ABI1

Summary

ABI1 (abl interactor 1, HGNC:11320) is a protein-coding gene on chromosome 10p12.1, encoding Abl interactor 1 (Q8IZP0). May act in negative regulation of cell growth and transformation by interacting with nonreceptor tyrosine kinases ABL1 and/or ABL2.

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.

Source: NCBI Gene 10006 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 81 total — 5 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_001012750

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11320
Approved symbol	ABI1
Name	abl interactor 1
Location	10p12.1
Locus type	gene with protein product
Status	Approved
Aliases	E3B1, ABI-1
Ensembl gene	ENSG00000136754
Ensembl biotype	protein_coding
OMIM	603050
Entrez	10006

Gene structure

Transcript identifiers

Ensembl transcripts: 48 — 47 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000346832, ENST00000359188, ENST00000376137, ENST00000376138, ENST00000376139, ENST00000376140, ENST00000376142, ENST00000376160, ENST00000376166, ENST00000376170, ENST00000473481, ENST00000490841, ENST00000536334, ENST00000869228, ENST00000869231, ENST00000869233, ENST00000869235, ENST00000869237, ENST00000869238, ENST00000869240, ENST00000869242, ENST00000869244, ENST00000869245, ENST00000869246, ENST00000869247, ENST00000869248, ENST00000869249, ENST00000869250, ENST00000869251, ENST00000869252, ENST00000869253, ENST00000869254, ENST00000869255, ENST00000869256, ENST00000869257, ENST00000869258, ENST00000869259, ENST00000869260, ENST00000869261, ENST00000869262, ENST00000869263, ENST00000931317, ENST00000931318, ENST00000951409, ENST00000951410, ENST00000951411, ENST00000951412, ENST00000951413

RefSeq mRNA: 19 — MANE Select: NM_001012750 NM_001012750, NM_001012751, NM_001012752, NM_001178116, NM_001178119, NM_001178120, NM_001178121, NM_001178122, NM_001178123, NM_001178124, NM_001178125, NM_001348029, NM_001348030, NM_001348031, NM_001348032, NM_001348033, NM_001348034, NM_001410909, NM_005470

CCDS: CCDS31169, CCDS31170, CCDS31171, CCDS53497, CCDS53498, CCDS53499, CCDS53500, CCDS53501, CCDS7150, CCDS73077, CCDS73078, CCDS91224

Canonical transcript exons

ENST00000376140 — 11 exons

Exon	Start	End
ENSE00000926070	26823138	26823305
ENSE00001098421	26755655	26755741
ENSE00001098423	26751598	26751783
ENSE00001098426	26768852	26768992
ENSE00001098428	26759062	26759238
ENSE00001098430	26770245	26770345
ENSE00001098440	26765218	26765318
ENSE00001603723	26777065	26777241
ENSE00001719412	26771075	26771089
ENSE00001820059	26860747	26860958
ENSE00001869699	26746596	26748745

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 98.11.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 62.3191 / max 783.5622, expressed in 1823 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
108739	32.7422	1814
108738	21.1762	1793
108740	7.8199	1722
108733	0.5808	311

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
epithelium of nasopharynx	UBERON:0001951	98.11	gold quality
amniotic fluid	UBERON:0000173	97.73	gold quality
palpebral conjunctiva	UBERON:0001812	97.26	gold quality
cartilage tissue	UBERON:0002418	97.03	gold quality
oral cavity	UBERON:0000167	96.63	gold quality
esophagus squamous epithelium	UBERON:0006920	96.50	gold quality
epithelium of esophagus	UBERON:0001976	96.18	gold quality
cervix squamous epithelium	UBERON:0006922	95.99	gold quality
squamous epithelium	UBERON:0006914	95.90	gold quality
bronchial epithelial cell	CL:0002328	95.86	gold quality
upper arm skin	UBERON:0004263	95.80	gold quality
cervix epithelium	UBERON:0004801	95.62	gold quality
bone marrow	UBERON:0002371	95.42	gold quality
thymus	UBERON:0002370	95.27	gold quality
mucosa of paranasal sinus	UBERON:0005030	95.27	gold quality
penis	UBERON:0000989	95.14	gold quality
jejunal mucosa	UBERON:0000399	95.07	gold quality
gingiva	UBERON:0001828	95.06	gold quality
pharyngeal mucosa	UBERON:0000355	94.98	gold quality
hair follicle	UBERON:0002073	94.98	gold quality
monocyte	CL:0000576	94.92	gold quality
mononuclear cell	CL:0000842	94.90	gold quality
mucosa of sigmoid colon	UBERON:0004993	94.90	gold quality
leukocyte	CL:0000738	94.85	gold quality
superficial temporal artery	UBERON:0001614	94.74	gold quality
upper leg skin	UBERON:0004262	94.74	gold quality
colonic mucosa	UBERON:0000317	94.70	gold quality
nasal cavity mucosa	UBERON:0001826	94.64	gold quality
nasal cavity epithelium	UBERON:0005384	94.59	gold quality
endometrium epithelium	UBERON:0004811	94.50	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-2983	no	1210.83
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

164 targeting ABI1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3924	100.00	72.09	2394
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-338-5P	99.92	72.34	2951

Literature-anchored findings (GeneRIF, showing 40)

• Human SSH3BP1 is a marker of macropinocytic vesicles and potential regulator of macropinocytosis in mammalian cells. SSH3BP1 may play a role in fusion of macropinocytic vesicles. (PMID:11034908)
• t(10;11)(p11.2;q23) involving MLL and this gene is associated with congenital acute monocytic leukemia (PMID:12547160)
• Abi-1 regulates c-Abl-mediated phosphorylation of Mena by interacting with both proteins (PMID:12672821)
• Abi1 interacts directly with the WHD domain of WAVE2, increases WAVE2 actin polymerization activity and mediates the assembly of a WAVE2-Abi1-Nap1-PIR121 complex. (PMID:15048123)
• Abi enhances Abl-mediated downregulation and phosphorylation of Cdc2 kinase (PMID:15591787)
• Abi-1-mediated coupling of Abl to WAVE2 promotes Abl-evoked WAVE2 tyrosine phosphorylation required to link WAVE2 with activated Rac and with actin polymerization and remodeling at the cell periphery. (PMID:15657136)
• We demonstrate a cell-type-dependent requirement for various WASP-related proteins in Listeria entry and InlB-induced membrane ruffling; Abi1, a key component of WAVE complexes, is recruited at the entry site (PMID:15769844)
• Abi-1 promotes Abl-mediated BCAP phosphorylation and suggest that Abi-1 in general coordinates kinase-substrate interactions (PMID:15893754)
• Overexpression of e3B1 in NIH3T3/EGFR cells sensitized EGF-induced activation of Rac1, whereas it had no impact on EGF-induced activation of p21Ras. (PMID:16182283)
• results suggest that the Eps8/Abi1 complex is capable of regulating the localization and/or activity of actin nucleators (PMID:16225669)
• c-Abl activates WAVE2 via tyrosine phosphorylation to promote actin remodeling in vivo; Abi-1 forms the crucial link between these two factors (PMID:16899465)
• NESH (Abi-3), like Abi-1 and Abi-2, is a component of the Abi/WAVE complex, but likely plays a different role in the regulation of c-Abl. (PMID:17101133)
• Data show that Chlamydia trachomatis activates Rac and promotes its interaction with WAVE2 and Abi-1 to activate the Arp2/3 complex resulting in the induction of actin cytoskeletal rearrangements that are required for invasion. (PMID:17501982)
• by activating the Abi1 pathway, Bcr-Abl induces a translocation of MT1-MMP to a membrane-associated structural complex enriched with F-actin and adhesion molecules. (PMID:17943163)
• ABI-1 plays an important role in the spread of breast cancer and this role may be mediated via the phosphatidylinositol 3-kinase pathway. (PMID:17951403)
• c-Abl kinase inhibition mediated by a phosphotyrosine located in trans in the c-Abl substrate, Abi1. (PMID:18328268)
• These findings uncover a novel link between cadherin-mediated adhesion and the regulation of actin dynamics through the requirement for an Abi/Dia complex for the formation and stability of cell-cell junctions. (PMID:19158278)
• Downregulation of ABI1 expression in human gastric carcinoma may play a critical role in tumor progression and in determining patient prognosis. (PMID:19554484)
• Abl interactor 1 regulates Src-Id1-matrix metalloproteinase 9 axis and is required for invadopodia formation, extracellular matrix degradation and tumor growth of human breast cancer cells (PMID:19843640)
• Combination of experimental and computational interactome research was used for the analysis of protein-protein interactions between Abi-1 and VASP in human platelets. (PMID:20110575)
