ABI1

protein-coding

abl interactor 1

Gene summary

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]

Previous symbols:

SSH3BP1

MANE transcript

NM_001012750.3

Inheritance

—

ClinVar variants

U:50B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.2

Max pathogenic AF

—

Genomic locus

chr10:26,746,593-26,861,087

External References & Databases

Ensembl (ENSG00000136754)

Transcript & Mutation Effects

hg38 • Region Span ~114.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ABI1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 40

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001012750.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	1 clinvar	1 clinvar	3
missense			44 clinvar	1 clinvar		45
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	50	2	1	53

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 135 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001012750.3	RefSeq	NP_001012768.1	11	MANE Select
ENST00000376140.4	Ensembl	ENSP00000365310.3	11	MANE Select
NM_001012751.3	RefSeq	NP_001012769.1	10	Standard
NM_001012752.3	RefSeq	NP_001012770.1	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

EGF-EGFR Signaling Pathway
Signal Transduction
VEGFA-VEGFR2 Pathway
Fcgamma receptor (FCGR) dependent phagocytosis
Innate Immune System

Biological Process

somitogenesis
transmembrane receptor protein tyrosine kinase signaling pathway
actin polymerization or depolymerization
negative regulation of cell population proliferation
viral process

Molecular Function

protein binding
cytoskeletal protein binding
SH3 domain binding
protein tyrosine kinase activator activity
cadherin binding

Cellular Component

nucleus
endoplasmic reticulum
cytosol
cytoskeleton
postsynaptic density

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000376142
Coding exons: 12
Length: 114495
Individuals with no LoFs: 125696
Homozygous LoFs: 0
Heterozygous LoFs: 4
Defined: 125700
p: 0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.09	182	281	0.648	0.0000138	3268
Missense (PolyPhen)		49	97.349	0.50334		1215
Synonymous	-0.195	101	98.5	1.03	0.00000481	1055
Loss of Function	3.72	5	25.1	0.199	0.00000135	291

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.00021	0.00020	rare
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0.000039	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May act in negative regulation of cell growth and transformation by interacting with nonreceptor tyrosine kinases ABL1 and/or ABL2. May play a role in regulation of EGF-induced Erk pathway activation. Involved in cytoskeletal reorganization and EGFR signaling. Together with EPS8 participates in transduction of signals from Ras to Rac. In vitro, a trimeric complex of ABI1, EPS8 and SOS1 exhibits Rac specific guanine nucleotide exchange factor (GEF) activity and ABI1 seems to act as an adapter in the complex. Regulates ABL1/c-Abl-mediated phosphorylation of ENAH. Recruits WASF1 to lamellipodia and there seems to regulate WASF1 protein level. In brain, seems to regulate the dendritic outgrowth and branching as well as to determine the shape and number of synaptic contacts of developing neurons. {ECO:0000269|PubMed:11003655, ECO:0000269|PubMed:18328268}.;
Disease: DISEASE: Note=A chromosomal aberration involving ABI1 is a cause of acute leukemias. Translocation t(10;11)(p11.2;q23) with KMT2A/MLL1. ABI1 isoform 2 was found to be present in acute leukemia KMT2A/MLL1-ABI1 fusion transcript. {ECO:0000269|PubMed:9694699}.;

Recessive Scores

pRec: 0.297

Intolerance Scores

LoFtool: 0.0520
RVIS EVS: -0.32
RVIS percentile EVS: 31.69

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.707

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium