AMPD1

protein-coding

adenosine monophosphate deaminase 1, the group of Adenosine deaminase family

Gene summary

Adenosine monophosphate deaminase 1 catalyzes the deamination of AMP to IMP in skeletal muscle and plays an important role in the purine nucleotide cycle. Two other genes have been identified, AMPD2 and AMPD3, for the liver- and erythocyte-specific isoforms, respectively. Deficiency of the muscle-specific enzyme is apparently a common cause of exercise-induced myopathy and probably the most common cause of metabolic myopathy in the human. Alternatively spliced transcript variants encoding different isoforms have been identified in this gene.[provided by RefSeq, Feb 2010]

MANE transcript

NM_000036.3

Inheritance

ClinVar variants

P:8U:316B:115

Top phenotype

Myoadenylate deaminase deficiency

gnomAD constraint

pLI —, LoF o/e 0.9

Max pathogenic AF

—

Genomic locus

chr1:114,673,090-114,695,618

External References & Databases

Ensembl (ENSG00000116748)

Transcript & Mutation Effects

hg38 • Region Span ~22.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

myopathy due to myoadenylate deaminase deficiencyLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0014220

Submitter: PanelApp Australia

myopathy due to myoadenylate deaminase deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014220

Submitter: Labcorp Genetics (formerly Invitae)

adenosine monophosphate deaminase deficiencySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0013028

Submitter: Orphanet

Clinical Genomic Database (CGD)

Myoadenylate deaminase deficiencyAR

Manifestation: Biochemical; Musculoskeletal

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 1631143; 10086964; 10996775; 11102975; 11331279; 22538307

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to AMPD1 variants in ClinVar

7 Conditions Cataloged

Muscle AMP deaminase deficiencyTotal: 467

Inborn genetic diseasesTotal: 104

not providedTotal: 76

not specifiedTotal: 32

AMPD1-related disorderTotal: 17

AutismTotal: 11

Hypercholesterolemia, autosomal dominant, type BTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000036.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			6 clinvar	99 clinvar	6 clinvar	111
missense		1 clinvar	283 clinvar	8 clinvar		292
nonsense		4 clinvar	8 clinvar			12
start loss			1 clinvar			1
frameshift		2 clinvar	7 clinvar	1 clinvar		10
splice donor/acceptor (+/-2bp)	1 clinvar		11 clinvar	1 clinvar		13
Total	1	7	316	109	6	439

Highest pathogenic variant AF is 0.00077697093

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000036.3	RefSeq	NP_000027.3	16	MANE Select
ENST00000520113.7	Ensembl	ENSP00000430075.3	16	MANE Select
NM_001172626.2	RefSeq	NP_001166097.2	15	Standard
ENST00000369538.4	Ensembl	ENSP00000358551.4	15	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Purine metabolism - Homo sapiens (human)
Purine Nucleoside Phosphorylase Deficiency
Mercaptopurine Action Pathway
Azathioprine Action Pathway
Xanthine Dehydrogenase Deficiency (Xanthinuria)

Biological Process

response to organic substance
IMP salvage
purine-containing compound salvage

Molecular Function

AMP deaminase activity
myosin heavy chain binding
metal ion binding

Cellular Component

cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000520113
Coding exons: 16
Length: 22521
Individuals with no LoFs: 125491
Homozygous LoFs: 0
Heterozygous LoFs: 257
Defined: 125748
p: 0.00102

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.457	452	425	1.06	0.0000238	5208
Missense (PolyPhen)		211	203.92	1.0347		2407
Synonymous	-0.497	159	151	1.05	0.00000811	1426
Loss of Function	0.552	34	37.7	0.903	0.00000207	463

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0052	0.0051	notable
Latino/Admixed American	0.00087	0.00087	rare
Ashkenazi Jewish	0.00050	0.00050	rare
East Asian	0.00092	0.00092	rare
Finnish	0.00023	0.00023	rare
European (Non-Finnish)	0.00063	0.00062	rare
South Asian	0.0014	0.0014	notable
Other	0.00065	0.00065	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: AMP deaminase plays a critical role in energy metabolism.;
Disease: DISEASE: Myopathy due to myoadenylate deaminase deficiency (MMDD) [MIM:615511]: A metabolic disorder resulting in exercise-related myopathy. It is characterized by exercise-induced muscle aches, cramps, and early fatigue. {ECO:0000269|PubMed:11102975}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.449

Intolerance Scores

LoFtool: 0.126
RVIS EVS: 0.07
RVIS percentile EVS: 59.17

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.124

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium