MYCBP2MYC binding protein 2
Autism Reports / Total Reports
9 / 10Rare Variants / Common Variants
30 / 0Aliases
-Associated Syndromes
-Chromosome Band
13q22.3Associated Disorders
-Relevance to Autism
A number of de novo coding variants in the MYCBP2 gene, includiing three de novo loss-of-function (LoF) variants, have been identified in ASD probands from multiple cohorts (De Rubeis et al., 2014; Yuen et al., 2016; Yuen et al., 2017; Feliciano et al., 2019; Satterstrom et al., 2020; Zhou et al., 2022). AlAbdiet al., 2022 described a cohort of eight patients with a neurodevelopmental disorder characterized by a range of deficits including corpus callosum abnormalities, developmental delay, intellectual disability, epilepsy, and autism or autistic features who harbored de novo variants in the MYCBP2 gene; introduction of these disease-associated variants into conserved residues in the C. elegans MYCBP2 ortholog, RPM-1, demonstrated that C. elegans carrying the corresponding human mutations in rpm-1 displayed axonal and behavioral abnormalities.
Molecular Function
This gene encodes an E3 ubiquitin-protein ligase and member of the PHR (Phr1/MYCBP2, highwire and RPM-1) family of proteins. The encoded protein plays a role in axon guidance and synapse formation in the developing nervous system. In mammalian cells, this protein regulates the cAMP and mTOR signaling pathways, and may additionally regulate autophagy. Reduced expression of this gene has been observed in acute lymphoblastic leukemia patients and a mutation in this gene has been identified in patients with a rare inherited vision defect.
External Links
SFARI Genomic Platforms
Reports related to MYCBP2 (10 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 | Genome-wide characteristics of de novo mutations in autism | Yuen RK et al. (2016) | Yes | - |
| 3 | Support | Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder | C Yuen RK et al. (2017) | Yes | - |
| 4 | Support | Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes | Feliciano P et al. (2019) | Yes | - |
| 5 | Support | Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism | Satterstrom FK et al. (2020) | Yes | - |
| 6 | Recent Recommendation | - | Zhou X et al. (2022) | Yes | - |
| 7 | Recent Recommendation | - | AlAbdi L et al. (2022) | No | ASD or autistic features, ID, epilepsy/seizures |
| 8 | Support | - | Chen WX et al. (2022) | Yes | - |
| 9 | Support | - | Sheth F et al. (2023) | Yes | DD, ID |
| 10 | Support | - | Shenglan Li et al. (2024) | Yes | - |
Rare Variants (30)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| c.12463C>T | p.Arg4155Ter | stop_gained | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.13647+1G>C | - | splice_site_variant | De novo | - | - | 36200388 | AlAbdi L et al. (2022) | |
| c.8005C>T | p.Arg2669Ter | stop_gained | De novo | - | - | 36200388 | AlAbdi L et al. (2022) | |
| c.13438-21A>C | - | intron_variant | De novo | - | - | 31981491 | Satterstrom FK et al. (2020) | |
| c.2708A>G | p.Gln903Arg | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.2763G>C | p.Lys921Asn | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.120G>A | p.Pro40%3D | synonymous_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.4859T>C | p.Val1620Ala | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.6754G>T | p.Gly2252Cys | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.8005C>T | p.Arg2669Ter | stop_gained | De novo | - | - | 38593811 | Shenglan Li et al. (2024) | |
| c.10279G>A | p.Val3427Ile | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.10357A>G | p.Met3453Val | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.9084C>T | p.Ala3028%3D | synonymous_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.9896T>G | p.Val3299Gly | missense_variant | De novo | - | - | 36200388 | AlAbdi L et al. (2022) | |
| c.11840A>T | p.Asp3947Val | missense_variant | De novo | - | - | 36200388 | AlAbdi L et al. (2022) | |
| c.11843T>A | p.Leu3948Gln | missense_variant | De novo | - | - | 36200388 | AlAbdi L et al. (2022) | |
| c.11888C>T | p.Thr3963Ile | missense_variant | De novo | - | - | 36200388 | AlAbdi L et al. (2022) | |
| c.13406C>A | p.Thr4469Lys | missense_variant | De novo | - | - | 36200388 | AlAbdi L et al. (2022) | |
| c.13669C>T | p.Arg4557Cys | missense_variant | De novo | - | - | 36200388 | AlAbdi L et al. (2022) | |
| c.2359C>T | p.Arg787Trp | missense_variant | De novo | - | - | 31452935 | Feliciano P et al. (2019) | |
| c.7769T>C | p.Met2590Thr | missense_variant | De novo | - | - | 25363760 | De Rubeis S , et al. (2014) | |
| c.2081G>A | p.Cys694Tyr | missense_variant | De novo | - | Simplex | 27525107 | Yuen RK et al. (2016) | |
| c.2708A>G | p.Gln903Arg | missense_variant | De novo | - | - | 31981491 | Satterstrom FK et al. (2020) | |
| c.5472+1_5472+13del | - | splice_site_variant | De novo | - | Simplex | 35982159 | Zhou X et al. (2022) | |
| c.6856A>G | p.Thr2286Ala | missense_variant | De novo | - | Simplex | 36320054 | Chen WX et al. (2022) | |
| c.4392C>G | p.Thr1464%3D | synonymous_variant | De novo | - | - | 25363760 | De Rubeis S , et al. (2014) | |
| c.3721G>A | p.Gly1241Arg | missense_variant | De novo | - | - | 31981491 | Satterstrom FK et al. (2020) | |
| c.12553G>A | p.Gly4185Ser | missense_variant | Unknown | - | Simplex | 37543562 | Sheth F et al. (2023) | |
| c.5055C>T | p.Ser1685%3D | synonymous_variant | De novo | - | Multiplex | 28263302 | C Yuen RK et al. (2017) | |
| c.9629dup | p.Lys3211GlufsTer8 | frameshift_variant | De novo | - | Simplex | 35982159 | Zhou X et al. (2022) |
Common Variants
No common variants reported.
SFARI Gene score
1
High Confidence
Score Delta: Score remained at 1
criteria met
See SFARI Gene'scoring criteriaWe considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.
1/1/2023
1
Increased from to 1
Krishnan Probability Score
Score 0.58657077181474
Ranking 508/25841 scored genes
[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning
approach on a human brain-specific gene network. The method was first presented in Nat
Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed
in column G of supplementary table 3 (see:
http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser,
with the ability to view networks of associated ASD risk genes, can be found at
asd.princeton.edu.
ExAC Score
Score 1
Ranking 11/18225 scored genes
[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has
been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by
Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at
exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of-
function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of-
function mutations in autism in such a gene would be more likely to confer risk. For a full list of
pLI scores see:
ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle
aned_exac_nonTCGA_z_pli_rec_null_data.txt
Sanders TADA Score
Score 0.95053140913995
Ranking 18529/18665 scored genes
[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013),
and is a statistic that integrates evidence from both de novo and transmitted mutations.
It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233
(2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper
(the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Zhang D Score
Score 0.47130671813328
Ranking 735/20870 scored genes
[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures),
or D score, was developed to combine evidence from de novo loss-of- function mutation with
evidence from cell-type- specific gene expression in the mouse brain (specifically translational
profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with
positive D scores are more likely to be associated with autism risk, with higher-confidence genes
having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204-
215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in
supplementary table 2 from that paper.