APBA2

Chr 15

amyloid beta precursor protein binding family A member 2

Also known as: D15S1518E, HsT16821, LIN-10, MGC:14091, MINT2, X11-BETA, X11L

NCBI Gene: 321 ENSG00000034053 UniProt: Q99767 OMIM: 602712

APBA2 encodes a neuronal adapter protein that functions in synaptic vesicle exocytosis by binding to STXBP1 and also modulates amyloid precursor protein processing. Mutations cause autosomal dominant epileptic encephalopathy with onset typically in infancy or early childhood. The gene shows significant constraint against loss-of-function variants, suggesting haploinsufficiency as a likely disease mechanism.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a member of the X11 protein family. It is a neuronal adapter protein that interacts with the Alzheimer's disease amyloid precursor protein (APP). It stabilizes APP and inhibits production of proteolytic APP fragments including the A beta peptide that is deposited in the brains of Alzheimer's disease patients. This gene product is believed to be involved in signal transduction processes. It is also regarded as a putative vesicular trafficking protein in the brain that can form a complex with the potential to couple synaptic vesicle exocytosis to neuronal cell adhesion. [provided by RefSeq, Jul 2017]

OMIM ResearchGenerating clinical summary…

LOEUF 0.38

Clinical Summary— APBA2

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.74) — some intolerance to loss-of-function variants.

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ClinVar Variants

107 VUS of 172 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.38LOEUF

pLI 0.743

Z-score 4.15

OE 0.19 (0.11–0.38)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.46Z-score

OE missense 0.81 (0.74–0.88)

363 obs / 450.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.19 (0.11–0.38)

0≤0.351.4

Missense OE?0.81 (0.74–0.88)

0≤0.61.4

Synonymous OE?1.14

0≤1.21.6

LoF obs/exp: 6 / 30.8Missense obs/exp: 363 / 450.1Syn Z: -1.53

ClinVar Variant Classifications

172 submitted variants in ClinVar

ClinVar

Classification Summary

VUS107

Likely Benign33

Benign15

107

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	107	0	0	107
Likely Benign	6	3	24	33
Benign	3	2	10	15
Total	116	5	34	155

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

View in ClinVar →

100 pathogenic / likely-pathogenic (of 158) ClinVar copy-number / structural variants overlap APBA2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →