Extended Data Fig. 1: The ubiquitously expressed ZNF808 is the first primate-specific gene confirmed to cause a congenital developmental disease.

a. ZNF808 is expressed across GTEx adult tissues. ZNF808 is expressed at variable levels across adult tissues with no tissue absent in expression. Boxplots describe ZNF808 expression in the GTEx (Genotype-Tissue Expression) project. Data shows sum of GTEx v8 isoform level transcripts per million data calculated with RSEM. Boxplot central line denotes median, box limit the interquartile range and whiskers extend to furthest point within 1.5 interquartile range, data points are outliers exceeding whiskers, median sample size n = 291. b. ZNF808 is maximally expressed in the embryonic pancreas and minimally expressed in the embryonic liver. Human embryo RNA-seq spanning CS14-22⁵ (data normalized as in original publication) for all MER11-binding KZFPs, tissues ordered by expression and mean of replicates shown. Dots give expression for all replicates, central line of boxplots denotes median, box marks interquartile range and whiskers 1.5x interquartile range. c. ZNF808 is the only primate-specific gene confirmed to cause a congenital developmental disease. Homology scores (including 1-to-1 and 1-to-many orthologues) for every protein-coding gene (Ensembl Biomart,10^th February 2020, release 98) for 26 primates and 70 non-primate mammals. The difference between the maximum % identity difference across all primates versus the maximum across all non-primates to human was calculated for each gene. Frequency densities (density estimations scaled to group size at 0.5% bin size) shown. Genes without a non-primate ortholog are plotted as percent identity between humans and primates (red), equivalent to a gene with 0% identity between primates and non-primates. Genes are grouped into non-disease causing (not present in OMIM-morbid; gray), disease causing (present in OMIM-morbid; green) and genetic causes of developmental disorders (present on DDG2P; blue). ZNF808 is highlighted (dotted line, ZNF808 is erroneously annotated as having a non-primate ortholog and its homology between primates and non-primates given). All OMIM-morbid and DDG2P genes with sequence identity difference >40 were manually checked with no evidence of a primate-specific disease gene causing a congenital developmental disorder found (Supplementary Table 4).