DIP2B

Chr 12AD

DIP2 acetate--CoA ligase B (putative)

NCBI Gene: 57609ENSG00000066084UniProt: Q9P265OMIM: 611379

The DIP2B protein negatively regulates axonal outgrowth, is essential for normal synaptic transmission, and promotes acetylation of alpha-tubulin. Mutations cause intellectual developmental disorder with autosomal dominant inheritance, specifically associated with the FRA12A fragile site on chromosome 12. This gene is highly constrained against loss-of-function variants (pLI = 0.999, LOEUF = 0.266), indicating that haploinsufficiency is likely not tolerated in the general population.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.271 OMIM phenotype
Clinical Summary— DIP2B
⚡
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
9 unique Pathogenic / Likely Pathogenic· 211 VUS of 299 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
0.27LOEUF
pLI 0.999
Z-score 7.30
OE 0.18 (0.12–0.27)
Highly constrained

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

Missense Constraint
3.18Z-score
OE missense 0.70 (0.66–0.75)
631 obs / 899.5 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.18 (0.12–0.27)
0≤0.351.4
Missense OE0.70 (0.66–0.75)
0≤0.61.4
Synonymous OE0.97
0≤1.21.6
LoF obs/exp: 16 / 91.3Missense obs/exp: 631 / 899.5Syn Z: 0.48
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedDIP2B-related intellectual developmental disorder, FRA12A typeOTHERAD
DN
0.3792th %ile
GOF
0.4184th %ile
LOF
0.73top 10%

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

LOFprediction above median · LOEUF 0.27

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

299 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic2
VUS211
Likely Benign27
Benign14
Conflicting3
7
Pathogenic
2
Likely Pathogenic
211
VUS
27
Likely Benign
14
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
7
0
7
Likely Pathogenic
0
1
1
0
2
VUS
9
195
6
1
211
Likely Benign
0
6
7
14
27
Benign
0
3
2
9
14
Conflicting
—3
Total92052324264

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

View in ClinVar →

Protein Context — Lollipop Plot

DIP2B · 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 4 full-text resultsSearch PubTator3 ↗
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