DENND1B

DENN domain containing 1B, the group of DENN domain containing

Basic information

Region (hg38): 1:197504748-197775696

Previous symbols: [ "FAM31B", "C1orf218" ]

Links

ENSG00000213047

∙ NCBI:163486 ∙ OMIM:613292 ∙ HGNC:28404 ∙ Uniprot:Q6P3S1 ∙ 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 DENND1B gene.

not_specified (42 variants)
not_provided (4 variants)
Autism (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DENND1B gene is commonly pathogenic or not. These statistics are base on transcript: NM_001195215.2. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar	2 clinvar	3
missense			41 clinvar	1 clinvar	1 clinvar	43
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	42	2	3

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DENND1B	protein_coding	protein_coding	ENST00000367396	16	270949

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.204	0.796	124773	0	12	124785	0.0000481

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.332	191	204	0.935	0.00000974	2781
Missense in Polyphen		79	93.857	0.84171		1237
Synonymous	0.0110	76	76.1	0.998	0.00000389	773
Loss of Function	3.45	6	24.4	0.246	0.00000109	339

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000123	0.000123
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000558	0.0000556
Finnish	0.0000467	0.0000464
European (Non-Finnish)	0.0000268	0.0000265
Middle Eastern	0.0000558	0.0000556
South Asian	0.0000655	0.0000654
Other	0.000331	0.000330

dbNSFP

Source: dbNSFP

Function: FUNCTION: Guanine nucleotide exchange factor (GEF) for RAB35 that acts as a regulator of T-cell receptor (TCR) internalization in TH2 cells (PubMed:20154091, PubMed:20937701, PubMed:24520163, PubMed:26774822). Acts by promoting the exchange of GDP to GTP, converting inactive GDP-bound RAB35 into its active GTP-bound form (PubMed:20154091, PubMed:20937701). Plays a role in clathrin- mediated endocytosis (PubMed:20154091). Controls cytokine production in TH2 lymphocytes by controlling the rate of TCR internalization and routing to endosomes: acts by mediating clathrin-mediated endocytosis of TCR via its interaction with the adapter protein complex 2 (AP-2) and GEF activity (PubMed:26774822). Dysregulation leads to impaired TCR down- modulation and recycling, affecting cytokine production in TH2 cells (PubMed:26774822). {ECO:0000269|PubMed:20154091, ECO:0000269|PubMed:20937701, ECO:0000269|PubMed:24520163, ECO:0000269|PubMed:26774822}.;
Disease: DISEASE: Asthma (ASTHMA) [MIM:600807]: The most common chronic disease affecting children and young adults. It is a complex genetic disorder with a heterogeneous phenotype, largely attributed to the interactions among many genes and between these genes and the environment. It is characterized by recurrent attacks of paroxysmal dyspnea, with wheezing due to spasmodic contraction of the bronchi. {ECO:0000269|PubMed:20032318, ECO:0000269|PubMed:26774822}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. Asthma susceptibility is probably caused by decreased TCR down-modulation and recycling in TH2 cells, causing prolonged TCR signaling and increased cytokine production in TH2 lymphocytes (PubMed:26774822). {ECO:0000269|PubMed:26774822}.;
Pathway: Vesicle-mediated transport;Membrane Trafficking;Rab regulation of trafficking;RAB GEFs exchange GTP for GDP on RABs (Consensus)

Recessive Scores

pRec: 0.0905

Intolerance Scores

loftool: 0.558
rvis_EVS: -0.43
rvis_percentile_EVS: 25.15

Haploinsufficiency Scores

pHI: 0.0451
hipred: Y
hipred_score: 0.547
ghis: 0.472

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.0499

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Dennd1b
Phenotype: growth/size/body region phenotype; immune system phenotype; respiratory system phenotype; hematopoietic system phenotype;

Gene ontology

Biological process: endocytosis;protein transport;endocytic recycling;T-helper 2 cell cytokine production;positive regulation of GTPase activity;regulation of immune response;T cell receptor signaling pathway
Cellular component: cytosol;nuclear speck;clathrin-coated vesicle;intracellular membrane-bounded organelle
Molecular function: Rab guanyl-nucleotide exchange factor activity;Rab GTPase binding;phosphatidylinositol phosphate binding