Human Gene Module / Chromosome 10 / ZMYND11

ZMYND11Zinc finger, MYND-type containing 11

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
5 / 15
Rare Variants / Common Variants
53 / 0
Aliases
ZMYND11, RP11-486H9.1,  BRAM1,  BS69
Associated Syndromes
-
Chromosome Band
10p15.3
Associated Disorders
ID, ASD
Relevance to Autism

A de novo LoF variant (splice-site) was identified in a simplex ASD case from the Simons Simplex Collection (Iossifov et al., 2012). More recently, five loss-of-function variants, one of which was de novo in origin and one which was inherited from a similarly affected parent, were identified in patients from DD/ID cohorts; one of these patients also presented with pervasive developmental disorder, and other patients presented with social difficulties and/or behavioral problems (Coe et al., 2014).

Molecular Function

Chromatin reader that specifically recognizes and binds histone H3.3 trimethylated at 'Lys-36' (H3.3K36me3) and regulates RNA polymerase II elongation. Colocalizes with highly expressed genes and functions as a transcription corepressor by modulating RNA polymerase II at the elongation stage. Acts as a tumor-suppressor by repressing a transcriptional program essential for tumor cell growth.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to ZMYND11 (15 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary De novo gene disruptions in children on the autistic spectrum Iossifov I , et al. (2012) Yes -
2 Recent Recommendation Refining analyses of copy number variation identifies specific genes associated with developmental delay Coe BP , et al. (2014) No ASD
3 Support A de novo mutation in ZMYND11, a candidate gene for 10p15.3 deletion syndrome, is associated with syndromic intellectual disability Cobben JM , et al. (2014) No -
4 Support Large-scale discovery of novel genetic causes of developmental disorders Deciphering Developmental Disorders Study (2014) No -
5 Recent Recommendation Low load for disruptive mutations in autism genes and their biased transmission Iossifov I , et al. (2015) Yes -
6 Support Mutations in HECW2 are associated with intellectual disability and epilepsy Halvardson J , et al. (2016) Yes -
7 Recent Recommendation Genome-wide association study of behavioral, physiological and gene expression traits in outbred CFW mice Parker CC , et al. (2016) No -
8 Support A de novo missense mutation in ZMYND11 is associated with global developmental delay, seizures, and hypotonia Moskowitz AM , et al. (2016) No -
9 Support Using medical exome sequencing to identify the causes of neurodevelopmental disorders: Experience of 2 clinical units and 216 patients Chrot E , et al. (2017) No Macrocephaly
10 Support Exome Pool-Seq in neurodevelopmental disorders Popp B , et al. (2017) No Macrocephaly, hypotonia, aggression
11 Support ZMYND11-related syndromic intellectual disability: 16 patients delineating and expanding the phenotypic spectrum Yates TM , et al. (2020) No ASD or autistic features
12 Support Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders Wang T et al. (2020) Yes ID
13 Support - Oates S et al. (2021) No ASD, ADHD, ID
14 Support - Amerh S Alqahtani et al. (2023) Yes -
15 Support - Axel Schmidt et al. (2024) No -
Rare Variants   (53)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - stop_gained De novo - Simplex 32097528 Yates TM , et al. (2020)
c.22C>T p.Arg8Ter stop_gained De novo - - 34216016 Oates S et al. (2021)
c.997-1G>A - splice_site_variant Unknown - - 33004838 Wang T et al. (2020)
c.82C>T p.Gln28Ter stop_gained De novo - - 34216016 Oates S et al. (2021)
c.466C>T p.Gln156Ter stop_gained Unknown - - 33004838 Wang T et al. (2020)
c.1159-1G>A - splice_site_variant Unknown - - 33004838 Wang T et al. (2020)
c.8G>A p.Arg3His missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.1159-2A>G - splice_site_variant De novo - - 34216016 Oates S et al. (2021)
c.1687-1G>A - splice_site_variant De novo - - 34216016 Oates S et al. (2021)
