ABI2

Summary

ABI2 (abl interactor 2, HGNC:24011) is a protein-coding gene on chromosome 2q33.2, encoding Abl interactor 2 (Q9NYB9). Regulator of actin cytoskeleton dynamics underlying cell motility and adhesion.

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.

Source: NCBI Gene 10152 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 56 total — 10 pathogenic
• MANE Select transcript: NM_001375670

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24011
Approved symbol	ABI2
Name	abl interactor 2
Location	2q33.2
Locus type	gene with protein product
Status	Approved
Aliases	ABI-2, AIP-1, ABI2B, AblBP3, argBPIA, SSH3BP2
Ensembl gene	ENSG00000138443
Ensembl biotype	protein_coding
OMIM	606442
Entrez	10152

Gene structure

Transcript identifiers

Ensembl transcripts: 81 — 66 protein_coding, 8 nonsense_mediated_decay, 6 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000261016, ENST00000261017, ENST00000261018, ENST00000295851, ENST00000376135, ENST00000411547, ENST00000413635, ENST00000416001, ENST00000416396, ENST00000417864, ENST00000422511, ENST00000422719, ENST00000424558, ENST00000425253, ENST00000430418, ENST00000430574, ENST00000431886, ENST00000441061, ENST00000444584, ENST00000447762, ENST00000451591, ENST00000454023, ENST00000464761, ENST00000494215, ENST00000880581, ENST00000880582, ENST00000880583, ENST00000880584, ENST00000880585, ENST00000880586, ENST00000880587, ENST00000880588, ENST00000880589, ENST00000880590, ENST00000880591, ENST00000880592, ENST00000880593, ENST00000880594, ENST00000880595, ENST00000880596, ENST00000880597, ENST00000880598, ENST00000880599, ENST00000880600, ENST00000880601, ENST00000880602, ENST00000880603, ENST00000918156, ENST00000918157, ENST00000918158, ENST00000918159, ENST00000918160, ENST00000918161, ENST00000918163, ENST00000918164, ENST00000918166, ENST00000918167, ENST00000918168, ENST00000918169, ENST00000918170, ENST00000955872, ENST00000955873, ENST00000955874, ENST00000955875, ENST00000955876, ENST00000955877, ENST00000955878, ENST00000955879, ENST00000955880, ENST00000955881, ENST00000955882, ENST00000955883, ENST00000955884, ENST00000955885, ENST00000955886, ENST00000955887, ENST00000955888, ENST00000955889, ENST00000955890, ENST00000955891, ENST00000955892

RefSeq mRNA: 88 — MANE Select: NM_001375670 NM_001282925, NM_001282926, NM_001282927, NM_001282932, NM_001375662, NM_001375663, NM_001375664, NM_001375665, NM_001375666, NM_001375667, NM_001375668, NM_001375669, NM_001375670, NM_001375671, NM_001375672, NM_001375673, NM_001375674, NM_001375675, NM_001375676, NM_001375677, NM_001375678, NM_001375679, NM_001375680, NM_001375681, NM_001375682, NM_001375683, NM_001375684, NM_001375685, NM_001375686, NM_001375687, NM_001375688, NM_001375689, NM_001375690, NM_001375691, NM_001375692, NM_001375693, NM_001375695, NM_001375696, NM_001375698, NM_001375699, NM_001375702, NM_001375704, NM_001375706, NM_001375707, NM_001375708, NM_001375709, NM_001375710, NM_001375711, NM_001375712, NM_001375714, NM_001375717, NM_001375719, NM_001375721, NM_001375722, NM_001375723, NM_001375724, NM_001375725, NM_001375726, NM_001375727, NM_001375728, NM_001375729, NM_001375730, NM_001375731, NM_001375732, NM_001375733, NM_001375734, NM_001375735, NM_001375736, NM_001375737, NM_001375738, NM_001375739, NM_001375740, NM_001375741, NM_001375742, NM_001375743, NM_001375744, NM_001375745, NM_001375746, NM_001375747, NM_001375748, NM_001375749, NM_001375750, NM_001375751, NM_001375752, NM_001375753, NM_001375754, NM_001375755, NM_005759

