SFARI Gene Release Notes for Q1 2017

July 10, 2017

Notes prepared by Eric Larsen, Marcel Estevez, Ishita Das, Anjali Sarkar, Ruei-Chiuan Lin, Wayne Pereanu, Ravi Kollu, and Sharmila Banerjee-Basu of MindSpec, Inc., and edited by Alan Packer of SFARI.

Human Gene Module

A total of 22 new genes were added to the Human Gene module, bringing the total number to 881. In-depth annotation of 436 rare variants and 26 common variants was also completed, and 98 new references were added. Noteworthy genes added include:


Homozygous loss-of-function missense variants in this gene were identified in two consanguineous families, with affected individuals displaying ASD, delays in gross motor, fine motor, and social milestones, delayed or absent language, microcephaly, and seizures. Deletion of Slc7a5 from the endothelial cells of the blood-brain barrier in mice resulted in an atypical amino acid profile in the brain, abnormal mRNA translation, reduced mini inhibitory postsynaptic current frequency in pyramidal cells of the somatosensory cortex and cerebellar Purkinje cells, and abnormalities in social interaction.

Read more here: https://gene.sfari.org/database/human-gene/SLC7A5


Whole-exome sequencing of five families in which second- and third-degree relatives were affected with autism identified a novel private missense variant exhibiting partial loss-of-function effects. An excess of rare missense variants in the same region of the protein was subsequently observed in a case-control mutation burden study of more than 1,000 familial cases.

Read more here: https://gene.sfari.org/database/human-gene/SCN9A


Six de novo deletions and four de novo loss-of-function point mutations in PSMD12 were identified in unrelated individuals presenting with a syndromic neurodevelopmental disorder characterized by intellectual disability. Of the four with point mutations, two were diagnosed with autism or ASD.

Read more here: https://gene.sfari.org/database/human-gene/PSMD12

Gene Scoring Module

A total of 39 gene scores were added, including 22 newly annotated genes. Additionally, eight previously scored genes were moved to a higher category based on recent publications. Another set of eight genes was updated with new evidence but did not merit a higher score. Genes with updated scores include TRIP12, NAA15, IQSEC2, KATNAL2, PARD3B, RELN, SOX5, and TNRCB. Newly scored genes include SLC7A5, SCN9A, AVPR1B, STAG1, CAMK2A, CNKSR2, CNOT3, PSMD12, NACC1, UNC13A, and HDC. Of note, TRIP12 was moved to category 1, making it a high-confidence ASD risk gene. For more information on the evidence for TRIP12, click here:


Copy Number Variant (CNV) Module

A total of 12 newly curated references and one novel CNV locus were added to the CNV module, resulting in a total of 515 curated references and 2,177 CNV loci.

Two references described multigenic deletions observed in cases with syndromic intellectual disability in which the minimal region of overlap of the deletions involved two new ASD candidate genes (STAG1 and PSMD12). Other highlights include a report describing a 15q11.2-q13.1 microduplication identified in three individuals with an ASD diagnosis, as well as reports identifying novel neurodevelopmental disorder cases with deletions of ASD risk genes such as TOP3B and SHANK2.

Follow these links to learn more:

Animal Models Module

The mouse model dataset was updated with five new genes, including Bckdk, Slc7a5, Hdc, Srrm4, and Tcf4. Additionally, 10 existing genes in the module were updated with new information: Shank2, Grin2b, Ash1l, Mef2c, Magel2, Cntnap2, Slc6a4, Pten, Foxp2, and Chd7. Four new inducers were also added to the database: in utero exposure to Cntnap2-specific antibodies, maternal immune activation by lipopolysaccharide (LPS), fluoxetine, and allergy to cow milk protein (casein, CMA). The existing inbred strain BTBR was also updated. All told, a total of 62 new models were annotated based on 22 references in this quarter.

Mouse model annotation highlights include:

The rat model dataset has been updated with 35 new models and new data for three existing models. There are 14 models from five new genes (Cntnap2, Hcn1, Shank3, Slc6a3 and Tcf4) and one existing genetic model (Nrxn1). The dataset also includes seven new models and one existing model from two existing environmental inducers (maternal isolation and valproic acid), and 10 models from three new inducers (HCN1 channel antagonist, amygdala inactivation, and hippocampus inactivation). These data were annotated from 13 references. Highlights include:

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