My Potential VO₂max Variants
This is my blog post on my potential VO₂max Variants.
I have a cardio response that doesn’t match what most people experience. I don’t get breathless, I don’t feel heart strain, my muscles don’t fatigue, and instead of running out of energy, I actually feel it rise the longer I go. I can hold extremely high heart rates without distress, and even the ADHD‑driven sympathetic activation that overwhelms other people feels stabilizing for me. Most people can’t imagine that combination, but it’s simply how my body operates.
To understand why, I asked Microsoft Copilot to generate a list of top VO₂max‑related genes based on biological process, molecular function, pathway position, and tissue expression—without relying on Eurocentric GWAS assumptions. Then I went through those genes to see whether I carry any regulatory variants in them and noted the relevant issues each gene is involved in, from oxygen sensing and cardiac output to vascular tone, metabolic switching, and lactate handling.
Using Gene Inspector Pro, I was looking specifically for variants that fall inside ENCODE 4 Promoter and Enhancer cCREs that also show TSS or Active Enhancer chromatin states in VO₂‑relevant tissues. A variant only has functional relevance if it sits in a promoter or enhancer element that is actually active in the heart, lung, skeletal muscle, endothelium, kidney cortex, liver, or large vessels. That’s why matching variants to both ENCODE 4 cCRE type and TSS/Active Enhancer chromatin state is essential when interpreting their impact. The variant has to be under 5% globally and under 5% in every non‑endogamous population, or it doesn’t meet my functional threshold.
Nine of my fifteen VO₂max variants fall in active adrenal enhancers of adrenal‑expressed genes, and my own cardio experience includes a strong, energizing adrenaline response. I’m not saying the variants explain that feeling, but both things fall within the same adrenal‑linked metabolic and stress‑response space, which makes the genomic pattern and my lived experience line up in a coherent way.
My most intense 1 hour high intensity workouts (I am 54 years old)
running in place - 178 bpm average with maximum heart rate of 189 bpm on February 11, 2026
running in place - 176 bpm average with maximum heart rate of 201 bpm on February 4, 2026
Most intense 30 minute high intensity workouts (I am 54 years old)
running in place - 185 bpm average with maximum heart rate of 201 bpm on March 24, 2026
running in place - 180 bpm average with maximum heart rate of 194 bpm on January 15, 2026
My VO2max Testing Discontinuous Protocol Results from Washington State University in Pullman
https://neurodivergence.blogspot.com/2025/09/my-vo2max-testing-discontinuous.html
ChatGPT Comprehensive Analysis of My Cardiovascular Workout Performance and my Interest in VO2 Max and Lactate Assessment
Mapping Quality (MQ) minimum: 60
Allele Depth (AD) minimum: 25 (30 for variants <1%) with 30% alt allele minimum
ACSL1-skeletal muscle, heart, liver, adipose tissue, endothelial tissue, adrenal gland
GeneCards Summary for ACSL1 Gene
ACSL1 (Acyl-CoA Synthetase Long Chain Family Member 1) is a Protein Coding gene. Diseases associated with ACSL1 include Platelet Glycoprotein Iv Deficiency and Osteogenesis Imperfecta, Type Xviii. Among its related pathways are Fatty acid metabolism and arachidonate biosynthesis III (metazoa). Gene Ontology (GO) annotations related to this gene include long-chain fatty acid-CoA ligase activity. An important paralog of this gene is ACSL6.
NCBI Gene Summary for ACSL1 Gene
The protein encoded by this gene is an isozyme of the long-chain fatty-acid-coenzyme A ligase family. Although differing in substrate specificity, subcellular localization, and tissue distribution, all isozymes of this family convert free long-chain fatty acids into fatty acyl-CoA esters, and thereby play a key role in lipid biosynthesis and fatty acid degradation. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2013]
https://www.genecards.org/cgi-bin/carddisp.pl?gene=ACSL1
rs928291108 4-184824637-G-C
Intron variant
10/152,174 (0.006571%) gnomAD
91/829,494 (0.011%) AllOfUs
Proximal Enhancer
https://screen.wenglab.org/GRCh38/ccre/EH38E2349264
Active TSS in skeletal muscle, heart, liver, adipose
Flanking TSS in skeletal muscle, heart, liver, endothelial tissue, adrenal gland
Flanking TSS downstream in skeletal muscle
Flanking TSS upstream in skeletal muscle
rs967669191 4-184811879-C-T
Intron variant
14/152,034 (0.009208%) gnomAD
118/829,552 (0.0142%) AllOfUs
Proximal Enhancer
https://screen.wenglab.org/GRCh38/ccre/EH38E3619235
Active TSS in skeletal muscle, liver
Flanking TSS downstream in skeletal muscle, liver
Active Enhancer in skeletal muscle, heart, liver, adipose tissue, adrenal gland
rs143598084 4-184804790-C-A
Intron variant
279/152,218 (0.1833%) gnomAD
1,430/1,071,310 (0.1335%) AllOfUs
https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_canonicalid?canonicalid=CA111944219Proximal Enhancer
https://screen.wenglab.org/GRCh38/ccre/EH38E3619226
Active TSS in skeletal muscle, heart, liver, adipose tissue
Flanking TSS in skeletal muscle, heart, liver adrenal gland
Flanking TSS downstream in skeletal muscle, heart, liver, adipose tissue
Active Enhancer in heart, adipose tissue
GeneCards Summary for EPAS1 Gene
EPAS1 (Endothelial PAS Domain Protein 1) is a Protein Coding gene. Diseases associated with EPAS1 include Erythrocytosis, Familial, 4 and Multiple Paragangliomas Associated With Polycythemia. Among its related pathways are Selective autophagy and Signaling by PTK6. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and protein heterodimerization activity. An important paralog of this gene is HIF1A.
NCBI Gene Summary for EPAS1 Gene
This gene encodes a transcription factor involved in the induction of genes regulated by oxygen, which is induced as oxygen levels fall. The encoded protein contains a basic-helix-loop-helix domain protein dimerization domain as well as a domain found in proteins in signal transduction pathways which respond to oxygen levels. Mutations in this gene are associated with erythrocytosis familial type 4. [provided by RefSeq, Nov 2009]
https://www.genecards.org/cgi-bin/carddisp.pl?gene=EPAS1
rs116180054 2-46353788-C-T
Intron variant
1,473/152,320 (0.967%) gnomAD
6,342/829,616 (0.7645%) AllOfUs
common in African/American genetic group
Distal Enhancer
https://screen.wenglab.org/GRCh38/ccre/EH38E3341742
Active Enhancer chromatin in heart
rs17035035 2-46353684-G-A
Intron variant
1,499/152,300 (0.9842%) gnomAD
6,431/829,642 (0.7752%) AllOfUs
common in African/African American genetic group
Distal Enhancer
https://screen.wenglab.org/GRCh38/ccre/EH38E3341742
Active Enhancer chromatin in heart
rs111696276 2-46304320-G-T
Intron variant
1,697/152216 (1.115%) gnomAD
7,110/829,586 (0.8571%) AllOfUs
common in African/African American genetic group
Distal Enhancer
https://screen.wenglab.org/GRCh38/ccre/EH38E3341697
Active Enhancer chromatin in heart, lung, endothelial cells, adrenal gland
rs183785295 2-46386759-G-A
500B Downstream variant
3,669/145606 (2.52%) gnomAD
21,748/799,344 (2.7207%) AllOfUs
common in Admixed American genetic group, European (non-Finnish) genetic group, Middle Eastern genetic group
Distal Enhancer
https://screen.wenglab.org/GRCh38/ccre/EH38E3341773
Enhancer chromatin in heart, lung, kidney cortex
rs114531395 2-46326157-G-C
Intron variant
3,760/152286 (2.469%) gnomAD
21,963/829,610 (2.6474%) AllOfUs
common in Admixed American genetic group, European (non-Finnish) genetic group
Distal Enhancer
https://screen.wenglab.org/GRCh38/ccre/EH38E3341713
Active Enhancer chromatin in heart, lung, kidney cortex, endothelial cells, adrenal gland
EGLN1 — heart, skeletal muscle, endothelial cells, adrenal gland
GeneCards Summary for EGLN1 Gene
EGLN1 (Egl-9 Family Hypoxia Inducible Factor 1) is a Protein Coding gene. Diseases associated with EGLN1 include Erythrocytosis, Familial, 3 and Hemoglobin, High Altitude Adaptation. Among its related pathways are Cellular responses to stimuli and Regulation of activated PAK-2p34 by proteasome mediated degradation. Gene Ontology (GO) annotations related to this gene include enzyme binding and iron ion binding. An important paralog of this gene is EGLN2.
NCBI Gene Summary for EGLN1 Gene
The protein encoded by this gene catalyzes the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. HIF is a transcriptional complex that plays a central role in mammalian oxygen homeostasis. This protein functions as a cellular oxygen sensor, and under normal oxygen concentration, modification by prolyl hydroxylation is a key regulatory event that targets HIF subunits for proteasomal destruction via the von Hippel-Lindau ubiquitylation complex. Mutations in this gene are associated with erythrocytosis familial type 3 (ECYT3). [provided by RefSeq, Nov 2009]
https://www.genecards.org/cgi-bin/carddisp.pl?gene=EGLN1
rs143735382 1-231378575-C-T
Intron variant
1,302/152218 (0.8554%) gnomAD
5,674/829,562 (0.684%) AllOfUs
common in African/African American genetic group
Distal Enhancer
https://screen.wenglab.org/GRCh38/ccre/EH38E1431365
Enhancer chromatin in skeletal muscle, adrenal gland
rs114424091 1-231385751-T-C
Intron variant
1,481/152350 (0.9721%) gnomAD
6,395/829,620 (0.7708%) AllOfUs
common in African/African American genetic group
Distal Enhancer
https://screen.wenglab.org/GRCh38/ccre/EH38E1431374
Active Enhancer in heart, skeletal muscle
NOS3 — aorta, coronary artery, endothelial cells, adrenal gland
GeneCards Summary for NOS3 Gene
NOS3 (Nitric Oxide Synthase 3) is a Protein Coding gene. Diseases associated with NOS3 include Stroke, Ischemic and Alzheimer Disease, Familial, 1. Among its related pathways are superpathway of L-citrulline metabolism and Activation of cAMP-Dependent PKA. Gene Ontology (GO) annotations related to this gene include oxidoreductase activity and iron ion binding. An important paralog of this gene is NOS1.
NCBI Gene Summary for NOS3 Gene
Nitric oxide is a reactive free radical which acts as a biologic mediator in several processes, including neurotransmission and antimicrobial and antitumoral activities. Nitric oxide is synthesized from L-arginine by nitric oxide synthases. Variations in this gene are associated with susceptibility to coronary spasm. Alternative splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Oct 2016]
https://www.genecards.org/cgi-bin/carddisp.pl?gene=NOS3
rs114840144 7-150989469-C-T
2KB Upstream variant
2,900/152356 (1.903%) gnomAD
14,113/829,648 (1.7011%) AllOfus
common in African/African-American genetic group, Middle Eastern genetic group, Admixed American genetic group
Proximal Enhancer
https://screen.wenglab.org/GRCh38/ccre/EH38E3808302
Enhancer chromatin in coronary artery, adrenal gland
PPARA — heart, skeletal muscle, liver, adrenal gland
GeneCards Summary for PPARA Gene
PPARA (Peroxisome Proliferator Activated Receptor Alpha) is a Protein Coding gene. Diseases associated with PPARA include Liver Disease and Congenital Nonspherocytic Hemolytic Anemia. Among its related pathways are Transcriptional regulation of white adipocyte differentiation and Expression of BMAL (ARNTL), CLOCK, and NPAS2. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and signaling receptor activity. An important paralog of this gene is PPARD.
