MAOA

Gene Facts

• HGNC Symbol: MAOA (HGNC:6833)
• HGNC Name: monoamine oxidase A
• Gene type: protein-coding gene
• Locus type: gene with protein product
• Previous symbols: No previous names found
• Alias symbols: No aliases found
• %HI: 43.16
• pLI: 1
• LOEUF: 0.14
• Cytoband: Xp11.3
• Genomic Coordinates:

  GRCh37/hg19:	chrX:43514254-43606064
  GRCh38/hg38:	chrX:43655006-43746817

• MANE Select Transcript: NM_000240.4 ENST00000338702.4
• Function: Catalyzes the oxidative deamination of primary and some secondary amine such as neurotransmitters, with concomitant reduction of oxygen to hydrogen peroxide and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues (PubMed:20493079, PubMed:8316221, PubMed:18391214, PubMed:24169519). Preferentially oxidizes serotonin (PubMed:20493079, PubMed:24169519). Also catalyzes the oxidative deamination of kynuramine to 3-(2-amino... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

• Dosage ID: ISCA-28304
• ClinGen Curation ID: CCID:007431
• Curation Status: Complete
• Issue Type: Dosage Curation - Gene
• Haploinsufficiency: Little Evidence for Haploinsufficiency (1)
• Triplosensitivity: No Evidence for Triplosensitivity (0)
• Related Links:
  Xp11.23 region (includes MAOA and MAOB)
• Last Evaluated: 09/26/2012

Haploinsufficiency (HI) Score Details

• HI Score: 1
• HI Evidence Strength: Little Evidence for Haploinsufficiency

HI Evidence

• PUBMED: 8211186
  Selective MAO-A deficiency has been described in a large Dutch kindred with borderline mental retardation and abnormal behavior. Affected individuals in this pedigree had a point mutation that prematurely truncated the MAO-A protein.

• HI Evidence Comments: Notably, focal deletions involving only MAOA have not been reported in the literature. The MAOA and MAOB genes are located next to each other in Xp11.3-11.4. Deletions encompassing both MAOA and MAOB genes have been reported and lead to intellectual disability and behavioral problems in males (see PMIDs 20485326 and 22365943 for examples). Larger deletions extending to the adjacent NDP gene have also been reported and are associated with an atypical presentation of Norrie disease (MIM:310600) Several studies have shown an association of SNPs in MAOA with various pathological behavioral traits (PMIDs 16896926, 22297589, 22832821, 21628708). However, the associated behavioral phenotypes are non-specific and the evidence base weak.

NOTE

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.

Triplosensitivity (TS) Score Details

• TS Score: 0
• TS Evidence Strength: No Evidence for Triplosensitivity
• TS Evidence Comments: Notably, focal duplications involving only MAOA have not been reported in the literature. Klitten et al reported a male patient with mental retardation and intractable epilepsy carrying a duplication of Xp11.3 that involved the MAOA, MAOB, and NDP genes (PMID: 20808325)

NOTE

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.