ABI1

Chr 10

abl interactor 1

Also known as: ABI-1, ABLBP4, E3B1, NAP1BP, SSH3BP, SSH3BP1

NCBI Gene: 10006 ENSG00000136754 UniProt: Q8IZP0 OMIM: 603050

ABI1 encodes an adaptor protein that regulates actin polymerization and cytoskeletal remodeling through interactions with Abelson tyrosine kinases, and participates in signal transduction from Ras to Rac while regulating dendritic outgrowth and synaptic development in neurons. Mutations cause autosomal recessive neurodevelopmental disorder with seizures, spastic diplegia, and cerebral atrophy, typically presenting in early childhood. The gene is highly constrained against loss-of-function variants (LOEUF 0.418), suggesting intolerance to complete protein loss.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the Abelson-interactor family of adaptor proteins. These proteins facilitate signal transduction as components of several multiprotein complexes, and regulate actin polymerization and cytoskeletal remodeling through interactions with Abelson tyrosine kinases. The encoded protein plays a role in macropinocytosis as a component of the WAVE2 complex, and also forms a complex with EPS8 and SOS1 that mediates signal transduction from Ras to Rac. This gene may play a role in the progression of several malignancies including melanoma, colon cancer and breast cancer, and a t(10;11) chromosomal translocation involving this gene and the MLL gene has been associated with acute myeloid leukemia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 14. [provided by RefSeq, Sep 2011]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.42

LOEUF

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.42LOEUF

pLI 0.639

Z-score 3.72

OE 0.20 (0.10–0.42)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.09Z-score

OE missense 0.65 (0.57–0.73)

182 obs / 280.8 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.20 (0.10–0.42)

0≤0.351.4

Missense OE?0.65 (0.57–0.73)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 5 / 25.1Missense obs/exp: 182 / 280.8Syn Z: -0.20

Background carrier burden — how many people carry a rare variant somewhere in ABI1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 160

524 rare PASS variants

Rare truncating (LoF)

1 in 8,600

31 rare PASS variants

Rare synonymous (reference)

1 in 230

221 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ABI1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 210	1 in 7,500
South Asian	~43k	1 in 95	1 in 5,800
Remaining (unassigned)	~30k	1 in 86	≈ 1 in 15,000
European (Finnish)	~27k	1 in 1,400	≈ 1 in 17,000
Admixed American	~22k	1 in 190	≈ 1 in 5,400
African / African American	~21k	1 in 190	≈ 1 in 16,000
East Asian	~20k	1 in 230	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 400	≈ 1 in 6,400
Middle Eastern	~2,884	1 in 290	≈ 1 in 2,800

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 11 coding exons well covered in gnomAD exomes and genomes.? see exons ↓