Human Gene Module / Chromosome 10 / PDZD8

PDZD8PDZ domain containing 8

SFARI Gene Score
S
Syndromic Syndromic
Autism Reports / Total Reports
2 / 4
Rare Variants / Common Variants
6 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
10q25.3-q26.11
Associated Disorders
-
Relevance to Autism

Al-Amri et al., 2022 identified homozygous truncating mutations in the PDZD8 gene in two independent consanguineous families from the Arabian peninsula in which affected individuals presented with syndromic intellectual disability with autistic features; furthermore, mice homozygous for a premature truncation codon in Pdzd8 exhibited restricted growth, structural brain alterations, spontaneous stereotypic behavior, decreased anxiety-like behavior, and impairments in long-term spatial memory and TBS-induced long term potentiation, while Drosphila melanogaster with knockdown of the PDZD8 ortholog exhibited impaired long-term courtship-based memory.

Molecular Function

Predicted to enable lipid binding activity and metal ion binding activity. Involved in several processes, including mitochondrial calcium ion homeostasis; mitochondrion-endoplasmic reticulum membrane tethering; and regulation of cell morphogenesis. Located in endoplasmic reticulum membrane and mitochondria-associated endoplasmic reticulum membrane. In neurons, involved in the regulation of dendritic Ca2+ dynamics by regulating mitochondrial Ca2+ uptake in neurons (Hirabayashi et al., 2017).

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to PDZD8 (4 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support - Hirabayashi Y et al. (2017) No -
2 Primary - Al-Amri AH et al. (2022) No ADHD, OCD, epilepsy/seizures
3 Support - Zhou X et al. (2022) Yes -
4 Support - Soo-Whee Kim et al. (2024) Yes -
Rare Variants   (6)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.517G>A p.Glu173Lys missense_variant De novo - - 39334436 Soo-Whee Kim et al. (2024)
c.1276T>C p.Ser426Pro missense_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.2977C>T p.Arg993Trp missense_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.3449C>T p.Pro1150Leu missense_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.894C>G p.Tyr298Ter stop_gained Familial Both parents Simplex 35227461 Al-Amri AH et al. (2022)
c.2197_2200del p.Ser733Ter frameshift_variant Familial Both parents Multiplex 35227461 Al-Amri AH et al. (2022)
Common Variants  

No common variants reported.

SFARI Gene score
S

Syndromic

Animal model

Score Delta: Score remained at S

criteria met
See SFARI Gene'scoring criteria
S

Syndromic

See all Category S Genes

The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."

Krishnan Probability Score

Score 0.44592515591005

Ranking 15121/25841 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 0.99726355740728

Ranking 1338/18225 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 0.94441127781794

Ranking 16065/18665 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 -0.18257533282565

Ranking 15031/20870 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
Submit New Gene

Report an Error