MIB1Mindbomb E3 ubiquitin protein ligase 1
Autism Reports / Total Reports
10 / 10Rare Variants / Common Variants
31 / 0Aliases
MIB1, DIP-1, DIP1, LVNC7, MIB, ZZANK2, ZZZ6Associated Syndromes
-Chromosome Band
18q11.2Associated Disorders
-Genetic Category
Rare Single Gene MutationRelevance to Autism
This gene was identified in an ASD whole-exome sequencing study and subsequent TADA (transmission and de novo association) analysis as a gene strongly enriched for variants likely to affect ASD risk with a false discovery rate (FDR) of <0.1 (De Rubeis et al., 2014).
Molecular Function
This gene encodes a protein that functions as an E3 ubiquitin ligase. The encoded protein positively regulates Notch signaling by ubiquitinating the Notch receptors, thereby facilitating their endocytosis. This protein may also promote the ubiquitination and degradation of death-associated protein kinase 1 (DAPK1).
External Links
SFARI Genomic Platforms
Reports related to MIB1 (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 | The contribution of de novo coding mutations to autism spectrum disorder | Iossifov I et al. (2014) | Yes | - |
| 3 | Support | Whole-genome sequencing of quartet families with autism spectrum disorder | Yuen RK , et al. (2015) | Yes | - |
| 4 | Support | Insights into Autism Spectrum Disorder Genomic Architecture and Biology from 71 Risk Loci | Sanders SJ , et al. (2015) | Yes | - |
| 5 | Support | Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder | Lim ET , et al. (2017) | Yes | - |
| 6 | Support | Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder | Takata A , et al. (2018) | Yes | - |
| 7 | Support | Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks | Ruzzo EK , et al. (2019) | Yes | - |
| 8 | Support | Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes | Feliciano P et al. (2019) | Yes | - |
| 9 | Support | - | Zhou X et al. (2022) | Yes | - |
| 10 | Support | - | Cirnigliaro M et al. (2023) | Yes | - |
Rare Variants (31)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| c.289C>T | p.Arg97Ter | stop_gained | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.2305C>T | p.Arg769Ter | stop_gained | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.2321A>G | p.Gln774Arg | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.1134C>T | p.Asp378= | synonymous_variant | De novo | - | - | 31452935 | Feliciano P et al. (2019) | |
| c.75dup | p.Trp26ValfsTer56 | frameshift_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.1479+2T>G | - | splice_site_variant | Unknown | - | Unknown | 25363760 | De Rubeis S , et al. (2014) | |
| c.1830-2A>C | - | splice_site_variant | Unknown | - | Unknown | 25363760 | De Rubeis S , et al. (2014) | |
| c.1328A>G | p.Asp443Gly | missense_variant | De novo | - | Simplex | 28714951 | Lim ET , et al. (2017) | |
| c.1588C>T | p.Arg530Ter | stop_gained | Unknown | - | Unknown | 25363760 | De Rubeis S , et al. (2014) | |
| c.2716C>T | p.Arg906Ter | stop_gained | Unknown | - | Unknown | 25363760 | De Rubeis S , et al. (2014) | |
| c.2962C>T | p.Arg988Cys | missense_variant | De novo | - | Simplex | 29346770 | Takata A , et al. (2018) | |
| c.2327C>G | p.Pro776Arg | missense_variant | De novo | - | Simplex | 25363768 | Iossifov I et al. (2014) | |
| c.309T>G | p.Cys103Trp | missense_variant | Unknown | - | Unknown | 25363760 | De Rubeis S , et al. (2014) | |
| c.2405G>A | p.Gly802Asp | missense_variant | Unknown | - | Unknown | 25363760 | De Rubeis S , et al. (2014) | |
| c.2743G>A | p.Gly915Arg | missense_variant | Unknown | - | Unknown | 25363760 | De Rubeis S , et al. (2014) | |
| c.2746G>A | p.Gly916Arg | missense_variant | Unknown | - | Unknown | 25363760 | De Rubeis S , et al. (2014) | |
| c.2906G>A | p.Arg969His | missense_variant | Unknown | - | Unknown | 25363760 | De Rubeis S , et al. (2014) | |
| c.532-2A>C | - | splice_site_variant | Familial | Paternal | Multiplex | 31398340 | Ruzzo EK , et al. (2019) | |
| c.289C>T | p.Arg97Ter | stop_gained | Familial | Paternal | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
| c.1111C>T | p.Arg371Ter | stop_gained | Familial | Maternal | Multiplex | 31398340 | Ruzzo EK , et al. (2019) | |
| c.2716C>T | p.Arg906Ter | stop_gained | Familial | Paternal | Multiplex | 31398340 | Ruzzo EK , et al. (2019) | |
| c.836T>G | p.Leu279Ter | stop_gained | Familial | Paternal | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
| c.2394-2A>G | - | splice_site_variant | Familial | Maternal | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
| c.1588C>T | p.Arg530Ter | stop_gained | Familial | Maternal | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
| c.2305C>T | p.Arg769Ter | stop_gained | Familial | Paternal | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
| c.2716C>T | p.Arg906Ter | stop_gained | Familial | Paternal | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
| c.1039C>T | p.Arg347Ter | stop_gained | Familial | Paternal | Multiplex | 37506195 | Cirnigliaro M et al. (2023) | |
| c.2673del | p.Asn892ThrfsTer2 | frameshift_variant | Unknown | - | Unknown | 25363760 | De Rubeis S , et al. (2014) | |
| c.2717del | p.Arg906GlnfsTer62 | frameshift_variant | Familial | Paternal | Multiplex | 25621899 | Yuen RK , et al. (2015) | |
| c.435dup | p.Ile146AspfsTer30 | frameshift_variant | Familial | Maternal | Simplex | 25363760 | De Rubeis S , et al. (2014) | |
| c.1901del | p.Thr634MetfsTer12 | frameshift_variant | Familial | Paternal | Simplex | 25363760 | De Rubeis S , et al. (2014) |
Common Variants
No common variants reported.
SFARI Gene score
2
Strong Candidate
Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified MIB1 as a gene meeting high statistical significance with a 0.01 < FDR 0.05, meaning that this gene had a 95% chance of being a true autism gene (PMID 25363760).
Score Delta: Score remained at 2
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.
4/1/2022
3
2
Decreased from 3 to 2
Description
Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified MIB1 as a gene meeting high statistical significance with a 0.01 < FDR 0.05, meaning that this gene had a 95% chance of being a true autism gene (PMID 25363760).
1/1/2020
3
3
Decreased from 3 to 3
Description
Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified MIB1 as a gene meeting high statistical significance with a 0.01 < FDR 0.05, meaning that this gene had a 95% chance of being a true autism gene (PMID 25363760).
10/1/2019
4
3
Decreased from 4 to 3
New Scoring Scheme
Description
Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified MIB1 as a gene meeting high statistical significance with a 0.01 < FDR 0.05, meaning that this gene had a 95% chance of being a true autism gene (PMID 25363760).
7/1/2019
4
4
Decreased from 4 to 4
Description
Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified MIB1 as a gene meeting high statistical significance with a 0.01 < FDR 0.05, meaning that this gene had a 95% chance of being a true autism gene (PMID 25363760).
7/1/2017
4
4
Decreased from 4 to 4
Description
Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified MIB1 as a gene meeting high statistical significance with a 0.01 < FDR ? 0.05, meaning that this gene had a ? 95% chance of being a true autism gene (PMID 25363760).
1/1/2016
4
4
Decreased from 4 to 4
Description
Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified MIB1 as a gene meeting high statistical significance with a 0.01
10/1/2014
4
Increased from to 4
Description
Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified MIB1 as a gene meeting high statistical significance with a 0.01
Krishnan Probability Score
Score 0.4952228753076
Ranking 3110/25841 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 1.0007180499768E-44
Ranking 18211/18225 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 0.047428125547235
Ranking 45/18665 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).
Larsen Cumulative Evidence Score
Score 31
Ranking 70/461 scored genes
[Show Scoring Methodology]
Larsen and colleagues generated gene scores based on the sum of evidence for all available
ASD-associated variants in a gene, with assessments based on mode of inheritance, effect size,
and variant frequency in the general population. The approach was first presented in Mol Autism
7:44 (2016), and scores for 461 genes can be found in column I in supplementary table 4 from
that paper.
Zhang D Score
Score -0.035204736663941
Ranking 9871/20870 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.
Interactome
- Protein Binding
- DNA Binding
- RNA Binding
- Protein Modification
- Direct Regulation
- ASD-Linked Genes
Interaction Table
| Interactor Symbol | Interactor Name | Interactor Organism | Interactor Type | Entrez ID | Uniprot ID |
|---|---|---|---|---|---|
| Acsbg1 | acyl-CoA synthetase bubblegum family member 1 | Rat | Protein Binding | 171410 | Q924N5 |
| Adgrl3 | adhesion G protein-coupled receptor L3 | Rat | Protein Binding | 170641 | Q9Z173 |
| Ankrd34c | ankyrin repeat domain 34C | Rat | Protein Binding | 300889 | D3ZI64 |
| ANKRD55 | Ankyrin repeat domain-containing protein 55 | Human | Protein Binding | 79722 | Q3KP44-2 |
| Arg1 | arginase 1 | Rat | Protein Binding | 29221 | P07824 |
| Arhgef25 | Rho guanine nucleotide exchange factor 25 | Rat | Protein Binding | 314904 | Q6P720 |
| Atp2a3 | ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 3 | Rat | Protein Binding | 25391 | P18596 |
| Bco2 | beta-carotene oxygenase 2 | Rat | Protein Binding | 315644 | A3KN98 |
| Bgn | biglycan | Rat | Protein Binding | 25181 | P47853 |
| C1qb | complement component 1, q subcomponent, B chain | Rat | Protein Binding | 29687 | P31721 |
| C1qc | complement component 1, q subcomponent, C chain | Rat | Protein Binding | 362634 | P31722 |
| C2cd5 | C2 calcium-dependent domain containing 5 | Rat | Protein Binding | 362461 | D4A5B3 |
| Cacng8 | calcium voltage-gated channel auxiliary subunit gamma 8 | Rat | Protein Binding | 140729 | Q8VHW5 |
| Car10 | carbonic anhydrase 10 | Rat | Protein Binding | 100360015 | M0R8A5 |
| Casq2 | calsequestrin 2 | Rat | Protein Binding | 29209 | P51868 |
| Cbln3 | cerebellin 3 precursor | Rat | Protein Binding | 501998 | D3Z9H1 |
| Ccar2 | cell cycle and apoptosis regulator 2 | Rat | Protein Binding | 306007 | F1LM55 |
| CHRNA3 | Neuronal acetylcholine receptor subunit alpha-3 | Human | Protein Binding | 1136 | P32297-1 |
| Col1a1 | collagen, type I, alpha 1 | Rat | Protein Binding | 29393 | P02454 |
| Coro1a | coronin 1A | Rat | Protein Binding | 155151 | Q91ZN1 |
| Coro6 | coronin 6 | Rat | Protein Binding | 245982 | Q920J3 |
| Crym | crystallin, mu | Rat | Protein Binding | 117024 | Q9QYU4 |
| Dhrs4 | dehydrogenase/reductase (SDR family) member 4 | Rat | Protein Binding | 266686 | Q8VID1 |
| Dll4 | delta-like 4 (Drosophila) | Mouse | Protein Binding | 54485 | Q9JI71 |
| EPN3 | Epsin-3 | Human | Protein Binding | 55040 | Q9H201-2 |
| Erbin | erbb2 interacting protein | Rat | Protein Binding | 365661 | |
| Fam109a | family with sequence similarity 109, member A | Rat | Protein Binding | 288664 | D3ZL52 |
| Gkap1 | G kinase anchoring protein 1 | Rat | Protein Binding | 361202 | Q5XIG5 |
| Gpc3 | glypican 3 | Rat | Protein Binding | 25236 | P13265 |
| Gpc4 | glypican 4 | Rat | Protein Binding | 317322 | Q642B0 |
| Gsdma | gasdermin A | Rat | Protein Binding | 360619 | D3ZA32 |
| Gsta5 | glutathione S-transferase alpha 5 | Rat | Protein Binding | 494499 | P04903 |
| Gstm1 | glutathione S-transferase mu 1 | Rat | Protein Binding | 24423 | P04905 |
| Gstm5 | glutathione S-transferase, mu 5 | Rat | Protein Binding | 64352 | Q9Z1B2 |
| Gstm6 | glutathione S-transferase, mu 6 | Rat | Protein Binding | 499688 | B0BN47 |
| Hist1h2bb | histone cluster 1, H2bb | Rat | Protein Binding | 679910 | |
