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: 321ENSG00000034053UniProt: Q99767

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]

310
ClinVar variants
99
Pathogenic / LP
0.74
pLI score
0
Active trials
Clinical Summary— APBA2
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.74) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
99 Pathogenic / Likely Pathogenic· 153 VUS of 310 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.38LOEUF
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?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.
1.46Z-score
OE missense 0.81 (0.74–0.88)
363 obs / 450.1 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.0.19 (0.11–0.38)
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 (0.74–0.88)
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.1.14
0≤1.21.6
LoF obs/exp: 6 / 30.8Missense obs/exp: 363 / 450.1Syn Z: -1.53

ClinVar Variant Classifications

310 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic93
Likely Pathogenic6
VUS153
Likely Benign41
Benign16
Conflicting1
93
Pathogenic
6
Likely Pathogenic
153
VUS
41
Likely Benign
16
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
93
0
93
Likely Pathogenic
0
0
6
0
6
VUS
0
106
47
0
153
Likely Benign
0
6
11
24
41
Benign
0
3
3
10
16
Conflicting
—1
Total011516034310

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

View in ClinVar →

Protein Context — Lollipop Plot

APBA2 · 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
Change in INSR, APBA2 and IDE Gene Expressions in Brains of Alzheimer's Disease Patients.
da Costa IB et al.·Curr Alzheimer Res
2017Cohort
A rare autism-associated MINT2/APBA2 mutation disrupts neurexin trafficking and synaptic function.
Lin AY et al.·Sci Rep
2019
Meta-analysis of GWA studies provides new insights on the genetic architecture of skin pigmentation in recently admixed populations.
Lona-Durazo F et al.·BMC Genet
2019Meta-analysis
Comparative genome hybridization suggests a role for NRXN1 and APBA2 in schizophrenia.
Kirov G et al.·Hum Mol Genet
2008
Special transcriptome landscape and molecular prognostic signature of non-smoking head and neck cancer patients.
Ji Y et al.·Funct Integr Genomics
2023Cohort
Exploratory locomotion, a predictor of addiction vulnerability, is oligogenic in rats selected for this phenotype.
Zhou Z et al.·Proc Natl Acad Sci U S A
2019
Chromosomal microarray analysis of Bulgarian patients with epilepsy and intellectual disability.
Peycheva V et al.·Gene
2018Cohort
Integrative genomics identifies APOE ε4 effectors in Alzheimer's disease.
Rhinn H et al.·Nature
2013
An integrated analysis of rare CNV and exome variation in Autism Spectrum Disorder using the Infinium PsychArray.
Bacchelli E et al.·Sci Rep
2020
Skin pigmentation and genetic variants in an admixed Brazilian population of primarily European ancestry.
Andersen JD et al.·Int J Legal Med
2020
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