SLC26A1

Chr 4AR

solute carrier family 26 member 1

Also known as: CAON, CAON1, EDM4, HYSULF, SAT-1, SAT1

The protein functions as a sodium-independent sulfate anion transporter that can also exchange other anions including bicarbonate, thiosulfate, and oxalate. Mutations cause autosomal recessive hypersulfaturia and calcium oxalate nephrolithiasis. The gene shows very low constraint against loss-of-function variants (LOEUF 1.48), and the phenotypes primarily involve renal manifestations related to altered anion transport.

Summary from RefSeq, OMIM, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

?HypersulfaturiaMIM #620372
AR
?Nephrolithiasis, calcium oxalate, 1MIM #167030
AR
0
Active trials
5
Pubs (1 yr)
58
P/LP submissions
7%
P/LP missense
1.48
LOEUF
Multiple*
Mechanism· predicted
Clinical SummarySLC26A1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
55 unique Pathogenic / Likely Pathogenic· 313 VUS of 500 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.48LOEUF
pLI 0.000
Z-score 0.04
OE 0.99 (0.681.48)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.37Z-score
OE missense 0.95 (0.881.03)
477 obs / 500.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.99 (0.681.48)
00.351.4
Missense OE0.95 (0.881.03)
00.61.4
Synonymous OE1.02
01.21.6
LoF obs/exp: 17 / 17.2Missense obs/exp: 477 / 500.1Syn Z: -0.20
DN
0.74top 25%
GOF
0.80top 10%
LOF
0.2776th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

500 submitted variants in ClinVar

Classification Summary

Pathogenic36
Likely Pathogenic19
VUS313
Likely Benign112
Benign4
Conflicting10
36
Pathogenic
19
Likely Pathogenic
313
VUS
112
Likely Benign
4
Benign
10
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
1
31
0
36
Likely Pathogenic
10
3
6
0
19
VUS
4
279
27
3
313
Likely Benign
0
8
16
88
112
Benign
0
1
0
3
4
Conflicting
10
Total182928094494

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SLC26A1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC