LMBRD2

Chr 5AD

LMBR1 domain containing 2

Also known as: DENBA

NCBI Gene: 92255ENSG00000164187UniProt: Q68DH5

Involved in adrenergic receptor signaling pathway. Located in membrane. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

Developmental delay with variable neurologic and brain abnormalitiesMIM #619694
AD
177
ClinVar variants
31
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— LMBRD2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
31 Pathogenic / Likely Pathogenic· 114 VUS of 177 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.55LOEUF
pLI 0.000
Z-score 3.81
OE 0.35 (0.23–0.55)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
2.27Z-score
OE missense 0.66 (0.60–0.74)
241 obs / 362.8 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.35 (0.23–0.55)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.66 (0.60–0.74)
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.0.90
0≤1.21.6
LoF obs/exp: 14 / 40.0Missense obs/exp: 241 / 362.8Syn Z: 0.85

ClinVar Variant Classifications

177 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17
Likely Pathogenic14
VUS114
Likely Benign7
Benign5
Conflicting1
17
Pathogenic
14
Likely Pathogenic
114
VUS
7
Likely Benign
5
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
17
0
17
Likely Pathogenic
0
10
4
0
14
VUS
3
101
10
0
114
Likely Benign
0
6
1
0
7
Benign
0
1
1
3
5
Conflicting
—1
Total3118333158

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

View in ClinVar →

Protein Context — Lollipop Plot

LMBRD2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

LMBRD2-related intellectual disability

limited
ADUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Developmental delay with variable neurologic and brain abnormalities

MIM #619694

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools