DENND5B

DENN domain containing 5B, the group of DENN domain containing

Basic information

Region (hg38): 12:31382226-31591136

Links

ENSG00000170456 ∙ NCBI:160518 ∙ OMIM:617279 ∙ HGNC:28338 ∙ Uniprot:Q6ZUT9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodevelopmental disorder (Moderate), mode of inheritance: AD
• hypoplastic left heart syndrome (Limited), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DENND5B gene.

• not_specified (110 variants)
• not_provided (49 variants)
• DENND5B-related_neurodevelopmental_disorder (7 variants)
• DENNDB5-associated_neurodevelopmental_disorder (1 variants)
• DENND5B_related_condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DENND5B gene is commonly pathogenic or not. These statistics are base on transcript: NM_000144973.4. 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				5		5
missense		1	141	11		153
nonsense			4			4
start loss						0
frameshift			2			2
splice donor/acceptor (+/-2bp)			4			4
Total	0	1	151	16	0

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DENND5B	protein_coding	protein_coding	ENST00000389082	21	208875

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	3.18e-7	124631	0	7	124638	0.0000281

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.39	413	658	0.628	0.0000346	8349
Missense in Polyphen		110	254.73	0.43183		3174
Synonymous	0.484	227	236	0.960	0.0000122	2397
Loss of Function	6.65	4	59.2	0.0676	0.00000304	752

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000290	0.0000290
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000474	0.0000442
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.000165	0.000165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Guanine nucleotide exchange factor (GEF) which may activate RAB39A and/or RAB39B. Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form. {ECO:0000269|PubMed:20937701}.
• Pathway: Vesicle-mediated transport;Membrane Trafficking;Rab regulation of trafficking;RAB GEFs exchange GTP for GDP on RABs (Consensus)

Intolerance Scores

• loftool: 0.497
• rvis_EVS: -0.44
• rvis_percentile_EVS: 24.6

Haploinsufficiency Scores

• hipred: Y
• hipred_score: 0.617
• ghis: 0.559

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.270

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Dennd5b

Gene ontology

• Cellular component: cytosol;integral component of membrane
• Molecular function: Rab guanyl-nucleotide exchange factor activity