Human Gene Module / Chromosome 2 / HDLBP

HDLBPhigh density lipoprotein binding protein

SFARI Gene Score
1
High Confidence Criteria 1.1
Autism Reports / Total Reports
5 / 6
Rare Variants / Common Variants
8 / 0
EAGLE Score
1.25
Limited Learn More
Aliases
HDLBP, HBP,  PRO2900,  VGL
Associated Syndromes
2q37.3 microdeletion syndrome
Chromosome Band
2q37.3
Associated Disorders
ASD
Genetic Category
Rare Single Gene Mutation
Relevance to Autism

De novo missense variants that were predicted in silico to be damaging were observed in the HDLBP gene in an ASD proband from the Simons Simplex Collection (O'Roak et al., 2012) and an ASD proband from the Autism Sequencing Consortium (De Rubeis et al., 2014). TADA-Denovo analysis using a combined dataset of previously published cohorts from the Simons Simplex Collection and the Autism Sequencing Consortium, as well as a novel cohort of 262 Japanese ASD trios, in Takata et al., 2018 identified HDLBP as a gene significantly enriched in damaging de novo mutations in ASD cases (pBH < 0.05). This gene resides within the 2q37.3 microdeletion syndrome locus, and it was previously demonstrated in Felder et al., 2009 that HDLBP expression was downregulated in lymphoblastoid cell lines from a patient with a 3.5 Mb de novo 2q37.3 deletion who presented with autism.

Molecular Function

The protein encoded by this gene binds high density lipoprotein (HDL) and may function to regulate excess cholesterol levels in cells. The encoded protein also binds RNA and can induce heterochromatin formation.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to HDLBP (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support FARP2, HDLBP and PASK are downregulated in a patient with autism and 2q37.3 deletion syndrome Felder B , et al. (2009) No ASD
2 Primary Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations O'Roak BJ , et al. (2012) Yes -
3 Support Synaptic, transcriptional and chromatin genes disrupted in autism De Rubeis S , et al. (2014) Yes -
4 Recent Recommendation Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder Takata A , et al. (2018) Yes -
5 Support Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism Satterstrom FK et al. (2020) Yes -
6 Support - Zhou X et al. (2022) Yes -
Rare Variants   (8)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.3010-4G>A - splice_region_variant De novo - - 35982159 Zhou X et al. (2022)
c.719C>T p.Pro240Leu missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.1521G>T p.Glu507Asp missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.733C>T p.Arg245Cys missense_variant De novo - - 25363760 De Rubeis S , et al. (2014)
c.3249C>T p.Asp1083%3D synonymous_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.1915G>T p.Ala639Ser missense_variant De novo - Simplex 22495309 O'Roak BJ , et al. (2012)
c.1441A>T p.Ile481Phe missense_variant De novo - Simplex 31981491 Satterstrom FK et al. (2020)
c.1542T>C p.Ile514= synonymous_variant De novo - Simplex 31981491 Satterstrom FK et al. (2020)
Common Variants  

No common variants reported.

SFARI Gene score
1

High Confidence

Score Delta: Score remained at 1

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.

4/1/2022
3
icon
1

Decreased from 3 to 1

1/1/2020
3
icon
3

Decreased from 3 to 3

Description

De novo missense variants that were predicted in silico to be damaging were observed in the HDLBP gene in an ASD proband from the Simons Simplex Collection (O'Roak et al., 2012) and an ASD proband from the Autism Sequencing Consortium (De Rubeis et al., 2014). TADA-Denovo analysis using a combined dataset of previously published cohorts from the Simons Simplex Collection and the Autism Sequencing Consortium, as well as a novel cohort of 262 Japanese ASD trios, in Takata et al., 2018 identified HDLBP as a gene significantly enriched in damaging de novo mutations in ASD cases (pBH < 0.05). This gene resides within the 2q37.3 microdeletion syndrome locus, and it was previously demonstrated in Felder et al., 2009 that HDLBP expression was downregulated in lymphoblastoid cell lines from a patient with a 3.5 Mb de novo 2q37.3 deletion who presented with autism.

Reports Added
[Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism2020]
10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

De novo missense variants that were predicted in silico to be damaging were observed in the HDLBP gene in an ASD proband from the Simons Simplex Collection (O'Roak et al., 2012) and an ASD proband from the Autism Sequencing Consortium (De Rubeis et al., 2014). TADA-Denovo analysis using a combined dataset of previously published cohorts from the Simons Simplex Collection and the Autism Sequencing Consortium, as well as a novel cohort of 262 Japanese ASD trios, in Takata et al., 2018 identified HDLBP as a gene significantly enriched in damaging de novo mutations in ASD cases (pBH < 0.05). This gene resides within the 2q37.3 microdeletion syndrome locus, and it was previously demonstrated in Felder et al., 2009 that HDLBP expression was downregulated in lymphoblastoid cell lines from a patient with a 3.5 Mb de novo 2q37.3 deletion who presented with autism.

Reports Added
[New Scoring Scheme]
7/1/2018
icon
4

Increased from to 4

Description

De novo missense variants that were predicted in silico to be damaging were observed in the HDLBP gene in an ASD proband from the Simons Simplex Collection (O'Roak et al., 2012) and an ASD proband from the Autism Sequencing Consortium (De Rubeis et al., 2014). TADA-Denovo analysis using a combined dataset of previously published cohorts from the Simons Simplex Collection and the Autism Sequencing Consortium, as well as a novel cohort of 262 Japanese ASD trios, in Takata et al., 2018 identified HDLBP as a gene significantly enriched in damaging de novo mutations in ASD cases (pBH < 0.05). This gene resides within the 2q37.3 microdeletion syndrome locus, and it was previously demonstrated in Felder et al., 2009 that HDLBP expression was downregulated in lymphoblastoid cell lines from a patient with a 3.5 Mb de novo 2q37.3 deletion who presented with autism.

Krishnan Probability Score

Score 0.43729428322959

Ranking 20229/25841 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 0.99999838297068

Ranking 334/18225 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 0.37296207627211

Ranking 247/18665 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 0.088198945992171

Ranking 6369/20870 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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