Gaucher disease: genes and variants
Gaucher disease is linked to 1 analyzed protein (GBA1). 132 DNA variants are known to cause it; 62 more are uncertain, and 6 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Also known as: Gaucher disease type 1; Gaucher disease type 2; Gaucher disease type 3; Gaucher disease type I; Gaucher disease type II; Gaucher disease type III
Genes linked to Gaucher disease
GBA1: Lysosomal acid glucosylceramidase
It degrades glucosylceramide within lysosomes and is essential for normal sphingolipid turnover. Biallelic pathogenic variants cause Gaucher disease, while heterozygous pathogenic variants are among the strongest genetic risk factors for Parkinson disease.
132 disease-causing and 62 uncertain variants in GBA1 are linked to Gaucher disease.
Known disease-causing variants in Gaucher disease
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| GBA1 R87Q | 87 | Disease-causing (★★) | |
| GBA1 R159Q | 159 | Disease-causing (★★) | |
| GBA1 R159W | 159 | Disease-causing (★★) | |
| GBA1 R170L | 170 | Disease-causing (★★) | |
| GBA1 R170C | 170 | Disease-causing (★★) | |
| GBA1 R209C | 209 | Disease-causing (★★) | |
| GBA1 P221T | 221 | Disease-causing (★★) | |
| GBA1 G234E | 234 | Disease-causing (★★) | |
| GBA1 F255Y | 255 | Disease-causing (★★) | |
| GBA1 I299T | 299 | Disease-causing (★★) | |
| GBA1 R392W | 392 | Disease-causing (★★) | |
| GBA1 W417G | 417 | Disease-causing (★★) | |
| GBA1 D419N | 419 | Disease-causing (★★) | |
| GBA1 D419A | 419 | Disease-causing (★★) | |
| GBA1 N501K | 501 | Disease-causing (★★) | |
| GBA1 R502H | 502 | Disease-causing (★★) | |
| GBA1 R502C | 502 | Disease-causing (★★) | |
| GBA1 R87W | 87 | Disease-causing (★★) | |
| GBA1 D448H | 448 | Disease-causing (★★) | |
| GBA1 R83C | 83 | Disease-causing (★★) | |
| GBA1 R83L | 83 | Disease-causing (★★) | |
| GBA1 G85E | 85 | Disease-causing (★★) | |
| GBA1 S164R | 164 | Disease-causing (★★) | |
| GBA1 N227S | 227 | Disease-causing (★★) | |
| GBA1 N227K | 227 | Disease-causing (★★) | |
| GBA1 K237E | 237 | Disease-causing (★★) | |
| GBA1 F252I | 252 | Disease-causing (★★) | |
| GBA1 R296Q | 296 | Disease-causing (★★) | |
| GBA1 F298L | 298 | Disease-causing (★★) | |
| GBA1 H350R | 350 | Disease-causing (★★) | |
| GBA1 Y352H | 352 | Disease-causing (★★) | |
| GBA1 L363P | 363 | Disease-causing (★★) | |
| GBA1 V391L | 391 | Disease-causing (★★) | |
| GBA1 S395F | 395 | Disease-causing (★★) | |
| GBA1 V414L | 414 | Disease-causing (★★) | |
| GBA1 G416S | 416 | Disease-causing (★★) | |
| GBA1 D419H | 419 | Disease-causing (★★) | |
| GBA1 L424P | 424 | Disease-causing (★★) | |
| GBA1 P430L | 430 | Disease-causing (★★) | |
| GBA1 V433L | 433 | Disease-causing (★★) | |
| GBA1 R434C | 434 | Disease-causing (★★) | |
| GBA1 D438N | 438 | Disease-causing (★★) | |
| GBA1 L483R | 483 | Disease-causing (★★) | |
| GBA1 M162K | 162 | Disease-causing (★★) | |
| GBA1 N227I | 227 | Disease-causing (★★) | |
| GBA1 T362I | 362 | Disease-causing (★★) | |
| GBA1 E388K | 388 | Disease-causing (★★) | |
| GBA1 S403T | 403 | Disease-causing (★★) | |
| GBA1 F450I | 450 | Disease-causing (★★) | |
| GBA1 S77R | 77 | Disease-causing (★★) | |
| GBA1 T82I | 82 | Disease-causing (★★) | |
| GBA1 T173I | 173 | Disease-causing (★★) | |
| GBA1 V230G | 230 | Disease-causing (★★) | |
| GBA1 S235P | 235 | Disease-causing (★★) | |
| GBA1 G241R | 241 | Disease-causing (★★) | |
| GBA1 Y259C | 259 | Disease-causing (★★) | |
| GBA1 Y283H | 283 | Disease-causing (★★) | |
| GBA1 G364R | 364 | Disease-causing (★★) | |
| GBA1 R398Q | 398 | Disease-causing (★★) | |
| GBA1 R535C | 535 | Disease-causing (★★) |
Showing 60 of 132.
Uncertain variants in Gaucher disease that look disease-causing
| Variant | Position | Protein part | Clinical label | Evidence |
|---|---|---|---|---|
| GBA1 D354H | 354 | Conflicting reports (★) | +6: 4 other pathogenic changes within 3 positions; D354N at the same position is pathogenic; REVEL 0.972 | |
| GBA1 P305A | 305 | Conflicting reports (★) | +6: 2 other pathogenic changes within 3 positions; P305L at the same position is pathogenic; REVEL 0.948 | |
| GBA1 M162T | 162 | Conflicting reports (★) | +6: 7 other pathogenic changes within 3 positions; M162K at the same position is pathogenic; REVEL 0.922 | |
| GBA1 G416R | 416 | Conflicting reports (★) | +6: 8 other pathogenic changes within 3 positions; G416S at the same position is pathogenic; REVEL 0.956 | |
| GBA1 R170H | 170 | Conflicting reports (★) | +6: 3 other pathogenic changes within 3 positions; R170L at the same position is pathogenic; REVEL 0.852 | |
| GBA1 N435K | 435 | Uncertain | +6: 5 other pathogenic changes within 3 positions; N435T at the same position is pathogenic; REVEL 0.862 |
Same protein, different disease
- Parkinson disease, late-onset is also caused by GBA1 variants; they fall in the same places as the Gaucher disease variants (8 disease-causing).
- Lewy body dementia is also caused by GBA1 variants; they fall in the same places as the Gaucher disease variants (6 disease-causing).
- Gaucher disease perinatal lethal is also caused by GBA1 variants; they fall in the same places as the Gaucher disease variants (5 disease-causing).
Diseases related to Gaucher disease
- Lewy body dementia, also linked to GBA1
- Parkinson disease, late-onset, also linked to GBA1
- Gaucher disease perinatal lethal, also linked to GBA1
- Gaucher disease-ophthalmoplegia-cardiovascular calcification syndrome, also linked to GBA1
- Parkinson disease, also linked to GBA1
Frequently asked questions
Which genes are linked to Gaucher disease?
In CATVariant, Gaucher disease is linked to 1 analyzed protein: GBA1 (Lysosomal acid glucosylceramidase).
How many genetic variants are linked to Gaucher disease?
222 variants: 132 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 62 are of uncertain significance or have conflicting reports.
Which uncertain variants in Gaucher disease look disease-causing?
6 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example GBA1 D354H, GBA1 P305A, GBA1 M162T, GBA1 G416R and GBA1 R170H. These are leads for expert review, not diagnoses.
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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