The Three Most Clinically Relevant Liver Disease Loci
Genome-wide association studies have reproducibly mapped three loci as the strongest common genetic determinants of NAFLD/MASLD severity, MASH progression, liver fibrosis, and hepatocellular carcinoma risk. Each acts through a distinct biological mechanism in hepatocytes and stellate cells.
The strongest common genetic determinant of NAFLD severity. The G allele impairs the enzyme's lipase activity, leading to accumulation of triglycerides and retinyl esters in hepatocytes and stellate cells. Associated with steatosis, MASH progression, accelerated fibrosis, and elevated HCC risk across multiple ancestral populations.
The T allele destabilizes TM6SF2, reducing hepatic VLDL secretion and increasing intracellular lipid retention. Associated with elevated steatohepatitis and fibrosis risk despite paradoxically reduced circulating LDL — reflecting impaired VLDL export, with implications for liver–cardiovascular crosstalk.
A protective loss-of-function variant. The TA insertion generates a truncated transcript, eliminating HSD17B13 activity. Associated with reduced MASH progression, cirrhosis risk, and protection against chronic liver disease. Particularly relevant for target validation, as HSD17B13 inhibition is under active clinical investigation.
Genotype-Confirmed Primary Human Liver Cells
| Cell Type | Catalog No. | PNPLA3 rs738409 | TM6SF2 rs58542926 | HSD17B13 rs72613567 |
|---|---|---|---|---|
| Human Hepatocytes Key metabolic functions retained | Cat. #5200 | CC (WT) CG (Het) GG (Risk) | Available | Available |
| Human Hepatic Stellate Cells Incl. homozygous PNPLA3 risk lots | Cat. #5300 | CC (WT) CG (Het) GG (Risk) | Available | Available |
Study Risk and Protective Backgrounds in the Same Primary Cell System
Standard hepatocyte and stellate cell lots are sourced from donors of unknown genotype. When PNPLA3, TM6SF2, and HSD17B13 status is uncontrolled, allele-driven differences in lipid handling, fibrogenic activation, and drug response contribute to variability that cannot be attributed to experimental conditions.
Study genotype–phenotype relationships directly
Link lipid accumulation, VLDL secretion, fibrogenic activation, or drug response to the allele status of each donor lot.
Compare risk and protective backgrounds
Run PNPLA3 risk-allele and wild-type hepatocytes side-by-side, or compare HSD17B13 loss-of-function donors against wild-type in the same assay.
Access the full allelic spectrum
Wild-type, heterozygous, and homozygous lots available for dose-response modeling across the complete genetic range.
Retain primary human liver biology
Native hepatocyte morphology, metabolism, CYP enzyme activity, and gene expression retained — no forced overexpression, no mutation artifacts.
Support pharmacogenomic drug development
Identify genotype-specific efficacy, safety, or toxicity signals in primary human cells before advancing to the clinic.
Target validation in relevant genetic backgrounds
HSD17B13 inhibitor studies are most meaningful in cells that carry the protective variant — now possible in primary human hepatocytes.
Applications Specific to Liver Genotype Biology
Available Cell Types
Human Hepatocytes — Cat. #5200
Genotyped for PNPLA3 (rs738409 & rs738408), TM6SF2 (rs58542926), and HSD17B13 (rs72613567). Key metabolic functions retained.
View product →Human Hepatic Stellate Cells — Cat. #5300
Genotyped across all three loci. Select lots include homozygous PNPLA3 risk-allele backgrounds critical for fibrosis mechanism studies.
View product →Requesting Genotype-Defined Liver Cell Lots
Genotype-defined lots are available by request. Lot availability varies by genotype. A selection and verification fee applies per vial.
Identify the Cell Type
Identify the cell type — hepatocytes (Cat. #5200) or hepatic stellate cells (Cat. #5300)
Specify Liver Cell Genotype
Specify the locus/loci and allele status required — single or multi-locus genotype combinations available
Submit Your Request
Our team will confirm available lots and provide a quote with COA documentation for all genotyped loci.
Please note that availability varies by genotype and donor lot. A selection and verification fee will be applied per vial and reflected in your quote.
For information on available genotypes, assistance selecting the right cells, or inquiries about additional genotypes and cell types, please contact us at info@sciencellonline.com, or call 1.877.602.8549.