MTSS2MTSS I-BAR domain containing 2
Autism Reports / Total Reports
3 / 6Rare Variants / Common Variants
12 / 0Aliases
-Associated Syndromes
-Chromosome Band
16q22.1Associated Disorders
-Relevance to Autism
A number of de novo variants in the MTSS2 gene, including a de novo loss-of-function (LoF) variant and several de novo missense variants, have been identified in ASD probands (Satterstrom et al., 2020; Zhou et al., 2022; Trost et al., 2022). Huang et al., 2022 described a cohort of five unrelated individuals with a recurrent de novo MTSS2 missense variant (c.2011C>T;p.Arg671Trp) presenting with a neurodevelopmental syndrome [Intellectual developmental disorder with ocular anomalies and distinctive facial features (IDDOF); OMIM 620086] characterized by global developmental delay and/or mild intellectual disability, ophthalmological anomalies, distinctive facial features (upslanting palpebral fissures, epicanthus, and bitemporal narrowing), and microcephaly; autism spectrum disorder was diagnosed in two of the three individuals from this cohort who were old enough to be evaluated. Functional analysis of the recurrent p.Arg617Trp missense variant in Drosophila in Huang et al., 2022 demonstrated a partial loss-of-function effect and increased toxicity compared to wild-type MTSS2, suggesting that this variant may act as a dominant-negative allele. A female ASD proband from the SPARK cohort was also found to have the functionally validated de novo p.Arg617Trp missense variant (Zhou et al., 2022).
Molecular Function
Enables GTPase activator activity and small GTPase binding activity. Involved in activation of GTPase activity and cellular response to platelet-derived growth factor stimulus. Located in ruffle membrane.
External Links
SFARI Genomic Platforms
Reports related to MTSS2 (6 Reports)
| # | Type | Title | Author, Year | Autism Report | Associated Disorders |
|---|---|---|---|---|---|
| 1 | Primary | Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism | Satterstrom FK et al. (2020) | Yes | - |
| 2 | Support | - | Zhou X et al. (2022) | Yes | - |
| 3 | Recent Recommendation | - | Huang Y et al. (2022) | No | ASD, ADHD |
| 4 | Support | - | Trost B et al. (2022) | Yes | - |
| 5 | Support | - | Corona-Rivera JR et al. (2023) | No | - |
| 6 | Support | - | Angela De Dominicis et al. () | No | ADHD, epilepsy/seizures |
Rare Variants (12)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| c.290+38A>C | - | intron_variant | De novo | - | - | 36368308 | Trost B et al. (2022) | |
| c.132-36del | - | intron_variant | De novo | - | - | 31981491 | Satterstrom FK et al. (2020) | |
| c.517G>A | p.Asp173Asn | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.2011C>T | p.Arg671Trp | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.2011C>T | p.Arg671Trp | missense_variant | De novo | - | - | 36067766 | Huang Y et al. (2022) | |
| c.1826G>A | p.Arg609Gln | missense_variant | De novo | - | - | 36368308 | Trost B et al. (2022) | |
| c.132-1G>C | - | splice_site_variant | De novo | - | - | 31981491 | Satterstrom FK et al. (2020) | |
| c.1726C>T | p.Arg576Cys | missense_variant | De novo | - | Simplex | 35982159 | Zhou X et al. (2022) | |
| c.2011C>T | p.Arg671Trp | missense_variant | De novo | - | Simplex | 36067766 | Huang Y et al. (2022) | |
| c.2011C>T | p.Arg671Trp | missense_variant | De novo | - | - | 39890443 | Angela De Dominicis et al. () | |
| c.2011C>T | p.Arg671Trp | missense_variant | Unknown | - | - | 39890443 | Angela De Dominicis et al. () | |
| c.2011C>T | p.Arg671Trp | missense_variant | Unknown | Not maternal | Simplex | 37657631 | Corona-Rivera JR et al. (2023) |
Common Variants
No common variants reported.
SFARI Gene score
Syndromic
Score Delta: Score remained at S
criteria met
See SFARI Gene'scoring criteriaThe 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."