APPBP2

Chr 17

amyloid beta precursor protein binding protein 2

Also known as: APP-BP2, HS.84084, PAT1

NCBI Gene: 10513UniProt: Q92624

The protein encoded by this gene interacts with microtubules and is functionally associated with beta-amyloid precursor protein transport and/or processing. The beta-amyloid precursor protein is a cell surface protein with signal-transducing properties, and it is thought to play a role in the pathogenesis of Alzheimer's disease. The encoded protein may be involved in regulating cell death. This gene has been found to be highly expressed in breast cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

0
Active trials
52
ClinVar variants
20
Pathogenic / LP
3.1
Missense Z
0.27
LOEUF· LoF intolerant
1
Pubs (2 yr)
Clinical Summary— APPBP2
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
20 Pathogenic / Likely Pathogenic· 31 VUS of 52 total submissions
Some data sources returned errors (1)

ensembl: TimeoutError: The operation was aborted due to timeout

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.
0.27LOEUF
pLI 0.996
Z-score 4.74
OE 0.12 (0.06–0.27)
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.
3.09Z-score
OE missense 0.50 (0.44–0.57)
154 obs / 306.0 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.0.12 (0.06–0.27)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.50 (0.44–0.57)
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.1.04
0≤1.21.6
LoF obs/exp: 4 / 33.7Missense obs/exp: 154 / 306.0Syn Z: -0.33

ClinVar Variant Classifications

52 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15
Likely Pathogenic5
VUS31
Likely Benign1
15
Pathogenic
5
Likely Pathogenic
31
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
15
0
15
Likely Pathogenic
0
0
5
0
5
VUS
0
25
6
0
31
Likely Benign
0
0
1
0
1
Benign
0
0
0
0
0
Total02527052

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

View in ClinVar →

Protein Context — Lollipop Plot

APPBP2 · 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
Circ_SETD3 regulates gefitinib sensitivity and tumor progression by miR-873-5p-dependent regulation of APPBP2 in non-small cell lung cancer.
Sheng J et al.·J Chemother
2022
Association of 17q21-q24 gain in ovarian clear cell adenocarcinomas with poor prognosis and identification of PPM1D and APPBP2 as likely amplification targets.
Hirasawa A et al.·Clin Cancer Res
2003
CRL2(APPBP2)-mediated TSPYL2 degradation counteracts human mesenchymal stem cell senescence.
Huang D et al.·Sci China Life Sci
2024
PPM1D is a potential target for 17q gain in neuroblastoma.
Saito-Ohara F et al.·Cancer Res
2003
An infectious retrovirus susceptible to an IFN antiviral pathway from human prostate tumors.
Dong B et al.·Proc Natl Acad Sci U S A
2007
Comprehensive copy number and gene expression profiling of the 17q23 amplicon in human breast cancer.
Monni O et al.·Proc Natl Acad Sci U S A
2001
Multiscale Analysis of Independent Alzheimer's Cohorts Finds Disruption of Molecular, Genetic, and Clinical Networks by Human Herpesvirus.
Readhead B et al.·Neuron
2018Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Post-translational control of beige fat biogenesis by PRDM16 stabilization
Wang Q et al.·Nature
2022
circBIRC6 contributes to the development of non-small cell lung cancer via regulating microRNA-217/amyloid beta precursor protein binding protein 2 axis
Ni D et al.·Chin Med J (Engl)
2022
Characterization, comparative, and functional analysis of arylacetamide deacetylase from Gnathostomata organisms
Diaz-Vidal T et al.·J Genet Eng Biotechnol
2022Functional
Targeted Protein Degradation to Overcome Resistance in Cancer Therapies: PROTAC and N-Degron Pathway
Kim H et al.·Biomedicines
2022
Latest advances in the regulatory genes of adipocyte thermogenesis
Nie T et al.·Front Endocrinol (Lausanne)
2023
The C-degron pathway eliminates mislocalized proteins and products of deubiquitinating enzymes
Yeh CW et al.·EMBO J
2021
Top 6 full-text resultsSearch PubTator3 ↗

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

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients