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.

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.

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				1	2	3
missense			19		1	20
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	19	1	3

Variants in DENND1B

This is a list of pathogenic ClinVar variants found in the DENND1B region.

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

Position	Type	Phenotype	Significance	ClinVar
1-197510627-G-A		not specified	Uncertain significance (Sep 01, 2021)
1-197510832-G-A			Benign (Dec 11, 2018)
1-197511754-T-C			Benign (Nov 09, 2018)
1-197511829-G-C		not specified	Uncertain significance (Sep 16, 2021)
1-197553045-A-T		not specified	Uncertain significance (Jul 08, 2021)
1-197553099-C-T		not specified	Uncertain significance (Apr 17, 2024)
1-197595228-C-T		not specified	Uncertain significance (May 16, 2024)
1-197595260-C-G		not specified	Uncertain significance (Jun 03, 2024)
1-197595276-C-G		not specified	Uncertain significance (Feb 06, 2024)
1-197595326-G-A		not specified	Uncertain significance (Oct 18, 2021)
1-197595329-G-A		not specified	Uncertain significance (Sep 09, 2021)
1-197607095-A-C		not specified	Uncertain significance (Oct 04, 2022)
1-197607125-G-C		not specified	Uncertain significance (Mar 02, 2023)
1-197607173-C-A		not specified	Uncertain significance (Aug 12, 2024)
1-197611960-G-C		not specified	Uncertain significance (Jul 30, 2024)
1-197617670-C-T			Benign (Dec 31, 2019)
1-197617699-A-G		not specified	Uncertain significance (Jan 11, 2023)
1-197617700-T-C		not specified	Uncertain significance (Apr 18, 2023)
1-197617713-T-A		not specified	Uncertain significance (Aug 13, 2021)
1-197642725-T-C		not specified	Uncertain significance (Nov 18, 2022)
1-197645704-T-G		not specified	Uncertain significance (May 31, 2022)
1-197652234-C-A		Autism	Uncertain significance (-)
1-197652258-T-G		not specified	Uncertain significance (Aug 12, 2021)
1-197652267-G-C		not specified	Uncertain significance (Jun 10, 2022)
1-197672056-T-C		not specified	Uncertain significance (Sep 25, 2024)

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