AP3B2

Chr 15

adaptor related protein complex 3 subunit beta 2

Also known as: DEE48, EIEE48, NAPTB

NCBI Gene: 8120 ENSG00000103723 UniProt: Q13367

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.

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]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.34

Clinical Summary— AP3B2

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Gene-Disease Validity (ClinGen)

genetic developmental and epileptic encephalopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.77) — some intolerance to loss-of-function variants.

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ClinVar Variants

51 unique Pathogenic / Likely Pathogenic· 364 VUS of 941 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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

ClinVar Variant Classifications

941 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic28

Likely Pathogenic23

VUS364

Likely Benign475

Benign20

Conflicting18

Pathogenic

Likely Pathogenic

364

VUS

475

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	28	0	0	0	28
Likely Pathogenic	21	1	0	1	23
VUS	5	329	27	3	364
Likely Benign	0	6	204	265	475
Benign	0	2	13	5	20
Conflicting	—				18
Total	54	338	244	274	928

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

View in ClinVar →

34 pathogenic / likely-pathogenic (of 42) ClinVar copy-number / structural variants overlap AP3B2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →