DENND2BDENN domain containing 2B
Autism Reports / Total Reports
5 / 6Rare Variants / Common Variants
6 / 0Aliases
-Associated Syndromes
-Chromosome Band
11p15.4Associated Disorders
-Relevance to Autism
Chen et al., 2025 integrated cortex cell-specific cis-regulatory element annotations, a deep learning-based variant prediction model, and massively parallel reporter assays to systematically evaluate the functional impact of 227,878 non-coding de novo mutations (ncDNMs) in ASD probands from Simons Simplex Collection (SSC) and Autism Speaks MSSNG resource (MSSNG) cohorts and identified a ncDNM that down-regulated expression of the DENND2B gene in a MSSNG proband. Additional de novo variants, including a loss-of-function variant and several missense variants, have been identified in this gene in ASD probands (Satterstrom et al., 2020; Zhou et al., 2022; Tan et al., 2024). Murthy et al., 2025 described 11 individuals with monoallelic variants in DENND2B with a shared constellation of features (developmental delay, intellectual disability and psychiatric/behavioral concerns, and episodes of psychosis and/or catatonia); 3/8 were reported to have an ASD diagnosis, and nine of the ten observed patient variants were confirmed to result in loss of DENND2B function in zebrafish.
Molecular Function
This gene was identified by its ability to suppress the tumorigenicity of Hela cells in nude mice. The protein encoded by this gene contains a C-terminal region that shares similarity with the Rab 3 family of small GTP binding proteins. This protein preferentially binds to the SH3 domain of c-Abl kinase, and acts as a regulator of MAPK1/ERK2 kinase, which may contribute to its ability to reduce the tumorigenic phenotype in cells.
SFARI Genomic Platforms
Reports related to DENND2B (6 Reports)
| # | Type | Title | Author, Year | Autism Report | Associated Disorders |
|---|---|---|---|---|---|
| 1 | Support | Both rare and common genetic variants contribute to autism in the Faroe Islands | Leblond CS , et al. (2019) | Yes | - |
| 2 | Support | Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism | Satterstrom FK et al. (2020) | Yes | - |
| 3 | Support | - | Zhou X et al. (2022) | Yes | - |
| 4 | Support | - | Senwei Tan et al. () | Yes | - |
| 5 | Recent Recommendation | - | Harsha Murthy et al. () | No | ASD, ADHD, epilepsy/seizures |
| 6 | Primary | - | Congcong Chen et al. () | Yes | - |
Rare Variants (6)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| G>C | - | intergenic_variant | De novo | - | Simplex | 40738258 | Congcong Chen et al. () | |
| c.1477+1G>A | p.? | splice_site_variant | De novo | - | Simplex | 39472663 | Senwei Tan et al. () | |
| c.1538G>A | p.Arg513Gln | missense_variant | Unknown | - | - | 30675382 | Leblond CS , et al. (2019) | |
| c.2163G>A | p.Gln721= | synonymous_variant | De novo | - | Simplex | 35982159 | Zhou X et al. (2022) | |
| c.1270T>C | p.Ser424Pro | missense_variant | De novo | - | - | 31981491 | Satterstrom FK et al. (2020) | |
| c.1859T>C | p.Ile620Thr | missense_variant | De novo | - | Multiplex | 35982159 | Zhou X et al. (2022) |
Common Variants
No common variants reported.