Human Gene Module / Chromosome 8 / MSR1

MSR1macrophage scavenger receptor 1

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
4 / 5
Rare Variants / Common Variants
7 / 1
Aliases
MSR1, CD204,  SCARA1,  SR-A,  SRA,  phSR1,  phSR2
Associated Syndromes
-
Chromosome Band
8p22
Associated Disorders
-
Relevance to Autism

Rare deletions in the MSR1 gene have been identified in individuals with ASD (ORoak et al., 2012).

Molecular Function

This gene encodes the class A macrophage scavenger receptors, which include three different types (1, 2, 3) generated by alternative splicing of this gene. These receptors or isoforms are macrophage-specific trimeric integral membrane glycoproteins and have been implicated in many macrophage-associated physiological and pathological processes including atherosclerosis, Alzheimer's disease, and host defense. These receptors mediate the endocytosis of a diverse group of macromolecules, including modified low density lipoproteins (LDL). Isoform III does not internalize actetylated LDL.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to MSR1 (5 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations O'Roak BJ , et al. (2012) Yes -
2 Support Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior Doan RN , et al. (2016) Yes -
3 Positive Association Genome-wide Burden of Rare Short Deletions Is Enriched in Major Depressive Disorder in Four Cohorts Zhang X , et al. (2019) No -
4 Support Homozygous deletions implicate non-coding epigenetic marks in Autism spectrum disorder Schmitz-Abe K et al. (2020) Yes -
5 Support - Zhou X et al. (2022) Yes -
Rare Variants   (7)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
G>C - intergenic_variant - - Unknown 27667684 Doan RN , et al. (2016)
T>G - intergenic_variant - - Unknown 27667684 Doan RN , et al. (2016)
c.1295G>C p.Arg432Pro missense_variant De novo - - 35982159 Zhou X et al. (2022)
- - copy_number_loss Familial Maternal Simplex 22495309 O'Roak BJ , et al. (2012)
- - copy_number_loss Familial Paternal Simplex 22495309 O'Roak BJ , et al. (2012)
- - copy_number_loss Familial Both parents Simplex 32820185 Schmitz-Abe K et al. (2020)
c.1056G>T p.Gln352His missense_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
Common Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
- - copy_number_loss - - - 31003785 Zhang X , et al. (2019)
SFARI Gene score
2

Strong Candidate

Two single gene inherited deletions were identified in 200 autistic probands, while found in controls at less than 1% (PMID 22495309). A meta-analysis of 5,780 cases with major depressive disorder (MDD) and 6,626 controls from four cohorts in Zhang et al., 2019 identified a CNV region containing exonic deletions in the MSR1 gene that was statistically enriched in MDD cases compared with controls (55 in cases vs. 32 in controls; odds ratio 1.96, P-value 1.9E-03).

Score Delta: Score remained at 2

criteria met
See SFARI Gene'scoring criteria
2

Strong Candidate

See all Category 2 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.

4/1/2022
3
icon
2

Decreased from 3 to 2

Description

Two single gene inherited deletions were identified in 200 autistic probands, while found in controls at less than 1% (PMID 22495309). A meta-analysis of 5,780 cases with major depressive disorder (MDD) and 6,626 controls from four cohorts in Zhang et al., 2019 identified a CNV region containing exonic deletions in the MSR1 gene that was statistically enriched in MDD cases compared with controls (55 in cases vs. 32 in controls; odds ratio 1.96, P-value 1.9E-03).

7/1/2020
3
icon
3

Decreased from 3 to 3

Description

Two single gene inherited deletions were identified in 200 autistic probands, while found in controls at less than 1% (PMID 22495309). A meta-analysis of 5,780 cases with major depressive disorder (MDD) and 6,626 controls from four cohorts in Zhang et al., 2019 identified a CNV region containing exonic deletions in the MSR1 gene that was statistically enriched in MDD cases compared with controls (55 in cases vs. 32 in controls; odds ratio 1.96, P-value 1.9E-03).

Reports Added
[Homozygous deletions implicate non-coding epigenetic marks in Autism spectrum disorder2020]
10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Two single gene inherited deletions were identified in 200 autistic probands, while found in controls at less than 1% (PMID 22495309). A meta-analysis of 5,780 cases with major depressive disorder (MDD) and 6,626 controls from four cohorts in Zhang et al., 2019 identified a CNV region containing exonic deletions in the MSR1 gene that was statistically enriched in MDD cases compared with controls (55 in cases vs. 32 in controls; odds ratio 1.96, P-value 1.9E-03).

Reports Added
[New Scoring Scheme]
4/1/2019
4
icon
4

Decreased from 4 to 4

Description

Two single gene inherited deletions were identified in 200 autistic probands, while found in controls at less than 1% (PMID 22495309).

Reports Added
[Genome-wide Burden of Rare Short Deletions Is Enriched in Major Depressive Disorder in Four Cohorts.2019]
10/1/2016
4
icon
4

Decreased from 4 to 4

Description

Two single gene inherited deletions were identified in 200 autistic probands, while found in controls at less than 1% (PMID 22495309).

Reports Added
[Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior.2016]
7/1/2014
No data
icon
4

Increased from No data to 4

Description

Two single gene inherited deletions were identified in 200 autistic probands, while found in controls at less than 1% (PMID 22495309).

4/1/2014
No data
icon
4

Increased from No data to 4

Description

Two single gene inherited deletions were identified in 200 autistic probands, while found in controls at less than 1% (PMID 22495309).

Krishnan Probability Score

Score 0.45035093404051

Ranking 10898/25841 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 8.2082684107328E-16

Ranking 17728/18225 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 0.92087751238785

Ranking 9268/18665 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 -0.055540525243603

Ranking 10616/20870 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
External PIN Data
BioGRIDHuman Protein Reference Database
Interactome
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
ACAN Aggrecan core protein Bovine Protein Binding 280985 P13608
ESA1 Histone acetyltransferase ESA1 Baker's yeast Direct Regulation 854418 Q08649
LAP3 leucine aminopeptidase 3 Bovine Protein Binding 781648 P00727
MALL mal, T-cell differentiation protein-like Human Protein Binding 7851 Q13021
NKG7 natural killer cell granule protein 7 Human Protein Binding 4818 Q16617
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