Human Gene Module / Chromosome 1 / ZFYVE9

ZFYVE9zinc finger FYVE-type containing 9

SFARI Gene Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
5 / 6
Rare Variants / Common Variants
6 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
1p32.3
Associated Disorders
-
Relevance to Autism

Functional assessment of de novo 5'UTR variants identified in ASD probands from the Simons Simplex Collection (SSC) by massively parallel reporter assay (MPRA) using polysomes from cell lines in Plassmeyer et al., 2025 reported an ASD-associated 5'UTR variant in the ZFYVE9 gene that resulted in a significant effect on 40S-total RNA enrichment in in cellulo MPRA studies in HEK cells, as well as increased protein expression in a dual-luciferase reporter assay (FDR-adjusted p-value < 0.05). Several de novo variants in this gene, including a de novo loss-of-function variant and a de novo missense variant that was predicted to be deleterious by CADD and REVEL, have been identified in ASD probands from the Simons Simplex Collection and the SPARK cohort (Iossifov et al., 2014; Zhou et al., 2022).

Molecular Function

This gene encodes a double zinc finger motif-containing protein that participates in the transforming growth factor-beta (TGFB) signalling pathway. The encoded protein interacts directly with SMAD2 and SMAD3, and recruits SMAD2 to the TGFB receptor. Suppresion of Zfyve9 in the developing mouse brain resulted in impaired neuronal orientation and migration across the intermediate zone, as well as increased surface expression of the L1 cell adhesion molecule in Zfyve9-suppressed neurons (Mestres et al., 2016).

SFARI Genomic Platforms
Reports related to ZFYVE9 (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
2 Support - Iván Mestres et al. (2016) No -
3 Support - Zhou X et al. (2022) Yes -
4 Support - Cirnigliaro M et al. (2023) Yes -
5 Support - Ashlesha Gogate et al. (2024) Yes -
6 Primary - Stephen P Plassmeyer et al. (2025) Yes -
Rare Variants   (6)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.2258G>A p.Cys753Tyr missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.1461T>G p.Gly487= synonymous_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.-162G>A - 5_prime_UTR_variant De novo - Simplex 41344325 Stephen P Plassmeyer et al. (2025)
c.1276dup p.Ser426LysfsTer4 frameshift_variant De novo - Unknown 35982159 Zhou X et al. (2022)
c.2642T>A p.Phe881Tyr missense_variant Unknown - Simplex 39632905 Ashlesha Gogate et al. (2024)
c.133_134insTG p.His45LeufsTer13 frameshift_variant Familial Paternal Simplex 37506195 Cirnigliaro M et al. (2023)
Common Variants  

No common variants reported.

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