SLCO1C1
Chr 12solute carrier organic anion transporter family member 1C1
Also known as: OATP-F, OATP-RP5, OATP1, OATP14, OATP1C1, OATPF, OATPRP5, SLC21A14
The encoded protein is a transmembrane transporter that mediates sodium-independent uptake of thyroid hormones, particularly thyroxine (T4) and triiodothyronine, across the blood-brain barrier and into brain cells. Mutations cause autosomal recessive brain hypothyroidism with neurological defects, characterized by intellectual disability, movement disorders, and developmental delays despite normal systemic thyroid function. This gene is not highly constrained against loss-of-function variants (pLI near zero), consistent with recessive inheritance where heterozygous carriers are typically unaffected.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Tolerant to missense variation
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.
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
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 37 | 0 | 37 |
Likely Pathogenic | 0 | 0 | 2 | 0 | 2 |
VUS | 0 | 78 | 5 | 0 | 83 |
Likely Benign | 0 | 4 | 1 | 0 | 5 |
Benign | 0 | 2 | 1 | 1 | 4 |
| Total | 0 | 84 | 46 | 1 | 131 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SLCO1C1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools