STRA6
protein-codingsignaling receptor and transporter of retinol STRA6
Gene summary
The protein encoded by this gene is a membrane protein involved in the metabolism of retinol. The encoded protein acts as a receptor for retinol/retinol binding protein complexes. This protein removes the retinol from the complex and transports it across the cell membrane. Defects in this gene are a cause of syndromic microphthalmia type 9 (MCOPS9). Several transcript variants encoding a few different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~32.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0000170
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0011010
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0011010
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0011010
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0011010
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic; Pulmonary; Renal
Intervention: Cardiovascular
Rationale: The condition can involve congenital cardiac anomalies, and awareness may allow early management
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to STRA6 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_022369.4. 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 | 8 | 43 | 2 | 53 | ||
| missense | 7 | 3 | 130 | 14 | 4 | 158 |
| nonsense | 3 | 2 | 1 | 6 | ||
| start loss | 0 | |||||
| frameshift | 10 | 3 | 13 | |||
| splice donor/acceptor (+/-2bp) | 1 | 5 | 7 | 13 | ||
| Total | 21 | 13 | 146 | 57 | 6 | 243 |
Highest pathogenic variant AF is 0.0000192082
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_071764.3 | 18 | MANE Select | |
| Ensembl | ENSP00000378537.4 | 18 | MANE Select | |
| RefSeq | NP_001136089.1 | 18 | Standard | |
| RefSeq | NP_001136090.1 | 18 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| stra6 | Danio rerio | Structure: nucleate erythrocyte Quality: position abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Signaling by GPCR
- Signal Transduction
- The canonical retinoid cycle in rods (twilight vision)
- G alpha (i) signalling events
- Visual phototransduction
Biological Process
- retinoid metabolic process
- blood vessel development
- kidney development
- pulmonary valve morphogenesis
- ventricular septum development
Molecular Function
- retinal binding
- retinol binding
- retinol transmembrane transporter activity
- signaling receptor activity
Cellular Component
- plasma membrane
- integral component of plasma membrane
- protein-containing complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000563965
- Coding exons
- 19
- Length
- 32802
- Individuals with no LoFs
- 125697
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 51
- Defined
- 125748
- p
- 0.000203
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.599 | 355 | 388 | 0.914 | 0.0000228 | 4441 |
| Missense (PolyPhen) | 63 | 97.497 | 0.64617 | 1226 | ||
| Synonymous | -1.19 | 191 | 171 | 1.12 | 0.0000105 | 1521 |
| Loss of Function | 2.42 | 22 | 38.1 | 0.577 | 0.00000191 | 424 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000068 | 0.000062 | rare |
| Latino/Admixed American | 0.00032 | 0.00032 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00029 | 0.00027 | rare |
| South Asian | 0.00016 | 0.00016 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Functions as retinol transporter. Accepts all-trans retinol from the extracellular retinol-binding protein RBP4, facilitates retinol transport across the cell membrane, and then transfers retinol to the cytoplasmic retinol-binding protein RBP1 (PubMed:9452451, PubMed:18316031, PubMed:22665496). Retinol uptake is enhanced by LRAT, an enzyme that converts retinol to all-trans retinyl esters, the storage forms of vitamin A (PubMed:18316031, PubMed:22665496). Contributes to the activation of a signaling cascade that depends on retinol transport and LRAT-dependent generation of retinol metabolites that then trigger activation of JAK2 and its target STAT5, and ultimately increase the expression of SOCS3 and inhibit cellular responses to insulin (PubMed:21368206, PubMed:22665496). Important for the homeostasis of vitamin A and its derivatives, such as retinoic acid (PubMed:18316031). STRA6-mediated transport is particularly important in the eye, and under conditions of dietary vitamin A deficiency (Probable). Does not transport retinoic acid (PubMed:18316031). {ECO:0000269|PubMed:18316031, ECO:0000269|PubMed:21901792, ECO:0000269|PubMed:22665496, ECO:0000269|PubMed:9452451, ECO:0000305}.;
- Disease
- DISEASE: Microphthalmia, syndromic, 9 (MCOPS9) [MIM:601186]: A rare clinical entity including as main characteristics anophthalmia or severe microphthalmia, and pulmonary hypoplasia or aplasia. Microphthalmia is a disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues (anophthalmia). In many cases, microphthalmia/anophthalmia occurs in association with syndromes that include non-ocular abnormalities. {ECO:0000269|PubMed:17273977, ECO:0000269|PubMed:17503335, ECO:0000269|PubMed:21368206, ECO:0000269|PubMed:21901792}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=Mutations in STRA6 may be a cause of isolated colobomatous microphthalmia, a disorder of the eye characterized by an abnormally small ocular globe. {ECO:0000269|PubMed:21901792}.;
Recessive Scores
- pRec
- 0.103
Intolerance Scores
- LoFtool
- 0.0677
- RVIS EVS
- 0.3
- RVIS percentile EVS
- 71.64
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.185
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |