What you carry at this position in your DNA and what research says about it.
Male Fertility Risk: 8/10 evidence, 20 publications.
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Sample genotype (not yours): G/G
Higher Risk of Male Infertility and Hearing Loss
Carrying two copies of the G allele is linked to reduced heat shock protein protection, elevating the risk of sperm damage from heat and susceptibility to noise-induced hearing loss.
What this genotype means: Increased risk of male infertility under thermal stress; Higher susceptibility to noise-induced hearing loss; Decreased severity of carbamazepine-induced hypersensitivity.
Sample genotype (not yours): A/A
Typical Risk of Male Infertility and Hearing Loss
Carrying two copies of the A allele is associated with standard heat shock protein function, providing typical protection against sperm heat stress and noise-induced hearing damage.
What this genotype means: Typical baseline risk for male infertility; Standard susceptibility to noise-induced hearing loss; Typical risk of carbamazepine-induced hypersensitivity.
Sample genotype (not yours): G/A
Moderately Higher Risk of Male Infertility and Hearing Loss
Carrying one copy of the G allele is linked to a moderate reduction in heat shock protein protection, slightly elevating the risk of sperm damage and noise-induced hearing loss.
What this genotype means: Moderately increased risk of male infertility; Slightly higher susceptibility to noise-induced hearing loss; Decreased severity of carbamazepine-induced hypersensitivity.
Gene function and biological role
Gene Function: The HSPA1L gene encodes a member of the heat shock protein 70 family, which acts as a molecular chaperone to help cells fold proteins correctly under stress. This protein is highly expressed in the testes, where it plays a vital role in protecting developing sperm cells from heat-induced damage and oxidative stress. When cells experience environmental stressors like elevated temperatures, these chaperone proteins stabilize cellular structures to prevent cell death. Variations in this gene can compromise this protective shield, leaving tissues more vulnerable to damage.
Variant Impact: This missense variant, also known as p.Thr493Met, is a single nucleotide change that alters the amino acid at position 493 of the HSPA1L protein from threonine to methionine. The G allele encodes the reference threonine residue, while the A allele encodes the variant methionine residue. This structural alteration is thought to impact the chaperone activity of the protein, particularly affecting its ability to protect cells during thermal stress. While the variant is highly common globally, its functional consequences vary depending on environmental exposures.
Key Insight: The HSPA1L protein acts as a thermal shield in the testes, meaning that carrying the risk allele makes sperm significantly more vulnerable to everyday heat sources like hot tubs or laptops.
Location: HSPA1L. Chromosome 6 · 6p21.33 · 31.8 Mb
Estimated prevalence by population
Global 1.9%; European 3.2%; African 0.1%; East Asian 3.8%; South Asian 1.2%; Americas 0.8%; Ashkenazi 0.4%; Finnish 2.4%; Middle Eastern 0.3%; Amish 5.4%.
Estimated GG genotype frequency.
Global 20.8%; European 29.3%; African 6.5%; East Asian 31.4%; South Asian 19.8%; Americas 16.1%; Ashkenazi 12.2%; Finnish 26.2%; Middle Eastern 11.0%; Amish 35.7%.
Estimated GA genotype frequency.
Global 77.3%; European 67.5%; African 93.4%; East Asian 64.8%; South Asian 78.9%; Americas 83.1%; Ashkenazi 87.3%; Finnish 71.4%; Middle Eastern 88.7%; Amish 58.9%.
Estimated AA genotype frequency.
Showing effects for G/G genotype
Endocrine & Reproductive
Male Reproductive Health & Fertility
Male Infertility. Evidence: 6/10. ~2-3x Increased Risk.
Organ Systems
Hearing & Balance
Noise-Induced Hearing Loss. Evidence: 3/10. Source: PMID 17009596. Increased Risk.
Pharmacogenomics
Adverse Drug Reactions
Drug Hypersensitivity. Evidence: 5/10. Source: PMID 16538175. Decreased Severity.
Immunity & Inflammation
Autoimmune Diseases
Rheumatoid Arthritis. Evidence: 8/10. Source: PMID 37377963. Associated.
Showing effects for A/A genotype
Male Infertility. Evidence: 6/10. Typical Risk.
Noise-Induced Hearing Loss. Evidence: 3/10. Source: PMID 17009596. Typical Risk.
Drug Hypersensitivity. Evidence: 5/10. Source: PMID 16538175. Typical Severity.
Showing effects for G/A genotype
Male Infertility. Evidence: 6/10. ~2x Increased Risk.
What this genotype means for the people who carry it
Sample genotype: GG (Homozygous)
Having two copies of the G allele is associated with a significantly higher risk of male infertility due to reduced chaperone protection in the testes. Under conditions of heat or oxidative stress, the compromised HSPA1L protein cannot fully protect developing sperm, which can lead to lower sperm counts and reduced motility. Additionally, this genotype is linked to an increased susceptibility to noise-induced hearing loss, as the inner ear relies on these same heat shock proteins to recover from acoustic trauma [1]. On a positive note, clinical studies suggest that this genotype may experience decreased severity of hypersensitivity reactions if treated with the medication carbamazepine [2]. Protecting the ears from loud noises and avoiding excessive testicular heat, such as from hot tubs or laptops, are highly relevant precautions for this genotype.
Increased risk of male infertility under thermal stress; Higher susceptibility to noise-induced hearing loss; Decreased severity of carbamazepine-induced hypersensitivity.
Sample genotype: AA (Homozygous)
Carrying two copies of the A allele represents the typical genetic baseline for the majority of the population. This genotype is associated with normal functioning of the HSPA1L chaperone protein, which provides standard protection against heat and oxidative stress in both the testes and the inner ear. Consequently, there is no elevated genetic risk for male infertility or noise-induced hearing loss from this specific variant [1]. However, if treated with the medication carbamazepine, this genotype does not benefit from the reduced risk of hypersensitivity seen in G allele carriers, meaning standard clinical monitoring for drug reactions is appropriate [2]. Maintaining general healthy habits remains the best way to support long-term reproductive and auditory health.
Typical baseline risk for male infertility; Standard susceptibility to noise-induced hearing loss; Typical risk of carbamazepine-induced hypersensitivity.
Sample genotype: GA (Heterozygous)
Carrying one copy of the G allele is associated with a moderately increased risk of male infertility compared to the typical baseline. Because one copy of the protective A allele is present, some chaperone function is maintained, but sperm remain somewhat more vulnerable to environmental stressors like heat. This genotype also shows a moderate increase in susceptibility to noise-induced hearing loss, as the cellular repair mechanisms in the inner ear are slightly less efficient [1]. Similar to the double-copy genotype, individuals with this result may experience a reduced severity of severe hypersensitivity reactions if they ever take the anti-seizure medication carbamazepine [2]. Taking proactive steps to protect hearing in loud environments and avoiding direct heat exposure to the testes can help mitigate these risks.
Moderately increased risk of male infertility; Slightly higher susceptibility to noise-induced hearing loss; Decreased severity of carbamazepine-induced hypersensitivity.
Variants with shared genetic architecture
rs1465618 · THADA Gene · Chr 2 · Prostate Cancer Risk
rs35887622 · GJB2 Gene · Chr 13 · Hearing Loss Risk
rs267606617 · MT-RNR1 Gene · Chr M · Antibiotic Hearing Loss
Serious carbamazepine-induced hypersensitivity reactions associated with the HSP70 gene cluster.
Content updated August 2026.
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