Relevance to Autism

A total of three de novo loss-of-function (LoF) variants in the ANK2 gene have been identified in ASD probands from the Simons Simplex Collection (PMIDs 22542183, 24267886, 25363768), while a fourth de novo LoF in this gene was identified in an ASD proband from the Autism Sequencing Consortium in De Rubeis et al., 2014 (PMID 25363760). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) in De Rubeis et al., 2014 identified ANK2 as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). A two-stage analysis of rare de novo and inherited coding variants in 42,607 ASD cases, including 35,130 new cases from the SPARK cohort, in Zhou et al., 2022 identified ANK2 as a gene reaching exome-wide significance (P < 2.5E-06).

Molecular Function

This gene encodes a member of the ankyrin family of proteins that link the integral membrane proteins to the underlying spectrin-actin cytoskeleton. This gene is associated with Long QT syndrome 4 (LQT4) [MIM:600919], a heart disorder characterized by a prolonged QT interval on the ECG and polymorphic ventricular arrhythmias.

External Links

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