MEIS2Meis homeobox 2
Autism Reports / Total Reports
3 / 8Rare Variants / Common Variants
23 / 0Aliases
MEIS2, CPCMR, HsT18361, MRG1Associated Syndromes
-Genetic Category
Rare Single Gene Mutation, SyndromicChromosome Band
15q14Associated Disorders
ASDRelevance to Autism
Heterozygous mutations in the MEIS2 gene, frequently in the form of 15q14 microdeletions, are responsible for cleft palate, cardiac defects, and mental retardation (CPCMR; OMIM 600987). A de novo in-frame deletion variant in the MEIS2 gene was identified in a female patient diagnosed with ASD in Louw et al., 2015. A de novo 15q14 microdeletion involving MEIS2 was observed in a patient presenting with autistic behavior in Shimojima et al., 2017. Douglas et al., 2018 reported four individuals with de novo predicted damaging missense variants in the MEIS2 gene; in addition to features resembling those observed in patients with 15q14 deletions, three of the individuals in Douglas et al., 2018 presented with autism or ASD.
Molecular Function
This gene encodes a homeobox protein belonging to the TALE ('three amino acid loop extension') family of homeodomain-containing proteins. TALE homeobox proteins are highly conserved transcription regulators, and several members have been shown to be essential contributors to developmental programs.
Reports related to MEIS2 (8 Reports)
# | Type | Title | Author, Year | Autism Report | Associated Disorders |
---|---|---|---|---|---|
1 | Primary | MEIS2 involvement in cardiac development, cleft palate, and intellectual disability. | Louw JJ , et al. (2015) | No | ASD |
2 | Support | Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder | C Yuen RK et al. (2017) | Yes | - |
3 | Support | A 15q14 microdeletion involving MEIS2 identified in a patient with autism spectrum disorder. | Shimojima K , et al. (2017) | No | Autistic behavior |
4 | Recent Recommendation | De novo missense variants in MEIS2 recapitulate the microdeletion phenotype of cardiac and palate abnormalities, developmental delay, intellectual ... | Douglas G , et al. (2018) | No | ASD |
5 | Support | Heterozygous loss-of-function variants of MEIS2 cause a triad of palatal defects, congenital heart defects, and intellectual disability. | Verheije R , et al. (2018) | No | ASD |
6 | Support | Whole genome paired-end sequencing elucidates functional and phenotypic consequences of balanced chromosomal rearrangement in patients with develop... | Schluth-Bolard C , et al. (2019) | No | Microcephaly |
7 | Support | Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes | Feliciano P et al. (2019) | Yes | - |
8 | Support | Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders | Wang T et al. (2020) | Yes | - |
Rare Variants (23)
Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
---|---|---|---|---|---|---|---|---|
- | - | copy_number_loss | Unknown | - | - | 30291340 | Verheije R , et al. (2018) | |
- | - | copy_number_loss | De novo | NA | - | 30291340 | Verheije R , et al. (2018) | |
- | - | copy_number_loss | De novo | NA | - | 28736618 | Shimojima K , et al. (2017) | |
- | - | translocation | De novo | NA | - | 30923172 | Schluth-Bolard C , et al. (2019) | |
c.520C>T | p.Arg174Ter | stop_gained | De novo | NA | - | 33004838 | Wang T et al. (2020) | |
- | - | copy_number_loss | Unknown | Not maternal | - | 30291340 | Verheije R , et al. (2018) | |
c.5-2A>G | - | splice_site_variant | Familial | Paternal | - | 33004838 | Wang T et al. (2020) | |
c.639+1G>A | - | splice_site_variant | De novo | NA | - | 30291340 | Verheije R , et al. (2018) | |
c.640-2A>G | - | splice_site_variant | De novo | NA | - | 30291340 | Verheije R , et al. (2018) | |
c.978-2A>G | - | splice_site_variant | De novo | NA | - | 30291340 | Verheije R , et al. (2018) | |
c.829C>T | p.Gln277Ter | stop_gained | De novo | NA | - | 30291340 | Verheije R , et al. (2018) | |
c.978G>A | p.Trp326Ter | stop_gained | De novo | NA | - | 30291340 | Verheije R , et al. (2018) | |
c.520C>T | p.Arg174Ter | stop_gained | De novo | NA | - | 31452935 | Feliciano P et al. (2019) | |
c.905C>T | p.Pro302Leu | missense_variant | De novo | NA | - | 30055086 | Douglas G , et al. (2018) | |
c.965A>T | p.Gln322Leu | missense_variant | De novo | NA | - | 30055086 | Douglas G , et al. (2018) | |
c.992G>A | p.Arg331Lys | missense_variant | De novo | NA | - | 30055086 | Douglas G , et al. (2018) | |
c.1004T>C | p.Val335Ala | missense_variant | De novo | NA | - | 30055086 | Douglas G , et al. (2018) | |
c.998G>A | p.Arg333Lys | missense_variant | De novo | NA | - | 30291340 | Verheije R , et al. (2018) | |
c.324_326del | p.Ala109del | inframe_deletion | De novo | NA | - | 25712757 | Louw JJ , et al. (2015) | |
c.956C>T | p.Thr319Ile | missense_variant | De novo | NA | Multiplex | 28263302 | C Yuen RK et al. (2017) | |
c.383del | p.Lys128SerfsTer19 | frameshift_variant | De novo | NA | - | 30291340 | Verheije R , et al. (2018) | |
c.868dup | p.Ile290AsnfsTer40 | frameshift_variant | De novo | NA | - | 30291340 | Verheije R , et al. (2018) | |
c.934_937del | p.Leu312ArgfsTer11 | frameshift_variant | De novo | NA | - | 30291340 | Verheije R , et al. (2018) |
Common Variants
No common variants reported.
SFARI Gene score
High Confidence


Heterozygous mutations in the MEIS2 gene, frequently in the form of 15q14 microdeletions, are responsible for cleft palate, cardiac defects, and mental retardation (CPCMR; OMIM 600987). A de novo in-frame deletion variant in the MEIS2 gene was identified in a female patient diagnosed with ASD in Louw et al., 2015. A de novo 15q14 microdeletion involving MEIS2 was observed in a patient presenting with autistic behavior in Shimojima et al., 2017. Douglas et al., 2018 reported four individuals with de novo predicted damaging missense variants in the MEIS2 gene; in addition to features resembling those observed in patients with 15q14 deletions, three of the individuals in Douglas et al., 2018 presented with autism or ASD. Verheije et al., 2018 collected 23 previously reported individuals with either a de novo sequence variant in MEIS2 (9 patients) or a 15q14 microdeletion affecting MEIS2 (14 patients) and determined that autism was observed in 2/9 patients with a de novo MEIS2 sequence variants and in 3/14 patients with a 15q14 microdeletion affecting MEIS2.
Score Delta: Score remained at S
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.
10/1/2020

Score remained at S
Description
Heterozygous mutations in the MEIS2 gene, frequently in the form of 15q14 microdeletions, are responsible for cleft palate, cardiac defects, and mental retardation (CPCMR; OMIM 600987). A de novo in-frame deletion variant in the MEIS2 gene was identified in a female patient diagnosed with ASD in Louw et al., 2015. A de novo 15q14 microdeletion involving MEIS2 was observed in a patient presenting with autistic behavior in Shimojima et al., 2017. Douglas et al., 2018 reported four individuals with de novo predicted damaging missense variants in the MEIS2 gene; in addition to features resembling those observed in patients with 15q14 deletions, three of the individuals in Douglas et al., 2018 presented with autism or ASD. Verheije et al., 2018 collected 23 previously reported individuals with either a de novo sequence variant in MEIS2 (9 patients) or a 15q14 microdeletion affecting MEIS2 (14 patients) and determined that autism was observed in 2/9 patients with a de novo MEIS2 sequence variants and in 3/14 patients with a 15q14 microdeletion affecting MEIS2.
10/1/2019

Increased from S to 1
New Scoring Scheme
Description
Heterozygous mutations in the MEIS2 gene, frequently in the form of 15q14 microdeletions, are responsible for cleft palate, cardiac defects, and mental retardation (CPCMR; OMIM 600987). A de novo in-frame deletion variant in the MEIS2 gene was identified in a female patient diagnosed with ASD in Louw et al., 2015. A de novo 15q14 microdeletion involving MEIS2 was observed in a patient presenting with autistic behavior in Shimojima et al., 2017. Douglas et al., 2018 reported four individuals with de novo predicted damaging missense variants in the MEIS2 gene; in addition to features resembling those observed in patients with 15q14 deletions, three of the individuals in Douglas et al., 2018 presented with autism or ASD. Verheije et al., 2018 collected 23 previously reported individuals with either a de novo sequence variant in MEIS2 (9 patients) or a 15q14 microdeletion affecting MEIS2 (14 patients) and determined that autism was observed in 2/9 patients with a de novo MEIS2 sequence variants and in 3/14 patients with a 15q14 microdeletion affecting MEIS2.
4/1/2019

Increased from S to S
Description
Heterozygous mutations in the MEIS2 gene, frequently in the form of 15q14 microdeletions, are responsible for cleft palate, cardiac defects, and mental retardation (CPCMR; OMIM 600987). A de novo in-frame deletion variant in the MEIS2 gene was identified in a female patient diagnosed with ASD in Louw et al., 2015. A de novo 15q14 microdeletion involving MEIS2 was observed in a patient presenting with autistic behavior in Shimojima et al., 2017. Douglas et al., 2018 reported four individuals with de novo predicted damaging missense variants in the MEIS2 gene; in addition to features resembling those observed in patients with 15q14 deletions, three of the individuals in Douglas et al., 2018 presented with autism or ASD. Verheije et al., 2018 collected 23 previously reported individuals with either a de novo sequence variant in MEIS2 (9 patients) or a 15q14 microdeletion affecting MEIS2 (14 patients) and determined that autism was observed in 2/9 patients with a de novo MEIS2 sequence variants and in 3/14 patients with a 15q14 microdeletion affecting MEIS2.
10/1/2018

Increased from S to S
Description
Heterozygous mutations in the MEIS2 gene, frequently in the form of 15q14 microdeletions, are responsible for cleft palate, cardiac defects, and mental retardation (CPCMR; OMIM 600987). A de novo in-frame deletion variant in the MEIS2 gene was identified in a female patient diagnosed with ASD in Louw et al., 2015. A de novo 15q14 microdeletion involving MEIS2 was observed in a patient presenting with autistic behavior in Shimojima et al., 2017. Douglas et al., 2018 reported four individuals with de novo predicted damaging missense variants in the MEIS2 gene; in addition to features resembling those observed in patients with 15q14 deletions, three of the individuals in Douglas et al., 2018 presented with autism or ASD. Verheije et al., 2018 collected 23 previously reported individuals with either a de novo sequence variant in MEIS2 (9 patients) or a 15q14 microdeletion affecting MEIS2 (14 patients) and determined that autism was observed in 2/9 patients with a de novo MEIS2 sequence variants and in 3/14 patients with a 15q14 microdeletion affecting MEIS2.
Krishnan Probability Score
Score 0.54359785644328
Ranking 1420/25841 scored genes
[Show Scoring Methodology]
ExAC Score
Score 0.99425495510655
Ranking 1586/18225 scored genes
[Show Scoring Methodology]
Sanders TADA Score
Score 0.93499763783444
Ranking 12740/18665 scored genes
[Show Scoring Methodology]
Zhang D Score
Score 0.083167833905367
Ranking 6472/20870 scored genes
[Show Scoring Methodology]