DAB2IP

DAB2 interacting protein, the group of C2 and RasGAP domain containing

Basic information

Region (hg38): 9:121567056-121785530

Links

ENSG00000136848 ∙ NCBI:153090 ∙ OMIM:609205 ∙ HGNC:17294 ∙ Uniprot:Q5VWQ8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DAB2IP gene.

• Inborn genetic diseases (50 variants)
• not provided (14 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DAB2IP gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				5	4	9
missense			51		3	54
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				1		1
Total	0	0	51	6	7

Variants in DAB2IP

This is a list of pathogenic ClinVar variants found in the DAB2IP region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
9-121678705-G-A		not specified	Uncertain significance (Aug 12, 2021)
9-121678705-G-T		not specified	Uncertain significance (May 06, 2022)
9-121678745-C-A		not specified	Uncertain significance (Dec 19, 2023)
9-121678757-G-C			Likely benign (Sep 01, 2022)
9-121678780-C-T		not specified	Uncertain significance (Nov 18, 2022)
9-121699325-G-A		not specified	Uncertain significance (Jan 24, 2023)
9-121699387-C-T			Benign/Likely benign (Mar 01, 2024)
9-121699437-C-T		not specified	Uncertain significance (Jun 27, 2022)
9-121737701-G-A			Likely benign (Mar 01, 2024)
9-121757028-G-A			Likely benign (Aug 01, 2022)
9-121757053-G-A		not specified	Uncertain significance (Aug 22, 2023)
9-121757077-G-T		not specified	Uncertain significance (Oct 25, 2023)
9-121757078-C-T		not specified	Uncertain significance (Oct 25, 2023)
9-121757153-A-G		not specified	Uncertain significance (Jun 06, 2022)
9-121758898-G-A		not specified	Uncertain significance (Jan 16, 2024)
9-121758905-C-T		not specified	Uncertain significance (Feb 07, 2023)
9-121758950-G-A		not specified	Uncertain significance (Dec 19, 2022)
9-121758976-C-A			Benign (Dec 31, 2019)
9-121758989-C-T		not specified	Uncertain significance (Nov 09, 2023)
9-121760000-G-A		not specified	Uncertain significance (Feb 28, 2023)
9-121760003-C-G		not specified	Uncertain significance (Dec 01, 2022)
9-121760075-G-A		not specified	Uncertain significance (May 24, 2023)
9-121760098-C-T		not specified	Uncertain significance (Apr 07, 2023)
9-121760121-G-A			Benign (Mar 29, 2018)
9-121760188-G-A		not specified	Uncertain significance (Oct 26, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DAB2IP	protein_coding	protein_coding	ENST00000259371	17	218474

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000496	125738	0	7	125745	0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.36	522	698	0.748	0.0000465	7266
Missense in Polyphen		246	373.62	0.65842		3871
Synonymous	-1.06	340	316	1.08	0.0000229	2322
Loss of Function	5.72	4	45.7	0.0876	0.00000221	534

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000870	0.0000870
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000354	0.0000352
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Functions as a scaffold protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Involved in several processes such as innate immune response, inflammation and cell growth inhibition, apoptosis, cell survival, angiogenesis, cell migration and maturation. Plays also a role in cell cycle checkpoint control; reduces G1 phase cyclin levels resulting in G0/G1 cell cycle arrest. Mediates signal transduction by receptor-mediated inflammatory signals, such as the tumor necrosis factor (TNF), interferon (IFN) or lipopolysaccharide (LPS). Modulates the balance between phosphatidylinositol 3-kinase (PI3K)-AKT-mediated cell survival and apoptosis stimulated kinase (MAP3K5)-JNK signaling pathways; sequesters both AKT1 and MAP3K5 and counterbalances the activity of each kinase by modulating their phosphorylation status in response to proinflammatory stimuli. Acts as a regulator of the endoplasmic reticulum (ER) unfolded protein response (UPR) pathway; specifically involved in transduction of the ER stress-response to the JNK cascade through ERN1. Mediates TNF-alpha-induced apoptosis activation by facilitating dissociation of inhibitor 14-3-3 from MAP3K5; recruits the PP2A phosphatase complex which dephosphorylates MAP3K5 on 'Ser-966', leading to the dissociation of 13-3-3 proteins and activation of the MAP3K5-JNK signaling pathway in endothelial cells. Mediates also TNF/TRAF2-induced MAP3K5-JNK activation, while it inhibits CHUK-NF-kappa-B signaling. Acts a negative regulator in the IFN-gamma-mediated JAK-STAT signaling cascade by inhibiting smooth muscle cell (VSMCs) proliferation and intimal expansion, and thus, prevents graft arteriosclerosis (GA). Acts as a GTPase-activating protein (GAP) for the ADP ribosylation factor 6 (ARF6) and Ras. Promotes hydrolysis of the ARF6-bound GTP and thus, negatively regulates phosphatidylinositol 4,5- bisphosphate (PIP2)-dependent TLR4-TIRAP-MyD88 and NF-kappa-B signaling pathways in endothelial cells in response to lipopolysaccharides (LPS). Binds specifically to phosphatidylinositol 4-phosphate (PtdIns4P) and phosphatidylinositol 3-phosphate (PtdIns3P). In response to vascular endothelial growth factor (VEGFA), acts as a negative regulator of the VEGFR2-PI3K-mediated angiogenic signaling pathway by inhibiting endothelial cell migration and tube formation. In the developing brain, promotes both the transition from the multipolar to the bipolar stage and the radial migration of cortical neurons from the ventricular zone toward the superficial layer of the neocortex in a glial-dependent locomotion process. Probable downstream effector of the Reelin signaling pathway; promotes Purkinje cell (PC) dendrites development and formation of cerebellar synapses. Functions also as a tumor suppressor protein in prostate cancer progression; prevents cell proliferation and epithelial-to-mesenchymal transition (EMT) through activation of the glycogen synthase kinase-3 beta (GSK3B)-induced beta-catenin and inhibition of PI3K-AKT and Ras-MAPK survival downstream signaling cascades, respectively. {ECO:0000269|PubMed:12813029, ECO:0000269|PubMed:17389591, ECO:0000269|PubMed:18292600, ECO:0000269|PubMed:19033661, ECO:0000269|PubMed:19903888, ECO:0000269|PubMed:19948740, ECO:0000269|PubMed:20080667, ECO:0000269|PubMed:20154697, ECO:0000269|PubMed:21700930, ECO:0000269|PubMed:22696229}.
• Disease: DISEASE: Note=A chromosomal aberration involving DAB2IP is found in a patient with acute myeloid leukemia (AML). Translocation t(9;11)(q34;q23) with KMT2A/MLL1. May give rise to a KMT2A/MLL1- DAB2IP fusion protein lacking the PH domain (PubMed:14978793). {ECO:0000269|PubMed:14978793}.
• Pathway: TNF signaling pathway - Homo sapiens (human);Apoptosis - Homo sapiens (human);Ebola Virus Pathway on Host;Ebola Virus Pathway on Host;Regulation of Ras family activation;Signal Transduction;Regulation of RAS by GAPs;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades (Consensus)

