{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE330nnn/GSE330364/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Genomics"],"species":["Homo sapiens"],"gds_type":["Genome binding/occupancy profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE330364"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"A massively parallel reporter assay of MECP2 cis-regulatory elements reveals genetic candidates for male-biased autism","description":"Autism affects males four times more often than females, yet the basis of this sex bias remains unclear. One hypothesis is that hypomorphic variants in X-linked genes—genes where loss-of-function alleles cause syndromic neurodevelopmental disorders (NDDs) predominantly in females—produce milder, non-syndromic phenotypes in hemizygous males. We tested this by investigating cis-regulatory elements (CREs) of MECP2, a dosage-sensitive X-linked gene. Using a massively parallel reporter assay in human neurons, we mapped transcription factor binding sites within MECP2 CREs and tested autism-associated variants for functional impact. We identified two noncoding variants that change CRE activity, each with a male-biased phenotype. One of these, a promoter variant, disrupts NFY binding and reduces MECP2 expression by ~30%, a magnitude that produces autism-like phenotypes in mice. These findings suggest noncoding MECP2 variants can cause non-syndromic, male-biased autism, and provide a framework for uncovering regulatory variants in other X-linked NDD genes that may contribute to autism’s missing heritability.","dates":{"publication":"2026/05/08"},"accession":"GSE330364","cross_references":{"GSM":["GSM9724729","GSM9724739","GSM9724728","GSM9724727","GSM9724749","GSM9724738","GSM9724748","GSM9724737","GSM9724726","GSM9724747","GSM9724736","GSM9724735","GSM9724746","GSM9724745","GSM9724734","GSM9724733","GSM9724744","GSM9724743","GSM9724732","GSM9724742","GSM9724731","GSM9724730","GSM9724741","GSM9724740"],"GPL":["34284"],"GSE":["330364"],"taxon":["Homo sapiens"]}}