SLCO3A1

Chr 15

solute carrier organic anion transporter family member 3A1

Also known as: OATP-D, OATP-RP3, OATP3A1, OATPD, OATPRP3, SLC21A11

The protein functions as an organic anion transporter with broad substrate specificity, mediating transport of thyroid hormones, prostaglandins, bile acids, and aromatic amino acids across cell membranes. Mutations cause autosomal recessive hypertension with brachydactyly and increased fibroblast growth factor 23, presenting in childhood with elevated blood pressure and shortened fingers or toes. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.442), suggesting some tolerance for reduced protein function.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.44
Clinical SummarySLCO3A1
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.22) despite low pLI — interpret in context.
📋
ClinVar Variants
11 unique Pathogenic / Likely Pathogenic· 69 VUS of 99 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.44LOEUF
pLI 0.390
Z-score 3.72
OE 0.22 (0.120.44)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.86Z-score
OE missense 0.62 (0.560.68)
277 obs / 447.3 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.22 (0.120.44)
00.351.4
Missense OE0.62 (0.560.68)
00.61.4
Synonymous OE1.10
01.21.6
LoF obs/exp: 6 / 26.8Missense obs/exp: 277 / 447.3Syn Z: -1.12
DN
0.6938th %ile
GOF
0.73top 25%
LOF
0.3454th %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

99 submitted variants in ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic2
VUS69
Likely Benign3
9
Pathogenic
2
Likely Pathogenic
69
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
9
0
9
Likely Pathogenic
0
0
2
0
2
VUS
0
67
2
0
69
Likely Benign
0
2
0
1
3
Benign
0
0
0
0
0
Total06913183

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

View in ClinVar →

Protein Context — Lollipop Plot

SLCO3A1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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