Lowe syndrome: genes and variants
Lowe syndrome is linked to 1 analyzed protein (OCRL). 17 DNA variants are known to cause it; 140 more are uncertain, and 1 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to Lowe syndrome
OCRL: Inositol polyphosphate 5-phosphatase OCRL
It dephosphorylates specific phosphoinositides on endosomal and Golgi membranes and thereby regulates membrane trafficking, actin dynamics, and primary-cilium function. Loss-of-function variants cause Lowe syndrome and Dent disease type 2.
17 disease-causing and 140 uncertain variants in OCRL are linked to Lowe syndrome.
Where Lowe syndrome variants cluster
- OCRL 5-PPase (positions 235–538): 12 of 17 disease-causing changes, 2.1× more than its size predicts.
Known disease-causing variants in Lowe syndrome
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| OCRL R318C | 318 | 5-PPase | Disease-causing (★★) |
| OCRL R318S | 318 | 5-PPase | Disease-causing (★★) |
| OCRL R318H | 318 | 5-PPase | Disease-causing (★★) |
| OCRL R493W | 493 | 5-PPase | Disease-causing (★★) |
| OCRL A861T | 861 | Rho-GAP | Disease-causing (★★) |
| OCRL R500Q | 500 | 5-PPase | Disease-causing (★★) |
| OCRL R493Q | 493 | 5-PPase | Disease-causing (★) |
| OCRL H524R | 524 | 5-PPase | Disease-causing (★) |
| OCRL P526L | 526 | 5-PPase | Disease-causing (★) |
| OCRL A861P | 861 | Rho-GAP | Disease-causing (★) |
| OCRL H660P | 660 | ASH | Disease-causing (★) |
| OCRL I274T | 274 | 5-PPase | Disease-causing (★) |
| OCRL C498R | 498 | 5-PPase | Disease-causing (★) |
| OCRL A797P | 797 | Rho-GAP | Disease-causing (★) |
| OCRL H524Q | 524 | 5-PPase | Disease-causing |
| OCRL V636E | 636 | ASH | Disease-causing |
| OCRL G275A | 275 | 5-PPase | Disease-causing |
Uncertain variants in Lowe syndrome that look disease-causing
| Variant | Position | Protein part | Clinical label | Evidence |
|---|---|---|---|---|
| OCRL A861S | 861 | Rho-GAP | Uncertain (★) | +6: 2 other pathogenic changes within 3 positions; A861P at the same position is pathogenic; not seen in the gnomAD population database; AlphaMissense 0.99 |
Which prediction tools work for Lowe syndrome
How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).
- PolyPhen-2: 100 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- CATVariant: 96 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- SIFT: 86 out of 100
- MetaLR: 82 out of 100 (learned from overlapping clinical labels, so this is optimistic)
Same protein, different disease
- Dent disease is also caused by OCRL variants; they fall mostly in different places as the Lowe syndrome variants (10 disease-causing).
Diseases related to Lowe syndrome
- Dent disease, also linked to OCRL
- Nephrolithiasis/nephrocalcinosis, also linked to OCRL
Frequently asked questions
Which genes are linked to Lowe syndrome?
In CATVariant, Lowe syndrome is linked to 1 analyzed protein: OCRL (Inositol polyphosphate 5-phosphatase OCRL).
How many genetic variants are linked to Lowe syndrome?
210 variants: 17 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 140 are of uncertain significance or have conflicting reports.
Which uncertain variants in Lowe syndrome look disease-causing?
1 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example OCRL A861S. These are leads for expert review, not diagnoses.
Which variant effect predictor works best for Lowe syndrome?
Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.86, based on 16 disease-causing and 35 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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