Pyruvate kinase deficiency of red cells: genes and variants
Pyruvate kinase deficiency of red cells is linked to 1 analyzed protein (PKLR). 23 DNA variants are known to cause it; 46 more are uncertain, and 3 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to Pyruvate kinase deficiency of red cells
PKLR: Pyruvate kinase PKLR
It catalyzes the final ATP-generating step of glycolysis in red blood cells and liver. Biallelic loss-of-function variants cause pyruvate kinase deficiency, leading to chronic nonspherocytic hemolytic anemia because erythrocytes cannot maintain adequate ATP production.
23 disease-causing and 44 uncertain variants in PKLR are linked to Pyruvate kinase deficiency of red cells.
Weakly linked (only a few uncertain records): NTRK1.
Known disease-causing variants in Pyruvate kinase deficiency of red cells
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| PKLR R510Q | 510 | Disease-causing (★★★★) | |
| PKLR R504L | 504 | Disease-causing (★★) | |
| PKLR R532W | 532 | Disease-causing (★★) | |
| PKLR G275R | 275 | Disease-causing (★★) | |
| PKLR T384M | 384 | Disease-causing (★★) | |
| PKLR R532P | 532 | Disease-causing (★★) | |
| PKLR G111R | 111 | Disease-causing (★★) | |
| PKLR D331E | 331 | Disease-causing (★★) | |
| PKLR G341A | 341 | Disease-causing (★★) | |
| PKLR R479H | 479 | Disease-causing (★★) | |
| PKLR N393S | 393 | Disease-causing (★★) | |
| PKLR R486W | 486 | Disease-causing (★★) | |
| PKLR R504H | 504 | Disease-causing (★) | |
| PKLR I471F | 471 | Disease-causing (★) | |
| PKLR R490L | 490 | Disease-causing (★) | |
| PKLR R498S | 498 | Disease-causing (★) | |
| PKLR R531S | 531 | Disease-causing (★) | |
| PKLR L75P | 75 | Disease-causing (★) | |
| PKLR G305E | 305 | Disease-causing (★) | |
| PKLR Q421K | 421 | Disease-causing | |
| PKLR S130Y | 130 | Disease-causing | |
| PKLR M356R | 356 | Disease-causing | |
| PKLR R359P | 359 | Disease-causing |
Uncertain variants in Pyruvate kinase deficiency of red cells that look disease-causing
| Variant | Position | Protein part | Clinical label | Evidence |
|---|---|---|---|---|
| PKLR R532Q | 532 | Conflicting reports (★) | +7: 3 other pathogenic changes within 3 positions; R532W at the same position is pathogenic; seen in 8.2e-06 of gnomAD DNA copies; REVEL 0.960 | |
| PKLR R504C | 504 | Conflicting reports (★) | +6: 2 other pathogenic changes within 3 positions; R504H at the same position is pathogenic; REVEL 0.974 | |
| PKLR R531C | 531 | Conflicting reports (★) | +6: 3 other pathogenic changes within 3 positions; R531S at the same position is pathogenic; seen in 1.4e-06 of gnomAD DNA copies; REVEL 0.719 |
Which prediction tools work for Pyruvate kinase deficiency of red cells
How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).
- CATVariant: 100 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- REVEL: 100 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- CADD: 91 out of 100
- PolyPhen-2: 85 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- SIFT: 82 out of 100
- phyloP: 80 out of 100
Diseases related to Pyruvate kinase deficiency of red cells
- Pyruvate kinase hyperactivity, also linked to PKLR
Frequently asked questions
Which genes are linked to Pyruvate kinase deficiency of red cells?
In CATVariant, Pyruvate kinase deficiency of red cells is linked to 1 analyzed protein: PKLR (Pyruvate kinase PKLR).
How many genetic variants are linked to Pyruvate kinase deficiency of red cells?
119 variants: 23 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 46 are of uncertain significance or have conflicting reports.
Which uncertain variants in Pyruvate kinase deficiency of red cells look disease-causing?
3 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example PKLR R532Q, PKLR R504C and PKLR R531C. These are leads for expert review, not diagnoses.
Which variant effect predictor works best for Pyruvate kinase deficiency of red cells?
Among tools not trained on clinical labels, CADD separates this disease's known disease-causing variants from harmless ones best (AUROC 0.91, based on 16 disease-causing and 21 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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