DAB2

DAB adaptor protein 2

Basic information

Region (hg38): 5:39371674-39462300

Links

ENSG00000153071 ∙ NCBI:1601 ∙ OMIM:601236 ∙ HGNC:2662 ∙ Uniprot:P98082 ∙ 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 DAB2 gene.

• Inborn genetic diseases (29 variants)
• not provided (16 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DAB2 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				4	3	7
missense			28	3	4	35
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding					1	1
Total	0	0	29	7	8

Variants in DAB2

This is a list of pathogenic ClinVar variants found in the DAB2 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-39375041-G-A		not specified	Uncertain significance (Jul 17, 2023)
5-39375046-C-T			Likely benign (May 16, 2018)
5-39375054-T-A		not specified	Uncertain significance (Dec 28, 2022)
5-39375999-A-G		not specified	Uncertain significance (Jan 19, 2024)
5-39376757-C-G		not specified	Uncertain significance (Aug 02, 2023)
5-39376782-G-C		not specified	Uncertain significance (Apr 05, 2023)
5-39376785-C-T		not specified	Uncertain significance (Jul 20, 2021)
5-39376790-A-C		not specified	Uncertain significance (Jul 13, 2022)
5-39376839-C-A		not specified	Uncertain significance (Dec 22, 2023)
5-39376891-G-C		not specified	Uncertain significance (Jan 19, 2024)
5-39376951-G-C		not specified	Uncertain significance (Sep 17, 2021)
5-39376973-G-T		not specified	Uncertain significance (Jun 06, 2023)
5-39377017-C-A		not specified	Uncertain significance (Jan 08, 2024)
5-39377028-T-C			Benign (Dec 31, 2019)
5-39377058-C-T		not specified	Uncertain significance (Aug 02, 2021)
5-39377157-C-T			Benign (Jul 26, 2018)
5-39377172-C-T		not specified	Uncertain significance (Dec 13, 2022)
5-39377200-C-T			Likely benign (May 14, 2018)
5-39377201-G-A		not specified	Uncertain significance (Feb 17, 2024)
5-39377204-G-A		not specified	Likely benign (Oct 03, 2022)
5-39377218-C-G			Likely benign (May 18, 2018)
5-39377273-G-A			Benign (Dec 31, 2019)
5-39381475-C-T		not specified	Uncertain significance (Jun 24, 2022)
5-39382653-T-A		not specified	Uncertain significance (Dec 28, 2023)
5-39382671-T-C			Likely benign (May 18, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DAB2	protein_coding	protein_coding	ENST00000320816	13	90623

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.407	0.593	125726	0	10	125736	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.203	397	409	0.972	0.0000211	5047
Missense in Polyphen		93	111.96	0.83066		1477
Synonymous	-0.996	172	156	1.10	0.00000922	1548
Loss of Function	4.04	7	31.4	0.223	0.00000141	383

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000904	0.0000904
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000268	0.0000264
Middle Eastern	0.000163	0.000163
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Adapter protein that functions as 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. {ECO:0000269|PubMed:11387212, ECO:0000269|PubMed:12805222, ECO:0000269|PubMed:16267015, ECO:0000269|PubMed:16984970, ECO:0000269|PubMed:19306879, ECO:0000269|PubMed:21995445, ECO:0000269|PubMed:22323290, ECO:0000269|PubMed:22491013}.
• Pathway: Endocytosis - Homo sapiens (human);WNT-Ncore;TGF-Ncore;Endoderm Differentiation;TGF-beta Signaling Pathway;Vesicle-mediated transport;Membrane Trafficking;Clathrin-mediated endocytosis;TGF_beta_Receptor;EGFR1;Cargo recognition for clathrin-mediated endocytosis;Formation of annular gap junctions;Gap junction degradation;Gap junction trafficking;Gap junction trafficking and regulation;TGF-beta receptor signaling (Consensus)

Recessive Scores

• pRec: 0.319

Intolerance Scores

• loftool: 0.134
• rvis_EVS: 1.05
• rvis_percentile_EVS: 91.34

Haploinsufficiency Scores

• pHI: 0.327
• hipred: Y
• hipred_score: 0.786
• ghis: 0.443

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.998

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dab2
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); embryo phenotype; renal/urinary system phenotype; growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: dab2
• Affected structure: post-vent vasculature
• Phenotype tag: abnormal
• Phenotype quality: decreased process quality

Gene ontology

• Biological process: positive regulation of protein phosphorylation;receptor-mediated endocytosis;apoptotic process;integrin-mediated signaling pathway;multicellular organism development;cell population proliferation;positive regulation of epithelial to mesenchymal transition;positive regulation of pathway-restricted SMAD protein phosphorylation;protein transport;Wnt signaling pathway;positive regulation of cell migration;positive regulation of transforming growth factor beta receptor signaling pathway;negative regulation of protein binding;positive regulation of proteasomal ubiquitin-dependent protein catabolic process;leading edge cell differentiation;negative regulation of apoptotic process;positive regulation of endocytosis;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;positive regulation of SMAD protein signal transduction;negative regulation of androgen receptor signaling pathway;membrane organization;negative regulation of canonical Wnt signaling pathway;negative regulation of protein localization to plasma membrane;positive regulation of Wnt signaling pathway, planar cell polarity pathway;positive regulation of clathrin-dependent endocytosis;positive regulation of early endosome to late endosome transport
• Cellular component: fibrillar center;lysosomal membrane;cytosol;plasma membrane;clathrin-coated pit;focal adhesion;clathrin-coated vesicle;clathrin-coated vesicle membrane;intracellular membrane-bounded organelle
• Molecular function: protein binding;protein C-terminus binding;clathrin adaptor activity;cargo receptor activity;SMAD binding