Pakistan Genome Resource Maps Thousands of Human Gene Knockouts

Overview

• A Nature paper published on 17 June 2026 reports analysis of 173,303 Pakistani genomes and exomes that found about 34,000 people with at least one homozygous loss-of-function 'knockout' and knockouts in nearly 6,500 genes.
• Researchers identified more than 6.6 million coding variants with roughly half absent from global databases, highlighting a major gap in South Asian representation in genomic resources.
• High rates of consanguineous marriage in the sampled population concentrate homozygous loss-of-function variants, making the PGR roughly 3.5 times more efficient at finding human knockouts than mainly European ancestry databases.
• Gene-level results include people missing CIDEB who show protection from liver disease, RXFP1 acting differently in humans than in mice, LRRK2 loss-of-function showing kidney-related signals, and PRDM9 not being essential for fertility in humans.
• The consortium of CNCD, Columbia CUIMC and Novartis says the recontactable resource can link genetic knockouts to clinical exams and family studies to improve target validation, reveal early safety signals, and help prioritize or de-risk drug candidates.