ABI2

Chr 2

abl interactor 2

Also known as: ABI-2, ABI2B, AIP-1, AIP1, AblBP3, SSH3BP2, argBP1, argBPIA

NCBI Gene: 10152 ENSG00000138443 UniProt: Q9NYB9 OMIM: 606442

The ABI2 protein regulates actin cytoskeleton dynamics as a component of the WAVE complex, controlling cell motility, adhesion, and dendritic spine morphogenesis in neurons. Mutations cause autosomal recessive developmental and epileptic encephalopathy with microcephaly, affecting neurological development and growth. The gene shows high constraint against loss-of-function mutations (LOEUF 0.46), indicating that complete loss of protein function is poorly tolerated.

OMIM ResearchSummary from RefSeq, UniProt

Enables several functions, including SH3 domain binding activity; proline-rich region binding activity; and ubiquitin protein ligase binding activity. Contributes to small GTPase binding activity. Involved in several processes, including Rac protein signal transduction; positive regulation of cellular component organization; and zonula adherens assembly. Acts upstream of or within peptidyl-tyrosine phosphorylation. Located in several cellular components, including actin filament; filopodium tip; and lamellipodium. Part of SCAR complex. Is active in adherens junction. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOEUF 0.46

Clinical Summary— ABI2

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.22) despite low pLI — interpret in context.

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ClinVar Variants

34 VUS of 45 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.46LOEUF

pLI 0.431

Z-score 3.46

OE 0.22 (0.11–0.46)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.25Z-score

OE missense 0.61 (0.54–0.70)

163 obs / 266.2 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.22 (0.11–0.46)

0≤0.351.4

Missense OE?0.61 (0.54–0.70)

0≤0.61.4

Synonymous OE?0.86

0≤1.21.6

LoF obs/exp: 5 / 22.9Missense obs/exp: 163 / 266.2Syn Z: 1.02

ClinVar Variant Classifications

45 submitted variants in ClinVar

ClinVar

Classification Summary

VUS34

Conflicting1

VUS

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	1	33	0	0	34
Likely Benign	0	0	0	0	0
Benign	0	0	0	0	0
Conflicting	—				1
Total	1	33	0	0	35

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

View in ClinVar →

29 pathogenic / likely-pathogenic (of 31) ClinVar copy-number / structural variants overlap ABI2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →