DOC2B

Chr 17

double C2 domain beta

Also known as: DOC2BL

NCBI Gene: 8447ENSG00000272636UniProt: Q14184OMIM: 604568

DOC2B encodes a calcium sensor protein that regulates SNARE-dependent vesicle fusion with membranes and is involved in neurotransmitter release and insulin secretion. Mutations cause autosomal recessive developmental and epileptic encephalopathy with onset in infancy, characterized by severe seizures, developmental delay, and movement disorders. The gene is not highly constrained against loss-of-function variants.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.06
Clinical Summary— DOC2B
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
33 unique Pathogenic / Likely Pathogenic· 65 VUS of 108 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.06LOEUF
pLI 0.017
Z-score 1.45
OE 0.47 (0.23–1.06)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
1.67Z-score
OE missense 0.58 (0.47–0.70)
71 obs / 123.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.47 (0.23–1.06)
0≤0.351.4
Missense OE0.58 (0.47–0.70)
0≤0.61.4
Synonymous OE1.01
0≤1.21.6
LoF obs/exp: 4 / 8.6Missense obs/exp: 71 / 123.3Syn Z: -0.06
DN
0.74top 25%
GOF
0.78top 25%
LOF
0.3939th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

108 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic28
Likely Pathogenic5
VUS65
Likely Benign6
Benign1
Conflicting1
28
Pathogenic
5
Likely Pathogenic
65
VUS
6
Likely Benign
1
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
28
0
28
Likely Pathogenic
0
0
5
0
5
VUS
0
47
18
0
65
Likely Benign
0
0
4
2
6
Benign
0
0
1
0
1
Conflicting
—1
Total047562106

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

View in ClinVar →

Protein Context — Lollipop Plot

DOC2B · 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 3 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Revisiting the Platelet-β-Cell Axis: Insights into How Platelet-Derived Mediators, Lipid Signaling, and DOC2B Pathways Converge to Drive β-Cell Dysfunction in Type 2 Diabetes.
Mustakin.·EJIFCC
2026Open Access
doc2a and doc2b contribute to locomotor and social behaviors by down-regulating npas4b in zebrafish.
Chi Y et al.·BMC Biol
2025Open AccessFunctional
DOC2b enrichment mitigates proinflammatory cytokine-induced CXCL10 expression by attenuating IKKβ and STAT-1 signaling in human islets.
Bhowmick DC et al.·Metabolism
2025
A Novel Role for DOC2B in Ameliorating Palmitate-Induced Glucose Uptake Dysfunction in Skeletal Muscle Cells via a Mechanism Involving β-AR Agonism and Cofilin.
Hwang J et al.·Int J Mol Sci
2023Open AccessFunctional
Double C-2 like domain beta (DOC2B) induces calcium dependent oxidative stress to promote lipotoxicity and mitochondrial dysfunction for its tumor suppressive function.
Adiga D et al.·Free Radic Biol Med
2023
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