Human Gene Module / Chromosome 6 / PLN

PLNphospholamban

SFARI Gene Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
1 / 4
Rare Variants / Common Variants
1 / 0
Aliases
PLN, RP3-509L4.2,  CMD1P,  CMH18,  PLB
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation
Chromosome Band
6q22.31
Associated Disorders
-
Relevance to Autism

Rare mutations in the PLN gene have been identified with autism (Marshall et al., 2008).

Molecular Function

The encoded protein is an inhibitor of cardiac muscle sarcoplasmic reticulum Ca (2+)-ATPase in the unphosphorylated state, but inhibition is relieved upon phosp horylation of the protein.

Reports related to PLN (4 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Highly Cited Chronic phospholamban-sarcoplasmic reticulum calcium ATPase interaction is the critical calcium cycling defect in dilated cardiomyopathy Minamisawa S , et al. (1999) No -
2 Highly Cited Dilated cardiomyopathy and heart failure caused by a mutation in phospholamban Schmitt JP , et al. (2003) No -
3 Primary Structural variation of chromosomes in autism spectrum disorder Marshall CR , et al. (2008) Yes -
4 Recent Recommendation Structural characterization of Ca(2+)-ATPase-bound phospholamban in lipid bilayers by solid-state nuclear magnetic resonance (NMR) spectroscopy Seidel K , et al. (2008) No -
Rare Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_gain Familial Paternal Simplex 18252227 Marshall CR , et al. (2008)
Common Variants  

No common variants reported.

SFARI Gene score
3

Suggestive Evidence

Paternally inherited gains have been observed in two unrelated autism cases (Marshall et al., 2008).

Score Delta: Score remained at 4

3

Suggestive Evidence

See all Category 3 Genes

The literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as "acc" in the score cards) could also boost a gene from category 4 to 3.

10/1/2019
4
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3

Decreased from 4 to 3

New Scoring Scheme
Description

Paternally inherited gains have been observed in two unrelated autism cases (Marshall et al., 2008).

Reports Added
[New Scoring Scheme]
7/1/2014
No data
icon
4

Increased from No data to 4

Description

Paternally inherited gains have been observed in two unrelated autism cases (Marshall et al., 2008).

4/1/2014
No data
icon
4

Increased from No data to 4

Description

Paternally inherited gains have been observed in two unrelated autism cases (Marshall et al., 2008).

Krishnan Probability Score

Score 0.48723459537758

Ranking 7018/25841 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.
ExAC Score

Score 0.11119422856632

Ranking 7745/18225 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
Sanders TADA Score

Score 0.87659697389307

Ranking 4647/18665 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).
Zhang D Score

Score 0.13364802291953

Ranking 5482/20870 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.
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
LDLRAD1 low density lipoprotein receptor class A domain containing 1 Human Protein Binding 388633 Q5T700
TMEM79 transmembrane protein 79 Human Protein Binding 84283 Q9BSE2
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