Human Gene Module / Chromosome 4 / CD38

CD38CD38 molecule

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
5 / 10
Rare Variants / Common Variants
3 / 10
Aliases
CD38, T10
Associated Syndromes
-
Chromosome Band
4p15.32
Associated Disorders
-
Relevance to Autism

Genetic association has been found between the CD38 gene and ASD in a high-functioning U.S. AGRE cohort as well as a smaller Japanese cohort (Munesue et al., 2010). In addition, a significant reduction in CD38 expression was seen in ASD subjects compared to their "unaffected" parents, and genetic association was found with several CD38 haplotypes and ASD in an Israeli population cohort (Lerer et al., 2010).

Molecular Function

CD38 is a novel multifunctional ectoenzyme widely expressed in cells and tissues especially in leukocytes. CD38 also functions in cell adhesion, signal transduction and calcium signaling. CD38 synthesizes cyclic ADP-ribose, a second messenger for glucose-induced insulin secretion. CD38 also has cADPr hydrolase activity and moonlights as a receptor in cells of the immune system.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
Mouse
Entrez GeneMouse Genome InformaticsAllen Brain Atlas
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to CD38 (10 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Two genetic variants of CD38 in subjects with autism spectrum disorder and controls Munesue T , et al. (2010) Yes -
2 Positive Association Low CD38 expression in lymphoblastoid cells and haplotypes are both associated with autism in a family-based study Lerer E , et al. (2010) Yes -
3 Recent Recommendation Effects of a common variant in the CD38 gene on social processing in an oxytocin challenge study: possible links to autism Sauer C , et al. (2012) No -
4 Recent Recommendation Social memory, amnesia, and autism: brain oxytocin secretion is regulated by NAD+ metabolites and single nucleotide polymorphisms of CD38 Higashida H , et al. (2012) No -
5 Support A deletion involving CD38 and BST1 results in a fusion transcript in a patient with autism and asthma Ceroni F , et al. (2014) Yes Asthma
6 Support Impaired learning and memory in CD38 null mutant mice Kim S , et al. (2016) No -
7 Recent Recommendation CD38 is Required for Dendritic Organization in Visual Cortex and Hippocampus Nelissen TP , et al. (2018) No -
8 Support De novo single-nucleotide and copy number variation in discordant monozygotic twins reveals disease-related genes Vadgama N , et al. (2019) Yes -
9 Positive association Preliminary Evidence That CD38 Moderates the Association of Neuroticism on Amygdala-Subgenual Cingulate Connectivity Tabak BA , et al. (2020) No -
10 Support - Zhou X et al. (2022) Yes -
Rare Variants   (3)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss Familial Maternal Multiplex 24634087 Ceroni F , et al. (2014)
c.352C>A p.Pro118Thr missense_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
- - copy_number_gain De novo - Multiplex (monozygotic twins) 30886340 Vadgama N , et al. (2019)
Common Variants   (10)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.660-810A>G - intron_variant - - - 21182206 Lerer E , et al. (2010)
c.*105T>G - 3_prime_UTR_variant - - - 21182206 Lerer E , et al. (2010)
c.*460C>T - 3_prime_UTR_variant - - - 21182206 Lerer E , et al. (2010)
c.363+285G>A C/T intron_variant - - - 21182206 Lerer E , et al. (2010)
c.840-176G>T A/C intron_variant - - - 21182206 Lerer E , et al. (2010)
c.233+5389C>T G/A intron_variant - - - 21182206 Lerer E , et al. (2010)
c.364-2437G>C C/G intron_variant - - - 21182206 Lerer E , et al. (2010)
c.840-176G>T A/C intron_variant - - - 20435366 Munesue T , et al. (2010)
c.234-3212C>T T/C intron_variant - - - 20435366 Munesue T , et al. (2010)
c.418C>T p.Arg140Trp missense_variant - - - 20435366 Munesue T , et al. (2010)
SFARI Gene score
2

Strong Candidate

Genetic association has been found between the CD38 gene and ASD in a high-functioning U.S. AGRE cohort as well as a smaller Japanese cohort (Munesue et al., 2010). In addition, a significant reduction in CD38 expression was seen in ASD subjects compared to their "unaffected" parents, and genetic association was found with several CD38 haplotypes and ASD in an Israeli population cohort (Lerer et al., 2010). Sauer et al., 2012 demonstrated that a common variant in CD38 affected social processing in an oxytocin challenge study in healthy males, while Higashida et al., 2012 showed that a different common variant in CD38 regulated A maternally-inherited deletion involving the CD38 and BST1 genes that results in a fusion transcript and apparent reduction in CD38 levels was identified in a female patient with autism and asthma; this deletion was mosaic in her unaffected mother and was not present in her less severely affected sister, and no similar deletions were observed in controls or DGV. CD38-knockout mice have been shown to exhibit changes in social behavior and ultrasonic vocalizations (Jin et al., 2007; Higashida et al., 2011).

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

Genetic association has been found between the CD38 gene and ASD in a high-functioning U.S. AGRE cohort as well as a smaller Japanese cohort (Munesue et al., 2010). In addition, a significant reduction in CD38 expression was seen in ASD subjects compared to their "unaffected" parents, and genetic association was found with several CD38 haplotypes and ASD in an Israeli population cohort (Lerer et al., 2010). Sauer et al., 2012 demonstrated that a common variant in CD38 affected social processing in an oxytocin challenge study in healthy males, while Higashida et al., 2012 showed that a different common variant in CD38 regulated A maternally-inherited deletion involving the CD38 and BST1 genes that results in a fusion transcript and apparent reduction in CD38 levels was identified in a female patient with autism and asthma; this deletion was mosaic in her unaffected mother and was not present in her less severely affected sister, and no similar deletions were observed in controls or DGV. CD38-knockout mice have been shown to exhibit changes in social behavior and ultrasonic vocalizations (Jin et al., 2007; Higashida et al., 2011).