CCDS: CCDS2358, CCDS63093, CCDS63094, CCDS92932, CCDS92933

Canonical transcript exons

ENST00000261018 — 12 exons

Exon	Start	End
ENSE00001790035	203328394	203328631
ENSE00003500152	203395656	203395780
ENSE00003538097	203366877	203367044
ENSE00003544689	203396785	203396967
ENSE00003578200	203411285	203411371
ENSE00003586181	203416908	203417081
ENSE00003679000	203382189	203382206
ENSE00003683511	203394700	203394846
ENSE00003690060	203380208	203380384
ENSE00003751427	203391046	203391143
ENSE00003790642	203402576	203402734
ENSE00003900687	203427177	203432169

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 99.21.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 56.3481 / max 454.0429, expressed in 1804 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
24749	28.5103	1790
24751	22.5594	1748
24752	1.8097	669
24750	1.5853	816
24753	0.9165	404
24755	0.5167	243
24759	0.4239	166
202539	0.0264	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 23	UBERON:0013554	99.21	gold quality
entorhinal cortex	UBERON:0002728	98.99	gold quality
middle temporal gyrus	UBERON:0002771	98.84	gold quality
parietal lobe	UBERON:0001872	98.77	gold quality
postcentral gyrus	UBERON:0002581	98.77	gold quality
lateral globus pallidus	UBERON:0002476	98.53	gold quality
medial globus pallidus	UBERON:0002477	98.28	gold quality
globus pallidus	UBERON:0001875	98.25	gold quality
superior frontal gyrus	UBERON:0002661	98.13	gold quality
cortical plate	UBERON:0005343	98.01	gold quality
superior vestibular nucleus	UBERON:0007227	97.99	gold quality
ventral tegmental area	UBERON:0002691	97.84	gold quality
lateral nuclear group of thalamus	UBERON:0002736	97.82	gold quality
substantia nigra pars compacta	UBERON:0001965	97.43	gold quality
subthalamic nucleus	UBERON:0001906	97.40	gold quality
ventricular zone	UBERON:0003053	97.39	gold quality
inferior vagus X ganglion	UBERON:0005363	97.28	gold quality
pons	UBERON:0000988	97.26	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.21	gold quality
caput epididymis	UBERON:0004358	97.21	gold quality
secondary oocyte	CL:0000655	96.73	gold quality
ganglionic eminence	UBERON:0004023	96.66	gold quality
primary visual cortex	UBERON:0002436	96.57	gold quality
corpus epididymis	UBERON:0004359	96.57	gold quality
cauda epididymis	UBERON:0004360	96.55	gold quality
occipital lobe	UBERON:0002021	96.47	gold quality
trigeminal ganglion	UBERON:0001675	96.12	gold quality
temporal lobe	UBERON:0001871	95.95	gold quality
germinal epithelium of ovary	UBERON:0001304	95.85	gold quality
saphenous vein	UBERON:0007318	95.80	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-9543	yes	6.78
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

165 targeting ABI2, 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-3163	100.00	77.23	8605
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-512-3P	99.97	67.35	1049

Literature-anchored findings (GeneRIF, showing 10)

• Abi-2 may have a key regulatory function in leiomyomas cellular/tissue structural organization during growth and regression (PMID:16488906)
• 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)
• disruption of the interaction between Bcr-Abl and Abi1 by mutations either in Bcr-Abl or Abi1 not only abolished tyrosine phosphorylation of Abi1 and membrane translocation of Abi1/WAVE2 (PMID:17389688)
• TRIM32 is a novel oncogene that promotes tumor growth, metastasis, and resistance to anticancer drugs via degradation of Abl-interactor 2 (PMID:18632609)
• 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)
• Abl-interactor 2 (ABI2) is a novel MLL translocation partner in acute myeloid leukemia. (PMID:22304832)
• TIS21 attenuated Doxorubicin-induced cancer cell senescence by inhibiting linear actin nucleation via Nox4-ROS-ABI2-DRF signal cascade (PMID:27932314)
• Association of Abl interactor 2, ABI2, with platelet/lymphocyte ratio in patients with renal cell carcinoma: A pilot study. (PMID:32496656)
• PIM1 phosphorylates ABI2 to enhance actin dynamics and promote tumor invasion. (PMID:37042842)
• The HHEX-ABI2/SLC17A9 axis induces cancer stem cell-like properties and tumorigenesis in HCC. (PMID:38844969)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	abi2b	ENSDARG00000014875
danio_rerio	abi2a	ENSDARG00000058207
mus_musculus	Abi2	ENSMUSG00000026782
rattus_norvegicus	Abi2	ENSRNOG00000017707

