OPN4
protein-codingopsin 4, the group of Opsin receptors
Gene summary
Opsins are members of the guanine nucleotide-binding protein (G protein)-coupled receptor superfamily. This gene encodes a photoreceptive opsin protein that is expressed within the ganglion and amacrine cell layers of the retina. In mouse, retinal ganglion cell axons expressing this gene projected to the suprachiasmatic nucleus and other brain nuclei involved in circadian photoentrainment. In mouse, this protein is coupled to a transient receptor potential (TRP) ion channel through a G protein signaling pathway and produces a physiologic light response via membrane depolarization and increased intracellular calcium. The protein functions as a sensory photopigment and may also have photoisomerase activity. Experiments with knockout mice indicate that this gene attenuates, but does not abolish, photoentrainment. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~11.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to OPN4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_033282.4. 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 | 1 | 1 | 2 | |||
| missense | 90 | 5 | 1 | 96 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 91 | 6 | 3 | 100 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_150598.1 | 10 | MANE Select | |
| Ensembl | ENSP00000241891.5 | 10 | MANE Select | |
| RefSeq | NP_001025186.1 | 11 | Standard | |
| Ensembl | ENSP00000361141.2 | 11 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| opn4a | Danio rerio | Structure: phototaxis Quality: process quality abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- GPCRs, Class A Rhodopsin-like
- Signaling by GPCR
- Signal Transduction
- Opsins
- Class A/1 (Rhodopsin-like receptors)
Biological Process
- G protein-coupled receptor signaling pathway
- visual perception
- phototransduction
- detection of visible light
- protein-chromophore linkage
Molecular Function
- 11-cis retinal binding
- G protein-coupled photoreceptor activity
Cellular Component
- integral component of plasma membrane
- integral component of membrane
- photoreceptor disc membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000372071
- Coding exons
- 11
- Length
- 12292
- Individuals with no LoFs
- 125179
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 568
- Defined
- 125748
- p
- 0.00227
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.479 | 334 | 310 | 1.08 | 0.0000196 | 3120 |
| Missense (PolyPhen) | 114 | 112.1 | 1.017 | 1182 | ||
| Synonymous | -0.259 | 131 | 127 | 1.03 | 0.00000848 | 1021 |
| Loss of Function | 0.485 | 20 | 22.5 | 0.890 | 9.61e-7 | 245 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00055 | 0.00055 | rare |
| Latino/Admixed American | 0.0014 | 0.0014 | notable |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00060 | 0.00060 | rare |
| Finnish | 0.0047 | 0.0047 | notable |
| European (Non-Finnish) | 0.0030 | 0.0030 | notable |
| South Asian | 0.0015 | 0.0015 | notable |
| Other | 0.0020 | 0.0020 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Photoreceptor required for regulation of circadian rhythm. Contributes to pupillar reflex and other non-image forming responses to light. May be able to isomerize covalently bound all- trans retinal back to 11-cis retinal (By similarity). {ECO:0000250, ECO:0000269|PubMed:10632589, ECO:0000269|PubMed:15674244}.;
Recessive Scores
- pRec
- 0.179
Intolerance Scores
- LoFtool
- 0.923
- RVIS EVS
- 0.27
- RVIS percentile EVS
- 70.69
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.102
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |