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Table 1 Examples of putative non-coding regulatory variants in ASD

From: Modeling neuronal consequences of autism-associated gene regulatory variants with human induced pluripotent stem cells

Element/gene Evidence Reference
A. Transcriptional regulatory elements
16q21 near CDH8 (×2)
3q24 near C3orf58 (×2)
Rare inherited CNVs affecting non-genic intervals near ASD-associated genes [13]
5′ UTR of MBD5 disruptions of 5′-UTR cause haploinsufficiency of this ASD-associated gene [14,15,16]
EFR3A promoter Predicted loss of transcription factor binding (×1) [4]
Cis regulatory elements of CTN4, LEO1, RAF1, MEST ASD with recurrent variants in intolerant genes paternally inherited deletions of the LEO1 promoter (×3) [10]
NEUROG1
DLGAP2
HES1
FEZF1
Network differential enrichment analysis: significant neighborhood excess of non-coding variants in Simons Simplex Collection probands and nearby non-coding variants had significant differential effects on activator activities [6]
regulatory APBB1 TADA-A (transmission and de novo association—annotation) analysis: single-nucleotide variants in a regulatory region (×3 (2 conserved)) [2]
near ARID1B, SCN2A,
NR3C2, PRKCA, DSCAM
Disruptive mutations in putative regulatory regions (DNase I hypersensitivity) [8]
NR3C2 promoter
DLG2 promoter
Disrupting deletion overlaps functional non-coding regulatory region in the human brain (×1)
Same 2.5-kb deletion in the DLG2 promoter (×3) functional, non-coding regulatory region in developing the human brain
[11]
B. Post-transcriptional regulatory elements
miR-873-5p embedded in LINGO2 intron Rare seed mutation [17]
CTNND2 and PTEN
ALDH5A1, GLI2, GRIN1, KCNH3,
LAMA2, and NISCH
Splicing/misregulated in genes with neurological phenotypes, increased in ASD [3]
SMEK1 De novo non-coding mutation lying outside of a canonical splice site predicted to disrupt splicing [6]
NRXN1, TANC2, PNPLA7 Splicing single-nucleotide variants [2]
C. Long non-coding RNAs
AK127244 (2p16.3) Deletions directly disrupting exonic sequence in ASD (×3)
rare inherited CNVs (×5)
[13, 18, 19]
PTCHD1-AS Deletions impacting exons of this gene in multiple males with ASD [18, 20, 21]
MSNP1-AS (5p14.1) Within ASD GWAS peak, increased expression in the ASD cortex, influences moesin protein levels [22]
LINC00689 (7q36.3) LINC00693 (3p24.1) Differentially expressed: upregulated in the ASD cortex [23]
lnc-NR2F1 (5q15) Shown to regulate autism risk genes and promote maturation of mouse stem cell-derived neurons [24]