Human Gene Module / Chromosome 10 / WDR37

WDR37WD repeat domain 37

SFARI Gene Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
3 / 6
Rare Variants / Common Variants
14 / 0
Aliases
-
Associated Syndromes
Neurooculocardiogenitourinary syndrome, DD, ID, ep, Neurooculocardiogenitourinary syndrome, DD, epilep
Chromosome Band
10p15.3
Associated Disorders
-
Relevance to Autism

De novo missense variants in the WDR37 gene have been identified in ASD probands from the Simons Simplex Collection and the BARAKA-Qatar Study (Iossifov et al., 2014; Abdi et al., 2023). One of the three individuals with neurooculocardiogenitourinary syndrome described in Sorokina et al., 2021 was reported to have been diagnosed with autism; in the same report, WDR37 was shown to interact with PACS1 and PACS2, two genes that are responsible for neurodevelopmental disorders in which a subset of affected individuals display autism spectrum disorder (Schuurs-Hoeijmakers syndrome and developmental and epileptic encephalopathy-66, respectively).

Molecular Function

This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. De novo heterozygous missense variants in this gene are responsible for neurooculocardiogenitourinary syndrome (NOCGUS; OMIM 618652), a multisystem disorder characterized by poor growth and anomalies of the ocular, craniofacial, neurologic, cardiovascular, genitourinary, skeletal, and gastrointestinal systems (Kanca et al., 2019; Reis et al., 2019; Sorokina et al., 2021).

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to WDR37 (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 - Oguz Kanca et al. (2019) No -
3 Support - Linda M Reis et al. (2019) No -
4 Support - Elena A Sorokina et al. (2021) No ASD
5 Support - Zhou X et al. (2022) Yes -
6 Primary - Mona Abdi et al. (2023) Yes DD, ID, epilepsy/seizures
Rare Variants   (14)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.795C>T p.Ser265= synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.377A>T p.Tyr126Phe missense_variant De novo - - 37805537 Mona Abdi et al. (2023)
c.356C>T p.Ser119Phe missense_variant De novo - - 31327508 Oguz Kanca et al. (2019)
c.374C>T p.Thr125Ile missense_variant De novo - - 31327508 Oguz Kanca et al. (2019)
c.386C>G p.Ser129Cys missense_variant De novo - - 31327508 Oguz Kanca et al. (2019)
c.389C>T p.Thr130Ile missense_variant De novo - - 31327508 Oguz Kanca et al. (2019)
c.356C>T p.Ser119Phe missense_variant De novo - - 31327510 Linda M Reis et al. (2019)
c.374C>T p.Thr125Ile missense_variant De novo - - 31327510 Linda M Reis et al. (2019)
c.386C>G p.Ser129Cys missense_variant De novo - - 31327510 Linda M Reis et al. (2019)
c.389C>T p.Thr130Ile missense_variant De novo - - 31327510 Linda M Reis et al. (2019)
c.20G>A p.Ser7Asn missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.659A>G p.Asp220Gly missense_variant De novo - Simplex 34642815 Elena A Sorokina et al. (2021)
c.778G>A p.Asp260Asn missense_variant De novo - Simplex 34642815 Elena A Sorokina et al. (2021)
c.770C>A p.Pro257His missense_variant Familial Maternal Simplex 34642815 Elena A Sorokina et al. (2021)
Common Variants  

No common variants reported.

SFARI Gene score
3

Suggestive Evidence

Score Delta: Score remained at 3

criteria met
See SFARI Gene'scoring criteria
3

Suggestive Evidence

See all Category 3 Genes

The literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as "acc" in the score cards) could also boost a gene from category 4 to 3.

1/1/2024
icon
3

Increased from to 3

Krishnan Probability Score

Score 0.49051446029431

Ranking 6084/25841 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 0.99676680299997

Ranking 1388/18225 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 0.92881938054143

Ranking 11010/18665 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 0.50344550483274

Ranking 501/20870 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