ZMYND8

Chr 20

zinc finger MYND-type containing 8

Also known as: PRKCBP1, PRO2893, RACK7

NCBI Gene: 23613ENSG00000101040UniProt: Q9ULU4

The encoded protein is a transcriptional regulator containing a bromodomain and two zinc fingers that binds to activated protein kinase C beta I. Loss-of-function mutations in ZMYND8 cause autosomal dominant neurodevelopmental disorder, as evidenced by the extremely high pLI score (>0.99) and very low LOEUF score (0.131) indicating strong intolerance to loss-of-function variants. The pathogenic mechanism involves haploinsufficiency of this nuclear transcriptional regulator.

Summary from RefSeq, UniProt, Mechanism
Research Assistant →
0
Active trials
16
Pubs (1 yr)
11
P/LP submissions
9%
P/LP missense
0.13
LOEUF· LoF intol.
LOF
Mechanism· G2P
Clinical Summary— ZMYND8
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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.
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ClinVar Variants
11 unique Pathogenic / Likely Pathogenic· 140 VUS of 203 total submissions
Explore recent and relevant literature in Research Assistant →
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
0.13LOEUF
pLI 1.000
Z-score 6.77
OE 0.05 (0.02–0.13)
Highly constrained

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

Missense Constraint
4.04Z-score
OE missense 0.57 (0.53–0.62)
399 obs / 699.6 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.05 (0.02–0.13)
0≤0.351.4
Missense OE0.57 (0.53–0.62)
0≤0.61.4
Synonymous OE1.03
0≤1.21.6
LoF obs/exp: 3 / 59.2Missense obs/exp: 399 / 699.6Syn Z: -0.39
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
moderateZMYND8-related neurodevelopmental disorderLOFAD
DN
0.17100th %ile
GOF
0.2398th %ile
LOF
0.88top 5%

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

LOFprediction above median · 18% of P/LP variants are LoF · LOEUF 0.13

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

ClinVar Variant Classifications

203 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8
Likely Pathogenic3
VUS140
Likely Benign18
Benign7
Conflicting3
8
Pathogenic
3
Likely Pathogenic
140
VUS
18
Likely Benign
7
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
7
0
8
Likely Pathogenic
1
1
1
0
3
VUS
6
120
13
1
140
Likely Benign
0
10
0
8
18
Benign
0
1
3
3
7
Conflicting
—3
Total81322412179

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

View in ClinVar →

Protein Context — Lollipop Plot

ZMYND8 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients