ALPL

Chr 1

alkaline phosphatase, biomineralization associated

Also known as: AP-TNAP, APTNAP, HOPS, HPPA, HPPC, HPPI, HPPO, TNALP

This gene encodes a member of the alkaline phosphatase family of proteins. There are at least four distinct but related alkaline phosphatases: intestinal, placental, placental-like, and liver/bone/kidney (tissue non-specific). The first three are located together on chromosome 2, while the tissue non-specific form is located on chromosome 1. The product of this gene is a membrane bound glycosylated enzyme that is not expressed in any particular tissue and is, therefore, referred to as the tissue-nonspecific form of the enzyme. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature enzyme. This enzyme may play a role in bone mineralization. Mutations in this gene have been linked to hypophosphatasia, a disorder that is characterized by hypercalcemia and skeletal defects. [provided by RefSeq, Oct 2015]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtHypophosphatasia
UniProtHypophosphatasia, childhood
UniProtHypophosphatasia, infantile

Clinical highlights

Gene-disease validity (ClinGen)
ALPL-related autosomal dominant hypophosphatasia · ADDefinitivesufficient evidence for diagnostic panels2 gene-disease associations curated in total
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.
7
Active trials
245
Pubs (1 yr)
P/LP submissions
P/LP missense
0.69
LOEUF
LOF
Mechanism· G2P
📖
GeneReview available — ALPL
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.69LOEUF
pLI 0.000
Z-score 2.71
OE 0.41 (0.250.69)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
1.27Z-score
OE missense 0.80 (0.730.89)
266 obs / 330.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.41 (0.250.69)
00.351.4
Missense OE?0.80 (0.730.89)
00.61.4
Synonymous OE?1.07
01.21.6
LoF obs/exp: 10 / 24.5Missense obs/exp: 266 / 330.9Syn Z: -0.72

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ALPL · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Hypophosphatasia

The Effect of Monoallelic Variants in the ALPL Gene on the Natural Course of Hypophosphatasia in Russia

RECRUITING
NCT07390240AstraZenecaStarted 2025-12-29
Hypophosphatasia

Natural History Study of Patients With Hypophosphatasia (HPP)

RECRUITING
NCT02237625Duke UniversityStarted 2014-09
Gene ExpressionGene Expression ProfilingInfection

Host Response to Infection by Direct Analysis of Leukocyte Single Cell-type Gene Expression/transcript Abundance, Direct LS-TA

ACTIVE NOT RECRUITING
NCT06838780Chinese University of Hong KongStarted 2018-01-01
No intervention
Hypophosphatasia

Characteristics of Hypophosphatasia in Adult Patients in Rheumatology and Their Value in Developing an Algorithm to HPP-diagnosis - the COHIR Multi-center Study

RECRUITING
NCT06574282University of BonnStarted 2024-08-25
Second alkaline phosphatase measurement
Obesity

Bone Marrow Adipose Tissue in Relation to Bone and Energy Metabolism in Obesity and Type 2 Diabetes Mellitus

RECRUITING
NCT07731438Phase NAGeneral University Hospital, PragueStarted 2023-05-01
Caloric Restriction
Gene Expression ProfilingOrthodentic Appliances

Genes Associated With Bone Metabolism in the Saliva During Orthodontic Treatment

ACTIVE NOT RECRUITING
NCT07303647Kurdistan Higher Council of Medical SpecialtiesStarted 2025-10-12
PCR
Single Cell Sequencing TechnologyGene Expression ProfilingGene Expression

Host Response to Infection by Direct Analysis of Leukocyte Single Cell-type Gene Expression/transcript Abundance, Direct LS-TA. a Prospective Study Will Evaluate the Performance of Direct LS-TA in Triage Febrile Patients Into Major Categories of Infections: Viral, Bacterial or Active Tuberculosis.

NOT YET RECRUITING
NCT06846645Chinese University of Hong KongStarted 2025-02
No intervention