Human Gene Module / Chromosome 7 / LEP

LEPLeptin

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
1 / 1
Rare Variants / Common Variants
2 / 0
Aliases
LEP, LEPD,  OB,  OBS
Associated Syndromes
-
Chromosome Band
7q32.1
Associated Disorders
-
Relevance to Autism

Two novel overlapping duplications involving the LEP gene were identified in unrelated ASD cases (Prasad et al., 2012).

Molecular Function

This gene encodes a protein that is secreted by white adipocytes into the circulation and plays a major role in the regulation of energy homeostasis. Circulating leptin binds to the leptin receptor in the brain, which activates downstream signaling pathways that inhibit feeding and promote energy expenditure. This protein also has several endocrine functions, and is involved in the regulation of immune and inflammatory responses, hematopoiesis, angiogenesis, reproduction, bone formation and wound healing.

SFARI Genomic Platforms
Reports related to LEP (1 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary A discovery resource of rare copy number variations in individuals with autism spectrum disorder Prasad A , et al. (2013) Yes -
Rare Variants   (2)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_gain Unknown - Simplex 23275889 Prasad A , et al. (2013)
- - copy_number_gain Familial Maternal Multiplex 23275889 Prasad A , et al. (2013)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

Two novel overlapping duplications involving the LEP gene were identified in unrelated ASD cases (Prasad et al., 2012).

Score Delta: Score remained at 2

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
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2

Decreased from 3 to 2

Description

Two novel overlapping duplications involving the LEP gene were identified in unrelated ASD cases (Prasad et al., 2012).

10/1/2019
4
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3

Decreased from 4 to 3

New Scoring Scheme
Description

Two novel overlapping duplications involving the LEP gene were identified in unrelated ASD cases (Prasad et al., 2012).

Reports Added
[New Scoring Scheme]
7/1/2015
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4

Increased from to 4

Description

Two novel overlapping duplications involving the LEP gene were identified in unrelated ASD cases (Prasad et al., 2012).

Krishnan Probability Score

Score 0.44726823475752

Ranking 13368/25841 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 0.31897102607548

Ranking 6403/18225 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 0.89632471474701

Ranking 6035/18665 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 0.025881135827266

Ranking 7908/20870 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.
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