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rs1805123 (KCNH2)

What you carry at this position in your DNA and what research says about it.

Heart Rhythm: 10/10 evidence, 31 publications.

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Sample genotype (not yours): T/T

Typical Heart Rhythm and Baseline BMI

This genotype represents the common baseline for cardiac repolarization and metabolic traits. It is associated with a slightly longer QT interval and typical body mass index.

What this genotype means: Baseline QT interval duration; Typical body mass index; Standard triglyceride to HDL ratio.

Sample genotype (not yours): G/G

Shorter QT Interval and Favorable BMI

Carrying two copies of the G allele is linked to the fastest heart recharge rate and the lowest baseline body mass index.

What this genotype means: Shortest QT interval duration; Lower baseline body mass index; Optimized triglyceride to HDL ratio.

Sample genotype (not yours): T/G

Slightly Shorter QT Interval and Lower BMI

Carrying one copy of the G allele is associated with a slightly faster heart recharge rate and a favorable metabolic profile.

What this genotype means: Slightly shorter QT interval; Slightly lower body mass index; Favorable lipid profile.

About KCNH2

Gene function and biological role

Gene Function: The KCNH2 gene encodes the pore-forming alpha subunit of a voltage-gated potassium channel, commonly known as hERG [1]. This channel conducts the rapid delayed rectifier potassium current, which is essential for the normal repolarization of cardiac cells after each heartbeat [1]. Mutations in this gene can lead to congenital long QT syndrome type 2, a condition characterized by abnormal heart rhythms [1]. Common variations in KCNH2 are also known to influence the duration of the QT interval in the general population [2]. Beyond cardiac function, KCNH2 is expressed in other tissues and has been investigated for roles in metabolic traits and schizophrenia [3].

Variant Impact: The rs1805123 variant is a missense mutation in the KCNH2 gene that results in the substitution of lysine with threonine at position 897 of the protein, often designated as K897T [4]. This amino acid change alters the intracellular C-terminal region of the potassium channel, which can modify channel gating and repolarization kinetics [4]. Research indicates that the threonine-encoding G allele tends to slightly shorten the cardiac QT interval, reflecting faster repolarization [2]. Although it influences heart rate-corrected QT interval duration, clinical databases classify this common variant as benign for major cardiac syndromes on its own [5]. It serves primarily as a genetic modifier of cardiac repolarization rather than a direct cause of disease [5].

Key Insight: Although KCNH2 is primarily famous for regulating the electrical activity of the heart, this specific variant is also consistently linked to metabolic traits like body mass index and lipid ratios.

Location: KCNH2. Chromosome 7 · 7q36.1 · 150.9 Mb

Genotype Frequencies

Estimated prevalence by population

Global 64.5%; European 51.4%; African 88.6%; East Asian 86.0%; South Asian 53.9%; Americas 62.3%; Ashkenazi 59.4%; Finnish 55.4%; Middle Eastern 52.7%; Amish 45.9%.

Estimated TT genotype frequency.

Global 30.4%; European 40.6%; African 11.0%; East Asian 13.5%; South Asian 39.0%; Americas 33.2%; Ashkenazi 35.4%; Finnish 38.1%; Middle Eastern 39.8%; Amish 43.7%.

Estimated TG genotype frequency.

Global 5.1%; European 8.0%; African 0.3%; East Asian 0.5%; South Asian 7.1%; Americas 4.4%; Ashkenazi 5.3%; Finnish 6.5%; Middle Eastern 7.5%; Amish 10.4%.

Estimated GG genotype frequency.

Associated Traits

Showing effects for T/T genotype

Cardiovascular & Metabolic

Heart Rhythm & Conduction

QT Interval. Evidence: 8/10. Source: PMID 29874175. ~3 ms longer.

Obesity & Body Composition

Body Mass Index. Evidence: 10/10. Source: PMID 29273807. Typical.

Lipids & Cholesterol

Triglyceride to HDL Ratio. Evidence: 7/10. Source: PMID 38200128. Typical.

Lifestyle, Fitness & Aging

Height & Body Size

Height. Evidence: 7/10. Source: PMID 32376654. Slightly Taller.

Showing effects for G/G genotype

QT Interval. Evidence: 8/10. Source: PMID 29874175. ~3 ms shorter.

Body Mass Index. Evidence: 10/10. Source: PMID 29273807. Lower.

Triglyceride to HDL Ratio. Evidence: 7/10. Source: PMID 38200128. Lower.

Height. Evidence: 7/10. Source: PMID 32376654. Slightly Shorter.

Showing effects for T/G genotype

QT Interval. Evidence: 8/10. Source: PMID 29874175. Typical.

Body Mass Index. Evidence: 10/10. Source: PMID 29273807. Slightly Lower.

Triglyceride to HDL Ratio. Evidence: 7/10. Source: PMID 38200128. Slightly Lower.

Height. Evidence: 7/10. Source: PMID 32376654. Typical.

What TT Genotype Means

What this genotype means for the people who carry it

Sample genotype: TT (Homozygous)

This genotype carries two copies of the major T allele, which encodes the baseline lysine residue at position 897 of the hERG potassium channel. Large-scale genetic studies show that this baseline state is associated with a slightly longer QT interval compared to carriers of the G allele [1]. A longer QT interval means the heart muscle takes slightly longer to recharge between beats, though this remains well within the normal physiological range [2]. This genotype is also associated with a slightly higher baseline body mass index and a higher triglyceride-to-HDL cholesterol ratio [3]. While it represents the most common genetic profile globally, it lacks the minor protective or lowering effects on these traits seen in G allele carriers [1]. Clinical databases confirm that this common genotype does not pose an elevated risk for cardiac diseases on its own [4].

Baseline QT interval duration; Typical body mass index; Standard triglyceride to HDL ratio.

What GG Genotype Means

Sample genotype: GG (Homozygous)

This genotype represents individuals who carry two copies of the threonine-encoding G allele. Having two copies of this variant is associated with the most pronounced shortening of the cardiac QT interval, reflecting highly efficient repolarization of the heart muscle [1]. This efficient electrical recovery is a healthy physiological variation [2]. Furthermore, this genotype is consistently associated with the lowest baseline body mass index and the most favorable triglyceride-to-HDL cholesterol ratio among the three groups [3]. These combined cardiac and metabolic characteristics support a highly favorable cardiovascular profile [3]. Despite these physiological differences, clinical databases emphasize that this variant is completely benign and carries no risk of cardiac disease [4].

Shortest QT interval duration; Lower baseline body mass index; Optimized triglyceride to HDL ratio.

What TG Genotype Means

Sample genotype: TG (Heterozygous)

This genotype represents individuals who carry one copy of the threonine-encoding G allele. Having one copy of this variant is associated with a modest shortening of the cardiac QT interval, meaning the heart's electrical system repolarizes slightly faster [1]. This faster repolarization is generally considered a favorable physiological trait under resting conditions [2]. In addition to cardiac benefits, carrying this variant is linked to a slightly lower body mass index and a more favorable triglyceride-to-HDL cholesterol ratio [3]. These subtle metabolic advantages contribute to an overall positive cardiovascular profile [3]. Clinical evaluations have confirmed that this variant is entirely benign and does not cause or predispose to cardiac arrhythmias [4].

Slightly shorter QT interval; Slightly lower body mass index; Favorable lipid profile.

Related Variants

Variants with shared genetic architecture

rs3807375 · KCNH2 Gene · Chr 7 · QT Interval Duration

rs1137617 · KCNH2 Gene · Chr 7 · Blood Pressure Drug Response

rs121912506 · KCNH2 Gene · Chr 7 · Long QT Syndrome Risk

Sources

The non-synonymous coding IKr-channel variant KCNH2-K897T is associated with atrial fibrillation: results from a systematic candidate gene-based analysis of KCNH2 (HERG).

Common variation in NOS1AP and KCNH2 genes and QT interval duration in young adults. The Cardiovascular Risk in Young Finns Study.

Two four-marker haplotypes on 7q36.1 region indicate that the potassium channel gene HERG1 (KCNH2, Kv11.1) is related to schizophrenia: a case control study.

A common polymorphism in KCNH2 (HERG) hastens cardiac repolarization.

KCNH2-K897T is a genetic modifier of latent congenital long-QT syndrome.

Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity.

Back to Variant Explorer

Content updated August 2026.

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