ADGRL1adhesion G protein-coupled receptor L1
Autism Reports / Total Reports
4 / 5Rare Variants / Common Variants
13 / 0Aliases
-Associated Syndromes
-Chromosome Band
19p13.12Associated Disorders
-Relevance to Autism
De novo missense variants in the ADGRL1 gene were identified in two ASD probands from the Autism Sequencing Consortium in De Rubeis et al., 2014, while a rare de novo nonsense variant in this gene was identified in an ASD proband from the Study of Autism Genetics Exploration (SAGE) collection in Guo et al., 2019. Vitobello et al., 2022 described ten individuals from 9 families with heterozygous variants in the ADGRL1 gene, including in the ASD proband originally reported in Guo et al., 2019, that presented with variable neurodevelopmental features includigng developmental delay, intellectual disability, autism spectrum disorder, ADHD, and epilepsy; ADGRL1 variants expressed in vitro in mouse neuroblastoma cells displayed abnormalities in ligand-induced regulation of intracellular calcium influx that were consistent with haploinsufficiency. Furthermore, Vitobello et al., 2022 showed that mice carrying a heterozygous Adgrl1 null allele on a non-permissive background exhibited neurological and developmental abnormalities, whereas Agrl1 -/- mice on a permissive background demonstrated stereotypic behaviors, sexual dysfunction, bimodal extremes of locomotion, augmented startle reflex, and attenuated pre-pulse inhibition.
Molecular Function
Calcium-independent receptor of high affinity for alpha-latrotoxin, an excitatory neurotoxin present in black widow spider venom which triggers massive exocytosis from neurons and neuroendocrine cells. Receptor for TENM2 that mediates heterophilic synaptic cell-cell contact and postsynaptic specialization. Receptor probably implicated in the regulation of exocytosis.
External Links
SFARI Genomic Platforms
Reports related to ADGRL1 (5 Reports)
| # | Type | Title | Author, Year | Autism Report | Associated Disorders |
|---|---|---|---|---|---|
| 1 | Primary | Synaptic, transcriptional and chromatin genes disrupted in autism | De Rubeis S , et al. (2014) | Yes | - |
| 2 | Support | The contribution of de novo coding mutations to autism spectrum disorder | Iossifov I et al. (2014) | Yes | - |
| 3 | Support | Insights into Autism Spectrum Disorder Genomic Architecture and Biology from 71 Risk Loci | Sanders SJ , et al. (2015) | Yes | - |
| 4 | Support | Genome sequencing identifies multiple deleterious variants in autism patients with more severe phenotypes | Guo H , et al. (2018) | Yes | - |
| 5 | Recent Recommendation | - | Vitobello A et al. (2022) | No | ASD, ADHD, epilepsy/seizures |
Rare Variants (13)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| c.1526-6C>A | - | intron_variant | De novo | - | - | 26402605 | Sanders SJ , et al. (2015) | |
| c.26G>A | p.Trp9Ter | stop_gained | De novo | - | Multiplex | 30504930 | Guo H , et al. (2018) | |
| c.1037A>G | p.Asn346Ser | missense_variant | De novo | - | - | 25363760 | De Rubeis S , et al. (2014) | |
| c.1637G>C | p.Ser546Thr | missense_variant | De novo | - | - | 25363760 | De Rubeis S , et al. (2014) | |
| c.3406C>T | p.Arg1136Ter | stop_gained | De novo | - | Simplex | 35907405 | Vitobello A et al. (2022) | |
| c.3532C>T | p.Arg1178Ter | stop_gained | De novo | - | Simplex | 35907405 | Vitobello A et al. (2022) | |
| c.2742C>T | p.Ile914%3D | synonymous_variant | De novo | - | Simplex | 25363768 | Iossifov I et al. (2014) | |
| c.3013T>C | p.Trp1005Arg | missense_variant | De novo | - | Simplex | 35907405 | Vitobello A et al. (2022) | |
| c.3455T>C | p.Met1152Thr | missense_variant | De novo | - | Simplex | 35907405 | Vitobello A et al. (2022) | |
| c.3491C>T | p.Ser1164Phe | missense_variant | De novo | - | Simplex | 35907405 | Vitobello A et al. (2022) | |
| c.834G>A | p.Trp278Ter | stop_gained | Familial | Paternal | Multiplex | 35907405 | Vitobello A et al. (2022) | |
| c.2064dup | p.Glu689ArgfsTer113 | frameshift_variant | De novo | - | Simplex | 35907405 | Vitobello A et al. (2022) | |
| c.1037A>G | p.Tyr346Cys | missense_variant | Familial | Paternal | Multiplex | 35907405 | Vitobello A et al. (2022) |
Common Variants
No common variants reported.
SFARI Gene score
Suggestive Evidence, Syndromic
Score Delta: Score remained at 3S
criteria met
See SFARI Gene'scoring criteriaThe literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as "acc" in the score cards) could also boost a gene from category 4 to 3.
The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."
1/1/2023
