Hypophosphataemia or rickets: genes and variants
Hypophosphataemia or rickets is linked to 2 analyzed proteins (ALPL and SLC34A3). 9 DNA variants are known to cause it; 4 more are uncertain, and 0 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to Hypophosphataemia or rickets
ALPL: Alkaline phosphatase, tissue-nonspecific isozyme
It hydrolyzes extracellular pyrophosphate and other phosphate-containing substrates, enabling normal mineralization of bone and teeth. Loss-of-function variants cause hypophosphatasia, with severity ranging from lethal perinatal skeletal hypomineralization to adult fractures and dental disease.
8 disease-causing and 4 uncertain variants in ALPL are linked to Hypophosphataemia or rickets.
SLC34A3: Sodium-dependent phosphate transport protein 2C
It reabsorbs phosphate in the renal proximal tubule under hormonal control and is essential for maintaining serum phosphate and bone mineralization. Biallelic or dominant pathogenic variants can cause hereditary hypophosphatemic rickets with hypercalciuria.
1 disease-causing and 0 uncertain variants in SLC34A3 are linked to Hypophosphataemia or rickets.
Known disease-causing variants in Hypophosphataemia or rickets
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| ALPL A176T | 176 | Disease-causing (★★★★) | |
| ALPL T173I | 173 | Disease-causing (★★) | |
| ALPL D294A | 294 | Disease-causing (★★) | |
| ALPL V459L | 459 | Disease-causing (★★) | |
| ALPL Q106H | 106 | Disease-causing (★★) | |
| ALPL R136C | 136 | Disease-causing (★★) | |
| ALPL N417S | 417 | Disease-causing (★★) | |
| ALPL V382L | 382 | Disease-causing (★★) | |
| SLC34A3 S192L | 192 | Transmembrane | Disease-causing (★★) |
Which prediction tools work for Hypophosphataemia or rickets
How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).
- CATVariant: 98 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- PolyPhen-2: 93 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- CADD: 91 out of 100
- phyloP: 90 out of 100
- SIFT: 86 out of 100
Same protein, different disease
- Hypophosphatasia is also caused by ALPL variants; they fall mostly in different places as the Hypophosphataemia or rickets variants (172 disease-causing).
- Adult hypophosphatasia is also caused by ALPL variants; they fall mostly in different places as the Hypophosphataemia or rickets variants (113 disease-causing).
- Childhood hypophosphatasia is also caused by ALPL variants; they fall mostly in different places as the Hypophosphataemia or rickets variants (60 disease-causing).
- Infantile hypophosphatasia is also caused by ALPL variants; they fall mostly in different places as the Hypophosphataemia or rickets variants (40 disease-causing).
- Semidominant ALPL-related disorders is also caused by ALPL variants; they fall partly in the same places as the Hypophosphataemia or rickets variants (6 disease-causing).
- Autosomal recessive hypophosphatemic bone disease is also caused by SLC34A3 variants; they fall mostly in different places as the Hypophosphataemia or rickets variants (13 disease-causing).
Diseases related to Hypophosphataemia or rickets
- Osteogenesis imperfecta, also linked to ALPL
- Hypophosphatasia, also linked to ALPL
- Adult hypophosphatasia, also linked to ALPL
- Childhood hypophosphatasia, also linked to ALPL
- Infantile hypophosphatasia, also linked to ALPL
- Autosomal recessive hypophosphatemic bone disease, also linked to SLC34A3
- Paediatric disorders, also linked to ALPL
- Semidominant ALPL-related disorders, also linked to ALPL
Frequently asked questions
Which genes are linked to Hypophosphataemia or rickets?
In CATVariant, Hypophosphataemia or rickets is linked to 2 analyzed proteins: ALPL (Alkaline phosphatase, tissue-nonspecific isozyme) and SLC34A3 (Sodium-dependent phosphate transport protein 2C).
How many genetic variants are linked to Hypophosphataemia or rickets?
13 variants: 9 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 4 are of uncertain significance or have conflicting reports.
Which uncertain variants in Hypophosphataemia or rickets 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 Hypophosphataemia or rickets?
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 8 disease-causing and 23 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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