Childhood hypophosphatasia

Summary

Childhood hypophosphatasia (MONDO:1010168) is a disease with 1 cohort gene and 1 clinical trial.

At a glance

• Prevalence: Unknown (Worldwide)
• Cohort genes: 1
• ClinVar variants: 247
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	childhood hypophosphatasia
Mondo ID	MONDO:1010168
MeSH	C562440
OMIM	241510
Orphanet	247667
DOID	DOID:0110915
SNOMED CT	30174008
UMLS	C0220743
MedGen	65089
GARD	0028132
Is cancer (heuristic)	no

Also known as: childhood hypophosphatasia · childhood-onset hypophosphatasia · hypophosphatasia of childhood · pediatric hypophosphatasia

Data availability: 247 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › developmental anomaly of metabolic origin › hypophosphatasia › childhood hypophosphatasia

Related subtypes (7): odontohypophosphatasia, ALPL-related autosomal dominant hypophosphatasia, ALPL-related autosomal recessive hypophosphatasia, moderate hypophosphatasia, prenatal benign hypophosphatasia, adult 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

247 retrieved; paginated sample, class counts are floors:

77 pathogenic/likely pathogenic, 42 conflicting classifications of pathogenicity, 40 uncertain significance, 26 likely pathogenic, 21 likely benign, 18 pathogenic, 18 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
1070177	NM_000478.6(ALPL):c.212G>A (p.Arg71His)	ALPL	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
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
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
1327508	NM_000478.6(ALPL):c.1479C>A (p.Asn493Lys)	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
13662	NM_000478.6(ALPL):c.535G>A (p.Ala179Thr)	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
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
13675	NM_000478.6(ALPL):c.407G>A (p.Arg136His)	ALPL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13676	NM_000478.6(ALPL):c.485G>T (p.Gly162Val)	ALPL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13677	NM_000478.6(ALPL):c.346G>A (p.Ala116Thr)	ALPL	Pathogenic	criteria provided, multiple submitters, no conflicts
13678	NM_000478.6(ALPL):c.648+1G>A	ALPL	Pathogenic	criteria provided, multiple submitters, no conflicts
13679	NM_000478.6(ALPL):c.1250A>G (p.Asn417Ser)	ALPL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13682	NM_000478.6(ALPL):c.746G>T (p.Gly249Val)	ALPL	Pathogenic	criteria provided, multiple submitters, no conflicts
13683	NM_000478.6(ALPL):c.526G>A (p.Ala176Thr)	ALPL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13684	NM_000478.6(ALPL):c.814C>T (p.Arg272Cys)	ALPL	Pathogenic	criteria provided, multiple submitters, no conflicts
1382079	NM_000478.6(ALPL):c.1A>G (p.Met1Val)	ALPL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1387764	NM_000478.6(ALPL):c.459G>A (p.Trp153Ter)	ALPL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1405036	NM_000478.6(ALPL):c.1354G>A (p.Glu452Lys)	ALPL	Pathogenic/Likely 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