SLCO4A1

Chr 20

solute carrier organic anion transporter family member 4A1

Also known as: OATP-E, OATP4A1, OATPE, OATPRP1, POAT, SLC21A12

NCBI Gene: 28231ENSG00000101187UniProt: Q96BD0

The protein functions as an organic anion antiporter that transports thyroid hormones (T3, T4), conjugated steroids, bile acids, and prostaglandins across cell membranes, particularly in kidney, liver, and placenta. Mutations cause autosomal recessive digenic brachydactyly with a very early onset in infancy. This gene shows minimal constraint against loss-of-function mutations based on population data.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
9
Pubs (1 yr)
27
P/LP submissions
0%
P/LP missense
1.00
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— SLCO4A1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
27 unique Pathogenic / Likely Pathogenic· 122 VUS of 177 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.00LOEUF
pLI 0.000
Z-score 1.56
OE 0.69 (0.48–1.00)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.43Z-score
OE missense 0.94 (0.87–1.02)
437 obs / 463.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.69 (0.48–1.00)
0≤0.351.4
Missense OE0.94 (0.87–1.02)
0≤0.61.4
Synonymous OE1.09
0≤1.21.6
LoF obs/exp: 20 / 29.1Missense obs/exp: 437 / 463.1Syn Z: -1.09
DN
0.76top 25%
GOF
0.7028th %ile
LOF
0.2777th %ile

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

DNprediction above median
GOFprediction 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

177 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic5
VUS122
Likely Benign20
22
Pathogenic
5
Likely Pathogenic
122
VUS
20
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
22
0
22
Likely Pathogenic
0
0
5
0
5
VUS
0
110
12
0
122
Likely Benign
0
16
1
3
20
Benign
0
0
0
0
0
Total0126403169

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

View in ClinVar →

Protein Context — Lollipop Plot

SLCO4A1 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
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
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients