Human Gene Module / Chromosome X / MSL3

MSL3MSL complex subunit 3

Score
1
High Confidence Criteria 1.1
Autism Reports / Total Reports
2 / 6
Rare Variants / Common Variants
36 / 0
Aliases
MSL3, MRSXBA,  MRXS36,  MRXSBAL1, MSL3
Associated Syndromes
Basilicata-Akhtar syndrome
Genetic Category
Rare Single Gene Mutation, Syndromic
Chromosome Band
Xp22.2
Associated Disorders
ID, ASD
Relevance to Autism

Brunet et al., 2020 delineated the genotypic and phenotypic spectrum of 25 individuals (15 males, 10 females) with X-linked, MSL3-related disorder (Basilicata-Akhtar syndrome) and found that 10/20 (50%) individuals had a diagnosis of autism spectrum disorder. De novo likely gene-disruptive (dnLGD) variants in the MSL3 gene were identified in an ASD proband from the SPARK cohort (Wang et al., 2020) and in four probands from the Deciphering Developmental Disorders study in 2017, while a de novo missense variant in MSL3 was identified in a female ASD proband from the Autism Sequencing Consortium in Satterstrom et al., 2020. Single-molecule molecular inversion probe (smMIP) sequencing of 125 genes in over 16,000 cases with neurodevelopmental disorders in Wang et al., 2020 identified an additional likely gene-disruptive variant in an ASD proband from the AGRE cohort.

Molecular Function

This gene encodes a nuclear protein that is similar to the product of the Drosophila male-specific lethal-3 gene. The Drosophila protein plays a critical role in a dosage-compensation pathway, which equalizes X-linked gene expression in males and females. Thus, the human protein is thought to play a similar function in chromatin remodeling and transcriptional regulation, and it has been found as part of a complex that is responsible for histone H4 lysine-16 acetylation. Hemizygous or heterozygous mutations in the MSL3 gene are responsible for Basilicata-Akhtar syndrome (MRXSBA; OMIM 301032), a disorder characterized by global developmental delay apparent from infancy, feeding difficulties, hypotonia, and poor or absent speech (Basilicata et al., 2018).

Reports related to MSL3 (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Prevalence and architecture of de novo mutations in developmental disorders et al. (2017) No -
2 Support De novo mutations in MSL3 cause an X-linked syndrome marked by impaired histone H4 lysine 16 acetylation Basilicata MF et al. (2018) No -
3 Support Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism Satterstrom FK et al. (2020) Yes -
4 Support Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders Wang T et al. (2020) Yes -
5 Primary Defining the genotypic and phenotypic spectrum of X-linked MSL3-related disorder Brunet T et al. (2020) No ASD
6 Support - Brunet T et al. (2021) No ID
Rare Variants   (36)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss De novo NA Simplex 33173220 Brunet T et al. (2020)
c.589-1G>A - splice_site_variant Unknown - - 33004838 Wang T et al. (2020)
c.1237C>T p.Gln413Ter stop_gained Unknown - - 33004838 Wang T et al. (2020)
c.1193C>A p.Ser398Ter stop_gained De novo NA - 33004838 Wang T et al. (2020)
c.1453G>T p.Asp485Tyr missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.982del p.Ala328LeufsTer9 frameshift_variant De novo NA - 28135719 et al. (2017)
c.1342_1345del p.Phe448Ter frameshift_variant De novo NA - 28135719 et al. (2017)
c.902dup p.Leu302PhefsTer18 frameshift_variant De novo NA - 28135719 et al. (2017)
c.913C>T p.Gln305Ter stop_gained De novo NA Simplex 33173220 Brunet T et al. (2020)
c.961C>T p.Gln321Ter stop_gained De novo NA Simplex 33173220 Brunet T et al. (2020)
c.1430+1G>A - splice_site_variant De novo NA Simplex 33173220 Brunet T et al. (2020)
c.1430+1G>A - splice_site_variant De novo NA Simplex 33619735 Brunet T et al. (2021)
c.1105C>T p.Gln369Ter stop_gained De novo NA Simplex 33173220 Brunet T et al. (2020)
c.1314C>A p.Tyr438Ter stop_gained De novo NA Simplex 33173220 Brunet T et al. (2020)
c.1372C>T p.Arg458Ter stop_gained De novo NA Simplex 33173220 Brunet T et al. (2020)
c.1314C>A p.Tyr438Ter stop_gained De novo NA Simplex 33619735 Brunet T et al. (2021)
c.865A>T p.Lys289Ter stop_gained De novo NA Multiplex 33173220 Brunet T et al. (2020)
c.530_531del p.Tyr177LeufsTer3 frameshift_variant De novo NA - 28135719 et al. (2017)
c.589-4_591del - splice_site_variant De novo NA Simplex 33173220 Brunet T et al. (2020)
c.1347C>A p.Tyr449Ter stop_gained De novo NA Multiplex 33173220 Brunet T et al. (2020)
c.1310A>C p.Asn437Thr missense_variant De novo NA Simplex 33173220 Brunet T et al. (2020)
c.1370T>C p.Leu457Pro missense_variant De novo NA Simplex 33173220 Brunet T et al. (2020)
c.566dup p.Tyr189Ter frameshift_variant De novo NA Simplex 33173220 Brunet T et al. (2020)
c.1382-1G>A - splice_site_variant Familial Maternal Simplex 33173220 Brunet T et al. (2020)
c.1135+2_1135+4del - splice_site_variant De novo NA Simplex 33173220 Brunet T et al. (2020)
c.1373G>T p.Arg458Leu missense_variant De novo NA Multiplex 33173220 Brunet T et al. (2020)
c.1362_1364del p.Gln454del inframe_deletion De novo NA Simplex 33173220 Brunet T et al. (2020)
c.590_593del p.Leu197Ter frameshift_variant De novo NA Simplex 33173220 Brunet T et al. (2020)
c.590_593del p.Leu197Ter frameshift_variant Unknown - Multiplex 33173220 Brunet T et al. (2020)
c.766G>A p.Glu256Lys missense_variant De novo NA Simplex 31981491 Satterstrom FK et al. (2020)
c.1319dup p.Gly441ArgfsTer2 frameshift_variant De novo NA Simplex 33173220 Brunet T et al. (2020)
c.1146del p.Lys383SerfsTer22 frameshift_variant De novo NA Simplex 33173220 Brunet T et al. (2020)
c.808_809del p.Pro270ValfsTer8 frameshift_variant Unknown - Multiplex 33173220 Brunet T et al. (2020)
c.973_974del p.Gln326AlafsTer5 frameshift_variant De novo NA Multiplex 33173220 Brunet T et al. (2020)
c.1089_1105dup p.Met369ArgfsTer30 frameshift_variant De novo NA Simplex 33173220 Brunet T et al. (2020)
c.1168_1169del p.Lys390GlufsTer6 frameshift_variant Unknown Not maternal Multiplex 33173220 Brunet T et al. (2020)
Common Variants  

No common variants reported.

Submit New Gene

Report an Error