Human Gene Module / Chromosome 5 / MAP1B

MAP1Bmicrotubule associated protein 1B

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
7 / 14
Rare Variants / Common Variants
17 / 0
Aliases
-
Associated Syndromes
ASD, Fragile X syndrome, Fragile X syndrome
Chromosome Band
5q13.2
Associated Disorders
-
Relevance to Autism

De novo variants in the MAP1B gene, including three loss-of-function variants, have been reported in individuals with a clinical diagnosis of ASD (De Rubeis et al., 2014; Satterstrom et al., 2020; Zhou et al., 2022; Spataro et al., 2023). Heterozygous mutations in MAP1B are also responsible for periventricular nodular heterotopia-9 (OMIM 618918), an autosomal dominant neurologic disorder characterized by malformation of cortical development (including anterior predominant PVNH, thin corpus callosum, and decreased white matter volume), developmental delay, cognitive defects associated with low IQ (range 50 to 80), learning disabilities, seizures, and behavior abnormalities; autism spectrum disorder was reported in a subset of affected individuals with this disorder (Heinzen et al., 2018; Walters et al., 2018; Julca et al., 2019; Arya et al., 2021). MAP1B has been shown to interact with FMRP, the protein encoded by the FMR1 gene, as well as with the protein encoded by the KIRREL3 gene (Zhang et al., 2001; Liu et al., 2015).

Molecular Function

This gene encodes a protein that belongs to the microtubule-associated protein family. The proteins of this family are thought to be involved in microtubule assembly, which is an essential step in neurogenesis. The product of this gene is a precursor polypeptide that presumably undergoes proteolytic processing to generate the final MAP1B heavy chain and LC1 light chain. Gene knockout studies of the mouse microtubule-associated protein 1B gene suggested an important role in development and function of the nervous system.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
Mouse
Entrez GeneMouse Genome InformaticsAllen Brain Atlas
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to MAP1B (14 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support - Zhang YQ et al. (2001) No -
2 Support Synaptic, transcriptional and chromatin genes disrupted in autism De Rubeis S , et al. (2014) Yes -
3 Support - Liu YF et al. (2015) No -
4 Support - Heinzen EL et al. (2018) No DD, ID, epilepsy/seizures
5 Support - Walters GB et al. (2018) No ASD
6 Support - Julca DM et al. (2019) No ADHD, DD, ID, epilepsy/seizures
7 Support Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism Satterstrom FK et al. (2020) Yes -
8 Support - Arya R et al. (2021) No DD, epilepsy/seizures
9 Support - Zhou X et al. (2022) Yes -
10 Primary - Spataro N et al. (2023) Yes -
11 Recent Recommendation - Guo Y et al. (2023) Yes -
12 Support - Cirnigliaro M et al. (2023) Yes -
13 Support - Sheth F et al. (2023) Yes DD, ID
14 Support - Salima Messaoudi et al. (2024) No -
Rare Variants   (17)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_gain Unknown Not maternal - 37365192 Guo Y et al. (2023)
c.1951G>T p.Glu651Ter stop_gained De novo - - 35982159 Zhou X et al. (2022)
c.2035G>T p.Glu679Ter stop_gained De novo - - 31317654 Julca DM et al. (2019)
c.-10+32G>A - intron_variant De novo - - 31981491 Satterstrom FK et al. (2020)
c.2995C>T p.Arg999Ter stop_gained De novo - - 36980980 Spataro N et al. (2023)
c.907C>T p.Arg303Ter stop_gained De novo - - 29738522 Heinzen EL et al. (2018)
c.5875A>G p.Ile1959Val missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.1456C>T p.Arg486Ter stop_gained De novo - - 31981491 Satterstrom FK et al. (2020)
c.1912G>T p.Val638Leu missense_variant De novo - - 25363760 De Rubeis S , et al. (2014)
c.1594C>T p.Gln532Ter stop_gained Familial Paternal - 29738522 Heinzen EL et al. (2018)
c.7157T>C p.Val2386Ala missense_variant Unknown - Simplex 37543562 Sheth F et al. (2023)
c.3316C>T p.Arg1106Ter stop_gained Familial Maternal - 29738522 Heinzen EL et al. (2018)
c.4990C>T p.Arg1664Ter stop_gained Familial Maternal Simplex 30150678 Walters GB et al. (2018)
c.3094G>T p.Glu1032Ter stop_gained Familial Maternal Multiplex 30150678 Walters GB et al. (2018)
c.441del p.Leu148CysfsTer4 frameshift_variant Familial Paternal - 29738522 Heinzen EL et al. (2018)
c.5793T>G p.Tyr1931Ter stop_gained Familial Maternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.1756del p.Glu586LysfsTer10 frameshift_variant Familial Maternal Multi-generational 30150678 Walters GB et al. (2018)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

Score Delta: Score remained at 2

criteria met
See SFARI Gene'scoring criteria
2

Strong Candidate

See all Category 2 Genes

We 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.

7/1/2023
icon
2

Increased from to 2

Krishnan Probability Score

Score 0.60780319606539

Ranking 300/25841 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.
Original Source
ExAC Score

Score 0.9999862477961

Ranking 483/18225 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
Original Source
Sanders TADA Score

Score 0.94911675528766

Ranking 17960/18665 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).
Original Source
Zhang D Score

Score 0.092684067081662

Ranking 6284/20870 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.
Original Source
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