STRA6: The Retinol Uptake Receptor and Its Role in Development and Disease
A comprehensive biomedical overview of STRA6, the membrane receptor for retinol-binding protein, its genetic variants, and associated pathologies.
Gene Information Card
| Symbol | STRA6 |
|---|---|
| Full Name | Signaling receptor and transporter of retinol STRA6 |
| Gene Type | Protein coding |
| Chromosomal Location | 15q24.1 |
| NCBI Gene ID | 64220 ncbi.nlm.nih.gov/gene/64220 |
| Ensembl ID | ENSG00000137868 |
| UniProt ID | Q9BX79 |
| OMIM ID | 610745 |
| HGNC ID | 30650 |
| Aliases | MCOPS9, PP14291, FLJ12529 |
Description
STRA6 (signaling receptor and transporter of retinol) encodes a multi-pass transmembrane protein that functions as the high-affinity receptor for retinol-binding protein (RBP4). It mediates cellular uptake of retinol from the RBP4-retinol complex, a critical step in vitamin A homeostasis. STRA6 also activates a JAK/STAT signaling cascade independent of retinol transport. Mutations in STRA6 cause Matthew-Wood syndrome (microphthalmia/anophthalmia/coloboma with pulmonary hypoplasia and diaphragmatic hernia) and are associated with anophthalmia/microphthalmia and other developmental defects.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Matthew-Wood syndrome (MCOPS9) | Loss-of-function mutations impair retinol uptake, leading to vitamin A deficiency in developing tissues, disrupting retinoic acid signaling and organogenesis. | OMIM #601186; PMID: 17632512 |
| Microphthalmia, isolated, with coloboma 9 | Heterozygous or homozygous STRA6 mutations reduce retinol transport, affecting eye development. | OMIM #610745; PMID: 17632512 |
| Anophthalmia-microphthalmia spectrum | Biallelic STRA6 mutations cause severe ocular malformations via disrupted retinoic acid signaling. | ClinVar; PMID: 17632512 |
| Pulmonary hypoplasia / diaphragmatic hernia | STRA6 deficiency impairs retinol-dependent lung and diaphragm development. | OMIM #601186; PMID: 17632512 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Eye | 5.2 | Low |
| Lung | 3.8 | Low |
| Kidney | 2.1 | Not detected |
| Placenta | 1.5 | Not detected |
| Testis | 0.9 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| ARPE-19 (retinal pigment epithelium) | 4.1 | Retinal cell line; relevant to eye function |
| HepG2 (liver) | 1.2 | Low expression |
| A549 (lung) | 3.5 | Lung epithelial line |
| MCF7 (breast) | 0.8 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1120C>T (p.Arg374*) | Nonsense | Rare | Loss of function; truncation of transmembrane domain |
| c.1195G>A (p.Gly399Arg) | Missense | Rare | Impaired retinol uptake; reduced RBP4 binding |
| c.1573C>T (p.Arg525Trp) | Missense | Rare | Dominant negative effect in some families |
| c.1975_1976del (p.Leu659Alafs*12) | Frameshift | Rare | Loss of function; premature stop |
Mutation functional classification
Loss of Function (LOF)
Most STRA6 disease-associated mutations are loss-of-function, reducing or abolishing retinol transport and JAK/STAT signaling, leading to vitamin A deficiency in target tissues.
Gain of Function (GOF)
No gain-of-function mutations have been reported for STRA6.
Dominant Negative (DN)
Some missense mutations (e.g., p.Arg525Trp) may exert a dominant-negative effect by interfering with wild-type STRA6 function in heterozygous carriers.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Vitamin A and carotenoid metabolism (Reactome: R-HSA-975634)
• Retinol metabolism (KEGG: hsa00830)
• JAK-STAT signaling (Reactome: R-HSA-913531)
Protein Summary
STRA6 is a 667-amino-acid multi-pass transmembrane protein (UniProt Q9BX79) localized to the plasma membrane. It acts as the receptor for retinol-binding protein (RBP4), facilitating cellular retinol uptake. The protein contains a conserved STRA6 domain and is involved in both retinol transport and JAK/STAT signaling. Structural studies indicate a homodimeric assembly with a central channel for retinol translocation. Mutations in STRA6 disrupt retinol homeostasis, leading to severe developmental anomalies.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| STRA6 Knockout HEK293 Cell Line | EDJ-KQ14773 | Human | 64220 | Details Get a Quote |
| STRA6 Knockout A-549 Cell Line | EDJ-KQ46402 | Human | 64220 | Details Get a Quote |
| STRA6 Knockout HeLa Cell Line | EDJ-KQ46403 | Human | 64220 | Details Get a Quote |
| STRA6 Knockout HCT 116 Cell Line | EDJ-KQ73982 | Human | 64220 | Details Get a Quote |
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