rs1124649 (TMEM214): Height Variant and KHK Expression

Key takeaways

• rs1124649 is one of 12,111 variants linked to adult height in a study of over 5.4 million people.
• Despite being annotated to TMEM214, this variant's strongest tissue signal in GTEx is on KHK expression, not TMEM214.
• The alternate allele consistently increases KHK expression across 8 tissues, with p-values as low as 4.9e-55.
• These are population-level statistics; no individual height prediction can be drawn from this single variant.

What the research says rs1124649, annotated to the TMEM214 gene, was identified among 12,111 independent SNPs significantly associated with adult height in a genome-wide association study (a systematic scan across the genome looking for variants linked to a trait) of 5.4 million individuals spanning five ancestry groups. That study estimated that these variants collectively account for approximately 40% of phenotypic height variance in populations of European ancestry and around 10-20% in other ancestries. In GTEx v11 tissue expression data (a database linking genetic variants to gene activity across human tissues, based on 953 donors), the alternate allele of rs1124649 is robustly associated with increased KHK gene expression across 8 tissue types, with effect sizes ranging from +0.38 to +0.53 in log2-normalized units GTEx Portal.

Reported associations

• Adult height: rs1124649 is one of 12,111 independent variants significantly associated with adult height in a multi-ancestry meta-analysis covering 5.4 million individuals; the specific per-SNP effect size for this variant was not reported in the provided study text.
• KHK expression in subcutaneous adipose tissue: The alternate allele is associated with increased KHK expression (slope +0.53, p=4.9e-55) GTEx Portal.
• KHK expression in skeletal muscle: Increased expression (slope +0.53, p=2.3e-52) GTEx Portal.
• KHK expression in sun-exposed skin (lower leg): Increased expression (slope +0.50, p=3.3e-64) GTEx Portal.
• KHK expression in testis: Increased expression (slope +0.50, p=2.8e-32) GTEx Portal.
• KHK expression in non-sun-exposed skin (suprapubic): Increased expression (slope +0.49, p=7.0e-47) GTEx Portal.
• KHK expression in stomach: Increased expression (slope +0.48, p=1.1e-26) GTEx Portal.
• KHK expression in tibial nerve: Increased expression (slope +0.38, p=9.9e-48) GTEx Portal.
• KHK expression in thyroid: Increased expression (slope +0.38, p=8.7e-34) GTEx Portal.

Evidence quality The height association evidence derives from a very large genome-wide association study of 5.4 million individuals across five ancestry groups: European (75.8%), East Asian (8.8%), Hispanic (8.5%), African (5.5%), and South Asian (1.4%). The 12,111 height-associated SNPs are estimated to account for nearly all common SNP-based heritability of height, approximately 40% of phenotypic variance in European-ancestry populations but only 10-20% in other ancestries, a gap attributed to differences in linkage disequilibrium (the tendency for nearby genetic variants to be inherited together) and allele frequencies across populations. The specific per-SNP effect size for rs1124649 was not provided in the available study text, which limits direct quantification of its individual contribution to height. The GTEx eQTL evidence for KHK is drawn from 953 donors at FDR less than 0.05, with p-values reaching as low as 4.9e-55 and a consistent positive direction across all 8 tissues tested, indicating a highly robust expression signal. No conflicting studies were provided in the source material. eQTL associations reflect statistical correlation with gene expression levels and do not by themselves establish a causal biological mechanism.

Tissue-specific expression effects

• KHK: The alternate allele is associated with increased expression in subcutaneous adipose tissue, skeletal muscle, sun-exposed skin (lower leg), testis, non-sun-exposed skin (suprapubic), stomach, tibial nerve, and thyroid, with log2-normalized slopes ranging from +0.38 to +0.53 across these tissues, all at high statistical significance GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.