Paralogs (2): ABI3 (ENSG00000108798), ABI1 (ENSG00000136754)

Protein

Protein identifiers

Abl interactor 2 — Q9NYB9 (reviewed: Q9NYB9)

Alternative names: Abelson interactor 2, Abl-binding protein 3, Arg-binding protein 1

All UniProt accessions (17): Q9NYB9, A0A0A0MQU9, A0A0C4DG21, A0A7D9NKC8, E7EP65, E7EUA1, E7EW77, E9PEZ7, F8WAL6, F8WAQ3, F8WAU3, F8WAZ8, F8WBL5, F8WCD7, F8WEB9, H0Y6B5, H7C3Q7

UniProt curated annotations — full annotation on UniProt →

Function. Regulator of actin cytoskeleton dynamics underlying cell motility and adhesion. Functions as a component of the WAVE complex, which activates actin nucleating machinery Arp2/3 to drive lamellipodia formation. Acts as a regulator and substrate of nonreceptor tyrosine kinases ABL1 and ABL2 involved in processes linked to cell growth and differentiation. Positively regulates ABL1-mediated phosphorylation of ENAH, which is required for proper polymerization of nucleated actin filaments at the leading edge. Contributes to the regulation of actin assembly at the tips of neuron projections. In particular, controls dendritic spine morphogenesis and may promote dendritic spine specification toward large mushroom-type spines known as repositories of memory in the brain. In hippocampal neurons, may mediate actin-dependent BDNF-NTRK2 early endocytic trafficking that triggers dendrite outgrowth. Participates in ocular lens morphogenesis, likely by regulating lamellipodia-driven adherens junction formation at the epithelial cell-secondary lens fiber interface. Also required for nascent adherens junction assembly in epithelial cells.

Subunit / interactions. Component of the WAVE complex composed of ABI2, CYFIP1 or CYFIP2, BRK1, NCKAP1 and WASF1/WAVE1. Within the complex, a heterodimer containing NCKAP1 and CYFIP1 interacts with a heterotrimer formed by WAVE1, ABI2 and BRK1. CYFIP2 binds to activated RAC1 which causes the complex to dissociate, releasing activated WASF1. Interacts (via SH3 domain) with ABL1 and ABL2. (Microbial infection) Interacts with human cytomegalovirus UL135.

Subcellular location. Cytoplasm. Nucleus Cell projection. Lamellipodium. Cell projection. Filopodium. Cytoskeleton. Cell junction. Adherens junction.

Tissue specificity. Widely expressed. Abundant in testes, ovary, thymus, and colon, with lower but detectable levels in prostate, peripheral blood leukocytes, and spleen.

Post-translational modifications. Phosphorylated by ABL1.

Disease relevance. There is evidence, including phenotypic data from ABI2-knockout mice, that loss-of-function variants in ABI2 may play a role in autosomal recessive intellectual disability.

Domain organisation. The SH3 domain is critical for binding to ABL1 and ABL2.

Similarity. Belongs to the ABI family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9NYB9-1	1, Abi-2b	yes
Q9NYB9-2	2
Q9NYB9-3	3, Abi-2a
Q9NYB9-4	4

RefSeq proteins (88): NP_001269854, NP_001269855, NP_001269856, NP_001269861, NP_001362591, NP_001362592, NP_001362593, NP_001362594, NP_001362595, NP_001362596, NP_001362597, NP_001362598, NP_001362599, NP_001362600, NP_001362601, NP_001362602, NP_001362603, NP_001362604, NP_001362605, NP_001362606, NP_001362607, NP_001362608, NP_001362609, NP_001362610, NP_001362611, NP_001362612, NP_001362613, NP_001362614, NP_001362615, NP_001362616, NP_001362617, NP_001362618, NP_001362619, NP_001362620, NP_001362621, NP_001362622, NP_001362624, NP_001362625, NP_001362627, NP_001362628, NP_001362631, NP_001362633, NP_001362635, NP_001362636, NP_001362637, NP_001362638, NP_001362639, NP_001362640, NP_001362641, NP_001362643, NP_001362646, NP_001362648, NP_001362650, NP_001362651, NP_001362652, NP_001362653, NP_001362654, NP_001362655, NP_001362656, NP_001362657, NP_001362658, NP_001362659, NP_001362660, NP_001362661, NP_001362662, NP_001362663, NP_001362664, NP_001362665, NP_001362666, NP_001362667, NP_001362668, NP_001362669, NP_001362670, NP_001362671, NP_001362672, NP_001362673, NP_001362674, NP_001362675, NP_001362676, NP_001362677, NP_001362678, NP_001362679, NP_001362680, NP_001362681, NP_001362682, NP_001362683, NP_001362684, NP_005750 (=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
IPR035726	Abi2_SH3	Domain
IPR036028	SH3-like_dom_sf	Homologous_superfamily

Pfam: PF00018, PF07815

UniProt features (40 total): sequence conflict 8, compositionally biased region 7, strand 6, modified residue 5, splice variant 5, helix 3, domain 2, chain 1, sequence variant 1, region of interest 1, turn 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
3P8C	X-RAY DIFFRACTION	2.29
4N78	X-RAY DIFFRACTION	2.43
7USC	ELECTRON MICROSCOPY	3
7USD	ELECTRON MICROSCOPY	3
7USE	ELECTRON MICROSCOPY	3
2ED0	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NYB9-F1	67.14	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.

Post-translational modifications (5): 40, 183, 227, 361, 368

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: 313 (showing top): GOBP_DENDRITE_DEVELOPMENT, E2F_Q4, GCM_MAP4K4, GOBP_LENS_FIBER_CELL_DIFFERENTIATION, GOBP_EPITHELIUM_DEVELOPMENT, WANG_CLIM2_TARGETS_UP, REACTOME_INNATE_IMMUNE_SYSTEM, GCM_PTPRD, GOBP_REGULATION_OF_ACTIN_NUCLEATION, GOBP_EPITHELIAL_CELL_DEVELOPMENT, GOBP_APICAL_JUNCTION_ASSEMBLY, GOBP_DENDRITIC_SPINE_DEVELOPMENT, GOBP_NEUROGENESIS, GOMF_GTPASE_BINDING, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION

GO Biological Process (14): mitophagy (GO:0000423), neuron migration (GO:0001764), cytoskeleton organization (GO:0007010), actin polymerization or depolymerization (GO:0008154), positive regulation of lamellipodium assembly (GO:0010592), cell migration (GO:0016477), Rac protein signal transduction (GO:0016601), peptidyl-tyrosine phosphorylation (GO:0018108), zonula adherens assembly (GO:0045186), cell projection morphogenesis (GO:0048858), regulation of dendritic spine morphogenesis (GO:0061001), lens fiber cell morphogenesis (GO:0070309), positive regulation of Arp2/3 complex-mediated actin nucleation (GO:2000601), nervous system development (GO:0007399)

GO Molecular Function (8): cytoskeletal adaptor activity (GO:0008093), SH3 domain binding (GO:0017124), kinase binding (GO:0019900), ubiquitin protein ligase binding (GO:0031625), signaling adaptor activity (GO:0035591), identical protein binding (GO:0042802), protein binding (GO:0005515), small GTPase binding (GO:0031267)

GO Cellular Component (14): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), cytoskeleton (GO:0005856), adherens junction (GO:0005912), lamellipodium (GO:0030027), SCAR complex (GO:0031209), filopodium tip (GO:0032433), dendritic spine (GO:0043197), actin-based cell projection (GO:0098858), nucleoplasm (GO:0005654), filopodium (GO:0030175), cell projection (GO:0042995), anchoring junction (GO:0070161)

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
cell morphogenesis	2
protein-macromolecule adaptor activity	2
cytoplasm	2
plasma membrane bounded cell projection	2
autophagy of mitochondrion	1
macroautophagy	1
cell migration	1
generation of neurons	1
organelle organization	1
actin filament organization	1
regulation of lamellipodium assembly	1
lamellipodium assembly	1
positive regulation of plasma membrane bounded cell projection assembly	1
positive regulation of lamellipodium organization	1
cell motility	1
small GTPase-mediated signal transduction	1
protein phosphorylation	1
peptidyl-tyrosine modification	1
adherens junction assembly	1
apical junction assembly	1
anatomical structure morphogenesis	1
cell projection organization	1
regulation of neuron projection development	1
regulation of anatomical structure morphogenesis	1
dendritic spine morphogenesis	1
regulation of postsynapse organization	1
lens morphogenesis in camera-type eye	1
lens fiber cell development	1
Arp2/3 complex-mediated actin nucleation	1
regulation of Arp2/3 complex-mediated actin nucleation	1
positive regulation of actin nucleation	1
system development	1
cytoskeletal protein binding	1
protein domain specific binding	1
enzyme binding	1
ubiquitin-like protein ligase binding	1
protein binding	1
binding	1
GTPase binding	1

Protein interactions and networks

STRING

1110 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ABI2	BRK1	Q8WUW1	999
ABI2	CYFIP2	Q96F07	999
ABI2	WASF1	Q92558	998
ABI2	NCKAP1	Q9Y2A7	998
ABI2	CYFIP1	Q7L576	996
ABI2	WASF2	Q9Y6W5	996
ABI2	NCKAP1L	P55160	975
ABI2	WASF3	Q9UPY6	960
ABI2	ABI1	Q8IZP0	864
ABI2	BAIAP2	Q9UQB8	861
ABI2	WASL	O00401	849
ABI2	ABL1	P00519	786
ABI2	SRGAP3	O43295	754
ABI2	FNBP1L	Q5T0N5	742
ABI2	WAS	P42768	729

IntAct

356 interactions, top by confidence:

A	B	Type	Score
ABI2	BRK1	psi-mi:“MI:0915”(physical association)	0.910
ABI2	CYFIP1	psi-mi:“MI:0915”(physical association)	0.870
ABI2	NCK2	psi-mi:“MI:0915”(physical association)	0.850
NCK2	ABI2	psi-mi:“MI:0915”(physical association)	0.850
TRIM32	ABI2	psi-mi:“MI:0915”(physical association)	0.800
ABI2	TRIM32	psi-mi:“MI:0915”(physical association)	0.800
HOMER3	ABI2	psi-mi:“MI:0915”(physical association)	0.740
DTNB	ABI2	psi-mi:“MI:0915”(physical association)	0.740
ABI2	VASP	psi-mi:“MI:0915”(physical association)	0.740
IFT20	ABI2	psi-mi:“MI:0915”(physical association)	0.740
EFS	ABI2	psi-mi:“MI:0915”(physical association)	0.740
KRT15	ABI2	psi-mi:“MI:0915”(physical association)	0.740
ABI2	NUP62	psi-mi:“MI:0915”(physical association)	0.740
IHO1	ABI2	psi-mi:“MI:0915”(physical association)	0.740
TFIP11	ABI2	psi-mi:“MI:0915”(physical association)	0.740
ABI2	HOMER3	psi-mi:“MI:0915”(physical association)	0.740

BioGRID (459): ABI2 (Two-hybrid), ABI2 (Two-hybrid), ABI2 (Two-hybrid), ABI2 (Two-hybrid), ABI2 (Two-hybrid), ABI2 (Two-hybrid), ABI2 (Two-hybrid), ABI2 (Two-hybrid), ABI2 (Two-hybrid), ABI2 (Two-hybrid), ABI2 (Two-hybrid), ABI2 (Two-hybrid), ABI2 (Two-hybrid), ABI2 (Two-hybrid), ABI2 (Two-hybrid)

ESM2 similar proteins: A1ZA47, B6RSP1, O14964, O17583, O35625, O42400, O54916, O60885, O74252, O75553, P0C090, P15330, P16554, P49757, P57094, P97318, P98078, Q0V8S0, Q21502, Q24212, Q24478, Q2LC84, Q5F464, Q5TYQ8, Q5XI07, Q62415, Q641G3, Q69ZW3, Q6DFF2, Q6NUC6, Q75BK1, Q8BG30, Q8CJH2, Q8IPJ3, Q8NDI1, Q96D71, Q96KQ4, Q9BGX5, Q9H3P2, Q9HBD1

Diamond homologs: A1X283, A1ZAY1, A2AAY5, A4RE77, A6NI72, A6SED8, A7EK16, A8MVU1, A8N2Y6, A8PWF6, B0CRJ3, F1M707, O00443, O43586, O77774, O89032, P0CP00, P0CP01, P10569, P14598, P29366, P62484, P97814, Q09014, Q1LYG0, Q2HDI2, Q2KJB5, Q54FG5, Q5I0D6, Q5RAY1, Q5TCX8, Q5TCZ1, Q61194, Q6WKZ7, Q7Z8J6, Q8IVI9, Q8VDG6, Q9NYB9, Q9QX73, Q9Y7Z8

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
NHS	“up-regulates activity”	ABI2	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 70 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	5	30.5×	2e-04
FCGR3A-mediated phagocytosis	5	18.0×	1e-03
Regulation of actin dynamics for phagocytic cup formation	5	17.7×	1e-03
Translocation of SLC2A4 (GLUT4) to the plasma membrane	5	14.8×	1e-03
VEGFA-VEGFR2 Pathway	5	13.4×	1e-03
TP53 Regulates Metabolic Genes	5	12.5×	1e-03
Formation of the cornified envelope	6	10.1×	1e-03
RAC1 GTPase cycle	7	8.2×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
morphogenesis of an epithelium	7	38.2×	4e-07
intermediate filament organization	6	22.9×	7e-05
epithelial cell differentiation	6	16.7×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	10
Likely pathogenic	0
Uncertain significance	36
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (10)

Variant ID	HGVS	Classification
147740	GRCh38/hg38 2q33.2-33.3(chr2:202631428-204929860)x1	Pathogenic
152538	GRCh38/hg38 2q33.1-34(chr2:199946494-209985195)x1	Pathogenic
1526943	GRCh37/hg19 2q33.1-34(chr2:200851079-209054267)	Pathogenic
155234	GRCh38/hg38 2q33.1-34(chr2:199937273-210031924)x1	Pathogenic
1808483	GRCh37/hg19 2q32.2-34(chr2:189909904-209468383)x1	Pathogenic
3062481	GRCh37/hg19 2q33.2-34(chr2:204110688-211638554)x1	Pathogenic
3062594	GRCh37/hg19 2q32.3-34(chr2:194305623-215261531)x1	Pathogenic
4279382	GRCh37/hg19 2q32.3-33.3(chr2:194127471-206791898)x1	Pathogenic
813263	Single allele	Pathogenic
813264	Single allele	Pathogenic

SpliceAI

3545 predictions. Top by Δscore:

Variant	Effect	Δscore
2:203328630:AGG:A	donor_loss	1.0000
2:203328631:GGTGC:G	donor_loss	1.0000
2:203328632:G:GA	donor_loss	1.0000
2:203366873:CCA:C	acceptor_loss	1.0000
2:203366874:CA:C	acceptor_loss	1.0000
2:203366875:A:AG	acceptor_gain	1.0000
2:203366875:A:AT	acceptor_loss	1.0000
2:203366876:G:A	acceptor_loss	1.0000
2:203366876:G:GT	acceptor_gain	1.0000
2:203366876:GT:G	acceptor_gain	1.0000
2:203366876:GTC:G	acceptor_gain	1.0000
2:203366876:GTCA:G	acceptor_gain	1.0000
2:203367014:G:GT	donor_gain	1.0000
2:203367045:G:GG	donor_gain	1.0000
2:203380193:C:G	acceptor_gain	1.0000
2:203380194:A:AG	acceptor_gain	1.0000
2:203380195:T:G	acceptor_gain	1.0000
2:203380198:T:G	acceptor_gain	1.0000
2:203380200:T:G	acceptor_gain	1.0000
2:203380382:AAGG:A	donor_loss	1.0000
2:203380384:GGTA:G	donor_loss	1.0000
2:203380385:G:GG	donor_gain	1.0000
2:203380385:G:T	donor_loss	1.0000
2:203396779:CCTCA:C	acceptor_loss	1.0000
2:203396780:CTCAG:C	acceptor_loss	1.0000
2:203396781:TCAG:T	acceptor_loss	1.0000
2:203396782:CA:C	acceptor_loss	1.0000
2:203396783:A:AG	acceptor_gain	1.0000
2:203396783:A:C	acceptor_loss	1.0000
2:203396784:G:GC	acceptor_gain	1.0000

AlphaMissense

3511 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000016132 (2:203386444 T>G), RS1000067158 (2:203407076 T>C,G), RS1000082260 (2:203364603 T>C), RS1000150120 (2:203351243 G>A), RS1000159201 (2:203369214 T>A,C), RS1000192348 (2:203412448 C>G), RS1000205485 (2:203380137 A>G,T), RS1000215999 (2:203344390 G>A,T), RS1000239719 (2:203328969 A>T), RS1000244399 (2:203336496 C>G,T), RS1000258450 (2:203419193 T>A,C), RS1000294873 (2:203336115 T>C), RS1000296517 (2:203375156 G>T), RS1000313438 (2:203349365 C>A,G), RS1000341329 (2:203375525 G>A,T)

Disease associations

OMIM: gene MIM:606442 | disease phenotypes:

GenCC curated gene-disease

Mondo (2): neurodevelopmental disorder (MONDO:0700092), pulmonary arterial hypertension (MONDO:0015924)

Orphanet (2): Pulmonary arterial hypertension (Orphanet:182090), Idiopathic/heritable pulmonary arterial hypertension (Orphanet:422)

HPO phenotypes

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

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST000087_4	Subclinical atherosclerosis traits (other)	4.000000e-07
GCST001207_2	Butyrylcholinesterase levels	4.000000e-18
GCST004250_4	Alanine aminotransferase (ALT) levels after remission induction therapy in actute lymphoblastic leukemia (ALL)	7.000000e-06
GCST006479_90	Diverticular disease	2.000000e-06
GCST008154_45	Trunk fat mass	8.000000e-06
GCST008790_12	Urinary albumin-to-creatinine ratio	1.000000e-09
GCST010698_18	Subcortical volume (min-P)	1.000000e-08
GCST010699_69	Brain morphology (min-P)	9.000000e-20
GCST010700_6	Cortical thickness (MOSTest)	2.000000e-14
GCST010701_36	Cortical surface area (MOSTest)	2.000000e-24
GCST010702_146	Subcortical volume (MOSTest)	2.000000e-13
GCST010703_42	Brain morphology (MOSTest)	1.000000e-08

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0005278	cardiovascular disease biomarker measurement
EFO:0004571	butyrylcholinesterase measurement
EFO:0007965	response to combination chemotherapy
EFO:0009959	diverticular disease
EFO:0007778	urinary albumin to creatinine ratio
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625
D000081029	Pulmonary Arterial Hypertension	C08.381.423.847