| Hmgcs2 | 3-hydroxy-3-methylglutaryl-CoA synthase 2 | Rat | Protein Binding | 24450 | Q68G44 |
| Hnrnpdl | heterogeneous nuclear ribonucleoprotein D-like | Rat | Protein Binding | 305178 | Q3SWU3 |
| Htra1 | HtrA serine peptidase 1 | Rat | Protein Binding | 65164 | Q9QZK5 |
| Htra2 | HtrA serine peptidase 2 | Rat | Protein Binding | 297376 | B0BNB9 |
| Igh-6 | immunoglobulin heavy chain 6 | Rat | Protein Binding | 299357 | Q569B3 |
| Kb15 | type II keratin Kb15 | Rat | Protein Binding | 366992 | A0A0G2JVA8 |
| LOC100910660 | serine/arginine-rich splicing factor 3-like | Rat | Protein Binding | 100910660 | Q0ZFS8 |
| LOC360933 | similar to Ac1591 | Rat | Protein Binding | 360933 | Q7TQ71 |
| LOC501110 | similar to Glutathione S-transferase A1 (GTH1) (HA subunit 1) (GST-epsilon) (GSTA1-1) (GST class-alpha) | Rat | Protein Binding | 501110 | Q6AXY0 |
| LRRCC1 | Leucine-rich repeat and coiled-coil domain-containing protein 1 | Human | Protein Binding | 85444 | Q9C099-2 |
| Nccrp1 | non-specific cytotoxic cell receptor protein 1 homolog (zebrafish) | Rat | Protein Binding | 292755 | D3ZQ18 |
| Phyhipl | phytanoyl-CoA 2-hydroxylase interacting protein-like | Rat | Protein Binding | 309901 | Q6AYN4 |
| Plbd1 | phospholipase B domain containing 1 | Rat | Protein Binding | 297694 | Q5U2V4 |
| Plg | plasminogen | Rat | Protein Binding | 85253 | Q01177 |
| Plppr4 | phospholipid phosphatase related 4 | Rat | Protein Binding | 295401 | G3V864 |
| Prss1 | protease, serine 1 | Rat | Protein Binding | 24691 | P00762 |
| Rbmxrtl | RNA binding motif protein, X chromosome retrogene-like | Rat | Protein Binding | 307779 | P84586 |
| RGD1304704 | similar to Hypothetical protein CGI-99 | Rat | Protein Binding | 302247 | F7EMB2 |
| RGD1306195 | similar to RAN protein | Rat | Protein Binding | 313163 | Q66H11 |
| RGD1562399 | similar to 40S ribosomal protein S2 | Rat | Protein Binding | 301438 | D3ZAS1 |
| RGD1563613 | similar to 40S ribosomal protein S25 | Rat | Protein Binding | 366605 | D4AE10 |
| RGD1564606 | similar to 60S ribosomal protein L23a | Rat | Protein Binding | 499523 | F1LT35 |
| Rpl5l1 | ribosomal protein L5-like 1 | Rat | Protein Binding | 501206 | D3ZHP8 |
| Rsu1 | Ras suppressor protein 1 | Rat | Protein Binding | 680419 | D4A8F2 |
| Rundc3b | RUN domain containing 3B | Rat | Protein Binding | 688590 | Q3B7K9 |
| Sdpr | serum deprivation response | Rat | Protein Binding | 316384 | Q66H98 |
| Sema5a | semaphorin 5A | Rat | Protein Binding | 310207 | D3ZTD8 |
| Sept2 | septin 2 | Rat | Protein Binding | 117515 | Q91Y81 |
| Serpinb13 | serpin peptidase inhibitor, clade B (ovalbumin), member 13 | Rat | Protein Binding | 304690 | D3ZKA0 |
| Spock1 | sparc/osteonectin, cwcv and kazal-like domains proteoglycan (testican) 1 | Rat | Protein Binding | 306759 | Q562B0 |
| Spock2 | sparc/osteonectin, cwcv and kazal-like domains proteoglycan (testican) 2 | Rat | Protein Binding | 361840 | A0A0G2K946 |
| Tfpi | tissue factor pathway inhibitor | Rat | Protein Binding | 29436 | Q02445 |
| Tgm1 | transglutaminase 1 | Rat | Protein Binding | 60335 | P23606 |
| Zc2hc1a | zinc finger, C2HC-type containing 1A | Rat | Protein Binding | 310244 | B5DF95 |
| Zfp598 | zinc finger protein 598 | Rat | Protein Binding | 287119 | D3ZR64 |