Aliases: IMP2, PSH1, PSL4, PRO4332, MDHV1887
Chromosome No: 12
Chromosome Band: 12q24.31
Genetic Category: Functional-Rare single gene variant-Rare single gene variant/Functional
ASD Reports: 5
Recent Reports: 0
Annotated variants: 4
Associated CNVs: 5
Evidence score: 3
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Relevance to Autism
Whole-genome sequencing of 3109 samples across 1033 Chinese ASD families from the ACGC cohort in Tan et al., 2026 identified two de novo missense variants in the SPPL3 gene that were predicted to be damaging with MPC scores > 2;; subsequent functional assessment of these two variants and a third de novo missense variant previously identified in an ASD proband from the Autism Sequencing Consortium found that all three variants resulted in disrupted Golgi targeting. A de novo loss-of-function variant in SPPL3 was previously identified in a Japanese ASD proband in Takata et al., 2018. TADA analysis of the ACGC cohort, as well as of an integrated cohort of over 40,000 ASD cases across unpublished and published global cohorts, in Tan et al., 2026 identified SPPL3 as an ASD risk gene with a false discovery rate of <0.05.
Molecular Function
Enables aspartic endopeptidase activity, intramembrane cleaving and protein homodimerization activity. Involved in T cell receptor signaling pathway; membrane protein proteolysis; and positive regulation of calcineurin-NFAT signaling cascade. Located in Golgi-associated vesicle membrane; endoplasmic reticulum; and plasma membrane.
External Links