• Expression of Abi1 is up-regulated in hepatocellular carcinoma tissues compared with corresponding para carcinomatous liver tissue, and is significantly correlated with tumor number, capsular formation, venous invasion, grade and prognosis. (PMID:20137729)
• The ABI1 gene is down-regulated in gastric cancer cells. ABI1 overexpression effectively inhibits cell proliferation. (PMID:20193272)
• Abi1 isoforms differentially regulate macropinocytosis as a consequence of their different relative affinities for activated Rac1 in Wave 2 complex. (PMID:20479892)
• Macropinocytosis is regulated by interactions between Abi1 pY213 and the C-terminal SH2 domain of p85-thereby linking Abl kinase signaling to p85-dependent regulation of macropinocytosis. (PMID:20598684)
• Breast tumors expressing high levels of Abi1 are significantly associated with early recurrence and worse survival on multivariate analysis. (PMID:21046228)
• Study implicates that the integrity of SOS1/EPS8/ABI1 tri-complex is a determinant of ovarian cancer metastasis. (PMID:21118970)
• Data show that disruption of phosphorylation sits Y398 and Y213 significantly weakens the binding of Abi-1 to c-Abl. (PMID:21320496)
• CDK1-mediated phosphorylation of Abi1 attenuates Bcr-Abl-induced F-actin assembly and tyrosine phosphorylation of WAVE complex during mitosis (PMID:21900237)
• The phosphorylation and dephosphorylation cycle of VASP by the Abi-1-bridged mechanism regulates association of VASP with focal adhesions, which may regulate adhesion of Bcr-Abl-transformed leukaemic cells. (PMID:22014333)
• Down-regulation of E3B1/ABI-1 expression in human carcinomas may play a critical role in tumor progression and in determining disease prognosis. (PMID:22430194)
• a possible role for Abi1 as a marker for early KRAS mutation in hyperplastic polyps (PMID:22808230)
• Data indicate that Abi1 is activated by the c-Abl-Crk-associated substrate (CAS) pathway, and Abi1 reciprocally controls the activation of its upstream regulator c-Abl. (PMID:23740246)
• Abi1 is expressed at the invasive front of colorectal carcinomas and localizes to the leading edge of lamellipodia in cultured colorectal carcinoma cells. (PMID:24196611)
• These results indicate that the alpha4-Abi-1 signaling pathway may mediate acquisition of the drug-resistant phenotype of leukemic cells. (PMID:24699303)
• Our data indicate that phosphorylated Abi1 contributes to the invasive properties of colorectal cancer. (PMID:24913355)
• Suggest that Abi1 acts as a tumor-promoting gene in epithelial ovarian cancer progression, which may lead to unfavorable prognosis. (PMID:26193797)
• these data indicate that HCV exploits host Abi1 protein via NS5A to modulate MEK/ERK signaling pathway for its own propagation. (PMID:27551040)
• our findings indicated that ABI1 contributes to the development and progression of hepatocellular carcinoma (HCC) as an oncogene and may serve as a valuable prognostic marker for HCC patients. (PMID:28339046)
• The expression of ABI1 was suppressed by miR-181a/b, and ABI1 was validated as a direct target of miR-181a/b. miR-181a/b were significantly upregulated in aggressive neuroblastoma, which enhanced its tumorigenesis and progression by suppressing the expression of ABI1. (PMID:29802737)
• These studies demonstrate a requirement for human herpesvirus 5 pUL135 interactions with Abi-1 and CIN85 for regulation of EGFR and mechanistically link the regulation of EGFR to virus reactivation. (PMID:30089695)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	abi1a	ENSDARG00000010155
danio_rerio	abi1b	ENSDARG00000062991
mus_musculus	Abi1	ENSMUSG00000058835
rattus_norvegicus	Abi1	ENSRNOG00000031325

Paralogs (2): ABI3 (ENSG00000108798), ABI2 (ENSG00000138443)

Protein

Protein identifiers

Abl interactor 1 — Q8IZP0 (reviewed: Q8IZP0)

Alternative names: Abelson interactor 1, Abl-binding protein 4, Eps8 SH3 domain-binding protein, Nap1-binding protein, Spectrin SH3 domain-binding protein 1, e3B1

All UniProt accessions (4): A0A0A0MRT6, B6VEX3, B6VEX4, Q8IZP0

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Interacts with ABL1, ENAH, STX1A, SNAP25, VAMP2, EPS8, and through its N-terminus with WASF1. Part of a complex consisting of ABI1, STX1A and SNAP25. Part of a complex consisting of ABI1, EPS8 and SOS1. Interacts with SOS1, SOS2, GRB2, SPTA1 and the first SH3 domain of NCK1. Isoform 6 does not interact with NCK1. Component of the WAVE2 complex composed of ABI1, CYFIP1/SRA1, NCKAP1/NAP1 (NCKAP1l/HEM1 in hematopoietic cells) and WASF2/WAVE2. Interacts (via SH3 domain) with SHANK2 and SHANK3, but not SHANK1; the interaction is direct. Interacts with the heterodimer MYC:MAX; the interaction may enhance MYC:MAX transcriptional activity. Interacts with FNBP1L (via the SH3 domain), WASF2, and CDC42, but only in the presence of FNBP1L. (Microbial infection) Interacts with human cytomegalovirus/HHV-5 protein UL135.

Subcellular location. Cytoplasm. Nucleus. Cell projection. Lamellipodium. Filopodium. Growth cone. Postsynaptic density. Cytoskeleton.

Tissue specificity. Widely expressed, with highest expression in brain.

Post-translational modifications. Phosphorylated on tyrosine residues after serum stimulation or induction by v-Abl. Seems to be phosphorylated at Tyr-53 by ABL1, required for nuclear but not for synaptic localization.

Disease relevance. 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.

Domain organisation. The t-SNARE coiled-coil homology domain is necessary and sufficient for interaction with STX1A.

Similarity. Belongs to the ABI family.

Isoforms (12)

UniProt ID	Names	Canonical?
Q8IZP0-1	1	yes
Q8IZP0-2	2, long, B48
Q8IZP0-3	3
Q8IZP0-4	4
Q8IZP0-5	5
Q8IZP0-6	6
Q8IZP0-7	7, 4
Q8IZP0-8	8, 5
Q8IZP0-9	9, 2
Q8IZP0-10	10, B30
Q8IZP0-11	11
Q8IZP0-12	12

RefSeq proteins (19): NP_001012768, NP_001012769, NP_001012770, NP_001171587, NP_001171590, NP_001171591, NP_001171592, NP_001171593, NP_001171594, NP_001171595, NP_001171596, NP_001334958, NP_001334959, NP_001334960, NP_001334961, NP_001334962, NP_001334963, NP_001397838, NP_005461 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000727	T_SNARE_dom	Domain
IPR001452	SH3_domain	Domain
IPR012849	Abl-interactor_HHR_dom	Domain
IPR028457	ABI	Family
IPR035725	Abi1_SH3	Domain
IPR036028	SH3-like_dom_sf	Homologous_superfamily

Pfam: PF00018, PF07815

UniProt features (46 total): modified residue 16, splice variant 9, compositionally biased region 8, region of interest 4, sequence conflict 3, domain 2, initiator methionine 1, chain 1, site 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7LXE	X-RAY DIFFRACTION	1.88

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IZP0-F1	66.57	0.41

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 95–96 (breakpoint for translocation to form kmt2a/mll1-abi1)

Post-translational modifications (16): 2, 53, 174, 178, 183, 187, 213, 215, 216, 222, 225, 319, 323, 455, 466, 507

Function

Pathways and Gene Ontology

Reactome pathways

23 pathways

ID	Pathway
R-HSA-2029482	Regulation of actin dynamics for phagocytic cup formation
R-HSA-4420097	VEGFA-VEGFR2 Pathway
R-HSA-5663213	RHO GTPases Activate WASPs and WAVEs
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-9013404	RAC2 GTPase cycle
R-HSA-9013423	RAC3 GTPase cycle
R-HSA-9664422	FCGR3A-mediated phagocytosis
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-194138	Signaling by VEGF
R-HSA-194315	Signaling by Rho GTPases
R-HSA-195258	RHO GTPase Effectors
R-HSA-2029480	Fcgamma receptor (FCGR) dependent phagocytosis
R-HSA-5663205	Infectious disease
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases
R-HSA-9012999	RHO GTPase cycle
R-HSA-9658195	Leishmania infection
R-HSA-9664407	Parasite infection
R-HSA-9664417	Leishmania phagocytosis
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3
R-HSA-9824443	Parasitic Infection Pathways

MSigDB gene sets: 320 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_DENDRITE_DEVELOPMENT, GOBP_REGULATION_OF_PROTEIN_TYROSINE_KINASE_ACTIVITY, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, REACTOME_INNATE_IMMUNE_SYSTEM, HNF3ALPHA_Q6, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_MYELOID_CELL_DEVELOPMENT, KENNY_CTNNB1_TARGETS_UP, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, GOBP_NEUROGENESIS, GGGTGGRR_PAX4_03, GOBP_POSITIVE_REGULATION_OF_PEPTIDYL_TYROSINE_PHOSPHORYLATION, GOMF_KINASE_ACTIVATOR_ACTIVITY

GO Biological Process (10): somitogenesis (GO:0001756), neuron migration (GO:0001764), cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), actin polymerization or depolymerization (GO:0008154), negative regulation of cell population proliferation (GO:0008285), megakaryocyte development (GO:0035855), dendrite morphogenesis (GO:0048813), cell projection morphogenesis (GO:0048858), positive regulation of protein tyrosine kinase activity (GO:0061098), lamellipodium morphogenesis (GO:0072673)

GO Molecular Function (6): cytoskeletal protein binding (GO:0008092), SH3 domain binding (GO:0017124), protein tyrosine kinase activator activity (GO:0030296), signaling adaptor activity (GO:0035591), cadherin binding (GO:0045296), protein binding (GO:0005515)

GO Cellular Component (17): nucleus (GO:0005634), endoplasmic reticulum (GO:0005783), cytosol (GO:0005829), cytoskeleton (GO:0005856), postsynaptic density (GO:0014069), lamellipodium (GO:0030027), growth cone (GO:0030426), SCAR complex (GO:0031209), filopodium tip (GO:0032433), extracellular exosome (GO:0070062), actin-based cell projection (GO:0098858), cytoplasm (GO:0005737), filopodium (GO:0030175), cell leading edge (GO:0031252), cell projection (GO:0042995), neuron projection (GO:0043005), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
RHO GTPase cycle	3
Signaling by Rho GTPases	2
Fcgamma receptor (FCGR) dependent phagocytosis	1
Signaling by VEGF	1
RHO GTPase Effectors	1
Leishmania phagocytosis	1
Immune System	1
Signaling by Receptor Tyrosine Kinases	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Innate Immune System	1
Disease	1
Signal Transduction	1
Parasitic Infection Pathways	1
Leishmania infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cytoplasm	3
plasma membrane bounded cell projection	3
protein tyrosine kinase activity	2
intracellular membrane-bounded organelle	2
anterior/posterior pattern specification	1
segmentation	1
chordate embryonic development	1
anatomical structure formation involved in morphogenesis	1
somite development	1
cell migration	1
generation of neurons	1
enzyme-linked receptor protein signaling pathway	1
actin filament organization	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
megakaryocyte differentiation	1
myeloid cell development	1
dendrite development	1
cell morphogenesis involved in neuron differentiation	1
neuron projection morphogenesis	1
cell morphogenesis	1
anatomical structure morphogenesis	1
cell projection organization	1
positive regulation of protein kinase activity	1
positive regulation of peptidyl-tyrosine phosphorylation	1
regulation of protein tyrosine kinase activity	1
lamellipodium organization	1
plasma membrane bounded cell projection morphogenesis	1
protein binding	1
protein domain specific binding	1
protein kinase activator activity	1
protein-macromolecule adaptor activity	1
cell adhesion molecule binding	1
binding	1
endomembrane system	1
intracellular membraneless organelle	1
asymmetric synapse	1
postsynaptic specialization	1

Protein interactions and networks

STRING

1396 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ABI1	EPS8	Q12929	999
ABI1	NCKAP1	Q9Y2A7	998
ABI1	WASF2	Q9Y6W5	998
ABI1	SOS1	Q07889	997
ABI1	CYFIP1	Q7L576	997
ABI1	BRK1	Q8WUW1	997
ABI1	CYFIP2	Q96F07	997
ABI1	NCKAP1L	P55160	994
ABI1	WASF1	Q92558	994
ABI1	ABL1	P00519	978
ABI1	WASF3	Q9UPY6	942
ABI1	WASL	O00401	922
ABI1	ABI2	Q9NYB9	864
ABI1	HNRNPK	P61978	857
ABI1	BAIAP2	Q9UQB8	848

IntAct

215 interactions, top by confidence:

A	B	Type	Score
NCKAP1	ABI1	psi-mi:“MI:0915”(physical association)	0.910
ABI1	NCKAP1	psi-mi:“MI:0915”(physical association)	0.910
ABI1	NCKAP1	psi-mi:“MI:0407”(direct interaction)	0.910
ABL1	ABI1	psi-mi:“MI:0915”(physical association)	0.900
ABI1	ABL1	psi-mi:“MI:0915”(physical association)	0.900
ABI1	ABL1	psi-mi:“MI:0407”(direct interaction)	0.900
ABL1	ABI1	psi-mi:“MI:0407”(direct interaction)	0.900
WASF2	ABI1	psi-mi:“MI:0403”(colocalization)	0.830
ABI1	WASF2	psi-mi:“MI:0915”(physical association)	0.830
WASF2	ABI1	psi-mi:“MI:0915”(physical association)	0.830
BAIAP2	YWHAZ	psi-mi:“MI:0914”(association)	0.800
BAIAP2	YWHAQ	psi-mi:“MI:0914”(association)	0.740
BRK1	HSBP1	psi-mi:“MI:0914”(association)	0.740
VASP	CEP43	psi-mi:“MI:0914”(association)	0.740
CYFIP1	ABI1	psi-mi:“MI:0915”(physical association)	0.740
NCKAP1	YWHAH	psi-mi:“MI:0914”(association)	0.730
ABI1	NCK1	psi-mi:“MI:0915”(physical association)	0.670
BAIAP2	ABI1	psi-mi:“MI:0915”(physical association)	0.670
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640

BioGRID (318): ABI1 (Biochemical Activity), ABL1 (Reconstituted Complex), ABI1 (Affinity Capture-Western), ENAH (Affinity Capture-Western), ENAH (Reconstituted Complex), WASF2 (Reconstituted Complex), ABI1 (Affinity Capture-MS), ABI1 (Affinity Capture-MS), ABI1 (Affinity Capture-MS), ABI1 (Affinity Capture-MS), ABI1 (Affinity Capture-MS), ABI1 (Affinity Capture-MS), ABI1 (Affinity Capture-MS), ABI1 (Affinity Capture-MS), ABI1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2JTZ2, A6QPB3, A8WR59, B3DM43, F1M8W4, O14974, O35167, O35348, O55000, O76368, O88207, O93383, P12107, P20908, P20909, P35710, P35711, P35712, P40645, P40647, P43322, P83371, Q02297, Q03637, Q05199, Q07563, Q10728, Q32NP7, Q571K4, Q5RCU4, Q60467, Q61245, Q6DR98, Q6DRG7, Q7TQG1, Q7ZXH3, Q80W00, Q86SQ0, Q8IPJ3, Q8IVL1

Diamond homologs: A4FU49, A6QLK6, A7A261, B1V8A0, E2RP94, E7F1U2, F1LRS8, G3V9M2, G5EC32, M0R4F8, O35179, O35180, O35964, O43125, O43586, O55043, O75886, O76041, O77506, O88811, O93436, P10569, P20929, P29355, P32793, P34416, P43603, P49710, P52735, P62484, P70297, P98171, Q06449, Q08012, Q0U6X7, Q13387, Q14155, Q14847, Q15811, Q2KJA1

SIGNOR signaling

16 interactions.

A	Effect	B	Mechanism
ABI1	up-regulates	CBL	binding
ABL1	up-regulates	ABI1	phosphorylation
MAPK1	up-regulates	ABI1	phosphorylation
MAPK3	up-regulates	ABI1	phosphorylation
ABI1	“form complex”	“WRC complex”	binding
ABI1	“form complex”	“WAVE complex”	binding
CDK1	“down-regulates activity”	ABI1	phosphorylation
CyclinB/CDK1	“down-regulates activity”	ABI1	phosphorylation
Gbeta	up-regulates	ABI1	phosphorylation
ERK1/2	up-regulates	ABI1	phosphorylation
PTEN	“down-regulates quantity by destabilization”	ABI1	dephosphorylation
ABI1	up-regulates	ABL1	binding
DTNBP1	“up-regulates activity”	ABI1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 166 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
RHO GTPases Activate WASPs and WAVEs	16	39.6×	3e-20
FCGR3A-mediated phagocytosis	25	36.6×	8e-31
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	9	36.5×	6e-11
Regulation of KIT signaling	7	32.9×	3e-08
Regulation of signaling by CBL	8	31.0×	4e-09
Parasite infection	11	29.7×	3e-12
Leishmania phagocytosis	11	29.7×	3e-12
Activation of BAD and translocation to mitochondria	5	29.7×	9e-06

GO biological processes:

GO term	Partners	Fold	FDR
Fc-gamma receptor signaling pathway involved in phagocytosis	9	42.4×	1e-10
peptidyl-tyrosine phosphorylation	11	31.1×	2e-11
Fc-epsilon receptor signaling pathway	6	29.5×	6e-06
negative regulation of inflammatory response to antigenic stimulus	7	28.3×	8e-07
leukocyte migration	6	25.1×	1e-05
positive regulation of actin filament polymerization	11	24.4×	2e-10
positive regulation of lamellipodium assembly	6	24.2×	1e-05
Rac protein signal transduction	6	22.6×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

81 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	1
Uncertain significance	43
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
150697	GRCh38/hg38 10p12.1-11.23(chr10:26823016-30248926)x1	Pathogenic
1527577	GRCh37/hg19 10p15.1-11.21(chr10:6273934-34732521)	Pathogenic
3063151	GRCh37/hg19 10p12.1-11.23(chr10:25646101-30715668)x1	Pathogenic
443260	GRCh37/hg19 10p15.3-q11.23(chr10:100026-50961640)x3	Pathogenic
59666	GRCh38/hg38 10p12.1(chr10:25484473-26963308)x3	Pathogenic
150600	GRCh38/hg38 10p12.31-11.22(chr10:19088161-32732293)x3	Likely pathogenic

SpliceAI

2661 predictions. Top by Δscore:

Variant	Effect	Δscore
10:26746331:AGAGT:A	acceptor_gain	1.0000
10:26746332:GA:G	acceptor_gain	1.0000
10:26746332:GAGTG:G	acceptor_gain	1.0000
10:26748743:CAA:C	acceptor_gain	1.0000
10:26748744:AAC:A	acceptor_loss	1.0000
10:26748745:ACTA:A	acceptor_loss	1.0000
10:26748746:C:CC	acceptor_gain	1.0000
10:26748746:CT:C	acceptor_loss	1.0000
10:26748748:A:C	acceptor_gain	1.0000
10:26751595:TACC:T	donor_loss	1.0000
10:26751596:A:AC	donor_gain	1.0000
10:26751597:C:CA	donor_loss	1.0000
10:26751597:C:CC	donor_gain	1.0000
10:26751597:CCTTT:C	donor_gain	1.0000
10:26751779:AGCAA:A	acceptor_gain	1.0000
10:26751781:CAA:C	acceptor_gain	1.0000
10:26751782:AA:A	acceptor_gain	1.0000
10:26751784:C:CC	acceptor_gain	1.0000
10:26765213:CACA:C	donor_loss	1.0000
10:26765214:ACAC:A	donor_loss	1.0000
10:26765215:CA:C	donor_loss	1.0000
10:26765216:ACC:A	donor_loss	1.0000
10:26765217:C:A	donor_loss	1.0000
10:26765314:TTCCA:T	acceptor_gain	1.0000
10:26765315:TCCA:T	acceptor_gain	1.0000
10:26765316:CCA:C	acceptor_gain	1.0000
10:26765316:CCAC:C	acceptor_gain	1.0000
10:26765317:CA:C	acceptor_gain	1.0000
10:26765317:CAC:C	acceptor_gain	1.0000
10:26765318:ACTGA:A	acceptor_loss	1.0000

