Adult hypophosphatasia
diseaseOn this page
Also known as hypophosphatasia of adults
Summary
Adult hypophosphatasia (MONDO:1010154) is a disease with 1 cohort gene and 1 clinical trial.
At a glance
- Prevalence: Unknown (Worldwide)
- Cohort genes: 1
- ClinVar variants: 343
- Clinical trials: 1
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | adult hypophosphatasia |
| Mondo ID | MONDO:1010154 |
| OMIM | 146300 |
| Orphanet | 247676 |
| DOID | DOID:0110913 |
| SNOMED CT | 20756002 |
| UMLS | C0268413 |
| MedGen | 120636 |
| GARD | 0028131 |
| Is cancer (heuristic) | no |
Also known as: adult hypophosphatasia · hypophosphatasia of adults
Data availability: 343 ClinVar variants.
Disease family
Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › developmental anomaly of metabolic origin › hypophosphatasia › adult hypophosphatasia
Related subtypes (7): odontohypophosphatasia, ALPL-related autosomal dominant hypophosphatasia, ALPL-related autosomal recessive hypophosphatasia, moderate hypophosphatasia, prenatal benign hypophosphatasia, childhood hypophosphatasia, infantile hypophosphatasia
Genetics & variants
GWAS landscape
No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.
Variant details and genetic-evidence tiers
ClinVar germline variants
343 retrieved; paginated sample, class counts are floors:
119 pathogenic/likely pathogenic, 53 conflicting classifications of pathogenicity, 49 uncertain significance, 40 pathogenic, 39 likely pathogenic, 21 likely benign, 17 benign, 5 benign/likely benign
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1003680 | NM_000478.6(ALPL):c.1022A>G (p.His341Arg) | ALPL | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1030812 | NM_000478.6(ALPL):c.1328C>T (p.Ala443Val) | ALPL | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1047062 | NM_000478.6(ALPL):c.655A>G (p.Met219Val) | ALPL | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1067343 | NM_000478.6(ALPL):c.508A>G (p.Asn170Asp) | ALPL | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1070177 | NM_000478.6(ALPL):c.212G>A (p.Arg71His) | ALPL | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1070178 | NM_000478.6(ALPL):c.223G>A (p.Gly75Ser) | ALPL | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1072423 | NM_000478.6(ALPL):c.1240C>A (p.Leu414Met) | ALPL | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1074126 | NM_000478.6(ALPL):c.976G>C (p.Gly326Arg) | ALPL | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1074643 | NM_000478.6(ALPL):c.997G>T (p.Gly333Ter) | ALPL | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1076060 | NM_000478.6(ALPL):c.203C>T (p.Thr68Met) | ALPL | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1076087 | NM_000478.6(ALPL):c.303C>A (p.Tyr101Ter) | ALPL | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1076159 | NM_000478.6(ALPL):c.484G>A (p.Gly162Ser) | ALPL | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1076160 | NM_000478.6(ALPL):c.532T>C (p.Tyr178His) | ALPL | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1076161 | NM_000478.6(ALPL):c.659G>C (p.Gly220Ala) | ALPL | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1224321 | NM_000478.6(ALPL):c.1166C>A (p.Thr389Asn) | ALPL | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1224381 | NM_000478.6(ALPL):c.657G>T (p.Met219Ile) | ALPL | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1300140 | NM_000478.6(ALPL):c.1427A>C (p.Glu476Ala) | ALPL | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1323883 | NM_000478.6(ALPL):c.874C>A (p.Pro292Thr) | ALPL | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1334796 | NM_000478.6(ALPL):c.214A>G (p.Ile72Val) | ALPL | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1339258 | NM_000478.6(ALPL):c.247G>T (p.Glu83Ter) | ALPL | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1355608 | NM_000478.6(ALPL):c.480del (p.Val161fs) | ALPL | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 13662 | NM_000478.6(ALPL):c.535G>A (p.Ala179Thr) | ALPL | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 13663 | NM_000478.6(ALPL):c.211C>T (p.Arg71Cys) | ALPL | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 13664 | NM_000478.6(ALPL):c.881A>C (p.Asp294Ala) | ALPL | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 13665 | NM_000478.6(ALPL):c.212G>C (p.Arg71Pro) | ALPL | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 13667 | NM_000478.6(ALPL):c.98C>T (p.Ala33Val) | ALPL | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 13671 | NM_000478.6(ALPL):c.1133A>T (p.Asp378Val) | ALPL | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 13672 | NM_000478.6(ALPL):c.1001G>A (p.Gly334Asp) | ALPL | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 13673 | NM_000478.6(ALPL):c.979T>C (p.Phe327Leu) | ALPL | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 13674 | NM_000478.6(ALPL):c.1559del (p.Leu520fs) | ALPL | Pathogenic | criteria provided, multiple submitters, no conflicts |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 0 · Orphanet: 6 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| ALPL | Orphanet:247623 | Perinatal lethal hypophosphatasia |
| ALPL | Orphanet:247638 | Prenatal benign hypophosphatasia |
| ALPL | Orphanet:247651 | Infantile hypophosphatasia |
| ALPL | Orphanet:247667 | Childhood-onset hypophosphatasia |
| ALPL | Orphanet:247676 | Adult hypophosphatasia |
| ALPL | Orphanet:247685 | Odontohypophosphatasia |
Cohort genes → proteins
1 cohort genes, 1 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 1 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| ALPL | HGNC:438 | ENSG00000162551 | P05186 | Alkaline phosphatase, tissue-nonspecific isozyme | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| ALPL | Alkaline phosphatase, tissue-nonspecific isozyme | Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis. |
Protein-family classification
Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0
Family distribution
Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.
| Family | Genes | Fold | FDR |
|---|---|---|---|
| Phosphatase | 1 | 83.9× | 0.012 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| ALPL | Phosphatase | yes | 3.1.3.1 | Alkaline_phosphatase, Alkaline_phosphatase_core_sf, Alkaline_phosphatase_AS |
Expression context
Cohort genes with no expression data: 0.
