AP3B2

Chr 15AR

adaptor related protein complex 3 subunit beta 2

Also known as: DEE48, EIEE48, NAPTB

NCBI Gene: 8120 ENSG00000103723 UniProt: Q13367 OMIM: 602166

The AP3B2 protein is the beta subunit of the neuron-specific adaptor protein complex 3 (AP-3), which mediates protein sorting in the late-Golgi/trans-Golgi network and targeting of cargos to neurites and nerve terminals. Biallelic mutations cause developmental and epileptic encephalopathy 48, an early-onset seizure disorder with autosomal recessive inheritance. The gene shows high constraint against loss-of-function variants (LOEUF 0.342), indicating that such variants are likely pathogenic.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Developmental and epileptic encephalopathy 48MIM #617276

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · genetic developmental and epileptic encephalopathy · AR · ClinGen 2025

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.34

LOEUF· LoF intol.

LOF

Mechanism· G2P

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

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?

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?

LoF OE?0.21 (0.13–0.34)

0≤0.351.4

Missense OE?0.67 (0.62–0.73)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 11 / 53.3Missense obs/exp: 413 / 617.3Syn Z: -0.15

Background carrier burden — how many people carry a rare variant somewhere in AP3B2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 45

1,520 rare PASS variants

Rare truncating (LoF)

1 in 280

200 rare PASS variants

Rare synonymous (reference)

1 in 84

640 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for AP3B2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 59	1 in 580
South Asian	~43k	1 in 56	1 in 190
Remaining (unassigned)	~30k	1 in 42	1 in 280
European (Finnish)	~27k	1 in 100	1 in 410
Admixed American	~22k	1 in 60	1 in 330
African / African American	~21k	1 in 37	1 in 890
East Asian	~20k	1 in 51	1 in 530
Ashkenazi Jewish	~13k	1 in 160	≈ 1 in 3,000
Middle Eastern	~2,884	1 in 53	1 in 350

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 26 of 27 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 27.? see exons ↓