Lost in the WASH. The functional human WASH complex 1 gene is on chromosome 20

Abstract

The WASH1 gene produces a protein that forms part of the developmentally important WASH complex. The WASH complex activates the Arp2/3 complex to initiate branched actin networks at the surface of endosomes. As a curiosity, the human reference gene set includes nine WASH1 genes. How many of these are pseudogenes and how many are bona fide coding genes is not clear. Eight of the nine WASH1 genes reside in rearrangement and duplication-prone subtelomeric regions. Many of these subtelomeric regions had gaps in the GRCh38 human genome assembly, but the recently published T2T-CHM13 assembly from the Telomere to Telomere (T2T) Consortium has filled in the gaps. As a result, the T2T Consortium has added four new WASH1 paralogues in previously unannotated subtelomeric regions. Here we show that one of these four novel WASH1 genes, LOC124908094, is the gene most likely to produce the functional WASH1 protein. We also demonstrate that the other twelve WASH1 genes derived from a single WASH8P pseudogene on chromosome 12. These 12 genes include WASHC1, the gene currently annotated as the functional WASH1 gene. We propose LOC124908094 should be annotated as a coding gene and all functional information relating to the WASHC1 gene on chromosome 9 should be transferred to LOC124908094. The remaining WASH1 genes, including WASHC1, should be annotated as pseudogenes. This work confirms that the T2T assembly has added at least one functionally relevant coding gene to the human reference set. It remains to be seen whether other important coding genes are missing from the GRCh38 reference assembly.