Human Gene Module / Chromosome 19 / MBOAT7

MBOAT7membrane bound O-acyltransferase domain containing 7

Score
1
High Confidence Criteria 1.1
Autism Reports / Total Reports
2 / 6
Rare Variants / Common Variants
15 / 0
Aliases
MBOAT7, BB1,  LENG4,  LPIAT,  LRC4,  MBOA7,  OACT7,  hMBOA-7
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation, Syndromic
Chromosome Band
19q13.42
Associated Disorders
DD/NDD, EPS, ASD
Relevance to Autism

Homozygous variants in the MBOAT7 gene were identified in 16 affected individuals presenting with intellectual disability from six consanguineous families; ASD was documented in seven of these individuals according to the Childhood Autism Rating Scale, and three additional individuals showed clinical autistic features (Johansen et al., 2016).

Molecular Function

This gene encodes a member of the membrane-bound O-acyltransferases family of integral membrane proteins that have acyltransferase activity. The encoded protein is a lysophosphatidylinositol acyltransferase that has specificity for arachidonoyl-CoA as an acyl donor. This protein is involved in the reacylation of phospholipids as part of the phospholipid remodeling pathway known as the Land cycle.

External Links
Gene CardPubMed
Human
Entrez GeneOMIMUniProtHumanBase
Reports related to MBOAT7 (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Synaptic, transcriptional and chromatin genes disrupted in autism. De Rubeis S , et al. (2014) Yes -
2 Primary Mutations in MBOAT7, Encoding Lysophosphatidylinositol Acyltransferase I, Lead to Intellectual Disability Accompanied by Epilepsy and Autistic Feat... Johansen A , et al. (2016) No Epilepsy/seizures, ASD or autistic features
3 Support Expanding the phenotype of phospholipid remodelling disease due to MBOAT7 gene defect. Yalnzolu D , et al. (2019) No Autistic features (hand stereotypies)
4 Support Lessons Learned from Large-Scale, First-Tier Clinical Exome Sequencing in a Highly Consanguineous Population. Monies D , et al. (2019) No DD, autistic features
5 Support Expanding the phenotypic spectrum of MBOAT7-related intellectual disability. Jacher JE , et al. (2019) No Macrocephaly
6 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks. Ruzzo EK , et al. (2019) Yes -
Rare Variants   (15)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.339G>A p.(=) synonymous_variant De novo - - 25363760 De Rubeis S , et al. (2014)
T>G p.? splice_site_variant Familial Maternal Multiplex 31398340 Ruzzo EK , et al. (2019)
- - copy_number_loss;copy_number_loss Familial Both parents Multiplex 30701556 Yalnzolu D , et al. (2019)
c.[604G>A];[604G>A] p.[Gly202Ser];[Gly202Ser] missense_variant;missense_variant - - Unknown 31130284 Monies D , et al. (2019)
c.[854+1G>C];[854+1G>C] - splice_site_variant;splice_site_variant Familial Both parents Multiplex 27616480 Johansen A , et al. (2016)
c.[259C>T];[259C>T] p.[Arg87Ter];[Arg87Ter] stop_gained;stop_gained Familial Both parents Multiplex 30701556 Yalnzolu D , et al. (2019)
c.[8552A>G];[855-2A>G] p.[?];[?] splice_site_variant;splice_site_variant Familial Both parents Simplex 31282596 Jacher JE , et al. (2019)
c.[1278G>A];[1278G>A] p.[Trp426Ter];[Trp426Ter] stop_gained;stop_gained Familial Both parents Multiplex 30701556 Yalnzolu D , et al. (2019)
c.[1000delT];[1000delT] p.[Tyr334MetfsTer41];[Tyr334MetfsTer41] frameshift_variant;frameshift_variant - - Unknown 31130284 Monies D , et al. (2019)
c.[1126G>A];[1126G>A] p.[Gln376Lys];[Gln376Lys] missense_variant;missense_variant Familial Both parents Simplex 30701556 Yalnzolu D , et al. (2019)
c.[423delG];[423delG] p.[Leu142CysfsTer8];[Leu142CysfsTer8] frameshift_variant;frameshift_variant Familial Both parents Multiplex 27616480 Johansen A , et al. (2016)
c.[680_690del];[680_690del] p.[Leu227ProfsTer65];[Leu227ProfsTer65] frameshift_variant;frameshift_variant Familial Both parents Simplex 30701556 Yalnzolu D , et al. (2019)
c.[758_778del21];[758_778del21] p.[Gln253_Ala259del];[Gln253_Ala259del] inframe_deletion;inframe_deletion Familial Both parents Multiplex 27616480 Johansen A , et al. (2016)
c.[820_826del];[820_826del] p.[Gly274ProfsTer47];[Gly274ProfsTer47] frameshift_variant;frameshift_variant Familial Both parents Extended multiplex 27616480 Johansen A , et al. (2016)
c.[126_145del20];[126_145del20] p.[Leu43HisfsTer69];[Leu43HisfsTer69] frameshift_variant;frameshift_variant Familial Both parents Extended multiplex 27616480 Johansen A , et al. (2016)
Common Variants  

