• 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
WDFY3 (HGNC:20751) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
WD repeat and FYVE domain containing 3
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
No previous names found
Alias symbols
KIAA0993, ALFY, ZFYVE25
%HI
21.08(Read more about the DECIPHER Haploinsufficiency Index)
pLI
1(Read more about gnomAD pLI score)
LOEUF
0.07(Read more about gnomAD LOEUF score)
Cytoband
4q21.23
Genomic Coordinates
GRCh37/hg19: chr4:85590750-85887843 NCBI Ensembl UCSC
GRCh38/hg38: chr4:84669597-84966690 NCBI Ensembl UCSC
MANE Select Transcript
NM_014991.6 ENST00000295888.9 (Read more about MANE Select)
Function
Required for selective macroautophagy (aggrephagy). Acts as an adapter protein by linking specific proteins destined for degradation to the core autophagic machinery members, such as the ATG5- ATG12-ATG16L E3-like ligase, SQSTM1 and LC3 (PubMed:20417604). Along with p62/SQSTM1, involved in the formation and autophagic degradation of cytoplasmic ubiquitin-containing inclusions (p62 bodies, ALIS/aggresome-like induced structures). Along with SQSTM1, required to recruit ubiquitinated proteins to PM... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-26764
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
10/10/2023

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
  • Complex Neurodevelopmental Disorder Monarch
HI Evidence:
  • PUBMED: 31327001
    Le Duc et al., 2019: Exome, genome, and array analysis of 13 individuals with heterozygous variants in WDFY3 and overlapping clinical features including neurodevelopmental delay, intellectual disability, macrocephaly, autism spectrum disorder, and attention deficit/hyperactivity disorder. Two variants were de novo nonsense variants. Three frameshift variants were also identified, including one de novo and two inherited from affected fathers.
  • PUBMED: 27824329
    Wang T et al., 2016. In this study, 189 risk genes were sequenced in 1,543 Chinese ASD probands (1,045 from trios). WDFY3 variants were found in three patients with ASD, including three de novo nonsense variants (p.R978*, p.R1128*, p.Q1760*). The proband with the p.Q1760* WDFY3 de novo nonsense variant has ID and macrocephaly and had severe GI disturbances up to 4 years of age, as well as hyperactivity, sleep problems, attention problems and anxiety.
  • PUBMED: 30564305
    Guo et al., 2018. From probands from the Autism Clinical and Genetic Resources in China phases I and II, sequencing was performed on 187 autism candidate genes in 784 probands, along with sequencing of 85 genes in 599 probands, along with a review of previous cohort studies (Wang 2016 PMID 27824329). One novel de novo, nonsense, likely gene disrupting variant was identified.
HI Evidence Comments:
In addition, Iossifov et al., 2012 (22542183) identified a de novo nonsense variant in WDFY3 (chr4:85719152 T>A, p.R978X) in an affected boy with autism spectrum (family ID 13094) from exome sequencing of 343 families, each with a single child on the autism spectrum and at least one unaffected sibling. Iossifov et al., 2014 (25363768) performed whole exome sequencing on >2500 simplex families, each having a child with an autistic spectrum disorder. In figure 2, two de novo nonsense variants (chr4:85715777:G>A and chr4:85719152:T>A) were found in two male patients with relative low non-verbal IQ. The second nonsense variant was reported previously (Iossifov et. al. 2012, PMID 22542183).

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)

Genomic View

Select assembly: (NC_000004.11) (NC_000004.12)