Childhood hypophosphatasia: genes and variants
Childhood hypophosphatasia is linked to 1 analyzed protein (ALPL). 60 DNA variants are known to cause it; 48 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 Childhood hypophosphatasia
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.
60 disease-causing and 48 uncertain variants in ALPL are linked to Childhood hypophosphatasia.
Known disease-causing variants in Childhood hypophosphatasia
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| ALPL A443V | 443 | Disease-causing (★★★★) | |
| ALPL A443S | 443 | Disease-causing (★★★★) | |
| ALPL A176T | 176 | Disease-causing (★★★★) | |
| ALPL G220E | 220 | Disease-causing (★★) | |
| ALPL G220A | 220 | Disease-causing (★★) | |
| ALPL E476A | 476 | Disease-causing (★★) | |
| ALPL A468V | 468 | Disease-causing (★★) | |
| ALPL E476K | 476 | Disease-causing (★★) | |
| ALPL G63V | 63 | Disease-causing (★★) | |
| ALPL R71H | 71 | Disease-causing (★★) | |
| ALPL I72T | 72 | Disease-causing (★★) | |
| ALPL T167M | 167 | Disease-causing (★★) | |
| ALPL Y178H | 178 | Disease-causing (★★) | |
| ALPL A179T | 179 | Disease-causing (★★) | |
| ALPL R184Q | 184 | Disease-causing (★★) | |
| ALPL M226I | 226 | Disease-causing (★★) | |
| ALPL G334D | 334 | Disease-causing (★★) | |
| ALPL D337G | 337 | Disease-causing (★★) | |
| ALPL A377V | 377 | Disease-causing (★★) | |
| ALPL D378V | 378 | Disease-causing (★★) | |
| ALPL S445P | 445 | Disease-causing (★★) | |
| ALPL E452K | 452 | Disease-causing (★★) | |
| ALPL G473S | 473 | Disease-causing (★★) | |
| ALPL T100M | 100 | Disease-causing (★★) | |
| ALPL A132G | 132 | Disease-causing (★★) | |
| ALPL A132V | 132 | Disease-causing (★★) | |
| ALPL R272C | 272 | Disease-causing (★★) | |
| ALPL R272H | 272 | Disease-causing (★★) | |
| ALPL E311K | 311 | Disease-causing (★★) | |
| ALPL F327L | 327 | Disease-causing (★★) | |
| ALPL H381R | 381 | Disease-causing (★★) | |
| ALPL R391C | 391 | Disease-causing (★★) | |
| ALPL A468S | 468 | Disease-causing (★★) | |
| ALPL A123D | 123 | Disease-causing (★★) | |
| ALPL T134H | 134 | Disease-causing (★★) | |
| ALPL M219I | 219 | Disease-causing (★★) | |
| ALPL R246S | 246 | Disease-causing (★★) | |
| ALPL D306Y | 306 | Disease-causing (★★) | |
| ALPL H341R | 341 | Disease-causing (★★) | |
| ALPL G426S | 426 | Disease-causing (★★) | |
| ALPL H472R | 472 | Disease-causing (★★) | |
| ALPL A487V | 487 | Disease-causing (★★) | |
| ALPL E298K | 298 | Disease-causing (★★) | |
| ALPL A348T | 348 | Disease-causing (★★) | |
| ALPL V374M | 374 | Disease-causing (★★) | |
| ALPL V382I | 382 | Disease-causing (★★) | |
| ALPL Y388C | 388 | Disease-causing (★★) | |
| ALPL I395V | 395 | Disease-causing (★★) | |
| ALPL G455S | 455 | Disease-causing (★★) | |
| ALPL G491R | 491 | Disease-causing (★★) | |
| ALPL N493K | 493 | Disease-causing (★★) | |
| ALPL M1V | 1 | Disease-causing (★★) | |
| ALPL I359M | 359 | Disease-causing (★★) | |
| ALPL T411A | 411 | Disease-causing (★★) | |
| ALPL K264R | 264 | Disease-causing (★★) | |
| ALPL G221A | 221 | Disease-causing (★) | |
| ALPL A33V | 33 | Disease-causing (★) | |
| ALPL G129E | 129 | Disease-causing (★) | |
| ALPL M295L | 295 | Disease-causing (★) | |
| ALPL G144A | 144 | Disease-causing (★) |
Uncertain variants in Childhood hypophosphatasia that look disease-causing
| Variant | Position | Protein part | Clinical label | Evidence |
|---|---|---|---|---|
| ALPL E452G | 452 | Uncertain (★) | +7: 2 other pathogenic changes within 3 positions; E452K at the same position is pathogenic; seen in 6.6e-06 of gnomAD DNA copies; REVEL 0.848 |
Same protein, different disease
- Hypophosphatasia is also caused by ALPL variants; they fall partly in the same places as the Childhood hypophosphatasia variants (172 disease-causing).
- Adult hypophosphatasia is also caused by ALPL variants; they fall partly in the same places as the Childhood hypophosphatasia variants (113 disease-causing).
- Hypophosphataemia or rickets is also caused by ALPL variants; they fall partly in the same places as the Childhood hypophosphatasia variants (8 disease-causing).
- Semidominant ALPL-related disorders is also caused by ALPL variants; they fall in the same places as the Childhood hypophosphatasia variants (6 disease-causing).
Diseases related to Childhood hypophosphatasia
- Osteogenesis imperfecta, also linked to ALPL
- Hypophosphatasia, also linked to ALPL
- Adult hypophosphatasia, also linked to ALPL
- Infantile hypophosphatasia, also linked to ALPL
- Hypophosphataemia or rickets, also linked to ALPL
- Paediatric disorders, also linked to ALPL
- Semidominant ALPL-related disorders, also linked to ALPL
Frequently asked questions
Which genes are linked to Childhood hypophosphatasia?
In CATVariant, Childhood hypophosphatasia is linked to 1 analyzed protein: ALPL (Alkaline phosphatase, tissue-nonspecific isozyme).
How many genetic variants are linked to Childhood hypophosphatasia?
109 variants: 60 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 48 are of uncertain significance or have conflicting reports.
Which uncertain variants in Childhood hypophosphatasia look disease-causing?
1 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example ALPL E452G. 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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