SLCO1C1
protein-codingsolute carrier organic anion transporter family member 1C1, the group of Solute carrier organic anion transporter family
Gene summary
This gene encodes a member of the organic anion transporter family. The encoded protein is a transmembrane receptor that mediates the sodium-independent uptake of thyroid hormones in brain tissues. This protein has particularly high affinity for the thyroid hormones thyroxine, tri-iodothyronine and reverse tri-iodothyronine. Polymorphisms in the gene encoding this protein may be associated with fatigue and depression in patients suffering from hyperthyroidism. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2009]
- SLC21A14
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~58.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0100038
Submitter: Ambry Genetics
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SLCO1C1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_017435.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | 1 | 3 | ||
| missense | 77 | 3 | 2 | 82 | ||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 81 | 4 | 3 | 88 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_059131.1 | 14 | MANE Select | |
| Ensembl | ENSP00000266509.2 | 14 | MANE Select | |
| RefSeq | NP_001139416.1 | 12 | Standard | |
| RefSeq | NP_001139417.1 | 13 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Thyroid hormone signaling pathway - Homo sapiens (human)
- Angiopoietin Like Protein 8 Regulatory Pathway
- Tyrosine metabolism
- Androgen and estrogen biosynthesis and metabolism
- Transport of vitamins, nucleosides, and related molecules
Biological Process
- bile acid and bile salt transport
- sodium-independent organic anion transport
- transmembrane transport
- thyroid hormone transport
Molecular Function
- bile acid transmembrane transporter activity
- sodium-independent organic anion transmembrane transporter activity
- thyroid hormone transmembrane transporter activity
Cellular Component
- plasma membrane
- integral component of plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000381552
- Coding exons
- 14
- Length
- 58032
- Individuals with no LoFs
- 125677
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 69
- Defined
- 125747
- p
- 0.000278
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.477 | 392 | 366 | 1.07 | 0.0000167 | 4731 |
| Missense (PolyPhen) | 120 | 118.67 | 1.0112 | 1460 | ||
| Synonymous | -0.446 | 137 | 131 | 1.05 | 0.00000623 | 1392 |
| Loss of Function | 1.69 | 23 | 33.5 | 0.686 | 0.00000150 | 468 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00037 | 0.00037 | rare |
| Latino/Admixed American | 0.00050 | 0.00046 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00035 | 0.00033 | rare |
| Finnish | 0.000099 | 0.000092 | rare |
| European (Non-Finnish) | 0.00031 | 0.00030 | rare |
| South Asian | 0.00021 | 0.00020 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Mediates the Na(+)-independent high affinity transport of organic anions such as the thyroid hormones thyroxine (T4) and rT3. Other potential substrates, such as triiodothyronine (T3), 17-beta-glucuronosyl estradiol, estrone-3-sulfate and sulfobromophthalein (BSP) are transported with much lower efficiency. May play a signifiant role in regulating T4 flux into and out of the brain (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.0890
Intolerance Scores
- LoFtool
- 0.943
- RVIS EVS
- 0.0000761
- RVIS percentile EVS
- 53.98
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.205
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | High | High |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |