Human Gene Module / Chromosome 7 / ADCY1

ADCY1adenylate cyclase 1

SFARI Gene Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
4 / 4
Rare Variants / Common Variants
4 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
7p12.3
Associated Disorders
-
Relevance to Autism

A de novo missense variant with a CADD score > 30 was identified in the ADCY1 gene in a Korean ASD proband in Kim et al., 2024; this gene was subsequently classified as an ASD candidate gene in males following a combined TADA analysis consisting of the Korean ASD cohort described in Kim et al., 2024 in addition to the Simons Simplex Collection and the SPARK cohort. A de novo loss-of-function variant and a de novo missense variant in ADCY1 had previously been reported in two SPARK probands (Zhou et al., 2022; Trost et al., 2022).

Molecular Function

This gene encodes a member of the of adenylate cyclase gene family that is primarily expressed in the brain. This protein is regulated by calcium/calmodulin concentration and may be involved in brain development.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to ADCY1 (4 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Exome sequencing of extended families with autism reveals genes shared across neurodevelopmental and neuropsychiatric disorders Cukier HN , et al. (2014) Yes -
2 Support - Zhou X et al. (2022) Yes -
3 Support - Trost B et al. (2022) Yes -
4 Primary - Soo-Whee Kim et al. (2024) Yes -
Rare Variants   (4)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.493C>T p.Gln165Ter stop_gained De novo - - 35982159 Zhou X et al. (2022)
c.1577A>G p.Asn526Ser missense_variant De novo - - 36368308 Trost B et al. (2022)
c.2684G>A p.Arg895Gln missense_variant De novo - - 39334436 Soo-Whee Kim et al. (2024)
c.2818G>A p.Ala940Thr missense_variant Familial - Extended multiplex 24410847 Cukier HN , et al. (2014)
Common Variants  

No common variants reported.

SFARI Gene score
3

Suggestive Evidence

Score Delta: Score remained at 3

criteria met
See SFARI Gene'scoring criteria
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.

10/1/2024
icon
3

Increased from to 3

Krishnan Probability Score

Score 0.59259997573799

Ranking 466/25841 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 0.99990962012557

Ranking 665/18225 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 0.94580712296039

Ranking 16617/18665 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 0.60401143038399

Ranking 78/20870 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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