Infantile hypophosphatasia: genes and variants
Infantile hypophosphatasia is linked to 1 analyzed protein (ALPL). 40 DNA variants are known to cause it; 41 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 Infantile 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.
40 disease-causing and 41 uncertain variants in ALPL are linked to Infantile hypophosphatasia.
Known disease-causing variants in Infantile hypophosphatasia
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| ALPL G220E | 220 | Disease-causing (★★) | |
| ALPL G220A | 220 | Disease-causing (★★) | |
| ALPL R272C | 272 | Disease-causing (★★) | |
| ALPL R272H | 272 | Disease-causing (★★) | |
| ALPL R272L | 272 | Disease-causing (★★) | |
| ALPL A468V | 468 | Disease-causing (★★) | |
| ALPL I72T | 72 | Disease-causing (★★) | |
| ALPL T167M | 167 | Disease-causing (★★) | |
| ALPL Q207P | 207 | Disease-causing (★★) | |
| ALPL M226I | 226 | Disease-causing (★★) | |
| ALPL G334D | 334 | Disease-causing (★★) | |
| ALPL E452K | 452 | Disease-causing (★★) | |
| ALPL E311K | 311 | Disease-causing (★★) | |
| ALPL F327L | 327 | Disease-causing (★★) | |
| ALPL A468S | 468 | Disease-causing (★★) | |
| ALPL A132T | 132 | Disease-causing (★★) | |
| ALPL Y178H | 178 | Disease-causing (★★) | |
| ALPL M219I | 219 | Disease-causing (★★) | |
| ALPL R246S | 246 | Disease-causing (★★) | |
| ALPL H341R | 341 | Disease-causing (★★) | |
| ALPL G426S | 426 | Disease-causing (★★) | |
| ALPL S445P | 445 | Disease-causing (★★) | |
| ALPL H472R | 472 | Disease-causing (★★) | |
| ALPL A348T | 348 | Disease-causing (★★) | |
| ALPL V374M | 374 | Disease-causing (★★) | |
| ALPL H381R | 381 | 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 M1V | 1 | Disease-causing (★★) | |
| ALPL T134H | 134 | 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 M295L | 295 | Disease-causing (★) | |
| ALPL G144A | 144 | Disease-causing (★) |
Uncertain variants in Infantile 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 Infantile hypophosphatasia variants (172 disease-causing).
- Adult hypophosphatasia is also caused by ALPL variants; they fall partly in the same places as the Infantile hypophosphatasia variants (113 disease-causing).
- Childhood hypophosphatasia is also caused by ALPL variants; they fall partly in the same places as the Infantile hypophosphatasia variants (60 disease-causing).
- Hypophosphataemia or rickets is also caused by ALPL variants; they fall partly in the same places as the Infantile hypophosphatasia variants (8 disease-causing).
- Semidominant ALPL-related disorders is also caused by ALPL variants; they fall in the same places as the Infantile hypophosphatasia variants (6 disease-causing).
Diseases related to Infantile hypophosphatasia
- Osteogenesis imperfecta, also linked to ALPL
- Hypophosphatasia, also linked to ALPL
- Adult hypophosphatasia, also linked to ALPL
- Childhood 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 Infantile hypophosphatasia?
In CATVariant, Infantile hypophosphatasia is linked to 1 analyzed protein: ALPL (Alkaline phosphatase, tissue-nonspecific isozyme).
How many genetic variants are linked to Infantile hypophosphatasia?
98 variants: 40 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 41 are of uncertain significance or have conflicting reports.
Which uncertain variants in Infantile 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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