Recessive Scores

• pRec: 0.140

Intolerance Scores

• loftool: 0.00482
• rvis_EVS: -1.52
• rvis_percentile_EVS: 3.47

Haploinsufficiency Scores

• pHI: 0.497
• hipred: Y
• hipred_score: 0.851
• ghis: 0.646

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.819

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dab2ip
• Phenotype: homeostasis/metabolism phenotype; cellular phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;MAPK cascade;activation of MAPKKK activity;angiogenesis;negative regulation of protein phosphorylation;inflammatory response;cell cycle;I-kappaB phosphorylation;activation of JUN kinase activity;negative regulation of cell population proliferation;extrinsic apoptotic signaling pathway via death domain receptors;negative regulation of endothelial cell migration;negative regulation of epithelial cell migration;negative regulation of epithelial to mesenchymal transition;positive regulation of neuron projection development;negative regulation of phosphatidylinositol 3-kinase signaling;negative regulation of angiogenesis;cell motility involved in cerebral cortex radial glia guided migration;layer formation in cerebral cortex;negative regulation of vascular endothelial growth factor receptor signaling pathway;negative regulation of NF-kappaB transcription factor activity;negative regulation of toll-like receptor 4 signaling pathway;negative regulation of GTPase activity;cellular response to unfolded protein;tube formation;cellular response to vascular endothelial growth factor stimulus;vascular endothelial growth factor receptor-2 signaling pathway;reelin-mediated signaling pathway;regulation of growth;negative regulation of epidermal growth factor receptor signaling pathway;positive regulation of apoptotic process;regulation of GTPase activity;regulation of I-kappaB kinase/NF-kappaB signaling;negative regulation of I-kappaB kinase/NF-kappaB signaling;regulation of protein complex assembly;negative regulation of MAP kinase activity;positive regulation of MAPK cascade;regulation of protein heterodimerization activity;positive regulation of JUN kinase activity;positive regulation of GTPase activity;negative regulation of phosphatidylinositol 3-kinase activity;cellular protein catabolic process;innate immune response;positive regulation of protein catabolic process;negative regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;positive regulation of JNK cascade;negative regulation of Ras protein signal transduction;negative regulation of fibroblast proliferation;neuron projection morphogenesis;negative regulation of epithelial cell proliferation;intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress;negative regulation of G0 to G1 transition;negative regulation of ERK1 and ERK2 cascade;positive regulation of cell cycle arrest;cellular response to lipopolysaccharide;cellular response to interleukin-1;cellular response to tumor necrosis factor;cellular response to epidermal growth factor stimulus;negative regulation of protein serine/threonine kinase activity;positive regulation of protein serine/threonine kinase activity;endothelial cell apoptotic process;negative regulation of canonical Wnt signaling pathway;positive regulation of synapse maturation;positive regulation of dendrite development;regulation of p38MAPK cascade;negative regulation of vascular endothelial growth factor signaling pathway;positive regulation of proteasomal protein catabolic process;negative regulation of cellular protein catabolic process;positive regulation of IRE1-mediated unfolded protein response;positive regulation of neuron migration;positive regulation of apoptotic signaling pathway
• Cellular component: cytoplasm;cytosol;plasma membrane;endocytic vesicle;axon;dendrite;neuronal cell body membrane;neuronal cell body;cerebellar mossy fiber;climbing fiber;parallel fiber;AIP1-IRE1 complex
• Molecular function: GTPase activator activity;death receptor binding;protein binding;SH3 domain binding;kinase binding;protein kinase binding;mitogen-activated protein kinase kinase binding;mitogen-activated protein kinase kinase kinase binding;phosphatidylinositol-3-phosphate binding;signaling adaptor activity;Toll-like receptor 4 binding;phosphatidylinositol 3-kinase regulatory subunit binding;identical protein binding;protein homodimerization activity;vascular endothelial growth factor receptor 2 binding;phosphatidylinositol 3-kinase binding;protein-containing complex binding;cadherin binding;protein phosphatase 2A binding;phosphatidylinositol-4-phosphate binding;14-3-3 protein binding