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, increases expression	4
sodium arsenite	increases expression, affects expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	2
Tobacco Smoke Pollution	decreases expression, increases methylation	2
Tretinoin	increases expression, decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, decreases expression	1
manganese chloride	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
Irinotecan	decreases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1
Acetaminophen	increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases expression	1
Caffeine	increases phosphorylation	1
Dexamethasone	affects cotreatment, decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Ivermectin	decreases expression	1
Manganese	increases expression	1
Oxygen	increases expression	1
Thiram	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Lithium Chloride	decreases expression	1
Copper Sulfate	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT00058929	PHASE4	COMPLETED	A Transition Study From Flolan® to Remodulin® in Patients With Pulmonary Arterial Hypertension
NCT00303459	PHASE4	COMPLETED	Effects of the Combination of Bosentan and Sildenafil Versus Sildenafil Monotherapy on Pulmonary Arterial Hypertension (PAH)
NCT00323297	PHASE4	COMPLETED	Assess the Efficacy and Safety of Sildenafil When Added to Bosentan in the Treatment of Pulmonary Arterial Hypertension
NCT00367770	PHASE4	COMPLETED	BREATHE 5-OL: Tracleer (Bosentan) in Patients With Pulmonary Arterial Hypertension Related to Eisenmenger Physiology
NCT00403650	PHASE4	COMPLETED	Inhaled Iloprost for Sarcoidosis-associated Pulmonary Hypertension
NCT00430716	PHASE4	TERMINATED	To Assess The Efficacy and Safety Of Oral Sildenafil in the Treatment of Pulmonary Arterial Hypertension.
NCT00433329	PHASE4	COMPLETED	Combination Therapy in Pulmonary Arterial Hypertension
NCT00439946	PHASE4	TERMINATED	Safety, Efficacy, and Treatment Satisfaction Switching From Flolan to Remodulin Using the Crono Five Ambulatory Pump in Patients With PAH
NCT00483626	PHASE4	UNKNOWN	Hemodynamic Response After Six Months of Sildenafil
NCT00494533	PHASE4	TERMINATED	Study of Intravenous Remodulin in Patients in India With Pulmonary Arterial Hypertension
NCT00617305	PHASE4	COMPLETED	Study of Add-on Ambrisentan Therapy to Background Phosphodiesterase Type-5 Inhibitor (PDE5i) Therapy in Pulmonary Arterial Hypertension (ATHENA-1)
NCT00625079	PHASE4	WITHDRAWN	Pulmonary Hypertension Secondary to Idiopathic Pulmonary Fibrosis And Treatment With Sildenafil
NCT00625469	PHASE4	WITHDRAWN	Pulmonary Arterial Hypertension Secondary to Idiopathic Pulmonary Fibrosis and Treatment With Bosentan
NCT00705588	PHASE4	UNKNOWN	Long Acting Phosphodiesterase 5 Inhibitors as Add-on Therapy for Patients With Pulmonary Hypertension Treated With Prostanoids.
NCT00741819	PHASE4	COMPLETED	Safety Evaluation of Inhaled Treprostinil Administration Following Transition From Inhaled Ventavis in Pulmonary Arterial Hypertension (PAH) Subjects
NCT01042158	PHASE4	COMPLETED	A Clinical Trial of Ambrisentan and Tadalafil in Pulmonary Arterial Hypertension Associated With Systemic Sclerosis
NCT01105091	PHASE4	COMPLETED	Epoprostenol for Injection in Pulmonary Arterial Hypertension
NCT01105117	PHASE4	COMPLETED	Epoprostenol for Injection in Pulmonary Arterial Hypertension - Extension of AC-066A401
NCT01268553	PHASE4	COMPLETED	Transition From Injectable Prostacyclin Medication to Inhaled Prostacyclin Medication
NCT01302444	PHASE4	TERMINATED	Treprostinil Combined With Tadalafil for Pulmonary Hypertension
NCT01330108	PHASE4	COMPLETED	Safely Change From Bosentan to Ambrisentan in Pulmonary Hypertension
NCT01433328	PHASE4	TERMINATED	Lidocaine Subcutaneous Infusion for Control of Treprostinil Related Site Pain
NCT01508780	PHASE4	WITHDRAWN	Combined Use of Angiography, Optical Coherence Tomography and Intravascular Ultrasound in Evaluation of Pulmonary Vascular Structure and Function in Patients With Pulmonary Arterial Hypertension Treated With Oral Bosentan
NCT01615627	PHASE4	WITHDRAWN	Hypotonic Treprostinil Subcutaneous Infusion for Control of Treprostinil Related Site Pain
NCT01642407	PHASE4	COMPLETED	Safety And Efficacy Of Sildenafil In Children With Pulmonary Arterial Hypertension
NCT01649739	PHASE4	UNKNOWN	Vardenafil as add-on Therapy for Patients With Pulmonary Hypertension Treated With Inhaled Iloprost
NCT02060487	PHASE4	TERMINATED	Effects of Oral Sildenafil on Mortality in Adults With PAH
NCT02253394	PHASE4	TERMINATED	The Combination Ambrisentan Plus Spironolactone in Pulmonary Arterial Hypertension Study
NCT02284737	PHASE4	TERMINATED	A Study to Investigate the Efficacy of PADN to Improved Functional Capacity and Hemodynamics in Patients With PAH
NCT02310672	PHASE4	COMPLETED	REPAIR: Right vEntricular Remodeling in Pulmonary ArterIal hypeRtension
NCT02847260	PHASE4	COMPLETED	Safety and Tolerability of Rapid Dose Titration of Subcutaneous Remodulin® Therapy in PAH Subjects (RAPID)
NCT02882126	PHASE4	WITHDRAWN	An Open Label Extension Study to Evaluate the Safety of Continued Therapy of Subcutanous Remodulin® in Pulmonary Arterial Hypertension
NCT02885012	PHASE4	TERMINATED	Crossover Study From Macitentan or Bosentan Over to Ambrisentan
NCT02891850	PHASE4	COMPLETED	Riociguat rEplacing PDE-5i Therapy evaLuated Against Continued PDE-5i thErapy
NCT02893995	PHASE4	WITHDRAWN	Safety, Tolerability, Pharmacokinetics and Efficacy of Two Different Rates of Subcutanous Remodulin® Dose Titration in Pulmonary Arterial Hypertension
NCT02968901	PHASE4	TERMINATED	Clinical Study Evaluating the Effects of First-line Oral cOmbination theraPy of maciTentan and tadalafIl in Patients With Newly Diagnosed pulMonary Arterial Hypertension (OPTIMA)
NCT03055221	PHASE4	COMPLETED	TRUST-2: Safety and Efficacy of Intravenous Remodulin® in Patients in India With Pulmonary Arterial Hypertension (PAH)
NCT03078907	PHASE4	COMPLETED	Effect of Selexipag on Daily Life Physical Activity of Patients With Pulmonary Arterial Hypertension.