DOC2B

Chr 17

double C2 domain beta

Also known as: DOC2BL

NCBI Gene: 8447ENSG00000272636UniProt: Q14184

There are at least two protein isoforms of the Double C2 protein, namely alpha (DOC2A) and beta (DOC2B), which contain two C2-like domains. DOC2A and DOC2B are encoded by different genes; these genes are at times confused with the unrelated DAB2 gene which was initially named DOC-2. DOC2B is expressed ubiquitously and is suggested to be involved in Ca(2+)-dependent intracellular vesicle trafficking in various types of cells. [provided by RefSeq, Jul 2008]

104
ClinVar variants
33
Pathogenic / LP
0.02
pLI score
0
Active trials
Clinical Summary— DOC2B
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
33 Pathogenic / Likely Pathogenic· 65 VUS of 104 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
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?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.
1.67Z-score
OE missense 0.58 (0.47–0.70)
71 obs / 123.3 exp
Tolerant

Mild missense constraint

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.0.47 (0.23–1.06)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.58 (0.47–0.70)
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.1.01
0≤1.21.6
LoF obs/exp: 4 / 8.6Missense obs/exp: 71 / 123.3Syn Z: -0.06

ClinVar Variant Classifications

104 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic28
Likely Pathogenic5
VUS65
Likely Benign4
Benign1
Conflicting1
28
Pathogenic
5
Likely Pathogenic
65
VUS
4
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
3
1
4
Benign
0
0
1
0
1
Conflicting
—1
Total047551104

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
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
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
2026🔓 Open Access
doc2a and doc2b contribute to locomotor and social behaviors by down-regulating npas4b in zebrafish.
Chi Y et al.·BMC Biol
2025🔓 Open 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
2023🔓 Open 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 ↗

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