Myopathy due to myoadenylate deaminase deficiency

Summary

Myopathy due to myoadenylate deaminase deficiency (MONDO:0014220) is a disease caused by AMPD1 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: AMPD1 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 485

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	myopathy due to myoadenylate deaminase deficiency
Mondo ID	MONDO:0014220
OMIM	615511
NCIT	C157504
UMLS	C3714933
MedGen	811508
GARD	0015248
Is cancer (heuristic)	no

Also known as: adenosine monophosphate deaminase 1 deficiency · adenosine monophosphate deaminase deficiency · AMP deaminase 1 deficiency · AMP deaminase deficiency · AMPD1 deficiency · MMDD · myoadenylate deaminase deficiency · myopathy due to myoadenylate deaminase deficiency

Data availability: 485 ClinVar variants · 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 › myopathy due to myoadenylate deaminase deficiency

Related subtypes (31): polyglucosan body myopathy, muscular atrophy, myopathy of extraocular muscle, acute quadriplegic myopathy, myofascial pain syndrome, myopathy with abnormal lipid metabolism, proximal myopathy with focal depletion of mitochondria, Brody myopathy, rippling muscle disease, proximal myopathy with extrapyramidal signs, intermediate nemaline myopathy, hereditary inclusion-body myopathy, hereditary continuous muscle fiber activity, congenital myopathy, muscular dystrophy, metabolic myopathy, myositis disease, collagen 6-related myopathy, myopathy caused by variation in CRPPA, drug-induced myopathy, myopathy caused by variation in FKRP, myopathy caused by variation in FKTN, myopathy caused by variation in POMGNT1, myopathy caused by variation in POMGNT2, myopathy caused by variation in POMT1, myopathy caused by variation in POMT2, myopathy caused by variation in GMPPB, FHL1-related myopathy, myopathy, sarcoplasmic body, myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis 2, myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis

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

485 retrieved; paginated sample, class counts are floors:

275 uncertain significance, 153 likely benign, 31 conflicting classifications of pathogenicity, 16 benign, 4 benign/likely benign, 2 likely pathogenic, 2 conflicting classifications of pathogenicity; other, 2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3247662	NC_000001.10:g.(?115231162)(115238191_?)del	AMPD1	Pathogenic	criteria provided, single submitter
4277942	NM_000036.3(AMPD1):c.1679+2T>C	AMPD1	Pathogenic	criteria provided, single submitter
1030545	NM_000036.3(AMPD1):c.2181T>A (p.Tyr727Ter)	AMPD1	Likely pathogenic	criteria provided, single submitter
4845819	NM_000036.3(AMPD1):c.1957C>T (p.Gln653Ter)	AMPD1	Likely pathogenic	criteria provided, single submitter
1084439	NM_000036.3(AMPD1):c.577G>A (p.Asp193Asn)	AMPD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1326503	NM_000036.3(AMPD1):c.216-9C>T	AMPD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1564733	NC_000001.11:g.114695547A>G	AMPD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
18271	NM_000036.3(AMPD1):c.34C>T (p.Gln12Ter)	AMPD1	Conflicting classifications of pathogenicity; other	criteria provided, conflicting classifications
18272	NM_000036.3(AMPD1):c.1162C>T (p.Arg388Trp)	AMPD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
18273	NM_000036.3(AMPD1):c.1274G>A (p.Arg425His)	AMPD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
197097	NM_000036.3(AMPD1):c.334G>A (p.Val112Met)	AMPD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
197620	NM_000036.3(AMPD1):c.468G>T (p.Gln156His)	AMPD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
198036	NM_000036.3(AMPD1):c.636C>T (p.Asp212=)	AMPD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1989580	NM_000036.3(AMPD1):c.-15A>G	AMPD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
281130	NM_000036.3(AMPD1):c.215+8G>A	AMPD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
285434	NM_000036.3(AMPD1):c.548-9T>C	AMPD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
286655	NM_000036.3(AMPD1):c.1721G>A (p.Gly574Glu)	AMPD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
287426	NM_000036.3(AMPD1):c.1191C>T (p.Tyr397=)	AMPD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
289235	NM_000036.3(AMPD1):c.1819T>C (p.Leu607=)	AMPD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
290016	NM_000036.3(AMPD1):c.1170C>G (p.Leu390=)	AMPD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
290874	NM_000036.3(AMPD1):c.144G>A (p.Pro48=)	AMPD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
291055	NM_000036.3(AMPD1):c.462G>A (p.Ser154=)	AMPD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
291059	NM_000036.3(AMPD1):c.513T>A (p.Gly171=)	AMPD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
291929	NM_000036.3(AMPD1):c.1570T>A (p.Ser524Thr)	AMPD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
445418	NM_000036.3(AMPD1):c.1389-16T>A	AMPD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
451200	NM_000036.3(AMPD1):c.1365G>A (p.Trp455Ter)	AMPD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
50897	NM_000036.3(AMPD1):c.143C>T (p.Pro48Leu)	AMPD1	Conflicting classifications of pathogenicity; other	criteria provided, conflicting classifications
559258	NM_000036.3(AMPD1):c.512G>A (p.Gly171Asp)	AMPD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
576813	NM_000036.3(AMPD1):c.323C>T (p.Thr108Ile)	AMPD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
747527	NM_000036.3(AMPD1):c.381+1G>C	AMPD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
AMPD1	Orphanet:45	Adenosine monophosphate deaminase deficiency
APOB	Orphanet:391665	Homozygous familial hypercholesterolemia

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
AMPD1	HGNC:468	ENSG00000116748	P23109	AMP deaminase 1	gencc,clinvar
APOB	HGNC:603	ENSG00000084674	P04114	Apolipoprotein B-100	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
AMPD1	AMP deaminase 1	AMP deaminase plays a critical role in energy metabolism.
APOB	Apolipoprotein B-100	Apolipoprotein B is a major protein constituent of chylomicrons (apo B-48), LDL (apo B-100) and VLDL (apo B-100).

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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)	1	6.0×	0.320
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
AMPD1	Enzyme (other)	yes	3.5.4.6	AMPD, A/AMP_deam_AS, Metal_Hydrolase
APOB	Other/Unknown	no		Vitellogenin_N, Lipid_transpt_open_b-sht, Lipovitellin_superhlx_dom

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
quadriceps femoris	1
triceps brachii	1
vastus lateralis	1
ileal mucosa	1
jejunal mucosa	1
liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
AMPD1	175	tissue_specific	marker	triceps brachii, vastus lateralis, quadriceps femoris
APOB	116	broad	marker	jejunal mucosa, liver, ileal mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
APOB	5,244
AMPD1	1,830

Structural data

PDB: 1 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
APOB	P04114	8

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
AMPD1	P23109	86.84

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 45. 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
Scavenging by Class H Receptors	1	1427.5×	0.008	APOB
VLDL assembly	1	1142.0×	0.008	APOB
Chylomicron clearance	1	1142.0×	0.008	APOB
Scavenging by Class F Receptors	1	951.7×	0.008	APOB
LDL remodeling	1	951.7×	0.008	APOB
VLDL clearance	1	951.7×	0.008	APOB
Nucleotide salvage	1	571.0×	0.009	AMPD1
Chylomicron assembly	1	571.0×	0.009	APOB
Chylomicron remodeling	1	571.0×	0.009	APOB
Scavenging by Class B Receptors	1	519.1×	0.009	APOB
Purine salvage	1	439.2×	0.009	AMPD1
Plasma lipoprotein assembly	1	356.9×	0.010	APOB
Platelet sensitization by LDL	1	335.9×	0.010	APOB
Scavenging by Class A Receptors	1	300.5×	0.010	APOB
Binding and Uptake of Ligands by Scavenger Receptors	1	271.9×	0.010	APOB
LDL clearance	1	271.9×	0.010	APOB
Regulation of TLR by endogenous ligand	1	248.3×	0.010	APOB
Plasma lipoprotein remodeling	1	237.9×	0.010	APOB
Plasma lipoprotein clearance	1	237.9×	0.010	APOB
Metabolism of fat-soluble vitamins	1	190.3×	0.012	APOB
Metabolism of nucleotides	1	150.3×	0.014	AMPD1
Platelet homeostasis	1	139.3×	0.014	APOB
Visual phototransduction	1	129.8×	0.014	APOB
Metabolism	2	11.6×	0.014	AMPD1, APOB
Retinoid metabolism and transport	1	124.1×	0.014	APOB
Plasma lipoprotein assembly, remodeling, and clearance	1	114.2×	0.015	APOB
Heme signaling	1	107.7×	0.015	APOB
Toll-like Receptor Cascades	1	62.1×	0.026	APOB
Metabolism of vitamins and cofactors	1	58.3×	0.027	APOB
Cargo recognition for clathrin-mediated endocytosis	1	52.4×	0.028	APOB

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	1	2808.7×	0.003	AMPD1
triglyceride mobilization	1	2106.5×	0.003	APOB
IMP salvage	1	1685.2×	0.003	AMPD1
cellular response to lipoprotein particle stimulus	1	1685.2×	0.003	APOB
GMP salvage	1	1404.3×	0.003	AMPD1
lipoprotein biosynthetic process	1	1404.3×	0.003	APOB
positive regulation of cholesterol storage	1	1203.7×	0.003	APOB
lipoprotein catabolic process	1	1203.7×	0.003	APOB
AMP metabolic process	1	936.2×	0.004	AMPD1
regulation of cholesterol biosynthetic process	1	766.0×	0.004	APOB
positive regulation of lipid storage	1	702.2×	0.004	APOB
very-low-density lipoprotein particle assembly	1	601.9×	0.004	APOB
low-density lipoprotein particle remodeling	1	526.6×	0.004	APOB
low-density lipoprotein particle clearance	1	495.6×	0.004	APOB
lipoprotein transport	1	495.6×	0.004	APOB
positive regulation of macrophage derived foam cell differentiation	1	421.3×	0.005	APOB
triglyceride catabolic process	1	401.2×	0.005	APOB
cholesterol transport	1	366.4×	0.005	APOB
artery morphogenesis	1	337.0×	0.005	APOB
cholesterol efflux	1	263.3×	0.006	APOB
fertilization	1	156.0×	0.009	APOB
post-embryonic development	1	102.8×	0.014	APOB
cholesterol metabolic process	1	98.0×	0.014	APOB
establishment of localization in cell	1	80.2×	0.016	APOB
cholesterol homeostasis	1	78.0×	0.016	APOB
response to virus	1	72.0×	0.016	APOB
flagellated sperm motility	1	58.5×	0.020	APOB
in utero embryonic development	1	36.0×	0.031	APOB
nervous system development	1	23.0×	0.046	APOB
positive regulation of gene expression	1	19.4×	0.053	APOB

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

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
AMPD1	0	0
APOB	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
AMPD1	3	Binding:3
APOB	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
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

0 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.

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	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	AMPD1
E	Difficult family or no structure, no drug	1	APOB

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
AMPD1	3	—
APOB	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.