DENND3

DENN domain containing 3, the group of WD repeat domain containing|DENN domain containing

Basic information

Region (hg38): 8:141117278-141195808

Links

ENSG00000105339 ∙ NCBI:22898 ∙ OMIM:617503 ∙ HGNC:29134 ∙ Uniprot:A2RUS2 ∙ 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 DENND3 gene.

• not_specified (158 variants)
• not_provided (17 variants)
• Hirschsprung_disease,_susceptibility_to,_1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DENND3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001352890.3. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2	6	8
missense			146	14	4	164
nonsense						0
start loss						0
frameshift		1				1
splice donor/acceptor (+/-2bp)						0
Total	0	1	146	16	10

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DENND3	protein_coding	protein_coding	ENST00000262585	22	78531

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.30e-11	1.00	125521	2	225	125748	0.000903

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.37	556	737	0.755	0.0000467	7891
Missense in Polyphen		160	270.14	0.59229		2998
Synonymous	0.175	332	336	0.988	0.0000257	2320
Loss of Function	3.65	28	58.0	0.483	0.00000290	650

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000584	0.000584
Ashkenazi Jewish	0.000200	0.000198
East Asian	0.00799	0.00797
Finnish	0.000141	0.000139
European (Non-Finnish)	0.000371	0.000325
Middle Eastern	0.00799	0.00797
South Asian	0.000659	0.000653
Other	0.000331	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Guanine nucleotide exchange factor (GEF) activating RAB12. Promotes the exchange of GDP to GTP, converting inactive GDP-bound RAB12 into its active GTP-bound form (PubMed:20937701). Regulates autophagy in response to starvation through RAB12 activation. Starvation leads to ULK1/2-dependent phosphorylation of Ser-472 and Ser-490, which in turn allows recruitment of 14-3-3 adapter proteins and leads to up-regulation of GEF activity towards RAB12 (By similarity). Also plays a role in protein transport from recycling endosomes to lysosomes, regulating, for instance, the degradation of the transferrin receptor and of the amino acid transporter PAT4 (PubMed:20937701). Starvation also induces phosphorylation at Tyr-858, which leads to up-regulated GEF activity and initiates autophagy (By similarity). {ECO:0000250|UniProtKB:A2RT67, ECO:0000269|PubMed:20937701}.
• Pathway: Vesicle-mediated transport;Membrane Trafficking;Rab regulation of trafficking;RAB GEFs exchange GTP for GDP on RABs (Consensus)

Recessive Scores

• pRec: 0.0864

Intolerance Scores

• loftool: 0.603
• rvis_EVS: -0.56
• rvis_percentile_EVS: 19.06

Haploinsufficiency Scores

• pHI: 0.0983
• hipred: Y
• hipred_score: 0.563
• ghis: 0.502

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.752

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dennd3

Gene ontology

• Biological process: endosome to lysosome transport;cellular protein catabolic process
• Cellular component: cytosol
• Molecular function: Rab guanyl-nucleotide exchange factor activity