SFARI Gene release notes for Q2 2017

October 12, 2017

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

Human Gene Module

A total of 29 new genes were added to the Human Gene module, bringing the total number to 910. In depth annotation of 608 rare variants and 64 common variants was also completed, and 95 new references were added. Noteworthy genes added include:


De novo loss-of-function mutations have been identified in the Simons Simplex and MSSNG cohorts, and CIC is very infrequently the target of mutation in unaffected populations (ExAC pLI > 0.9). Deletion of Cic from the developing mouse forebrain results in hyperactivity, impaired learning and memory, and abnormal maturation and maintenance of upper-layer cortical neurons, and deletion from the mouse hypothalamus and medial amygdala results in abnormal social behavior.

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


Multiple de novo missense mutations have been identified in DYNC1H1 in cohorts characterized both by autism and intellectual disability, and are associated with neuronal migration defects resulting in cortical malformations.

Read more here: https://gene.sfari.org/database/human-gene/DYNC1H1


A series of truncating variants in PPM1D was identified in a group of individuals with intellectual disability, with an ASD diagnosis reported in a subset.

Read more here: https://gene.sfari.org/database/human-gene/PPM1D

Gene Scoring module

A total of 45 gene scores were added, including 29 newly annotated genes. Additionally, 10 previously scored genes were moved to a higher category based on recent publications. Another set of five genes were updated with new evidence but did not merit a higher score. Genes with updated scores include CACNA1D, CNOT3, DDX3X, KMT2A, SCN1A, SMARCC2, SRCAP, TBL1XR1, TCF20, and UPF3B. Of note, KMT2A was moved to category 1S, making it a high-confidence ASD risk gene.

For more information on the evidence for TRIP12, see here: https://gene.sfari.org/database/human-gene/KMT2A#score-tab

Copy Number Variant (CNV) module

A total of 16 newly curated references and 24 novel CNV loci were added to the CNV module, resulting in a total of 531 curated references and 2,197 CNV loci.

One reference identified two individuals with de novo deletions at 9q31.2 involving the ASD candidate gene ZNF462, while another reported two ASD probands with de novo deletions at 16q23.2-q23.3, involving CMIP. An additional report identified genes flanking the high-confidence ASD risk gene ANKRD11 as contributing to phenotypic differences observed between cases with ANKRD11-associated KBG syndrome.

Read more here: https://gene.sfari.org/database/cnv/9q31.2
Read more here: https://gene.sfari.org/database/cnv/16q23.2-q23.3
Read more here: https://gene.sfari.org/database/cnv/16q24.3

Animal Models Module

The mouse model dataset was updated with five new genes, including Slc6a1, Camk2a, Usp7, Spast, and Cic. Additionally, many mouse models based on high-confidence genes were added, including Foxp1, Adnp, Pten, Dscam, Shank3, Bcl11a, and Chd8. Sixteen new rescue models were also added, and all told a total of 75 new models were annotated based on 26 references in this quarter.

Mouse model annotation highlights include:

Ube3a overexpression: roles and mechanisms of action in specific cell types and regions of the brain Krishnan et al., 2017)
See https://gene.sfari.org/database/animal-models/genetic-animal-models/UBE3A?Mus musculus

Brain-region-specific roles of Cic in mouse behavior (Lu et al., 2017)
See https://gene.sfari.org/database/animal-models/genetic-animal-models/CIC/Mus musculus

Partial rescue of behavioral deficits by re-expressing Shank3 in adult mice lacking functional Shank3 (Mei et al., 2016)
See https://gene.sfari.org/database/animal-models/genetic-animal-models/SHANK3/Mus musculus

The rat model dataset has been updated with 18 new models and new data for three existing models. The dataset includes 11 new ASD models and three existing models from four existing environmental inducers (lipopolysaccharide, maternal isolation, propionic acid and valproic acid), and seven models from two new inducers (GRP receptor antagonist and polychlorinated biphenyls). Highlights include:

A series of studies explored the effects of injection of gastin releasing peptide receptor (GRPR) blockers on social interaction and other behavioral phenotypes in rats (Presti-Torres et al., 2007, 2012; Merali et al., 2014).
See https://gene.sfari.org/database/animal-models/induced-animal-models/RC3095/Rattus norvegicus

Pre- and post-natal exposure to polychlorinated biphenyls impaired social recognition and social investigation in rats (Jolous-Jamshidi et al., 2010).
See https://gene.sfari.org/database/animal-models/induced-animal-models/PCB/Rattus norvegicus

Injection of proprionic acid affected a range of phenotypes in rats, including social behaviors (Shultz et al., 2008, 2009).
See https://gene.sfari.org/database/animal-models/induced-animal-models/PPA/Rattus norvegicus


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