ZMYND11

Chr 10AD

zinc finger MYND-type containing 11

Also known as: BRAM1, BS69, MRD30

NCBI Gene: 10771ENSG00000015171UniProt: Q15326

The protein encoded by this gene was first identified by its ability to bind the adenovirus E1A protein. The protein localizes to the nucleus. It functions as a transcriptional repressor, and expression of E1A inhibits this repression. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Intellectual developmental disorder, autosomal dominant 30MIM #616083
AD
482
ClinVar variants
129
Pathogenic / LP
1.00
pLI score· haploinsufficient
1
Active trials
Clinical Summary— ZMYND11
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Gene-Disease Validity (ClinGen)
syndromic complex neurodevelopmental disorder · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
129 Pathogenic / Likely Pathogenic· 193 VUS of 482 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.12LOEUF
pLI 1.000
Z-score 5.68
OE 0.03 (0.01–0.12)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
3.71Z-score
OE missense 0.45 (0.39–0.51)
158 obs / 354.7 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.03 (0.01–0.12)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.45 (0.39–0.51)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.05
0≤1.21.6
LoF obs/exp: 1 / 39.6Missense obs/exp: 158 / 354.7Syn Z: -0.41

ClinVar Variant Classifications

482 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic84
Likely Pathogenic45
VUS193
Likely Benign115
Benign34
Conflicting11
84
Pathogenic
45
Likely Pathogenic
193
VUS
115
Likely Benign
34
Benign
11
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
27
1
56
0
84
Likely Pathogenic
12
17
16
0
45
VUS
6
132
52
3
193
Likely Benign
0
11
57
47
115
Benign
1
11
20
2
34
Conflicting
—11
Total4617220152482

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ZMYND11 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

ZMYND11-related intellectual disability

strong
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Intellectual developmental disorder, autosomal dominant 30

MIM #616083

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Refining analyses of copy number variation identifies specific genes associated with developmental delay.
Coe BP et al.·Nat Genet
2014
Histone H3.3 phosphorylation amplifies stimulation-induced transcription.
Armache A et al.·Nature
2020
ZMYND11-related syndromic intellectual disability: 16 patients delineating and expanding the phenotypic spectrum.
Yates TM et al.·Hum Mutat
2020Cohort
Epigenetic reader ZMYND11 noncanonical function restricts HNRNPA1-mediated stress granule formation and oncogenic activity.
Lian C et al.·Signal Transduct Target Ther
2024
Further Delineation of Clinical Phenotype of ZMYND11 Variants in Patients with Neurodevelopmental Dysmorphic Syndrome.
Bodetko A et al.·Genes (Basel)
2024Case report
Whole-exome sequencing analysis identifies risk genes for schizophrenia.
Chick SL et al.·Nat Commun
2025
ZMYND11 functions in bimodal regulation of latent genes and brain-like splicing to safeguard corticogenesis.
Chang X et al.·Nat Commun
2025
The natural history of progressive myoclonus ataxia.
van der Veen S et al.·Neurobiol Dis
2024Natural history
Genetic Diversity and Expanded Phenotypes in Dystonia: Insights From Large-Scale Exome Sequencing.
Thomsen M et al.·Ann Clin Transl Neurol
2025
Pathogenic variants in chromatin-related genes: Linking immune dysregulation to neuroregression and acute neuropsychiatric disorders.
Dale RC et al.·Dev Med Child Neurol
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Rare DisordersUndiagnosed DisordersDisorders of Unknown Prevalence

Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford

RECRUITING
NCT01793168Sanford HealthStarted 2010-07

External Resources

Links to major genomics databases and tools