ZMYND11

Chr 10AD

zinc finger MYND-type containing 11

Also known as: BRAM1, BS69, MRD30

NCBI Gene: 10771 ENSG00000015171 UniProt: Q15326 OMIM: 608668

The protein encoded by ZMYND11 localizes to the nucleus and functions as a transcriptional repressor. Heterozygous loss-of-function mutations cause autosomal dominant intellectual developmental disorder. The gene is highly intolerant to loss-of-function variation, consistent with haploinsufficiency as the disease mechanism.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismADLOEUF 0.121 OMIM phenotype

Clinical Summary— ZMYND11

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Gene-Disease Validity (ClinGen)

syndromic complex neurodevelopmental disorder · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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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.

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ClinVar Variants

89 unique Pathogenic / Likely Pathogenic· 170 VUS of 435 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — ZMYND11

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

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?

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?

LoF OE?0.03 (0.01–0.12)

0≤0.351.4

Missense OE?0.45 (0.39–0.51)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 1 / 39.6Missense obs/exp: 158 / 354.7Syn Z: -0.41

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongZMYND11-related intellectual disabilityLOFAD

This gene — mechanism propensity

0.2099th %ile

GOF

0.2796th %ile

LOF

0.83top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · 71% of P/LP variants are LoF · LOEUF 0.12 · ClinGen HI: Sufficient evidence for dosage pathogenicity

Literature Evidence

LOFHaploinsufficiency of the ZMYND11 gene may underlie the manifestations of 10p15.3 microdeletion syndrome.1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

References

1.PMID 30950019 ↗

ClinVar Variant Classifications

435 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic46

Likely Pathogenic43

VUS170

Likely Benign114

Benign32

Conflicting13

Pathogenic

Likely Pathogenic

170

VUS

114

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	42	1	3	0	46
Likely Pathogenic	21	20	2	0	43
VUS	7	139	21	3	170
Likely Benign	1	11	56	46	114
Benign	1	12	17	2	32
Conflicting	—				13
Total	72	183	99	51	418

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

View in ClinVar →

43 pathogenic / likely-pathogenic (of 76) ClinVar copy-number / structural variants overlap ZMYND11 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →