DOC2A

Chr 16

double C2 domain alpha

Also known as: Doc2

NCBI Gene: 8448ENSG00000149927UniProt: Q14183

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. DOC2A is mainly expressed in brain and is suggested to be involved in Ca(2+)-dependent neurotransmitter release. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

358
ClinVar variants
277
Pathogenic / LP
0.01
pLI score
0
Active trials
Clinical Summary— DOC2A
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
277 Pathogenic / Likely Pathogenic· 74 VUS of 358 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.
0.69LOEUF
pLI 0.007
Z-score 2.56
OE 0.37 (0.21–0.69)
Tolerant

Typical tolerance to LoF variation

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.
1.09Z-score
OE missense 0.81 (0.72–0.91)
210 obs / 259.3 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.0.37 (0.21–0.69)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.81 (0.72–0.91)
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: 7 / 19.1Missense obs/exp: 210 / 259.3Syn Z: -0.08

ClinVar Variant Classifications

358 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic233
Likely Pathogenic44
VUS74
Likely Benign3
Benign4
233
Pathogenic
44
Likely Pathogenic
74
VUS
3
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
233
0
233
Likely Pathogenic
0
0
44
0
44
VUS
0
64
10
0
74
Likely Benign
0
2
1
0
3
Benign
0
3
1
0
4
Total0692890358

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

View in ClinVar →

Protein Context — Lollipop Plot

DOC2A · 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
A causal coding variant regulating alternative splicing of DOC2A at 16p.11.2 GWAS locus influences susceptibility to schizophrenia.
Zhou D et al.·Sci Adv
2026
Genome-wide association study provides insights into the genetic basis of Lewy body dementia.
Zhu P et al.·Mol Psychiatry
2025Meta-analysis
Identification of Common Brain Protein and Genetic Loci Between Parkinson's Disease and Lewy Body Dementia.
Jia T et al.·CNS Neurosci Ther
2025
Strong synaptic transmission impact by copy number variations in schizophrenia.
Glessner JT et al.·Proc Natl Acad Sci U S A
2010
O-C2 angle as a predictor of dyspnea and/or dysphagia after occipitocervical fusion.
Miyata M et al.·Spine (Phila Pa 1976)
2009
Duplication 16p11.2 in a child with infantile seizure disorder.
Bedoyan JK et al.·Am J Med Genet A
2010Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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