1 cohort gene are a single-cell marker in ≥1 SCXA experiment.
Breadth distribution (Bgee present_calls)
| Bucket | Genes |
|---|---|
| narrow (1-5 tissues) | 0 |
| moderate (6-20) | 0 |
| broad (>20) | 1 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| left adrenal gland cortex | 1 |
| right adrenal gland | 1 |
| right adrenal gland cortex | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| ALPL | 200 | broad | marker | right adrenal gland, right adrenal gland cortex, left adrenal gland cortex |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| ALPL | 2,146 |
Structural data
PDB: 1 · AlphaFold-only: 0 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| ALPL | P05186 | 5 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).
Pathways by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Post-translational modification: synthesis of GPI-anchored proteins | 1 | 167.9× | 0.006 | ALPL |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| pyridoxal 5’-phosphate metabolic process | 1 | 16852.0× | 8e-04 | ALPL |
| response to vitamin B6 | 1 | 8426.0× | 8e-04 | ALPL |
| futile creatine cycle | 1 | 8426.0× | 8e-04 | ALPL |
| response to macrophage colony-stimulating factor | 1 | 4213.0× | 1e-03 | ALPL |
| inhibition of non-skeletal tissue mineralization | 1 | 4213.0× | 1e-03 | ALPL |
| developmental process involved in reproduction | 1 | 3370.4× | 0.001 | ALPL |
| cementum mineralization | 1 | 2407.4× | 0.001 | ALPL |
| response to sodium phosphate | 1 | 1685.2× | 0.002 | ALPL |
| phosphate ion homeostasis | 1 | 1053.2× | 0.002 | ALPL |
| cellular homeostasis | 1 | 802.5× | 0.002 | ALPL |
| response to vitamin D | 1 | 802.5× | 0.002 | ALPL |
| response to antibiotic | 1 | 702.2× | 0.002 | ALPL |
| endochondral ossification | 1 | 543.6× | 0.003 | ALPL |
| calcium ion homeostasis | 1 | 443.5× | 0.003 | ALPL |
| response to glucocorticoid | 1 | 324.1× | 0.004 | ALPL |
| bone mineralization | 1 | 271.8× | 0.005 | ALPL |
| response to insulin | 1 | 230.8× | 0.005 | ALPL |
| positive regulation of cold-induced thermogenesis | 1 | 163.6× | 0.007 | ALPL |
| skeletal system development | 1 | 125.8× | 0.008 | ALPL |
| response to lipopolysaccharide | 1 | 124.8× | 0.008 | ALPL |
| osteoblast differentiation | 1 | 121.2× | 0.008 | ALPL |
Therapeutics
Drug target analysis
Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0
Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Genes with an approved drug
The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.
| Symbol | Example approved molecule |
|---|---|
| ALPL | SULCONAZOLE NITRATE |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| ALPL | 7 | 4 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| SULCONAZOLE NITRATE | 4 | ALPL |
| THEOPHYLLINE | 4 | ALPL |
| LEVAMISOLE | 4 | ALPL |
| MICONAZOLE NITRATE | 4 | ALPL |
| LEVAMISOLE HYDROCHLORIDE | 4 | ALPL |
| ISOQUERCETIN | 2 | ALPL |
| (-)-EPICATECHIN | 2 | ALPL |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 1.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| ALPL | 58 | Binding:50, Functional:4, ADMET:3, Toxicity:1 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| ALPL | 3.1.3.1 | alkaline phosphatase |
Pharmacogenomics
Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.
No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).
Chemical tractability of cohort targets
7 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.
| Compound | Max phase | Cohort target (bioactivity) |
|---|---|---|
| SULCONAZOLE NITRATE | 4 | ALPL |
| THEOPHYLLINE | 4 | ALPL |
| LEVAMISOLE | 4 | ALPL |
| MICONAZOLE NITRATE | 4 | ALPL |
| LEVAMISOLE HYDROCHLORIDE | 4 | ALPL |
| ISOQUERCETIN | 2 | ALPL |
| (-)-EPICATECHIN | 2 | ALPL |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 1 | ALPL |
| B | Phased (≥1) drug, not yet approved | 0 | |
| C | Druggable family + PDB, no drug | 0 | |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 0 |
Undrugged target profiles
0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
Clinical trials & evidence
Clinical trials
Clinical trials: 1.
Phase distribution (across all retrieved trials)
| Phase | Trials |
|---|---|
| Not specified | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT01793168 | Not specified | RECRUITING | Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford |
Related Atlas pages
- Cohort genes: ALPL