SLCO3A1

Chr 15

solute carrier organic anion transporter family member 3A1

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

NCBI Gene: 28232 ENSG00000176463 UniProt: Q9UIG8 OMIM: 612435

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.

OMIM ResearchSummary from RefSeq, UniProt

Enables organic anion transmembrane transporter activity and prostaglandin transmembrane transporter activity. Involved in positive regulation of MAPK cascade; positive regulation of canonical NF-kappaB signal transduction; and prostaglandin transport. Located in basal plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.44

Clinical Summary— SLCO3A1

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.22) despite low pLI — interpret in context.

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ClinVar Variants

67 VUS of 88 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.44LOEUF

pLI 0.390

Z-score 3.72

OE 0.22 (0.12–0.44)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.86Z-score

OE missense 0.62 (0.56–0.68)

277 obs / 447.3 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.22 (0.12–0.44)

0≤0.351.4

Missense OE?0.62 (0.56–0.68)

0≤0.61.4

Synonymous OE?1.10

0≤1.21.6

LoF obs/exp: 6 / 26.8Missense obs/exp: 277 / 447.3Syn Z: -1.12

This gene — mechanism propensity

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

88 submitted variants in ClinVar

ClinVar

Classification Summary

VUS67

Likely Benign3

Benign2

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	67	0	0	67
Likely Benign	2	0	1	3
Benign	0	2	0	2
Total	69	2	1	72

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

View in ClinVar →

44 pathogenic / likely-pathogenic (of 49) ClinVar copy-number / structural variants overlap SLCO3A1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →