Enhanced S-cone syndrome: genes and variants
Enhanced S-cone syndrome is linked to 1 analyzed protein (NR2E3). 12 DNA variants are known to cause it; 44 more are uncertain, and 0 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Also known as: ENHANCED S-CONE SYNDROME 1
Genes linked to Enhanced S-cone syndrome
NR2E3: Photoreceptor-specific nuclear receptor
It directs rod-photoreceptor differentiation while repressing inappropriate cone gene programs during retinal development. Pathogenic variants cause enhanced S-cone syndrome, retinitis pigmentosa, and related inherited retinal dystrophies.
12 disease-causing and 44 uncertain variants in NR2E3 are linked to Enhanced S-cone syndrome.
Where Enhanced S-cone syndrome variants cluster
- NR2E3 Nuclear receptor (positions 44–120): 6 of 12 disease-causing changes, 2.7× more than its size predicts.
Known disease-causing variants in Enhanced S-cone syndrome
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| NR2E3 R309G | 309 | NR LBD | Disease-causing (★★) |
| NR2E3 R311Q | 311 | NR LBD | Disease-causing (★★) |
| NR2E3 R76Q | 76 | Nuclear receptor | Disease-causing (★★) |
| NR2E3 Y81C | 81 | Nuclear receptor | Disease-causing (★★) |
| NR2E3 R97H | 97 | Nuclear receptor | Disease-causing (★★) |
| NR2E3 A102D | 102 | Nuclear receptor | Disease-causing (★★) |
| NR2E3 R104W | 104 | Nuclear receptor | Disease-causing (★★) |
| NR2E3 V118M | 118 | Nuclear receptor | Disease-causing (★★) |
| NR2E3 G216S | 216 | NR LBD | Disease-causing (★★) |
| NR2E3 V342A | 342 | NR LBD | Disease-causing (★★) |
| NR2E3 M407K | 407 | NR LBD | Disease-causing (★★) |
| NR2E3 R309L | 309 | NR LBD | Disease-causing (★) |
Which prediction tools work for Enhanced S-cone syndrome
How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).
- PolyPhen-2: 86 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- CADD: 79 out of 100
- SIFT: 79 out of 100
- CATVariant: 77 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- phyloP: 70 out of 100
Same protein, different disease
- Retinitis pigmentosa is also caused by NR2E3 variants; they fall mostly in different places as the Enhanced S-cone syndrome variants (11 disease-causing).
Diseases related to Enhanced S-cone syndrome
- Retinitis pigmentosa, also linked to NR2E3
Frequently asked questions
Which genes are linked to Enhanced S-cone syndrome?
In CATVariant, Enhanced S-cone syndrome is linked to 1 analyzed protein: NR2E3 (Photoreceptor-specific nuclear receptor).
How many genetic variants are linked to Enhanced S-cone syndrome?
78 variants: 12 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 44 are of uncertain significance or have conflicting reports.
Which uncertain variants in Enhanced S-cone syndrome look disease-causing?
None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.
Which variant effect predictor works best for Enhanced S-cone syndrome?
Among tools not trained on clinical labels, CADD separates this disease's known disease-causing variants from harmless ones best (AUROC 0.79, based on 11 disease-causing and 9 harmless variants).
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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