DAB2

Summary

DAB2 (DAB adaptor protein 2, HGNC:2662) is a protein-coding gene on chromosome 5p13.1, encoding Disabled homolog 2 (P98082). Adapter protein that functions as a clathrin-associated sorting protein (CLASP) required for clathrin-mediated endocytosis of selected cargo proteins.

This gene encodes a mitogen-responsive phosphoprotein. It is expressed in normal ovarian epithelial cells, but is down-regulated or absent from ovarian carcinoma cell lines, suggesting its role as a tumor suppressor. This protein binds to the SH3 domains of GRB2, an adaptor protein that couples tyrosine kinase receptors to SOS (a guanine nucleotide exchange factor for Ras), via its C-terminal proline-rich sequences, and may thus modulate growth factor/Ras pathways by competing with SOS for binding to GRB2. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 1601 — RefSeq curated summary.

At a glance

• GWAS associations: 39
• Clinical variants (ClinVar): 145 total
• MANE Select transcript: NM_001343

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2662
Approved symbol	DAB2
Name	DAB adaptor protein 2
Location	5p13.1
Locus type	gene with protein product
Status	Approved
Aliases	DOC-2
Ensembl gene	ENSG00000153071
Ensembl biotype	protein_coding
OMIM	601236
Entrez	1601

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 21 protein_coding, 6 protein_coding_CDS_not_defined, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000320816, ENST00000339788, ENST00000502388, ENST00000502879, ENST00000503513, ENST00000505968, ENST00000507539, ENST00000507990, ENST00000509337, ENST00000509457, ENST00000511536, ENST00000511792, ENST00000512525, ENST00000513052, ENST00000515269, ENST00000515700, ENST00000545653, ENST00000908971, ENST00000908972, ENST00000908973, ENST00000908974, ENST00000908975, ENST00000908976, ENST00000908977, ENST00000908978, ENST00000908979, ENST00000908980, ENST00000908981, ENST00000908982, ENST00000955947, ENST00000955948

RefSeq mRNA: 2 — MANE Select: NM_001343 NM_001244871, NM_001343

CCDS: CCDS34149, CCDS58946

Canonical transcript exons

ENST00000320816 — 15 exons

Exon	Start	End
ENSE00001008650	39375014	39375084
ENSE00001008652	39376650	39377282
ENSE00001008660	39375997	39376106
ENSE00001008662	39381454	39381616
ENSE00001083681	39392365	39392463
ENSE00001083685	39393254	39393393
ENSE00001083689	39382618	39383271
ENSE00001388207	39394230	39394421
ENSE00002050443	39424804	39424980
ENSE00003492814	39388799	39388852
ENSE00003597198	39389097	39389123
ENSE00003623681	39388305	39388367
ENSE00003661019	39390444	39390575
ENSE00003665318	39389852	39389932
ENSE00003845201	39371677	39373425

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 99.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.5228 / max 997.1908, expressed in 1432 samples.

FANTOM5 promoters (22 alternative TSS)

Promoter ID	TPM avg	Samples expressed
61415	29.4540	1376
61411	19.5228	1432
61414	11.8880	1329
61418	7.2193	1369
61419	3.0626	1131
61407	0.6189	357
61417	0.4540	259
61412	0.2732	112
61408	0.2492	101
61423	0.1938	63

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
caput epididymis	UBERON:0004358	99.52	gold quality
corpus epididymis	UBERON:0004359	99.48	gold quality
placenta	UBERON:0001987	99.01	gold quality
tendon of biceps brachii	UBERON:0008188	99.01	gold quality
synovial joint	UBERON:0002217	98.86	gold quality
calcaneal tendon	UBERON:0003701	98.70	gold quality
tendon	UBERON:0000043	98.54	gold quality
right adrenal gland cortex	UBERON:0035827	98.45	gold quality
right adrenal gland	UBERON:0001233	98.25	gold quality
adult mammalian kidney	UBERON:0000082	98.21	gold quality
layer of synovial tissue	UBERON:0007616	98.09	gold quality
adrenal cortex	UBERON:0001235	98.01	gold quality
adrenal gland	UBERON:0002369	98.01	gold quality
left adrenal gland	UBERON:0001234	98.00	gold quality
left adrenal gland cortex	UBERON:0035825	97.84	gold quality
adrenal tissue	UBERON:0018303	97.79	gold quality
renal medulla	UBERON:0000362	97.76	gold quality
germinal epithelium of ovary	UBERON:0001304	97.64	gold quality
stromal cell of endometrium	CL:0002255	97.62	gold quality
nephron tubule	UBERON:0001231	97.57	gold quality
parietal pleura	UBERON:0002400	97.40	gold quality
kidney	UBERON:0002113	97.35	gold quality
kidney epithelium	UBERON:0004819	97.32	gold quality
skin of hip	UBERON:0001554	96.94	gold quality
pleura	UBERON:0000977	96.91	gold quality
cauda epididymis	UBERON:0004360	96.89	gold quality
renal glomerulus	UBERON:0000074	96.84	gold quality
superficial temporal artery	UBERON:0001614	96.84	gold quality
mammary duct	UBERON:0001765	96.82	gold quality
metanephric glomerulus	UBERON:0004736	96.80	gold quality

Single-cell (SCXA)

Detected in 25 experiment(s), a significant marker in 22.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	2655.55
E-MTAB-6701	yes	2488.51
E-HCAD-36	yes	2406.73
E-MTAB-10042	yes	1931.68
E-MTAB-9906	yes	1726.91
E-MTAB-7407	yes	1714.11
E-MTAB-8205	yes	1289.38
E-ANND-5	yes	647.81
E-CURD-112	yes	599.05
E-MTAB-6075	yes	357.48
E-GEOD-98556	yes	310.80
E-GEOD-86618	yes	145.32
E-HCAD-1	yes	82.47
E-CURD-122	yes	69.21
E-HCAD-10	yes	51.98

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXO3, FOXP3, GATA6, IRF8, SPI1, TP53, VHL

miRNA regulators (miRDB)

116 targeting DAB2, 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-3925-3P	100.00	69.95	1237
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-96-5P	99.95	72.80	2140
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-498-5P	99.76	69.64	1807

Literature-anchored findings (GeneRIF, showing 40)

• mechanism of growth inhibitory effect in prostate cancer (PMID:11812785)
• DOC2 has a role in regulating c-Src in prostatic epithelium and cancer (PMID:12473651)
• Results suggest that disabled-2 functions as a negative regulator of canonical Wnt signaling by stabilizing the beta-catenin degradation complex. (PMID:12805222)
• CIN85 association with Dab2 is essential for its recruitment to clathrin coat and appears to be modulated by growth factor stimulation (PMID:14596919)
• Loss in dab-2 expression is correlated with the loss of epithelial basement membrane in morphologically normal areas (PMID:14669280)
• a binding affinity of Dab phosphotyrosine interaction domain for megalin CT of K(D) = 2.6 x 10(-7) +/- 5.3 x 10(-8) (PMID:15134832)
• findings indicate Ser(24) phosphorylation as a molecular basis for DAB2 acting as a negative regulator in alpha(IIb)beta(3) inside-out signaling (PMID:15280374)
• signaling pathway proceeding from the TGFbeta receptors to Dab2 and TAK1, leading to TGFbeta-stimulated JNK activation, FN expression, and cell migration (PMID:15894542)
• DAB2 expression during megakaryocytic differentiation expression is regulated by platelet-derived growth factor. (PMID:16061224)
• DOC-2/DAB2 can modulate androgen receptor-mediated cell growth in both normal and malignant prostatic epithelial cells. (PMID:16267015)
• Dab2 expression is exceptionally low in hepatocytes, likely accounting for the pathological hypercholesterolemia that accompanies ARH loss. (PMID:16870701)
• Results suggest that Dab2 is a cargo-specific endocytic adaptor protein, stably associating with phospholipids and clathrin to sort LDLR to nascent-coated pits. (PMID:16984970)
• Loss of Disabled-2 (DAB2) protein expression occurs in early pre-neoplastic stages of development of esophageal cancer and is sustained down the tumorigenic pathway. (PMID:17009406)
• analysis of Dab2 protein loss and infrequent promoter hypermethylation in breast cancer (PMID:17115114)
• Decreased DOC-2/DAB2 expression is associated with urothelial carcinoma of the bladder (PMID:17671122)
• These results suggest that Dab2 is a ligand dependent bi-directional regulator of ERK1,2 activity. (PMID:18070591)
• Doc2alpha-Muunc13-4 system regulates Ca(2+)-dependent secretory lysosome exocytosis in mast cells (PMID:18354201)
• These results suggest that DAB2, via Src and focal adhesion signaling, plays a role in human endothelial cell function. (PMID:18582465)
• Dab2 internalizes integrins freely diffusing on the cell surface and Dab2 regulates migration. (PMID:19581412)
• Conditional Dab2 knockout mice maintain normal numbers of circulating regulatory T cells (Tregs), suggesting that DAB2 may be required for amplification, rather than maintenance, of transforming growth factor (TGF)beta signaling. (PMID:19767570)
• Data show that downregulation of myosin VI expression results in a significant reduction in PSA and VEGF secretion in LNCaP cells, and the intracellular targeting seems to involve myosin VI-interacting proteins, GIPC and LMTK2 and Dab2. (PMID:19855435)
• two pools of Dab2 co-exist at the platelet surface, in both sulfatide- and integrin receptor-bound states, and their balance controls the extent of the clotting response (PMID:19956625)
• Demonstrate frequent DAB2 promoter hypermethylation in nasopharyngeal carcinoma and support the putative tumour suppressor effect of DAB2. (PMID:20525238)
• DAB2 acts as a tumor suppressor by dictating tumor cell TGF-beta responses, identify a biomarker for squamous cell carcinomas progression. (PMID:20592473)
• Loss of Dab2 expression, commonly observed in breast cancer, may facilitate TGFbeta-stimulated epithelial-to-mesenchymal transition (EMT), and therefore increase the propensity for metastasis. (PMID:21063401)
• Dab2 is part of an accommodation of the cell to the altered physicochemical conditions prevalent in mitosis, aimed at allowing endocytic activity throughout the cell cycle. (PMID:21097498)
• Expressions of Disabled-2 and Axin were concurrently reduced and correlated with the malignant phenotype of lung cancers. (PMID:21496867)
• Results indicate that miR-187 directly targeted Disabled homolog-2 (Dab2). (PMID:21725366)
• Dab2 depletion increased the CFTR half-life ~3-fold, in addition to inhibiting CFTR endocytosis. (PMID:21995445)
• It was concluded that PKB/Akt is part of an endocytic machinery and it mediates albumin uptake through its interaction with Dab2. (PMID:22218591)
• Dab2 is required for the TGFbeta-induced gene expression of angiogenic factors such as VEGF and FGF2 (PMID:22265793)
• FCHO2 regulates the size of clathrin structures, and its interaction with Dab2 is needed for LDLR endocytosis under conditions of low AP2. (PMID:22323290)
• Dab2 mediates AP-2 independent recruitment of CFTR to CCVs in polarized human airway epithelial cells. (PMID:22399289)
• These data suggest that Dab2-mediated recruitment of EH domain proteins selectively drives the internalization of the Dab2 cargo, integrin b1. (PMID:22648170)
• These findings thereby define an adaptor-specific mechanism in the control of fibrinogen uptake and implicate that DAB2 is the key adaptor in the clathrin-associated endocytic complexes to mediate fibrinogen internalization. (PMID:22705885)
• inhibition of Dab2 decreases phosphorylation of SMAD-1, 5, and 8 (PMID:22898784)
• Data indicate that disabled-2 (Dab2) sulfatide-binding motif contains two helices when embedded in micelles, reversibly binds to sulfatides with moderate affinity, lies parallel to the micelle surface. (PMID:22977233)
• The Dab2 gene is inactivated in part by DNA methylation, and the suppression of Dab2 expression by DNA methylation may play a role in the development of myelodysplastic syndrome. (PMID:23005040)
• Megalin and Dab2 were expressed in prostate and colon epithelial cells, which was markedly enhanced following treatment with retinoic acid (PMID:23909735)
• Aberrant hypermethylation and reduced expression of disabled-2 promote the development of lung cancers. (PMID:24002585)

Cross-species orthologs

14 orthologs

Organism	Symbol	Gene ID
danio_rerio	dab2	ENSDARG00000031761
danio_rerio	DAB2	ENSDARG00000053091
mus_musculus	Dab2	ENSMUSG00000022150
rattus_norvegicus	Dab2	ENSRNOG00000028930
drosophila_melanogaster	Dab	FBGN0000414
drosophila_melanogaster	numb	FBGN0002973
drosophila_melanogaster	CG8312	FBGN0037720
drosophila_melanogaster	Aplip1	FBGN0040281
drosophila_melanogaster	CG42673	FBGN0261555
caenorhabditis_elegans		WBGENE00000894
caenorhabditis_elegans		WBGENE00001116
caenorhabditis_elegans		WBGENE00002176
caenorhabditis_elegans		WBGENE00003830
caenorhabditis_elegans		WBGENE00009930

Paralogs (11): MAPK8IP2 (ENSG00000008735), NUMBL (ENSG00000105245), MAPK8IP1 (ENSG00000121653), NUMB (ENSG00000133961), GULP1 (ENSG00000144366), LDLRAP1 (ENSG00000157978), DAB1 (ENSG00000173406), FAM43B (ENSG00000183114), FAM43A (ENSG00000185112), NOS1AP (ENSG00000198929), C1orf226 (ENSG00000239887)

Protein

Protein identifiers

Disabled homolog 2 — P98082 (reviewed: P98082)

Alternative names: Adaptor molecule disabled-2, Differentially expressed in ovarian carcinoma 2, Differentially-expressed protein 2

All UniProt accessions (5): P98082, D6REB1, D6RFF7, D6RGZ1, D6RIA5

UniProt curated annotations — full annotation on UniProt →

Function. Adapter protein that functions as a clathrin-associated sorting protein (CLASP) required for clathrin-mediated endocytosis of selected cargo proteins. Can bind and assemble clathrin, and binds simultaneously to phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and cargos containing non-phosphorylated NPXY internalization motifs, such as the LDL receptor, to recruit them to clathrin-coated pits. Can function in clathrin-mediated endocytosis independently of the AP-2 complex. Involved in endocytosis of integrin beta-1; this function seems to redundant with the AP-2 complex and seems to require DAB2 binding to endocytosis accessory EH domain-containing proteins such as EPS15, EPS15L1 and ITSN1. Involved in endocytosis of cystic fibrosis transmembrane conductance regulator/CFTR. Involved in endocytosis of megalin/LRP2 lipoprotein receptor during embryonal development. Required for recycling of the TGF-beta receptor. Involved in CFTR trafficking to the late endosome. Involved in several receptor-mediated signaling pathways. Involved in TGF-beta receptor signaling and facilitates phosphorylation of the signal transducer SMAD2. Mediates TFG-beta-stimulated JNK activation. May inhibit the canoniocal Wnt/beta-catenin signaling pathway by stabilizing the beta-catenin destruction complex through a competing association with axin preventing its dephosphorylation through protein phosphatase 1 (PP1). Sequesters LRP6 towards clathrin-mediated endocytosis, leading to inhibition of Wnt/beta-catenin signaling. May activate non-canonical Wnt signaling. In cell surface growth factor/Ras signaling pathways proposed to inhibit ERK activation by interrupting the binding of GRB2 to SOS1 and to inhibit SRC by preventing its activating phosphorylation at ‘Tyr-419’. Proposed to be involved in modulation of androgen receptor (AR) signaling mediated by SRC activation; seems to compete with AR for interaction with SRC. Plays a role in the CSF-1 signal transduction pathway. Plays a role in cellular differentiation. Involved in cell positioning and formation of visceral endoderm (VE) during embryogenesis and proposed to be required in the VE to respond to Nodal signaling coming from the epiblast. Required for the epithelial to mesenchymal transition, a process necessary for proper embryonic development. May be involved in myeloid cell differentiation and can induce macrophage adhesion and spreading. May act as a tumor suppressor.

Subunit / interactions. Interacts (via NPXY motif) with DAB2 (via PID domain). Can interact (via PID domain) with LDLR, APP, APLP1 and APLP2, and weakly with INPP5D (via NPXY motifs); the interaction is impaired by tyrosine phosphorylation of the respective NPXY motifs. Can weakly interact (via PID domain) with LRP1 (via NPXY motif); the interaction is enhanced by tyrosine phosphorylation of the NPXY motif. Interacts with LRP2 (via NPXY motif); the interaction is not affected by tyrosine phosphorylation of the NPXY motif. Interacts with clathrin; in vitro can assemble clathrin triskelia into polyhedral coats. Interacts with AP2A2, ITGB1, ITGB3, ITGB5, PIAS2, DAB2IP, NOSTRIN, FCHO1, DVL3, EPS15, ITSN1 and EPS15L1. Interacts with SH3KBP1 (via SH3 domains). Interacts with GRB2; competes with SOS1 for binding to GRB2 and the interaction is enhanced by EGF and NT-3 stimulation. Interacts with MAP3K7; the interaction is induced by TGF-beta stimulation and may mediate TGF-beta stimulated JNK activation. Interacts with AXIN1 and PPP1CA; the interactions are mutually exclusive. Interacts with the globular tail of MYO6. Interacts (via DPF motifs) with FCHO2; the interaction is direct and required for DAB2-mediated LDLR endocytosis. Interacts with LRP6; the interaction involves LRP6 phosphorylation by CK2 and sequesters LRP6 towards clathrin-mediated endocytosis. Associates with the TGF-beta receptor complex. Interacts with SMAD2 and SMAD3; the interactions are enhanced upon TGF-beta stimulation. Interacts with GRB2; the interaction is enhanced by EGF and NT-3 stimulation. Interacts with SRC; the interaction is enhanced by EGF stimulation.

Subcellular location. Cytoplasm. Cytoplasmic vesicle. Clathrin-coated vesicle membrane. Membrane. Clathrin-coated pit.

Tissue specificity. Expressed in deep invaginations, inclusion cysts and the surface epithelial cells of the ovary. Also expressed in breast epithelial cells, spleen, thymus, prostate, testis, macrophages, fibroblasts, lung epithelial cells, placenta, brain stem, heart and small intestine. Expressed in kidney proximal tubular epithelial cells (at protein level).

Post-translational modifications. Phosphorylated. Phosphorylation during mitosis is leading to membrane displacement.

Domain organisation. The PID domain binds to predominantly non-phosphorylated NPXY internalization motifs present in members of the LDLR and APP family; it also mediates simultaneous binding to phosphatidylinositol 4,5-bisphosphate. The Asn-Pro-Phe (NPF) motifs, which are found in proteins involved in the endocytic pathway, mediate the interaction with the EH domain of EPS15, EPS15R and ITSN1.

Isoforms (3)

UniProt ID	Names	Canonical?
P98082-1	1	yes
P98082-2	2
P98082-3	3

RefSeq proteins (2): NP_001231800, NP_001334* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006020	PTB/PI_dom	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR048559	DAB1/2_SBM	Conserved_site
IPR048561	Dab_PTB	Domain

Pfam: PF00640, PF21792

UniProt features (62 total): region of interest 10, modified residue 10, strand 9, sequence conflict 8, compositionally biased region 7, helix 4, mutagenesis site 3, short sequence motif 2, splice variant 2, sequence variant 2, turn 2, initiator methionine 1, chain 1, domain 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
6O5O	X-RAY DIFFRACTION	1.75
6OVF	X-RAY DIFFRACTION	1.95
2LSW	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P98082-F1	54.33	0.19

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 (10): 2, 2, 170, 193, 326, 328, 401, 675, 723, 729

Mutagenesis-validated functional residues (3):

Position	Phenotype
166	impairs tgf-beta receptor signaling, no effect on interaction with smad2.
684–686	greatly reduced binding to myo6.
720	abolishes interaction with sh3kbp1.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-190873	Gap junction degradation
R-HSA-196025	Formation of annular gap junctions
R-HSA-8856825	Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828	Clathrin-mediated endocytosis

MSigDB gene sets: 642 (showing top): GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, GOBP_SMAD_PROTEIN_SIGNAL_TRANSDUCTION, WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, FXR_IR1_Q6, GOBP_NEGATIVE_REGULATION_OF_ERK1_AND_ERK2_CASCADE, MODULE_52, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_POSITIVE_REGULATION_OF_EPITHELIAL_TO_MESENCHYMAL_TRANSITION, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOCC_VACUOLAR_MEMBRANE, GOBP_NON_CANONICAL_WNT_SIGNALING_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, GOBP_REGULATION_OF_NON_CANONICAL_WNT_SIGNALING_PATHWAY

GO Biological Process (34): negative regulation of transcription by RNA polymerase II (GO:0000122), receptor-mediated endocytosis (GO:0006898), apoptotic process (GO:0006915), transforming growth factor beta receptor signaling pathway (GO:0007179), positive regulation of epithelial to mesenchymal transition (GO:0010718), negative regulation of neuron projection development (GO:0010977), protein transport (GO:0015031), Wnt signaling pathway (GO:0016055), negative regulation of cell growth (GO:0030308), positive regulation of cell migration (GO:0030335), positive regulation of aldosterone biosynthetic process (GO:0032349), positive regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032436), leading edge cell differentiation (GO:0035026), negative regulation of apoptotic process (GO:0043066), positive regulation of endocytosis (GO:0045807), positive regulation of transcription by RNA polymerase II (GO:0045944), clathrin coat assembly (GO:0048268), response to steroid hormone (GO:0048545), negative regulation of epithelial cell proliferation (GO:0050680), positive regulation of SMAD protein signal transduction (GO:0060391), negative regulation of androgen receptor signaling pathway (GO:0060766), negative regulation of ERK1 and ERK2 cascade (GO:0070373), cellular response to epidermal growth factor stimulus (GO:0071364), negative regulation of canonical Wnt signaling pathway (GO:0090090), positive regulation of substrate adhesion-dependent cell spreading (GO:1900026), response to salt (GO:1902074), negative regulation of protein localization to plasma membrane (GO:1903077), positive regulation of Wnt signaling pathway, planar cell polarity pathway (GO:2000096), positive regulation of clathrin-dependent endocytosis (GO:2000370), positive regulation of early endosome to late endosome transport (GO:2000643), positive regulation of aldosterone secretion (GO:2000860), endocytosis (GO:0006897), cell differentiation (GO:0030154), cellular response to transforming growth factor beta stimulus (GO:0071560)

GO Molecular Function (5): clathrin-cargo adaptor activity (GO:0035615), cargo receptor activity (GO:0038024), SMAD binding (GO:0046332), low-density lipoprotein particle receptor binding (GO:0050750), protein binding (GO:0005515)

GO Cellular Component (12): fibrillar center (GO:0001650), cytoplasm (GO:0005737), lysosomal membrane (GO:0005765), cytosol (GO:0005829), plasma membrane (GO:0005886), clathrin-coated pit (GO:0005905), focal adhesion (GO:0005925), clathrin-coated vesicle (GO:0030136), clathrin-coated vesicle membrane (GO:0030665), perinuclear region of cytoplasm (GO:0048471), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Gap junction trafficking	1
Gap junction degradation	1
Clathrin-mediated endocytosis	1
Membrane Trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cytoplasm	3
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
endocytosis	2
membrane	2
negative regulation of DNA-templated transcription	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cellular response to transforming growth factor beta stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
epithelial to mesenchymal transition	1
regulation of epithelial to mesenchymal transition	1
positive regulation of cell differentiation	1
positive regulation of multicellular organismal process	1
regulation of neuron projection development	1
neuron projection development	1
negative regulation of cell projection organization	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
cell surface receptor signaling pathway	1
regulation of cell growth	1
cell growth	1
negative regulation of growth	1
negative regulation of cellular process	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
aldosterone biosynthetic process	1
regulation of aldosterone biosynthetic process	1
positive regulation of steroid hormone biosynthetic process	1
positive regulation of alcohol biosynthetic process	1
regulation of proteasomal ubiquitin-dependent protein catabolic process	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
positive regulation of proteasomal protein catabolic process	1
positive regulation of ubiquitin-dependent protein catabolic process	1
epithelial cell differentiation	1
apoptotic process	1

Protein interactions and networks

STRING

2434 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DAB2	DAB2IP	Q5VWQ8	989
DAB2	LRP2	P98164	916
DAB2	DVL3	Q92997	877
DAB2	HIP1R	O75146	834
DAB2	AXIN1	O15169	829
DAB2	TGFBR1	P36897	828
DAB2	CUBN	O60494	811
DAB2	MYO6	Q9UM54	775
DAB2	AMN	Q9BXJ7	758
DAB2	GRB2	P29354	726
DAB2	CLASRP	Q8N2M8	704
DAB2	EPN2	O95208	696
DAB2	AP2B1	P21851	689
DAB2	EPN3	Q9H201	678
DAB2	SNAP91	O60641	665

IntAct

119 interactions, top by confidence:

A	B	Type	Score
NEUROG3	GXYLT2	psi-mi:“MI:0914”(association)	0.640
DAB2	GRB2	psi-mi:“MI:0915”(physical association)	0.570
SOD1	DAB2	psi-mi:“MI:0915”(physical association)	0.560
APP	DAB2	psi-mi:“MI:0915”(physical association)	0.560
SH3KBP1	DAB2	psi-mi:“MI:0915”(physical association)	0.550
MYO6	DAB2	psi-mi:“MI:0915”(physical association)	0.540
MYO6	DAB2	psi-mi:“MI:0403”(colocalization)	0.540
SLC25A41	NUDT19	psi-mi:“MI:0914”(association)	0.530
DAB2	FCHO2	psi-mi:“MI:0914”(association)	0.530
HDGFL2	CDC7	psi-mi:“MI:0914”(association)	0.530
PIP	TBKBP1	psi-mi:“MI:0914”(association)	0.530
DAB2	SMAD2	psi-mi:“MI:0915”(physical association)	0.520
DAB2	SMAD3	psi-mi:“MI:0915”(physical association)	0.520
SMAD3	DAB2	psi-mi:“MI:0915”(physical association)	0.520
DAB2	LRP6	psi-mi:“MI:0915”(physical association)	0.520
LRP6	DAB2	psi-mi:“MI:0915”(physical association)	0.520

BioGRID (191): DAB2 (Affinity Capture-MS), DAB2 (Biochemical Activity), DAB2 (Biochemical Activity), DAB2 (Biochemical Activity), DAB2 (Affinity Capture-MS), DAB2 (Affinity Capture-MS), DAB2 (Affinity Capture-MS), DAB2 (Affinity Capture-MS), DAB2 (Affinity Capture-MS), DAB2 (Affinity Capture-MS), DAB2 (Affinity Capture-MS), DAB2 (Affinity Capture-MS), DAB2 (Affinity Capture-MS), DAB2 (Affinity Capture-MS), DAB2 (Affinity Capture-MS)

ESM2 similar proteins: A0JME2, A5H447, A6NF01, A8CG34, E9Q3G8, F4ID16, G0SDP9, G5E8Z2, O08587, O15504, O88797, O95081, P20676, P49790, P49791, P52591, P52594, P98082, Q03173, Q0VA45, Q2TA45, Q4KLH5, Q5FVW4, Q5PRE5, Q5RB98, Q5SV85, Q5XGN1, Q5ZI22, Q5ZIE8, Q5ZM88, Q64028, Q640Z6, Q6P0U9, Q80WC7, Q86XN7, Q8CIC2, Q8K2K6, Q8K3Z9, Q8L7F7, Q8R080

Diamond homologs: A1L1I3, O08919, O88797, P16554, P49757, P98078, P98081, P98082, Q2LC84, Q5PQS4, Q5SW96, Q801G1, Q8C142, Q8K2A1, Q9QZS3, Q9UBP9, Q9XTY6, Q9Y6R0, O75553, P97318, Q8CJH2, Q9BGX5

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
PRKCD	down-regulates	DAB2	phosphorylation
DAB2	down-regulates	LRP6	binding
DAB2	“up-regulates activity”	DAB2IP	binding
VHL	“up-regulates quantity by expression”	DAB2	“transcriptional regulation”
“AP-2 complex”	“up-regulates activity”	DAB2	binding
PRKCB	unknown	DAB2	phosphorylation
PRKCG	unknown	DAB2	phosphorylation
PRKCD	unknown	DAB2	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 104 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
Nephrin family interactions	6	36.6×	1e-06
Downregulation of TGF-beta receptor signaling	5	26.1×	5e-05
Antigen activates B Cell Receptor (BCR) leading to generation of second messengers	5	22.9×	9e-05
Parasite infection	5	22.2×	9e-05
Leishmania phagocytosis	5	22.2×	9e-05
RHOU GTPase cycle	6	21.4×	2e-05
RHO GTPases Activate WASPs and WAVEs	5	20.3×	1e-04
Clathrin-mediated endocytosis	18	19.7×	5e-16

GO biological processes:

GO term	Partners	Fold	FDR
clathrin coat assembly	8	82.5×	3e-11
clathrin-dependent endocytosis	8	54.1×	7e-10
positive regulation of fibroblast proliferation	5	17.2×	1e-03
endocytosis	11	12.2×	6e-07
response to endoplasmic reticulum stress	5	9.7×	9e-03
actin filament organization	7	9.7×	1e-03
transforming growth factor beta receptor signaling pathway	5	9.2×	1e-02
in utero embryonic development	8	6.7×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	101
Likely benign	9
Benign	8

Top pathogenic / likely-pathogenic (0)

SpliceAI

1999 predictions. Top by Δscore:

Variant	Effect	Δscore
5:39375012:A:AC	donor_gain	1.0000
5:39375013:C:CC	donor_gain	1.0000
5:39375013:CAGA:C	donor_gain	1.0000
5:39375995:A:AC	donor_gain	1.0000
5:39375996:C:CC	donor_gain	1.0000
5:39383278:CATT:C	acceptor_gain	1.0000
5:39383281:T:C	acceptor_gain	1.0000
5:39383281:T:TC	acceptor_gain	1.0000
5:39388303:A:AC	donor_gain	1.0000
5:39388304:C:CC	donor_gain	1.0000
5:39388367:CCT:C	acceptor_gain	1.0000
5:39388368:C:T	acceptor_gain	1.0000
5:39390438:GCTCA:G	donor_loss	1.0000
5:39390439:CTCA:C	donor_loss	1.0000
5:39390440:TCACC:T	donor_loss	1.0000
5:39390441:CACC:C	donor_loss	1.0000
5:39390443:C:T	donor_loss	1.0000
5:39390527:C:CT	acceptor_gain	1.0000
5:39390572:TTAC:T	acceptor_gain	1.0000
5:39390575:CC:C	acceptor_loss	1.0000
5:39390575:CCT:C	acceptor_gain	1.0000
5:39390576:CTT:C	acceptor_loss	1.0000
5:39390577:T:C	acceptor_gain	1.0000
5:39390577:T:TC	acceptor_gain	1.0000
5:39393248:TTTTA:T	donor_loss	1.0000
5:39393249:TTTAC:T	donor_loss	1.0000
5:39393250:TTACC:T	donor_loss	1.0000
5:39393251:TACC:T	donor_loss	1.0000
5:39393252:A:T	donor_loss	1.0000
5:39393253:C:T	donor_loss	1.0000

AlphaMissense

5068 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:39389901:A:G	L165P	1.000
5:39389910:A:G	L162P	1.000
5:39389919:A:T	V159D	1.000
5:39390456:T:A	K150N	1.000
5:39390456:T:G	K150N	1.000
5:39390458:T:C	K150E	1.000
5:39390460:A:C	I149R	1.000
5:39390460:A:T	I149K	1.000
5:39390463:G:T	A148D	1.000
5:39390469:A:G	F146S	1.000
5:39390502:C:T	G135D	1.000
5:39390503:C:G	G135R	1.000
5:39390504:A:C	F134L	1.000
5:39390504:A:T	F134L	1.000
5:39390506:A:G	F134L	1.000
5:39390511:C:G	R132P	1.000
5:39390517:T:A	D130V	1.000
5:39390518:C:G	D130H	1.000
5:39390527:C:G	D127H	1.000
5:39390532:G:T	A125D	1.000
5:39390535:A:T	I124N	1.000
5:39390537:G:C	F123L	1.000
5:39390537:G:T	F123L	1.000
5:39390539:A:G	F123L	1.000
5:39392403:A:G	S98P	1.000
5:39392425:T:A	K90N	1.000
5:39392425:T:G	K90N	1.000
5:39392427:T:C	K90E	1.000
5:39393254:C:A	K77N	1.000
5:39393254:C:G	K77N	1.000

dbSNP variants (sampled 300 via entrez): RS1000040804 (5:39386874 A>G), RS1000084795 (5:39424422 C>A), RS1000186632 (5:39419139 A>C), RS1000235024 (5:39375138 A>T), RS1000249522 (5:39387816 T>C), RS1000281024 (5:39388066 A>G), RS1000371790 (5:39395034 A>G), RS1000377475 (5:39413264 G>C,T), RS1000378685 (5:39411797 G>A), RS1000417375 (5:39405702 T>C), RS1000502257 (5:39374863 A>G), RS1000519120 (5:39420745 A>G), RS1000540193 (5:39389091 T>G), RS1000595755 (5:39413135 G>A), RS1000596614 (5:39382047 C>G,T)

Disease associations

OMIM: gene MIM:601236 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): teratocarcinoma (MONDO:0002599)

Orphanet (0):

HPO phenotypes

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

GWAS associations

39 associations (top):

Study	Trait	p-value
GCST000649_22	Chronic kidney disease	1.000000e-07
GCST001350_4	Pancreatic cancer	4.000000e-10
GCST001791_40	Urate levels	4.000000e-06
GCST002083_17	Self-reported allergy	8.000000e-11
GCST003372_15	Glomerular filtration rate (creatinine)	2.000000e-20
GCST003401_33	Glomerular filtration rate in non diabetics (creatinine)	7.000000e-19
GCST004292_40	Glomerular filtration rate (creatinine)	2.000000e-18
GCST004867_32	Systemic lupus erythematosus	8.000000e-06
GCST005038_17	Allergic disease (asthma, hay fever or eczema)	6.000000e-10
GCST005518_3	Premature menopause in childhood cancer survivors	4.000000e-06
GCST005987_35	Albumin-globulin ratio	4.000000e-10
GCST005990_50	Non-albumin protein levels	2.000000e-11
GCST005999_11	Aspartate aminotransferase levels	7.000000e-09
GCST006288_214	Heel bone mineral density	1.000000e-07
GCST006288_319	Heel bone mineral density	4.000000e-09
GCST006288_533	Heel bone mineral density	3.000000e-14
GCST006479_47	Diverticular disease	4.000000e-06
GCST006979_765	Heel bone mineral density	2.000000e-36
GCST006979_766	Heel bone mineral density	9.000000e-21
GCST007344_114	Estimated glomerular filtration rate	9.000000e-10
GCST007344_129	Estimated glomerular filtration rate	2.000000e-17
GCST007344_81	Estimated glomerular filtration rate	3.000000e-06
GCST007876_20	Estimated glomerular filtration rate	9.000000e-28
GCST007877_5	Creatinine levels	5.000000e-12
GCST008058_202	Estimated glomerular filtration rate	7.000000e-65
GCST008059_110	Estimated glomerular filtration rate	9.000000e-67
GCST008064_35	Chronic kidney disease	5.000000e-11
GCST008155_78	Waist-hip ratio	6.000000e-06
GCST008362_218	Birth weight	4.000000e-09
GCST008513_9	Health literacy	8.000000e-06

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement
EFO:0005128	albumin:globulin ratio measurement
EFO:0004736	aspartate aminotransferase measurement
EFO:0009270	heel bone mineral density
EFO:0009959	diverticular disease
EFO:0004343	waist-hip ratio
EFO:0004344	birth weight
EFO:0010104	health literacy measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004980	appendicular lean mass

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018243	Teratocarcinoma	C04.557.465.900

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects expression, affects cotreatment, increases expression, decreases expression	5
sodium arsenite	affects reaction, affects cotreatment, decreases expression, increases expression, affects localization	4
Benzo(a)pyrene	affects methylation, decreases expression	4
Tetrachlorodibenzodioxin	affects cotreatment, increases expression, decreases expression	3
Tretinoin	increases expression	3
bisphenol A	increases expression, affects cotreatment, increases methylation	2
Arsenic Trioxide	affects expression, decreases expression	2
Air Pollutants	decreases expression, increases abundance	2
Hydrogen Peroxide	affects expression, affects cotreatment, decreases expression	2
Methylnitronitrosoguanidine	increases expression	2
Nickel	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Valproic Acid	decreases expression, affects expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cadmium Chloride	decreases expression, increases expression, affects cotreatment	2
Okadaic Acid	affects phosphorylation, decreases expression	2
FR900359	decreases phosphorylation	1
bufotalin	increases expression	1
testosterone enanthate	affects expression	1
juglone	affects phosphorylation	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
lead acetate	affects cotreatment, decreases expression	1
sodium arsenate	increases abundance, increases expression	1
decabromobiphenyl ether	decreases expression	1
trichostatin A	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
sodium bichromate	decreases expression	1
afimoxifene	increases expression	1
sulforaphane	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1PS	Abcam HeLa DAB2 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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