SLCO4A1

Chr 20

solute carrier organic anion transporter family member 4A1

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

NCBI Gene: 28231 ENSG00000101187 UniProt: Q96BD0 OMIM: 612436

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.

OMIM ResearchSummary from RefSeq, UniProt

Enables organic anion transmembrane transporter activity and prostaglandin transmembrane transporter activity. Predicted to be involved in sodium-independent organic anion transport. Predicted to be located in plasma membrane. Predicted to be active in basolateral plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.00

Clinical Summary— SLCO4A1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

111 VUS of 138 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 OE?0.69 (0.48–1.00)

0≤0.351.4

Missense OE?0.94 (0.87–1.02)

0≤0.61.4

Synonymous OE?1.09

0≤1.21.6

LoF obs/exp: 20 / 29.1Missense obs/exp: 437 / 463.1Syn Z: -1.09

This gene — mechanism propensity

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

138 submitted variants in ClinVar

ClinVar

Classification Summary

VUS111

Likely Benign19

111

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	111	0	111
Likely Benign	16	3	19
Benign	0	0	0
Total	127	3	130

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

View in ClinVar →

27 pathogenic / likely-pathogenic (of 40) ClinVar copy-number / structural variants overlap SLCO4A1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →