Relevance to Autism

Recurrent mutations in the ADNP gene have been identified in multiple individuals with ASD as described below. Two de novo frameshift variants in ADNP were identified in unrelated simplex ASD cases in two reports by O'Roak and colleagues in 2012 (PMIDs 22495309 and 23160955). An additional seven de novo LoF variants were identified in patients with ASD in Helsmoortel et al., 2014, giving a current total of nine de novo LoF variants in ADNP gene in ASD cases; the probability of detecting eight or more de novo truncating events in ADNP was given as P=2.65 x 10-18 in this report (PMID 24531329). Furthermore, the frequency of shared clinical characteristics in ASD cases with LoF variants in ADNP (intellectual disability, facial dysmorphisms) led Helsmoortel and colleagues to conclude that ADNP mutations resulted in an autism syndrome. 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 ADNP 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 ADNP as a gene reaching exome-wide significance (P < 2.5E-06).

Molecular Function

Potential transcription factor that may mediate some of the neuroprotective peptide VIP-associated effects involving normal growth and cancer proliferation. In brain, expression is stronger in the cerebellum and cortex regions.

External Links

References