Human Gene Module / Chromosome 6 / SCGN

SCGNsecretagogin, EF-hand calcium binding protein

SFARI Gene Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
4 / 4
Rare Variants / Common Variants
3 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
6p22.2
Associated Disorders
-
Relevance to Autism

Whole-exome sequencing in a cohort of 168 Chinese ASD probands in Liu et al., 2022 identified two male probands with maternally-inherited variants in the SCGN gene; one of these variants was a missense variant (p.Arg79Trp) that was experimentally shown to fail to rescue neuronal morphology defects in scgn-deficient zebrafish. In the same report, deletion of Scgn in zebrafish or mice resulted in autism-like behaviors and impaired brain development, as well as disrupted oxytocin signalling and an abnormal activation in inflammation. A de novo loss-of-function variant in the SCGN gene was identified in a male ASD proband from a multiplex family from the MSSNG cohort (Zhou et al., 2022). Reduced plasma secretagogin (SCGN) levels had previously been reported in children with ASD compared to age- and gender-matched healthy controls in Alhowikan et al., 2017.

Molecular Function

he encoded protein is a secreted calcium-binding protein which is found in the cytoplasm. It is related to calbindin D-28K and calretinin. This protein is thought to be involved in KCL-stimulated calcium flux and cell proliferation.

External Links
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Human
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Mouse
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SFARI Genomic Platforms
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Reports related to SCGN (4 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support - Alhowikan AM et al. (2017) Yes -
2 Support - Zhou X et al. (2022) Yes -
3 Primary - Liu Z et al. (2023) Yes DD
4 Support - Wang QW et al. (2023) Yes -
Rare Variants   (3)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.702+2T>G - splice_site_variant Familial Maternal - 36588101 Liu Z et al. (2023)
c.235C>T p.Arg79Trp missense_variant Familial Maternal - 36588101 Liu Z et al. (2023)
c.146del p.Gly49ValfsTer7 frameshift_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
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.

4/1/2023
icon
3

Increased from to 3

Krishnan Probability Score

Score 0.49657071926893

Ranking 2564/25841 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 0.035946002284876

Ranking 8892/18225 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 0.91742526810842

Ranking 8647/18665 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 -0.13042059487244

Ranking 13502/20870 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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