AlphaMissense

3122 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:26748598:A:T	V500D	1.000
10:26748610:G:T	P496H	1.000
10:26748613:A:G	F495S	1.000
10:26748619:C:T	G493D	1.000
10:26748620:C:G	G493R	1.000
10:26748640:C:T	G486E	1.000
10:26748641:C:G	G486R	1.000
10:26748641:C:T	G486R	1.000
10:26748648:C:A	W483C	1.000
10:26748648:C:G	W483C	1.000
10:26748650:A:G	W483R	1.000
10:26748650:A:T	W483R	1.000
10:26748697:A:G	F467S	1.000
10:26748703:A:G	L465P	1.000
10:26748739:G:T	A453E	1.000
10:26777192:A:C	L112W	1.000
10:26777192:A:G	L112S	1.000
10:26777198:C:A	G110V	1.000
10:26777198:C:T	G110D	1.000
10:26777199:C:A	G110C	1.000
10:26777199:C:G	G110R	1.000
10:26777201:A:C	I109S	1.000
10:26777201:A:T	I109N	1.000
10:26777203:C:A	E108D	1.000
10:26777203:C:G	E108D	1.000
10:26777204:T:A	E108V	1.000
10:26777204:T:C	E108G	1.000
10:26777204:T:G	E108A	1.000
10:26777205:C:T	E108K	1.000
10:26777206:T:A	R107S	1.000

dbSNP variants (sampled 300 via entrez): RS1000001829 (10:26757236 G>A), RS1000101720 (10:26837114 G>A), RS1000144843 (10:26794941 T>G), RS1000171995 (10:26824850 G>A), RS1000196465 (10:26750461 T>A), RS1000215674 (10:26796473 T>C), RS1000258089 (10:26782204 C>T), RS1000262600 (10:26758012 G>T), RS1000332904 (10:26830514 G>A), RS1000386337 (10:26764946 G>A), RS1000396660 (10:26849132 G>A), RS1000403498 (10:26807861 G>A), RS1000447924 (10:26757621 G>T), RS1000460300 (10:26848936 T>C), RS1000516530 (10:26794784 T>C)

Disease associations

OMIM: gene MIM:603050 | disease phenotypes: MIM:614651

GenCC curated gene-disease

Mondo (1): deafness-encephaloneuropathy-obesity-valvulopathy syndrome (MONDO:0013837)

Orphanet (1): Deafness-encephaloneuropathy-obesity-valvulopathy syndrome (Orphanet:254898)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

44 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, affects expression	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, affects expression	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Ozone	affects expression, affects cotreatment, increases oxidation, increases abundance	2
Cadmium Chloride	decreases expression, increases abundance	2
FR900359	affects phosphorylation	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, increases oxidation	1
bisphenol A	affects methylation	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression	1
cobaltous chloride	increases expression	1
benzo(e)pyrene	decreases methylation	1
coumarin	decreases phosphorylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
nutlin 3	increases secretion, affects cotreatment	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases expression, increases response to substance	1
Bortezomib	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Cadmium	decreases expression, increases abundance	1
Caffeine	affects phosphorylation	1
Coumestrol	decreases expression	1
Dactinomycin	affects cotreatment, increases secretion	1
Dimethyl Sulfoxide	decreases expression	1
Doxorubicin	decreases expression	1
Furaldehyde	affects cotreatment, decreases expression, affects localization	1
Gallic Acid	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D2HQ	Abcam Raji ABI1 KO	Cancer cell line	Male
CVCL_UQ00	Abcam Jurkat ABI1 KO	Cancer cell line	Male
CVCL_WQ84	Abcam K-562 ABI1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.