Adenosine monophosphate deaminase deficiency

Summary

Adenosine monophosphate deaminase deficiency (MONDO:0013028) is a disease with 2 cohort genes.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Cohort genes: 2
• ClinVar variants: 1
• Phenotypes (HPO): 7

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		100	Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

7 HPO clinical features (Orphanet curated; top 7 by frequency):

HPO ID	Term	Frequency
HP:0003326	Myalgia	Very frequent (80-99%)
HP:0003394	Muscle spasm	Very frequent (80-99%)
HP:0003690	Limb muscle weakness	Very frequent (80-99%)
HP:0003738	Exercise-induced myalgia	Very frequent (80-99%)
HP:0009020	Exercise-induced muscle fatigue	Very frequent (80-99%)
HP:0002151	Increased circulating lactate concentration	Excluded (0%)
HP:0008331	Elevated creatine kinase after exercise	Excluded (0%)

Identifiers

Disease identifiers

Field	Value
Canonical name	adenosine monophosphate deaminase deficiency
Mondo ID	MONDO:0013028
MeSH	C538234
Orphanet	45
ICD-10-CM	E79.2
ICD-11	550341491
SNOMED CT	9105005
UMLS	C2931781
MedGen	444140
GARD	0000547
Is cancer (heuristic)	no

Also known as: AMP deaminase deficiency · myoadenylate deaminase deficiency

Data availability: 1 ClinVar variant · 2 GenCC gene-disease records · 2 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › muscle tissue disorder › skeletal muscle disorder › myopathy › congenital myopathy › congenital structural myopathy › inborn mitochondrial myopathy › adenosine monophosphate deaminase deficiency

Related subtypes (23): myopathy, lactic acidosis, and sideroblastic anemia, mitochondrial encephalomyopathy, progressive external ophthalmoplegia, mitochondrial myopathy with a defect in mitochondrial-protein transport, Barth syndrome, mitochondrial myopathy with diabetes, mitochondrial myopathy with reversible cytochrome C oxidase deficiency, lethal infantile mitochondrial myopathy, sensory ataxic neuropathy, dysarthria, and ophthalmoparesis, mitochondrial trifunctional protein deficiency, congenital cataract-progressive muscular hypotonia-hearing loss-developmental delay syndrome, autosomal dominant mitochondrial myopathy with exercise intolerance, fatal infantile encephalocardiomyopathy, mitochondrial myopathy-lactic acidosis-deafness syndrome, mitochondrial neurogastrointestinal encephalomyopathy, adult-onset chronic progressive external ophthalmoplegia with mitochondrial myopathy, maternally-inherited progressive external ophthalmoplegia, mitochondrial myopathy, episodic, with optic atrophy and reversible leukoencephalopathy, mitochondrial complex II deficiency, nuclear type, mitochondrial myopathy-cerebellar ataxia-pigmentary retinopathy syndrome, X-linked recessive mitochondrial myopathy, mitochondrial complex I deficiency, nuclear type 1, COX deficiency, benign infantile mitochondrial myopathy

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

1 retrieved; paginated sample, class counts are floors:

1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
3779454	NM_001025389.2(AMPD3):c.1402C>T (p.Arg468Cys)	AMPD3	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
AMPD1	Strong	Autosomal recessive	myopathy due to myoadenylate deaminase deficiency	3
AMPD3	Supportive	Autosomal recessive	adenosine monophosphate deaminase deficiency	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
AMPD3	Orphanet:45	Adenosine monophosphate deaminase deficiency
AMPD1	Orphanet:45	Adenosine monophosphate deaminase deficiency

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
AMPD3	HGNC:470	ENSG00000133805	Q01432	AMP deaminase 3	gencc,clinvar
AMPD1	HGNC:468	ENSG00000116748	P23109	AMP deaminase 1	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
AMPD3	AMP deaminase 3	AMP deaminase plays a critical role in energy metabolism.
AMPD1	AMP deaminase 1	AMP deaminase plays a critical role in energy metabolism.

Protein-family classification

Druggable: 2 · 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
Enzyme (other)	2	12.0×	0.007

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
AMPD3	Enzyme (other)	yes	3.5.4.6	AMPD, A/AMP_deam_AS, Metal_Hydrolase
AMPD1	Enzyme (other)	yes	3.5.4.6	AMPD, A/AMP_deam_AS, Metal_Hydrolase

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
dorsal motor nucleus of vagus nerve	1
gluteal muscle	1
tibialis anterior	1
quadriceps femoris	1
triceps brachii	1
vastus lateralis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
AMPD3	281	ubiquitous	marker	gluteal muscle, dorsal motor nucleus of vagus nerve, tibialis anterior
AMPD1	175	tissue_specific	marker	triceps brachii, vastus lateralis, quadriceps femoris

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
AMPD1	1,830
AMPD3	1,739

Intra-cohort edges

A	B	Sources
AMPD1	AMPD3	biogrid_interaction, intact

Structural data

PDB: 0 · AlphaFold-only: 2 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
AMPD1	P23109	86.84
AMPD3	Q01432	85.74

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Nucleotide salvage	2	1142.0×	4e-06	AMPD3, AMPD1
Purine salvage	2	878.5×	4e-06	AMPD3, AMPD1
Metabolism of nucleotides	2	300.5×	3e-05	AMPD3, AMPD1
Metabolism	2	11.6×	0.013	AMPD3, AMPD1
Innate Immune System	1	12.8×	0.099	AMPD3
Neutrophil degranulation	1	11.5×	0.099	AMPD3
Immune System	1	6.5×	0.148	AMPD3

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
IMP biosynthetic process	2	5617.3×	1e-07	AMPD3, AMPD1
IMP salvage	2	3370.4×	2e-07	AMPD3, AMPD1
AMP metabolic process	2	1872.4×	4e-07	AMPD3, AMPD1
GMP salvage	1	1404.3×	8e-04	AMPD1
AMP catabolic process	1	1203.7×	8e-04	AMPD3

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 1 · Undrugged: 1

Druggability breadth: 2 of 2 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
AMPD3	1	2
AMPD1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
COFORMYCIN	2	AMPD3

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
AMPD3	4	Binding:4
AMPD1	3	Binding:3

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
AMPD3	3.5.4.6	AMP deaminase
AMPD1	3.5.4.6	AMP deaminase

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

1 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)
COFORMYCIN	2	AMPD3

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	1	AMPD3
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	AMPD1
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
AMPD1	3	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.