NCBI Gene Summary for PPARA Gene
Peroxisome proliferators include hypolipidemic drugs, herbicides, leukotriene antagonists, and plasticizers; this term arises because they induce an increase in the size and number of peroxisomes. Peroxisomes are subcellular organelles found in plants and animals that contain enzymes for respiration and for cholesterol and lipid metabolism. The action of peroxisome proliferators is thought to be mediated via specific receptors, called PPARs, which belong to the steroid hormone receptor superfamily. PPARs affect the expression of target genes involved in cell proliferation, cell differentiation and in immune and inflammation responses. Three closely related subtypes (alpha, beta/delta, and gamma) have been identified. This gene encodes the subtype PPAR-alpha, which is a nuclear transcription factor. Multiple alternatively spliced transcript variants have been described for this gene, although the full-length nature of only two has been determined. [provided by RefSeq, Jul 2008]
https://www.genecards.org/cgi-bin/carddisp.pl?gene=PPARA
rs115042329 22-46241770-A-T
3 Prime Untranslated Region variant
1,559/152326 (1.023%) gnomAD
7,618/829,602 (0.9183%) AllOfUs
common in African-African American genetic group, Middle Eastern genetic group
Distal Enhancer
https://screen.wenglab.org/GRCh38/ccre/EH38E4284726
Enhancer chromatin in coronary artery, liver, adrenal gland
PPARD — skeletal muscle, heart, adipose, adrenal gland
GeneCards Summary for PPARD Gene
PPARD (Peroxisome Proliferator Activated Receptor Delta) is a Protein Coding gene. Diseases associated with PPARD include Congenital Nonspherocytic Hemolytic Anemia and Hematologic Cancer. Among its related pathways are Gene expression (Transcription) and Nuclear receptors. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and transcription coactivator activity. An important paralog of this gene is PPARA.
NCBI Gene Summary for PPARD Gene
This gene encodes a member of the peroxisome proliferator-activated receptor (PPAR) family. The encoded protein is thought to function as an integrator of transcriptional repression and nuclear receptor signaling. It may inhibit the ligand-induced transcriptional activity of peroxisome proliferator activated receptors alpha and gamma, though evidence for this effect is inconsistent. Expression of this gene in colorectal cancer cells may be variable but is typically relatively low. Knockout studies in mice suggested a role for this protein in myelination of the corpus callosum, lipid metabolism, differentiation, and epidermal cell proliferation. Alternative splicing results in multiple transcript variants encoding distinct protein isoforms. [provided by RefSeq, Aug 2017]
https://www.genecards.org/cgi-bin/carddisp.pl?gene=PPARD
rs149911426 6-35390324-C-A
Intron variant
454/152336 (0.298%) gnomAD
1,879/829,648 (0.2265%) AllOfUs
common in African/African American genetic group
Distal Enhancer
https://screen.wenglab.org/GRCh38/ccre/EH38E3703794
Enhancer chromatin in heart, skeletal muscle
SLC16A1 — oxidative skeletal muscle, heart
GeneCards Summary for SLC16A1 Gene
SLC16A1 (Solute Carrier Family 16 Member 1) is a Protein Coding gene. Diseases associated with SLC16A1 include Erythrocyte Lactate Transporter Defect and Hyperinsulinemic Hypoglycemia, Familial, 7. Among its related pathways are Transport of inorganic cations/anions and amino acids/oligopeptides and Blood-Brain Barrier and Immune Cell Transmigration: Overview. Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and monocarboxylic acid transmembrane transporter activity. An important paralog of this gene is SLC16A7.
NCBI Gene Summary for SLC16A1 Gene
The protein encoded by this gene is a proton-linked monocarboxylate transporter that catalyzes the movement of many monocarboxylates, such as lactate and pyruvate, across the plasma membrane. Mutations in this gene are associated with erythrocyte lactate transporter defect. Alternatively spliced transcript variants have been found for this gene.[provided by RefSeq, Oct 2009]
https://www.genecards.org/cgi-bin/carddisp.pl?gene=SLC16A1
rs73000320 1-112956698-C-A
2KB Upstream variant
7,090/397930 (1.782% gnomAD
17,929/829,570 (2.1612%) AllOfUs
common in African/African American genetic group, Admixed American genetic group, European (non-Finnish) genetic group, Middle Eastern genetic group
Promoter
https://screen.wenglab.org/GRCh38/ccre/EH38E1377384
Active TSS chromatin in oxidative skeletal muscle, heart
Flanking TSS upstream chromatin in heart
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