c.848T>C p.Leu283Pro missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.850G>C p.Val284Leu missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.76C>T p.Arg26Trp missense_variant De novo - - 28708303 Chrot E , et al. (2017)
c.1799G>A p.Arg600Gln missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.926G>A p.Arg309His missense_variant De novo - - 34216016 Oates S et al. (2021)
c.1724G>A p.Cys575Tyr missense_variant De novo - - 34216016 Oates S et al. (2021)
c.1793G>C p.Cys598Ser missense_variant De novo - - 34216016 Oates S et al. (2021)
c.8G>A p.Arg3His missense_variant Unknown - Simplex 33004838 Wang T et al. (2020)
c.976C>T p.Gln326Ter stop_gained Unknown - Unknown 25217958 Coe BP , et al. (2014)
c.117-2A>T - splice_site_variant Unknown - Simplex 32097528 Yates TM , et al. (2020)
c.7C>T p.Arg3Cys missense_variant Familial Maternal - 33004838 Wang T et al. (2020)
c.709C>T p.Gln237Ter stop_gained De novo - Multiplex 34216016 Oates S et al. (2021)
c.630C>G p.Tyr210Ter stop_gained De novo - Simplex 32097528 Yates TM , et al. (2020)
c.1089G>A p.Trp363Ter stop_gained De novo - Simplex 32097528 Yates TM , et al. (2020)
c.570G>T p.Arg190Ser missense_variant Unknown - - 39039281 Axel Schmidt et al. (2024)
c.803G>A p.Arg268His missense_variant Unknown - Simplex 33004838 Wang T et al. (2020)
c.1159-1G>A - splice_site_variant De novo - Simplex 22542183 Iossifov I , et al. (2012)
c.1053G>A p.Glu351= missense_variant De novo - Simplex 32097528 Yates TM , et al. (2020)
c.1685G>C p.Trp562Ser missense_variant Familial Maternal - 34216016 Oates S et al. (2021)
c.1129del p.Ser377ProfsTer11 frameshift_variant De novo - - 34216016 Oates S et al. (2021)
c.1720T>C p.Cys574Arg missense_variant De novo - Simplex 32097528 Yates TM , et al. (2020)
c.581_582del p.Thr194MetfsTer3 frameshift_variant De novo - - 33004838 Wang T et al. (2020)
c.744_745del p.Cys249SerfsTer2 frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.1379dup p.Asn460LysfsTer2 frameshift_variant De novo - - 32097528 Yates TM , et al. (2020)
c.1798C>T p.Arg600Trp missense_variant De novo - Simplex 25281490 Cobben JM , et al. (2014)
c.737_738del p.Lys246ArgfsTer5 frameshift_variant Unknown - - 34216016 Oates S et al. (2021)
c.1531C>T p.Gln511Ter stop_gained Familial Paternal Simplex 32097528 Yates TM , et al. (2020)
c.1636C>T p.Arg546Trp missense_variant De novo - Simplex 27334371 Halvardson J , et al. (2016)
c.1262G>A p.Ser421Asn missense_variant De novo - Simplex 27626064 Moskowitz AM , et al. (2016)
c.1597del p.Gln533ArgfsTer59 inframe_deletion De novo - Unknown 25217958 Coe BP , et al. (2014)
c.1084del p.Glu362LysfsTer3 frameshift_variant Unknown - Unknown 25217958 Coe BP , et al. (2014)
c.1155_1158del p.Thr386ArgfsTer3 frameshift_variant Unknown - - 32097528 Yates TM , et al. (2020)
c.1332_1333del p.Lys446AlafsTer4 frameshift_variant Unknown - - 32097528 Yates TM , et al. (2020)
c.1756C>T p.Gln586Ter stop_gained Familial Maternal Multiplex 32097528 Yates TM , et al. (2020)
c.701_704del p.Asp234ValfsTer54 frameshift_variant Unknown - - 39039281 Axel Schmidt et al. (2024)
c.1129del p.Ser377ProfsTer11 frameshift_variant De novo - Simplex 32097528 Yates TM , et al. (2020)
c.292_293insC p.Asn98ThrfsTer26 frameshift_variant Unknown - Unknown 25217958 Coe BP , et al. (2014)
c.456_459del p.Asn152LysfsTer22 frameshift_variant De novo - Simplex 32097528 Yates TM , et al. (2020)
c.876_882del p.Phe293GlnfsTer43 frameshift_variant Unknown - - 37799141 Amerh S Alqahtani et al. (2023)
c.399del p.Met133IlefsTer19 frameshift_variant Familial Paternal Simplex 25217958 Coe BP , et al. (2014)
c.383del p.Ser128LeufsTer42 frameshift_variant Familial Paternal Simplex 29158550 Popp B , et al. (2017)
c.1581dup p.Cys528MetfsTer2 frameshift_variant Familial Maternal Multiplex 34216016 Oates S et al. (2021)
NM_006624.5:g.255918dup p.Thr70AsnfsTer12 frameshift_variant De novo - Unknown 25217958 Coe BP , et al. (2014)
c.1798C>T p.Arg600Trp missense_variant De novo - Unknown 25533962 Deciphering Developmental Disorders Study (2014)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

A de novo LoF variant in the ZMYND11 gene was identified in an ASD proband from the Simons Simplex Collection (PMID 22542183). Loss-of-function variants in this gene have also been identified in patients with developmental delay/intellectual disability, many of whom present with social difficulties and/or other behavioral problems (PMID 25217958).

Score Delta: Score remained at 2

criteria met
See SFARI Gene'scoring criteria
2

Strong Candidate

See all Category 2 Genes

We considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.

10/1/2020
2
icon
2

Score remained at 2

Description

A de novo LoF variant in the ZMYND11 gene was identified in an ASD proband from the Simons Simplex Collection (PMID 22542183). Loss-of-function variants in this gene have also been identified in patients with developmental delay/intellectual disability, many of whom present with social difficulties and/or other behavioral problems (PMID 25217958).

Reports Added
[Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders2020]
1/1/2020
2
icon
2

Score remained at 2

Description

A de novo LoF variant in the ZMYND11 gene was identified in an ASD proband from the Simons Simplex Collection (PMID 22542183). Loss-of-function variants in this gene have also been identified in patients with developmental delay/intellectual disability, many of whom present with social difficulties and/or other behavioral problems (PMID 25217958).

Reports Added
[ZMYND11-related syndromic intellectual disability: 16 patients delineating and expanding the phenotypic spectrum.2020]
10/1/2019
3
icon
2

Decreased from 3 to 2

New Scoring Scheme
Description

A de novo LoF variant in the ZMYND11 gene was identified in an ASD proband from the Simons Simplex Collection (PMID 22542183). Loss-of-function variants in this gene have also been identified in patients with developmental delay/intellectual disability, many of whom present with social difficulties and/or other behavioral problems (PMID 25217958).

Reports Added
[New Scoring Scheme]
10/1/2017
3
icon
3

Decreased from 3 to 3

Description

A de novo LoF variant in the ZMYND11 gene was identified in an ASD proband from the Simons Simplex Collection (PMID 22542183). Loss-of-function variants in this gene have also been identified in patients with developmental delay/intellectual disability, many of whom present with social difficulties and/or other behavioral problems (PMID 25217958).

Reports Added
[Exome Pool-Seq in neurodevelopmental disorders.2017]
7/1/2017
3
icon
3

Decreased from 3 to 3

Description

A de novo LoF variant in the ZMYND11 gene was identified in an ASD proband from the Simons Simplex Collection (PMID 22542183). Loss-of-function variants in this gene have also been identified in patients with developmental delay/intellectual disability, many of whom present with social difficulties and/or other behavioral problems (PMID 25217958).

Reports Added
[Using medical exome sequencing to identify the causes of neurodevelopmental disorders: experience of two clinical units and 216 patients.2017]
10/1/2016
3
icon
3

Decreased from 3 to 3

Description

A de novo LoF variant in the ZMYND11 gene was identified in an ASD proband from the Simons Simplex Collection (PMID 22542183). Loss-of-function variants in this gene have also been identified in patients with developmental delay/intellectual disability, many of whom present with social difficulties and/or other behavioral problems (PMID 25217958).

Reports Added
[A de novo missense mutation in ZMYND11 is associated with global developmental delay, seizures, and hypotonia.2016]
7/1/2016
3
icon
3

Decreased from 3 to 3

Description

A de novo LoF variant in the ZMYND11 gene was identified in an ASD proband from the Simons Simplex Collection (PMID 22542183). Loss-of-function variants in this gene have also been identified in patients with developmental delay/intellectual disability, many of whom present with social difficulties and/or other behavioral problems (PMID 25217958).

Reports Added
[Mutations in HECW2 are associated with intellectual disability and epilepsy.2016] [Genome-wide association study of behavioral, physiological and gene expression traits in outbred CFW mice.2016]
1/1/2016
3
icon
3

Decreased from 3 to 3

Description

A de novo LoF variant in the ZMYND11 gene was identified in an ASD proband from the Simons Simplex Collection (PMID 22542183). Loss-of-function variants in this gene have also been identified in patients with developmental delay/intellectual disability, many of whom present with social difficulties and/or other behavioral problems (PMID 25217958).

Reports Added
[De novo gene disruptions in children on the autistic spectrum.2012] [Refining analyses of copy number variation identifies specific genes associated with developmental delay.2014] [A de novo mutation in ZMYND11, a candidate gene for 10p15.3 deletion syndrome, is associated with syndromic intellectual disability.2014] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [Low load for disruptive mutations in autism genes and their biased transmission.2015]
10/1/2014
icon
3

Increased from to 3

Description

A de novo LoF variant in the ZMYND11 gene was identified in an ASD proband from the Simons Simplex Collection (PMID 22542183). Loss-of-function variants in this gene have also been identified in patients with developmental delay/intellectual disability, many of whom present with social difficulties and/or other behavioral problems (PMID 25217958).

Krishnan Probability Score

Score 0.59500332703849

Ranking 448/25841 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 0.99996358635019

Ranking 559/18225 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
Iossifov Probability Score

Score 0.836

Ranking 206/239 scored genes


[Show Scoring Methodology]
Supplementary dataset S2 in the paper by Iossifov et al. (PNAS 112, E5600-E5607 (2015)) lists 239 genes with a probability of at least 0.8 of being associated with autism risk (column I). This probability metric combines the evidence from de novo likely-gene- disrupting and missense mutations and assesses it against the background mutation rate in unaffected individuals from the University of Washington’s Exome Variant Sequence database (evs.gs.washington.edu/EVS/). The list of probability scores can be found here: www.pnas.org/lookup/suppl/doi:10.1073/pnas.1516376112/- /DCSupplemental/pnas.1516376112.sd02.xlsx
Original Source
Sanders TADA Score

Score 0.47375185068229

Ranking 395/18665 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
Larsen Cumulative Evidence Score

Score 14

Ranking 142/461 scored genes


[Show Scoring Methodology]
Larsen and colleagues generated gene scores based on the sum of evidence for all available ASD-associated variants in a gene, with assessments based on mode of inheritance, effect size, and variant frequency in the general population. The approach was first presented in Mol Autism 7:44 (2016), and scores for 461 genes can be found in column I in supplementary table 4 from that paper.
Original Source
Zhang D Score

Score 0.62432484518091

Ranking 45/20870 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
Interactome
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
LMP1 Latent membrane protein 1 HHV-4 Protein Binding 3783750 P03230
MAGEC2 Melanoma-associated antigen C2 Human Protein Binding 51438 Q9UBF1
UL122 Viral transcription factor IE2 HHV-5 Protein Binding 3077563 Q6SW29
Submit New Gene

Report an Error