1/1/2020
3
icon
3

Decreased from 3 to 3

Description

Genetic association has been found between the CD38 gene and ASD in a high-functioning U.S. AGRE cohort as well as a smaller Japanese cohort (Munesue et al., 2010). In addition, a significant reduction in CD38 expression was seen in ASD subjects compared to their "unaffected" parents, and genetic association was found with several CD38 haplotypes and ASD in an Israeli population cohort (Lerer et al., 2010). Sauer et al., 2012 demonstrated that a common variant in CD38 affected social processing in an oxytocin challenge study in healthy males, while Higashida et al., 2012 showed that a different common variant in CD38 regulated A maternally-inherited deletion involving the CD38 and BST1 genes that results in a fusion transcript and apparent reduction in CD38 levels was identified in a female patient with autism and asthma; this deletion was mosaic in her unaffected mother and was not present in her less severely affected sister, and no similar deletions were observed in controls or DGV. CD38-knockout mice have been shown to exhibit changes in social behavior and ultrasonic vocalizations (Jin et al., 2007; Higashida et al., 2011).

Reports Added
[Preliminary Evidence That CD38 Moderates the Association of Neuroticism on Amygdala-Subgenual Cingulate Connectivity.2020]
10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Genetic association has been found between the CD38 gene and ASD in a high-functioning U.S. AGRE cohort as well as a smaller Japanese cohort (Munesue et al., 2010). In addition, a significant reduction in CD38 expression was seen in ASD subjects compared to their "unaffected" parents, and genetic association was found with several CD38 haplotypes and ASD in an Israeli population cohort (Lerer et al., 2010). Sauer et al., 2012 demonstrated that a common variant in CD38 affected social processing in an oxytocin challenge study in healthy males, while Higashida et al., 2012 showed that a different common variant in CD38 regulated A maternally-inherited deletion involving the CD38 and BST1 genes that results in a fusion transcript and apparent reduction in CD38 levels was identified in a female patient with autism and asthma; this deletion was mosaic in her unaffected mother and was not present in her less severely affected sister, and no similar deletions were observed in controls or DGV. CD38-knockout mice have been shown to exhibit changes in social behavior and ultrasonic vocalizations (Jin et al., 2007; Higashida et al., 2011).

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

Decreased from 4 to 4

Description

Genetic association has been found between the CD38 gene and ASD in a high-functioning U.S. AGRE cohort as well as a smaller Japanese cohort (Munesue et al., 2010). In addition, a significant reduction in CD38 expression was seen in ASD subjects compared to their "unaffected" parents, and genetic association was found with several CD38 haplotypes and ASD in an Israeli population cohort (Lerer et al., 2010). Sauer et al., 2012 demonstrated that a common variant in CD38 affected social processing in an oxytocin challenge study in healthy males, while Higashida et al., 2012 showed that a different common variant in CD38 regulated A maternally-inherited deletion involving the CD38 and BST1 genes that results in a fusion transcript and apparent reduction in CD38 levels was identified in a female patient with autism and asthma; this deletion was mosaic in her unaffected mother and was not present in her less severely affected sister, and no similar deletions were observed in controls or DGV. CD38-knockout mice have been shown to exhibit changes in social behavior and ultrasonic vocalizations (Jin et al., 2007; Higashida et al., 2011).

Reports Added
[De novo single-nucleotide and copy number variation in discordant monozygotic twins reveals disease-related genes.2019]
7/1/2018
icon
4

Increased from to 4

Description

Genetic association has been found between the CD38 gene and ASD in a high-functioning U.S. AGRE cohort as well as a smaller Japanese cohort (Munesue et al., 2010). In addition, a significant reduction in CD38 expression was seen in ASD subjects compared to their "unaffected" parents, and genetic association was found with several CD38 haplotypes and ASD in an Israeli population cohort (Lerer et al., 2010). Sauer et al., 2012 demonstrated that a common variant in CD38 affected social processing in an oxytocin challenge study in healthy males, while Higashida et al., 2012 showed that a different common variant in CD38 regulated A maternally-inherited deletion involving the CD38 and BST1 genes that results in a fusion transcript and apparent reduction in CD38 levels was identified in a female patient with autism and asthma; this deletion was mosaic in her unaffected mother and was not present in her less severely affected sister, and no similar deletions were observed in controls or DGV. CD38-knockout mice have been shown to exhibit changes in social behavior and ultrasonic vocalizations (Jin et al., 2007; Higashida et al., 2011).

Krishnan Probability Score

Score 0.4424717286056

Ranking 17453/25841 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 7.6567079832956E-5

Ranking 13242/18225 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 0.94719802610844

Ranking 17178/18665 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
Larsen Cumulative Evidence Score

Score 51

Ranking 31/461 scored genes


[Show Scoring Methodology]
Larsen and colleagues generated gene scores based on the sum of evidence for all available ASD-associated variants in a gene, with assessments based on mode of inheritance, effect size, and variant frequency in the general population. The approach was first presented in Mol Autism 7:44 (2016), and scores for 461 genes can be found in column I in supplementary table 4 from that paper.
Original Source
Zhang D Score

Score -0.51600500236664

Ranking 19385/20870 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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