ABI3

Chr 17

ABI family member 3

Also known as: NESH, SSH3BP3

NCBI Gene: 51225UniProt: Q9P2A4

This gene encodes a member of an adaptor protein family. Members of this family encode proteins containing a homeobox homology domain, proline rich region and Src-homology 3 (SH3) domain, and are components of the Abi/WAVE complex which regulates actin polymerization. The encoded protein inhibits ectopic metastasis of tumor cells as well as cell migration. This may be accomplished through interaction with p21-activated kinase. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

0
Active trials
83
ClinVar variants
12
Pathogenic / LP
0.4
Missense Z
1.04
LOEUF
7
Pubs (2 yr)
Clinical Summary— ABI3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
12 Pathogenic / Likely Pathogenic· 65 VUS of 83 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
Tolerant — LoF & missense variants common in population
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.
1.04LOEUF
pLI 0.000
Z-score 1.45
OE 0.60 (0.36–1.04)
Tolerant

Highly tolerant — LoF variants common in population

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.
0.40Z-score
OE missense 0.92 (0.82–1.04)
204 obs / 220.5 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.0.60 (0.36–1.04)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.92 (0.82–1.04)
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.0.85
0≤1.21.6
LoF obs/exp: 9 / 15.1Missense obs/exp: 204 / 220.5Syn Z: 1.16

ClinVar Variant Classifications

83 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11
Likely Pathogenic1
VUS65
Likely Benign3
Benign3
11
Pathogenic
1
Likely Pathogenic
65
VUS
3
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
11
0
11
Likely Pathogenic
0
0
1
0
1
VUS
0
62
3
0
65
Likely Benign
0
3
0
0
3
Benign
0
0
1
2
3
Total06516283

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

View in ClinVar →

Protein Context — Lollipop Plot

ABI3 · 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
Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease.
Sims R et al.·Nat Genet
2017
Transethnic meta-analysis of rare coding variants in PLCG2, ABI3, and TREM2 supports their general contribution to Alzheimer's disease.
Dalmasso MC et al.·Transl Psychiatry
2019Meta-analysis
Deletion of Abi3/Gngt2 influences age-progressive amyloid β and tau pathologies in distinctive ways.
Ibanez KR et al.·Alzheimers Res Ther
2022
Association of ABI3 and PLCG2 missense variants with disease risk and neuropathology in Lewy body disease and progressive supranuclear palsy.
Strickland SL et al.·Acta Neuropathol Commun
2020
DNA methylation and stroke prognosis: an epigenome-wide association study.
Jiménez-Balado J et al.·Clin Epigenetics
2024Meta-analysis
Examination of the Effect of Rare Variants in TREM2, ABI3, and PLCG2 in LOAD Through Multiple Phenotypes.
Olive C et al.·J Alzheimers Dis
2020
Exploring microglia and their phenomenal concatenation of stress responses in neurodegenerative disorders.
Asveda T et al.·Life Sci
2023Review
The association of clinical phenotypes to known AD/FTD genetic risk loci and their inter-relationship.
Li QS et al.·PLoS One
2020
Common Variants in ABI3 Influence Cerebrospinal Fluid Total Tau Levels and Cognitive Decline in Progressive Mild Cognitive Impairment Patients.
Niu LD et al.·J Alzheimers Dis
2019Cohort
Leveraging a gene signature associated with disulfidptosis identified by machine learning to forecast clinical outcomes, immunological heterogeneities, and potential therapeutic targets within lower-grade glioma.
Zhou Y et al.·Front Immunol
2023
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
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