Adult hypophosphatasia: genes and variants
Adult hypophosphatasia is linked to 1 analyzed protein (ALPL). 113 DNA variants are known to cause it; 65 more are uncertain, and 4 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to Adult 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.
113 disease-causing and 65 uncertain variants in ALPL are linked to Adult hypophosphatasia.
Known disease-causing variants in Adult hypophosphatasia
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| ALPL A443V | 443 | Disease-causing (★★★★) | |
| ALPL A443S | 443 | Disease-causing (★★★★) | |
| ALPL A176T | 176 | Disease-causing (★★★★) | |
| ALPL R71C | 71 | Disease-causing (★★) | |
| ALPL R71H | 71 | Disease-causing (★★) | |
| ALPL R71S | 71 | Disease-causing (★★) | |
| ALPL I72T | 72 | Disease-causing (★★) | |
| ALPL A132T | 132 | Disease-causing (★★) | |
| ALPL T167M | 167 | Disease-causing (★★) | |
| ALPL G220R | 220 | Disease-causing (★★) | |
| ALPL G220E | 220 | Disease-causing (★★) | |
| ALPL G220A | 220 | Disease-causing (★★) | |
| ALPL G221R | 221 | Disease-causing (★★) | |
| ALPL F327C | 327 | Disease-causing (★★) | |
| ALPL D378H | 378 | Disease-causing (★★) | |
| ALPL Y388H | 388 | Disease-causing (★★) | |
| ALPL G426D | 426 | Disease-causing (★★) | |
| ALPL G426S | 426 | Disease-causing (★★) | |
| ALPL A468T | 468 | Disease-causing (★★) | |
| ALPL E476A | 476 | Disease-causing (★★) | |
| ALPL R71P | 71 | Disease-causing (★★) | |
| ALPL G162S | 162 | Disease-causing (★★) | |
| ALPL T167K | 167 | Disease-causing (★★) | |
| ALPL R223Q | 223 | Disease-causing (★★) | |
| ALPL R223W | 223 | Disease-causing (★★) | |
| ALPL R272H | 272 | Disease-causing (★★) | |
| ALPL R272L | 272 | Disease-causing (★★) | |
| ALPL F327L | 327 | Disease-causing (★★) | |
| ALPL D378Y | 378 | Disease-causing (★★) | |
| ALPL Y388C | 388 | Disease-causing (★★) | |
| ALPL A468V | 468 | Disease-causing (★★) | |
| ALPL A468S | 468 | Disease-causing (★★) | |
| ALPL E476K | 476 | Disease-causing (★★) | |
| ALPL L37P | 37 | Disease-causing (★★) | |
| ALPL T68M | 68 | Disease-causing (★★) | |
| ALPL G75S | 75 | Disease-causing (★★) | |
| ALPL A111T | 111 | Disease-causing (★★) | |
| ALPL A114T | 114 | Disease-causing (★★) | |
| ALPL T141N | 141 | Disease-causing (★★) | |
| ALPL G144R | 144 | Disease-causing (★★) | |
| ALPL H171R | 171 | Disease-causing (★★) | |
| ALPL Y178H | 178 | Disease-causing (★★) | |
| ALPL A179T | 179 | Disease-causing (★★) | |
| ALPL R184Q | 184 | Disease-causing (★★) | |
| ALPL M219I | 219 | Disease-causing (★★) | |
| ALPL M219V | 219 | Disease-causing (★★) | |
| ALPL M226I | 226 | Disease-causing (★★) | |
| ALPL L275P | 275 | Disease-causing (★★) | |
| ALPL G326R | 326 | Disease-causing (★★) | |
| ALPL G334D | 334 | Disease-causing (★★) | |
| ALPL D337G | 337 | Disease-causing (★★) | |
| ALPL A377V | 377 | Disease-causing (★★) | |
| ALPL T389N | 389 | Disease-causing (★★) | |
| ALPL L414M | 414 | Disease-causing (★★) | |
| ALPL R428Q | 428 | Disease-causing (★★) | |
| ALPL S445P | 445 | Disease-causing (★★) | |
| ALPL E452K | 452 | Disease-causing (★★) | |
| ALPL G456R | 456 | Disease-causing (★★) | |
| ALPL M467T | 467 | Disease-causing (★★) | |
| ALPL G473S | 473 | Disease-causing (★★) |
Showing 60 of 113.
Uncertain variants in Adult hypophosphatasia that look disease-causing
| Variant | Position | Protein part | Clinical label | Evidence |
|---|---|---|---|---|
| ALPL E452G | 452 | Uncertain (★) | +7: 3 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 | |
| ALPL A114V | 114 | Conflicting reports (★) | +6: 4 other pathogenic changes within 3 positions; A114T at the same position is pathogenic; REVEL 0.946 | |
| ALPL G144E | 144 | Conflicting reports (★) | +6: 3 other pathogenic changes within 3 positions; G144A at the same position is pathogenic; REVEL 0.817 | |
| ALPL M295T | 295 | Conflicting reports (★) | +6: 4 other pathogenic changes within 3 positions; M295L at the same position is pathogenic; REVEL 0.901 |
Same protein, different disease
- Hypophosphatasia is also caused by ALPL variants; they fall in the same places as the Adult hypophosphatasia variants (172 disease-causing).
- Hypophosphataemia or rickets is also caused by ALPL variants; they fall in the same places as the Adult hypophosphatasia variants (8 disease-causing).
Diseases related to Adult hypophosphatasia
- Osteogenesis imperfecta, also linked to ALPL
- Hypophosphatasia, also linked to ALPL
- Childhood 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 Adult hypophosphatasia?
In CATVariant, Adult hypophosphatasia is linked to 1 analyzed protein: ALPL (Alkaline phosphatase, tissue-nonspecific isozyme).
How many genetic variants are linked to Adult hypophosphatasia?
190 variants: 113 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 65 are of uncertain significance or have conflicting reports.
Which uncertain variants in Adult hypophosphatasia look disease-causing?
4 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example ALPL E452G, ALPL A114V, ALPL G144E and ALPL M295T. 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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