AP3B2

Chr 15AR

adaptor related protein complex 3 subunit beta 2

Also known as: DEE48, EIEE48, NAPTB

NCBI Gene: 8120ENSG00000103723UniProt: Q13367

Adaptor protein complex 3 (AP-3 complex) is a heterotrimeric protein complex involved in the formation of clathrin-coated synaptic vesicles. The protein encoded by this gene represents the beta subunit of the neuron-specific AP-3 complex and was first identified as the target antigen in human paraneoplastic neurologic disorders. The encoded subunit binds clathrin and is phosphorylated by a casein kinase-like protein, which mediates synaptic vesicle coat assembly. Defects in this gene are a cause of early-onset epileptic encephalopathy. [provided by RefSeq, Feb 2017]

Primary Disease Associations & Inheritance

Developmental and epileptic encephalopathy 48MIM #617276
AR
587
ClinVar variants
41
Pathogenic / LP
0.77
pLI score
0
Active trials
Clinical Summary— AP3B2
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.77) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
41 Pathogenic / Likely Pathogenic· 219 VUS of 587 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.34LOEUF
pLI 0.772
Z-score 5.37
OE 0.21 (0.13–0.34)
Highly constrained

Highly LoF-intolerant (top ~10% 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.
2.92Z-score
OE missense 0.67 (0.62–0.73)
413 obs / 617.3 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.0.21 (0.13–0.34)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.67 (0.62–0.73)
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: 11 / 53.3Missense obs/exp: 413 / 617.3Syn Z: -0.15

ClinVar Variant Classifications

587 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic14
VUS219
Likely Benign315
Benign5
Conflicting7
27
Pathogenic
14
Likely Pathogenic
219
VUS
315
Likely Benign
5
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
12
0
15
0
27
Likely Pathogenic
6
0
8
0
14
VUS
2
191
24
2
219
Likely Benign
0
3
142
170
315
Benign
0
0
4
1
5
Conflicting
—7
Total20194193173587

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

View in ClinVar →

Protein Context — Lollipop Plot

AP3B2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

AP3B2-related epileptic encephalopathy with optic atrophy

strong
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEye
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Developmental and epileptic encephalopathy 48

MIM #617276

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Autoimmune Vestibulocerebellar Syndromes.
Narayan RN et al.·Semin Neurol
2020Review
Cerebellar ataxia and myeloradiculopathy associated with AP3B2 antibody: a case report and literature review.
Mange L et al.·J Neurol
2021Review
Characterization of AP3B2_v2, a novel splice variant of human AP3B2.
Chen C et al.·DNA Seq
2007
Blended phenotype of combination of HERC2 and AP3B2 deficiency and Angelman syndrome caused by paternal isodisomy of chromosome 15.
Ueda K et al.·Am J Med Genet A
2021Case report
Autoimmune gait disturbance accompanying adaptor protein-3B2-IgG.
Honorat JA et al.·Neurology
2019
Novel homozygous AP3B2 mutations in four individuals with developmental and epileptic encephalopathy: A rare clinical entity.
Dilber C et al.·Clin Neurol Neurosurg
2022Case report
'Medusa head ataxia': the expanding spectrum of Purkinje cell antibodies in autoimmune cerebellar ataxia. Part 3: Anti-Yo/CDR2, anti-Nb/AP3B2, PCA-2, anti-Tr/DNER, other antibodies, diagnostic pitfalls, summary and outlook.
Jarius S et al.·J Neuroinflammation
2015Review
Variation in PTCHD2, CRISP3, NAP1L4, FSCB, and AP3B2 associated with spherical equivalent.
Chen F et al.·Mol Vis
2016
Case Report: Subacute combined degeneration of the spinal cord mimic accompanying adaptor protein-3B2-IgG.
Liu Y et al.·Front Immunol
2025Case report
Autoantibody profiles associated with clinical features in psychotic disorders.
Jernbom Falk A et al.·Transl Psychiatry
2021
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