLC26A2):c.2109del (p.Glu704fs)	Pathogenic
2033441	NM_000112.4(SLC26A2):c.104C>G (p.Ser35Ter)	Pathogenic
2086698	NM_000112.4(SLC26A2):c.1767C>A (p.Tyr589Ter)	Pathogenic
2098084	NM_000112.4(SLC26A2):c.1805_1808del (p.Gln602fs)	Pathogenic
2100679	NM_000112.4(SLC26A2):c.840dup (p.Asn281Ter)	Pathogenic
2110308	NM_000112.4(SLC26A2):c.118A>T (p.Lys40Ter)	Pathogenic
2130944	NM_000112.4(SLC26A2):c.2087dup (p.Asn696fs)	Pathogenic
2173257	NM_000112.4(SLC26A2):c.69del (p.Pro24fs)	Pathogenic

SpliceAI

730 predictions. Top by Δscore:

Variant	Effect	Δscore
5:149962191:G:T	donor_gain	1.0000
5:149960976:AGAGG:A	donor_loss	0.9900
5:149960977:GAG:G	donor_gain	0.9900
5:149960977:GAGG:G	donor_loss	0.9900
5:149960978:AGG:A	donor_loss	0.9900
5:149960980:G:GC	donor_loss	0.9900
5:149960981:T:G	donor_loss	0.9900
5:149960991:G:T	donor_gain	0.9900
5:149962195:GTCC:G	donor_gain	0.9900
5:149962196:TCCT:T	donor_gain	0.9900
5:149962206:C:G	donor_gain	0.9900
5:149962123:GTCC:G	donor_gain	0.9800
5:149962124:TCCT:T	donor_gain	0.9800
5:149962190:G:GT	donor_gain	0.9800
5:149962191:G:GT	donor_gain	0.9800
5:149962202:G:GT	donor_gain	0.9800
5:149977620:T:TA	acceptor_gain	0.9800
5:149977627:GGAA:G	acceptor_gain	0.9800
5:149977752:G:T	donor_gain	0.9800
5:149977840:A:G	donor_gain	0.9800
5:149977853:GGA:G	donor_gain	0.9800
5:149977854:GAG:G	donor_gain	0.9800
5:149981700:G:GT	donor_gain	0.9800
5:149981751:G:GT	donor_gain	0.9800
5:149962212:GCTC:G	donor_gain	0.9700
5:149977759:G:GG	donor_gain	0.9700
5:149981772:GGA:G	donor_gain	0.9700
5:149981773:GAG:G	donor_gain	0.9700
5:149960980:G:GG	donor_gain	0.9600
5:149960991:G:GT	donor_gain	0.9600

AlphaMissense

4852 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:149980515:A:C	S308R	0.999
5:149980517:C:A	S308R	0.999
5:149980517:C:G	S308R	0.999
5:149978157:T:C	C169R	0.997
5:149978341:G:A	G230E	0.997
5:149980858:G:A	G422D	0.997
5:149980902:A:C	S437R	0.997
5:149980904:T:A	S437R	0.997
5:149980904:T:G	S437R	0.997
5:149978159:C:G	C169W	0.996
5:149978340:G:A	G230R	0.996
5:149978340:G:C	G230R	0.996
5:149980357:G:A	G255E	0.996
5:149980369:G:A	G259D	0.996
5:149978007:G:C	G119R	0.995
5:149980792:T:C	L400P	0.995
5:149980868:T:A	N425K	0.995
5:149980868:T:G	N425K	0.995
5:149980892:T:G	C433W	0.995
5:149981185:T:C	L531P	0.995
5:149981193:G:A	G534R	0.995
5:149981193:G:C	G534R	0.995
5:149978028:T:C	S126P	0.994
5:149978050:C:A	A133D	0.994
5:149978071:G:A	G140D	0.994
5:149980461:T:A	W290R	0.994
5:149980461:T:C	W290R	0.994
5:149981193:G:T	G534W	0.994
5:149980857:G:C	G422R	0.993
5:149981136:T:A	W515R	0.993

dbSNP variants (sampled 300 via entrez): RS1000234877 (5:149982223 G>A), RS1000288809 (5:149960501 T>C), RS1000375222 (5:149974843 G>A), RS1000419317 (5:149974532 C>T), RS1000440283 (5:149966517 T>G), RS1000448357 (5:149961512 A>G), RS1000641540 (5:149967864 C>T), RS1000679023 (5:149958782 A>C,G), RS1000771504 (5:149961754 C>T), RS1001053540 (5:149978577 A>G), RS1001063817 (5:149987667 G>A), RS1001270887 (5:149970432 G>A,C), RS1001396297 (5:149976940 G>C), RS1001498573 (5:149984185 T>C), RS1001582749 (5:149963250 C>G,T)

Disease associations

OMIM: gene MIM:606718 | disease phenotypes: MIM:222600, MIM:226900, MIM:256050, MIM:600972, MIM:265050

GenCC curated gene-disease

Disease	Classification	Inheritance
multiple epiphyseal dysplasia type 4	Definitive	Autosomal recessive
achondrogenesis type IB	Definitive	Autosomal recessive
SLC26A2-related skeletal dysplasia	Definitive	Autosomal recessive
diastrophic dysplasia	Strong	Autosomal recessive
skeletal dysplasia	Strong	Autosomal recessive
atelosteogenesis type II	Moderate	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
SLC26A2-related skeletal dysplasia	Definitive	AR

Mondo (10): diastrophic dysplasia (MONDO:0009107), multiple epiphyseal dysplasia type 4 (MONDO:0009189), atelosteogenesis type II (MONDO:0009727), achondrogenesis type IB (MONDO:0010966), connective tissue disorder (MONDO:0003900), SLC26A2-related skeletal dysplasia (MONDO:0100592), osteochondrodysplasia (MONDO:0005516), 3MC syndrome 2 (MONDO:0009927), de la Chapelle dysplasia (MONDO:0800307), skeletal dysplasia (MONDO:0018230)

Orphanet (7): Atelosteogenesis type II (Orphanet:56304), Diastrophic dysplasia (Orphanet:628), Achondrogenesis (Orphanet:932), Achondrogenesis type 1B (Orphanet:93298), Multiple epiphyseal dysplasia type 4 (Orphanet:93307), 3MC syndrome (Orphanet:293843), Carnevale syndrome (Orphanet:2998)

HPO phenotypes

202 total (30 of 202 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000160	Narrow mouth
HP:0000175	Cleft palate
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000256	Macrocephaly
HP:0000272	Malar flattening
HP:0000286	Epicanthus
HP:0000293	Full cheeks
HP:0000316	Hypertelorism
HP:0000331	Short chin
HP:0000337	Broad forehead
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000363	Abnormal earlobe morphology
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000377	Abnormal pinna morphology
HP:0000396	Overfolded helix
HP:0000402	Stenosis of the external auditory canal
HP:0000430	Underdeveloped nasal alae
HP:0000460	Narrow nose
HP:0000463	Anteverted nares
HP:0000470	Short neck
HP:0000474	Thickened nuchal skin fold
HP:0000476	Cystic hygroma
HP:0000494	Downslanted palpebral fissures

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006951_43	Feeling hurt	1.000000e-08
GCST010244_427	Triglyceride levels	1.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009599	feeling emotionally hurt measurement
EFO:0004530	triglyceride measurement

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D003240	Connective Tissue Diseases	C17.300
D010009	Osteochondrodysplasias	C05.116.099.708; C16.320.728
C535395	Atelosteogenesis type 2 (supp.)
C535586	Carnevale syndrome (supp.)
C536170	Diastrophic dysplasia (supp.)
C535504	Epiphyseal dysplasia, multiple, 4 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — Selective sulphate transporters

CTD chemical–gene interactions

62 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects expression, affects cotreatment, decreases expression, increases expression	7
afimoxifene	decreases reaction, increases expression, decreases expression	2
sodium arsenite	decreases expression, increases abundance	2
Air Pollutants	decreases expression, increases abundance	2
Benzo(a)pyrene	increases expression, increases methylation	2
Cadmium	increases abundance, increases expression	2
Cisplatin	decreases expression	2
Coumestrol	increases expression, affects reaction, affects cotreatment	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Tretinoin	decreases expression	2
Valproic Acid	increases expression, affects expression	2
Cyclosporine	decreases expression, increases expression	2
Aflatoxin B1	affects expression, increases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
lead acetate	decreases expression	1
trichostatin A	increases expression	1
sulforaphane	increases expression	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	decreases expression	1
nickel chloride	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
cupric chloride	increases expression	1
coumarin	decreases phosphorylation	1
epigallocatechin gallate	affects cotreatment, decreases expression	1

Cellosaurus cell lines

5 cell lines: 4 cancer cell line, 1 finite cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D4EX	1321N1-SLC26A2-KO-c3	Cancer cell line	Male
CVCL_D4EY	1321N1-SLC26A2-KO-c7	Cancer cell line	Male
CVCL_HQ49	GM25515	Finite cell line	Female
CVCL_TM60	HAP1 SLC26A2 (-) 1	Cancer cell line	Male
CVCL_TM61	HAP1 SLC26A2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

92 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT01042158	PHASE4	COMPLETED	A Clinical Trial of Ambrisentan and Tadalafil in Pulmonary Arterial Hypertension Associated With Systemic Sclerosis
NCT03688191	PHASE4	UNKNOWN	Study of Sirolimus in CTD-TP in China
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04197050	PHASE4	UNKNOWN	Effect of Sacubitril/Valsartan on Reduced Right Ventricular Ejection Fraction in Patients With CTD
NCT04928586	PHASE4	UNKNOWN	Immunosuppressant Combined With Pirfenidone in CTD-ILD
NCT05440240	PHASE4	RECRUITING	Percutaneous Needle Fasciotomy +/- Corticosteroid Injection for Dupuytren’s Contracture
NCT05505409	PHASE4	UNKNOWN	Efficacy and Safety of Pirfenidone in CTD-ILD
NCT06499233	PHASE4	RECRUITING	Efficacy and Safety of Prophylactic Treatment for Pneumocystis Jirovecii Pneumonia in Patients With Autoimmune Inflammatory Rheumatic Disease
NCT00864201	PHASE3	UNKNOWN	A Study to Evaluate the Use of Bosentan in Patients With Exercise Induced Pulmonary Arterial Hypertension Associated With Connective Tissue Disease
NCT01196091	PHASE3	COMPLETED	A Study of LY2127399 in Participants With Systemic Lupus Erythematosus
NCT01205438	PHASE3	COMPLETED	A Study of LY2127399 in Participants With Systemic Lupus Erythematosus
NCT01488708	PHASE3	TERMINATED	On Open-Label Study in Participants With Systemic Lupus Erythematosus
NCT03626688	PHASE3	COMPLETED	A Study Evaluating the Efficacy and Safety of Ralinepag to Improve Treatment Outcomes in PAH Patients
NCT03683186	PHASE3	ENROLLING_BY_INVITATION	A Study Evaluating the Long-Term Efficacy and Safety of Ralinepag in Subjects With PAH Via an Open-Label Extension
NCT04084678	PHASE3	TERMINATED	A Study of Ralinepag to Evaluate Effects on Exercise Capacity by CPET in Subjects With WHO Group 1 PH
NCT06716606	PHASE3	RECRUITING	A Study to Investigate the Long-term Safety and Efficacy of Belimumab in Adults With Interstitial Lung Disease (ILD) Associated With Systemic Sclerosis (SSc) and Other Connective Tissue Diseases (CTD) (BLISSconneCTD-OLE)
NCT06917690	PHASE3	RECRUITING	A Study to Learn About the Safety and Efficacy of the Drug Oleogel-S10 in Japanese Patients With Epidermolysis Bullosa
NCT00004357	PHASE2	COMPLETED	Absorption of Corticosteroids in Children With Juvenile Dermatomyositis
NCT00005675	PHASE2	COMPLETED	Oral Type I Collagen for Relieving Scleroderma
NCT01808196	PHASE2	COMPLETED	Testing Effectiveness of Losartan in Patients With EoE With or Without a CTD
NCT02682511	PHASE2	ACTIVE_NOT_RECRUITING	Oral Ifetroban to Treat Diffuse Cutaneous Systemic Sclerosis (SSc) or SSc-associated Pulmonary Arterial Hypertension
NCT04993885	PHASE2	RECRUITING	Avatrombopag in the Treatment of Adult Immune Thrombocytopenia With Autoantibodies
NCT05516758	PHASE2	TERMINATED	A Study of Peresolimab (LY3462817) in Participants With Moderately-to-Severely Active Rheumatoid Arthritis
NCT05998759	PHASE2	RECRUITING	Telitacicept for the Treatment of Connective Tissue Disease-associated Thrombocytopenia
NCT06104228	PHASE2	RECRUITING	129 Xenon MRI as a Biomarker for Diagnosis and Response to Therapy in Pulmonary Arterial Hypertension (PAH)
NCT06067425	PHASE2	TERMINATED	Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of SAR442501 in Pediatric Participants With Achondroplasia
NCT01093911	PHASE1	COMPLETED	Safety Study of CDP7657 in Healthy Volunteers and Patients With Systemic Lupus Erythematosus (SLE)
NCT01764594	PHASE1	COMPLETED	Safety Study of CDP7657 in Patients With Systemic Lupus Erythematosus
NCT02392130	PHASE1	COMPLETED	A Clinical Trial to Assess the Potential of LEO 130852A Gel to Reduce Steroid Induced Skin Atrophy on Healthy Skin
NCT03337165	PHASE1	COMPLETED	Autologous Tolerogenic Dendritic Cells for Treatment of Patients With Rheumatoid Arthritis
NCT03929120	PHASE1	COMPLETED	Allogeneic Bone Marrow Mesenchymal Stem Cells for Patients With Interstitial Lung Disease (ILD) & Connective Tissue Disorders (CTD)
NCT05846009	PHASE1	COMPLETED	A First-in-human Single and Repeated Dose Escalation Study of SAR442501 in Healthy Adults Subjects
NCT00001754	Not specified	COMPLETED	Study of Skeletal Disorders and Short Stature
NCT02762318	Not specified	TERMINATED	Identification and Characterization of Bone-related Genetic Variants in Families
NCT03548779	Not specified	COMPLETED	North Carolina Genomic Evaluation by Next-generation Exome Sequencing, 2
NCT05247645	Not specified	RECRUITING	Data Collection of Patients With Rare Bone Diseases
NCT05876416	Not specified	RECRUITING	Decoding the Genetic Landscape of Skeletal Diseases
NCT05991609	Not specified	ACTIVE_NOT_RECRUITING	Extreme Morphology and Metabolic Health
NCT06002373	Not specified	UNKNOWN	Assessment of Artificial Intelligence for Treatment Decision Recommendation of Adult Skeletal Class III Patients
NCT01424033	PHASE2/PHASE3	TERMINATED	A Clinical Trial for CTD-ILD Treatment