No common variants reported.

SFARI Gene score
1

High Confidence

Homozygous variants in the MBOAT7 gene were identified in 16 affected individuals presenting with intellectual disability from six consanguineous families; ASD was documented in seven of these individuals according to the Childhood Autism Rating Scale, and three additional individuals showed clinical autistic features (Johansen et al., 2016). In addition to intellectual disability and ASD/autistic features, affected individuals frequently presented with epilepsy, truncal hypotonia and appendicular hypertonia; structural brain abnormalities were only observed in a few cases (cortical atrophy in two cases, possible polymicrogyria in others), and few if any dysmorphic features were reported. Yalnizoglu et al., 2019 presented an additional 12 patients from 7 consanguineous Turkish families with homozygous MBOAT7 variants; 4 of these individuals presented with autistic features (stereotypic hand movements).

Score Delta: Score remained at 2S

criteria met
See SFARI Gene'scoring criteria
1

High Confidence

See all Category 1 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.

7/1/2019
2S
icon
2S

Score remained at 2S

Description

Homozygous variants in the MBOAT7 gene were identified in 16 affected individuals presenting with intellectual disability from six consanguineous families; ASD was documented in seven of these individuals according to the Childhood Autism Rating Scale, and three additional individuals showed clinical autistic features (Johansen et al., 2016). In addition to intellectual disability and ASD/autistic features, affected individuals frequently presented with epilepsy, truncal hypotonia and appendicular hypertonia; structural brain abnormalities were only observed in a few cases (cortical atrophy in two cases, possible polymicrogyria in others), and few if any dysmorphic features were reported. Yalnizoglu et al., 2019 presented an additional 12 patients from 7 consanguineous Turkish families with homozygous MBOAT7 variants; 4 of these individuals presented with autistic features (stereotypic hand movements).

Reports Added
[Lessons Learned from Large-Scale, First-Tier Clinical Exome Sequencing in a Highly Consanguineous Population.2019] [Expanding the phenotypic spectrum of MBOAT7-related intellectual disability.2019] [Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019]
4/1/2019
2S
icon
2S

Score remained at 2S

Description

2019 Q3 Rescoring regime

Reports Added
[Expanding the phenotype of phospholipid remodelling disease due to MBOAT7 gene defect.2019]
10/1/2016
icon
2S

Increased from to 2S

Description

Homozygous variants in the MBOAT7 gene were identified in 16 affected individuals presenting with intellectual disability from six consanguineous families; ASD was documented in seven of these individuals according to the Childhood Autism Rating Scale, and three additional individuals showed clinical autistic features (Johansen et al., 2016). In addition to intellectual disability and ASD/autistic features, affected individuals frequently presented with epilepsy, truncal hypotonia and appendicular hypertonia; structural brain abnormalities were only observed in a few cases (cortical atrophy in two cases, possible polymicrogyria in others), and few if any dysmorphic features were reported.

Krishnan Probability Score

Score 0.53897402696166

Ranking 1452/25841 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 0.046319589476461

Ranking 8636/18225 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 0.9307631445874

Ranking 11516/18665 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 0.052787652039636

Ranking 7163/20870 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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