GMEB2

Chr 20

glucocorticoid modulatory element binding protein 2

Also known as: GMEB-2, P79PIF, PIF79

NCBI Gene: 26205ENSG00000101216UniProt: Q9UKD1OMIM: 607451

The GMEB2 protein is a transcriptional regulator that binds to glucocorticoid modulatory elements and enhances glucocorticoid sensitivity, and also serves as an essential factor for parvovirus replication. Mutations in GMEB2 cause neurodevelopmental disorders with intellectual disability, typically presenting in early childhood. The gene shows autosomal dominant inheritance and is highly constrained against loss-of-function mutations.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.24
Clinical Summary— GMEB2
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
54 unique Pathogenic / Likely Pathogenic· 84 VUS of 153 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.24LOEUF
pLI 0.995
Z-score 3.95
OE 0.05 (0.02–0.24)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.20Z-score
OE missense 0.66 (0.59–0.74)
220 obs / 333.1 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.05 (0.02–0.24)
0≤0.351.4
Missense OE0.66 (0.59–0.74)
0≤0.61.4
Synonymous OE1.02
0≤1.21.6
LoF obs/exp: 1 / 20.1Missense obs/exp: 220 / 333.1Syn Z: -0.16
DN
0.2698th %ile
GOF
0.2398th %ile
LOF
0.79top 5%

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

LOFprediction above median · LOEUF 0.24

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

153 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic45
Likely Pathogenic9
VUS84
Likely Benign6
Conflicting1
45
Pathogenic
9
Likely Pathogenic
84
VUS
6
Likely Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
45
0
45
Likely Pathogenic
0
0
9
0
9
VUS
0
60
24
0
84
Likely Benign
0
4
0
2
6
Benign
0
0
0
0
0
Conflicting
—1
Total064782145

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

View in ClinVar →

Protein Context — Lollipop Plot

GMEB2 · 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 →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 4 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