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Intellectual disability

Gene: MAP1B

Amber List (moderate evidence)

MAP1B (microtubule associated protein 1B)
EnsemblGeneIds (GRCh38): ENSG00000131711
EnsemblGeneIds (GRCh37): ENSG00000131711
OMIM: 157129, Gene2Phenotype
MAP1B is in 2 panels

3 reviews

Zornitza Stark (Australian Genomics)

Green List (high evidence)

More than five families recently described with mono allelic variants in this gene, intellectual disability and variable other features including brain malformations.
Created: 6 Mar 2020, 10:03 a.m. | Last Modified: 6 Mar 2020, 10:03 a.m.
Panel Version: 3.3

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Intellectual disability; seizures; PVNH; dysmorphic features

Publications

Variants in this GENE are reported as part of current diagnostic practice

Ivone Leong (Genomics England Curator)

Comment on list classification: New gene added by external expert and reviewed by curation team. MAP1B has been given an amber gene rating based on the evidence provided by the expert review. It is not associated with any phenotype on OMIM or Gene2Phenotype.
Created: 18 Feb 2019, 1:07 p.m.

Konstantinos Varvagiannis (Other)

I don't know

In PMID 30150678 the authors report on a family with 5 individuals diagnosed with intellectual disability (ID, IQ <= 70 and associated impairments in adaptive function) and 3 further relatives with IQ below 70, not fulfilling the criteria for a clinical diagnosis of ID. A frameshift variant in MAP1B segregated with the ID/low IQ phenotype. This variant was not found in 31463 Icelanders for whom whole genome sequencing data were available.

The authors confirmed association of MAP1B loss-of-function (LoF) variants by demonstrating the presence of 2 other stopgain mutations in 2 further families. Among the 6 mutation carriers in these families, the average IQ was 81 with 2 of these subjects fulfilling the criteria for intellectual disability. 3 of the 6 mutation carriers had a diagnosis of autism spectrum disorder. Carriers demonstrated 24% less white matter volume (-2.1 SD) and 47% less corpus callosum volume (-2.4 SD) compared to controls.

Mean full-scale IQ, performance IQ and verbal IQ were 68.3 (with a SD of 10.5), 66.4 (SD of 9.3) and 74.5 (SD of 14.8) in MAP1B LoF carriers.

All 3 LoF variants reported result in a truncated but stable MAP1B protein as demonstrated by western blot analysis.

MAP1B undergoes post-translational modification and is cleaved (at position 2206) into a heavy chain and a light chain. The authors note that all LoF variants lead to truncation prior to the cleavage site.

As commented by the authors, LoF variants are found in publicly available databases at a frequency of approx. 1 in 10000.

One individual with de novo frameshift variant in Decipher ( https://decipher.sanger.ac.uk/search?q=gene%3AMAP1B#research-variants/results ).

De novo and inherited MAP1B variants have previously been described in individuals with periventricular nodular heterotopia (PMID: 29738522). This was also a feature in 9 individuals in the previous ID study.

Although PMID 30150678 is entitled "MAP1B mutations cause intellectual disability and extensive white matter deficit", intellectual disability was not a feature in all individuals or was rather mild when present.
Sources: Literature, Expert Review
Created: 12 Oct 2018, 10:27 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Intellectual disability

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Amber
Phenotypes
  • Intellectual disability
  • No OMIM number
OMIM
157129
Clinvar variants
Variants in MAP1B
Penetrance
unknown
Publications
Panels with this gene

History Filter Activity

18 Feb 2019, Gel status: 2

Entity classified by Genomics England curator

Ivone Leong (Genomics England Curator)

Gene: map1b has been classified as Amber List (Moderate Evidence).

18 Feb 2019, Gel status: 0

Set Phenotypes

Ivone Leong (Genomics England Curator)

Phenotypes for gene: MAP1B were changed from Intellectual disability to Intellectual disability; No OMIM number

12 Oct 2018, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes, Set penetrance

Konstantinos Varvagiannis (Other)

gene: MAP1B was added gene: MAP1B was added to Intellectual disability. Sources: Literature,Expert Review Mode of inheritance for gene: MAP1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MAP1B were set to 30150678; 29738522 Phenotypes for gene: MAP1B were set to Intellectual disability Penetrance for gene: MAP1B were set to unknown Review for gene: MAP1B was set to AMBER