What you carry at this position in your DNA and what research says about it.
Muscle Fatigue: 6/10 evidence, 20 publications.
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Sample genotype (not yours): G/G
Typical Muscle Energy
Normal levels of the AMPD1 enzyme help power muscles during intense exercise. Typical responses to physical exertion make genetic muscle cramps highly unlikely.
What this genotype means: Typical muscle energy metabolism; Standard cardiovascular survival rates.
Sample genotype (not yours): A/A
Higher Risk of Exercise-Induced Muscle Cramps
Two copies of the variant lead to a complete lack of the functional AMPD1 enzyme. Early fatigue, muscle pain, and cramping can occur during physical exertion.
What this genotype means: Increased risk of muscle pain and cramping during exercise; Better response to methotrexate therapy; Higher sensitivity to regadenoson side effects.
Sample genotype (not yours): G/A
Improved Cardiovascular Survival
A single copy of the variant is linked to significantly better survival rates during heart failure. Muscle energy metabolism remains typical, preventing exercise-induced cramping.
What this genotype means: Significantly improved survival rates in heart failure; Typical muscle performance without cramping; Better response to methotrexate therapy.
Gene function and biological role
Gene Function: The AMPD1 gene encodes adenosine monophosphate deaminase 1, an enzyme highly abundant in skeletal muscle [1]. It plays a critical role in the purine nucleotide cycle by converting AMP to IMP [1]. This enzymatic reaction helps maintain cellular energy balance and ATP levels during periods of rapid muscle contraction [2]. Deficiencies in this gene can disrupt muscle metabolism, leading to exercise intolerance [3]. Interestingly, the gene also influences cardiovascular health and response to certain medications [4].
Variant Impact: The rs17602729 variant, historically known as C34T, is a nonsense mutation in the second exon of the AMPD1 gene [1]. This single nucleotide change introduces a premature stop codon, resulting in a truncated, nonfunctional protein [2]. Individuals with two copies of the variant allele lack active AMP deaminase in their skeletal muscles [2]. This deficiency can impair the recycling of cellular energy during strenuous exercise [3]. Despite this metabolic block, many carriers of the variant remain asymptomatic or even show cardiovascular advantages [5].
Key Insight: While a complete lack of the AMPD1 enzyme can cause muscle cramps, many people with this deficiency experience no symptoms at all and some even become elite endurance athletes.
Location: AMPD1. Chromosome 1 · 1p13.2 · 114.7 Mb
Estimated prevalence by population
Global 84.0%; European 75.3%; African 95.7%; East Asian 99.9%; South Asian 94.5%; Americas 86.4%; Ashkenazi 86.1%; Finnish 77.8%; Middle Eastern 81.7%; Amish 76.7%.
Estimated GG genotype frequency.
Global 15.0%; European 23.0%; African 4.2%; East Asian 0.1%; South Asian 5.4%; Americas 13.1%; Ashkenazi 13.4%; Finnish 20.8%; Middle Eastern 17.3%; Amish 21.8%.
Estimated GA genotype frequency.
Global 1.0%; European 1.8%; African < 0.1%; East Asian < 0.1%; South Asian 0.1%; Americas 0.5%; Ashkenazi 0.5%; Finnish 1.4%; Middle Eastern 0.9%; Amish 1.5%.
Estimated AA genotype frequency.
Showing effects for G/G genotype
Lifestyle, Fitness & Aging
Muscle Strength & Power
Muscle Fatigue. Evidence: 4/10. Source: PMID 18852891. Typical.
Cardiovascular & Metabolic
Heart Disease
Heart Failure Survival. Evidence: 3/10. Source: PMID 10086964. Typical.
Pharmacogenomics
Immunosuppressant & Biologic Response
Methotrexate Response. Evidence: 6/10. Source: PMID 16947783. Typical Response.
Cardiovascular Drug Response
Regadenoson Sensitivity. Evidence: 5/10. Source: PMID 26554440. Typical.
Showing effects for A/A genotype
Muscle Fatigue. Evidence: 4/10. Source: PMID 18852891. Increased Risk.
Methotrexate Response. Evidence: 6/10. Source: PMID 16947783. Stronger Response.
Regadenoson Sensitivity. Evidence: 5/10. Source: PMID 26554440. Higher Side Effects.
Showing effects for G/A genotype
Heart Failure Survival. Evidence: 3/10. Source: PMID 10086964. 8.6x Higher Survival.
What this genotype means for the people who carry it
Sample genotype: GG (Homozygous)
The AMPD1 gene encodes adenosine monophosphate deaminase 1, an enzyme highly active in skeletal muscles [1]. This enzyme plays a key role in the purine nucleotide cycle, helping to recycle ATP and maintain cellular energy during strenuous exercise [1]. With two copies of the normal G allele, your body produces fully functional enzymes [2]. Consequently, you have typical muscle energy metabolism and a standard athletic capacity [2]. While this genotype is the most common globally, some studies suggest that individuals with this baseline profile do not experience the cardiovascular survival advantages seen in carriers of the A allele [3]. Specifically, those with the G/G genotype may have standard outcomes following heart failure or coronary artery disease compared to those with one copy of the variant [3] [4].
Typical muscle energy metabolism; Standard cardiovascular survival rates.
Sample genotype: AA (Homozygous)
Myoadenylate deaminase deficiency occurs when both copies of the AMPD1 gene are inactive [1]. The genetic change introduces a premature stop codon, halting the production of the active protein [2]. During intense exercise, your muscles may struggle to recycle energy efficiently, leading to early fatigue, pain, and cramping [1]. However, many individuals with this genotype remain completely asymptomatic and are unaware of any deficit [3]. On the therapeutic side, this profile is linked to a better clinical response to methotrexate therapy for rheumatoid arthritis [4]. Conversely, it may increase the severity of high blood pressure and toxicity when taking the cardiac stress-test drug regadenoson [5].
Increased risk of muscle pain and cramping during exercise; Better response to methotrexate therapy; Higher sensitivity to regadenoson side effects.
Sample genotype: GA (Heterozygous)
A single functional copy of the AMPD1 gene is paired with an inactive copy in this heterozygous state [1]. Interestingly, having one inactive copy does not seem to impair physical performance or cause muscle cramps [2]. In fact, some elite endurance athletes carry this exact genotype [2]. The most notable benefit of this profile is a dramatic increase in cardiovascular survival [3]. Research indicates that individuals with the G/A genotype are significantly more likely to survive five years without needing a heart transplant after heart failure hospitalization compared to those with the G/G genotype [3]. Additionally, this genotype is associated with a better therapeutic response to methotrexate, a common treatment for rheumatoid arthritis [4].
Significantly improved survival rates in heart failure; Typical muscle performance without cramping; Better response to methotrexate therapy.
Variants with shared genetic architecture
rs121918594 · RYR1 Gene · Chr 19 · Anesthetic Reaction Risk
rs113210953 · RYR1 Gene · Chr 19 · Anesthesia Reaction Risk
rs193922753 · RYR1 Gene · Chr 19 · Anesthesia Reaction Risk
Distribution and effects of nonsense polymorphisms in human genes.
Common variant in AMPD1 gene predicts improved clinical outcome in patients with heart failure.
AMPD1 polymorphism and response to regadenoson.
Is there an optimum endurance polygenic profile?
Content updated August 2026.
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