DENND5A

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

Basic information

Region (hg38): 11:9138825-9265959

Previous symbols: [ "RAB6IP1" ]

Links

ENSG00000184014 ∙ NCBI:23258 ∙ OMIM:617278 ∙ HGNC:19344 ∙ Uniprot:Q6IQ26 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Tourette syndrome (No Known Disease Relationship), mode of inheritance: Unknown
• developmental and epileptic encephalopathy, 49 (Strong), mode of inheritance: AR
• developmental and epileptic encephalopathy, 49 (Strong), mode of inheritance: AR
• developmental and epileptic encephalopathy, 49 (Strong), mode of inheritance: AR
• developmental and epileptic encephalopathy, 49 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Developmental and epileptic encephalopathy 49	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Neurologic	27431290; 27866705

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DENND5A gene.

• not_provided (583 variants)
• Inborn_genetic_diseases (131 variants)
• Developmental_and_epileptic_encephalopathy,_49 (26 variants)
• DENND5A-related_disorder (14 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DENND5A gene is commonly pathogenic or not. These statistics are base on transcript: NM_000015213.4. 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			3	224	8	235
missense		1	264	7	2	274
nonsense	5	4				9
start loss						0
frameshift	10	1	2			13
splice donor/acceptor (+/-2bp)	1	6				7
Total	16	12	269	231	10

Highest pathogenic variant AF is 0.0000087188955

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DENND5A	protein_coding	protein_coding	ENST00000328194	23	126566

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0575	0.942	125720	0	28	125748	0.000111

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.38	536	715	0.750	0.0000399	8484
Missense in Polyphen		144	258.12	0.55787		3086
Synonymous	-0.152	281	278	1.01	0.0000148	2481
Loss of Function	5.61	16	64.6	0.248	0.00000349	733

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000337	0.000337
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000109	0.000109
Finnish	0.000139	0.0000924
European (Non-Finnish)	0.000115	0.000114
Middle Eastern	0.000109	0.000109
South Asian	0.000136	0.0000980
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Guanine nucleotide exchange factor (GEF) which may activate RAB6A and RAB39A and/or RAB39B. Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form. Involved in the negative regulation of neurite outgrowth (By similarity). {ECO:0000250|UniProtKB:G3V7Q0, ECO:0000269|PubMed:20937701}.
• Disease: DISEASE: Epileptic encephalopathy, early infantile, 49 (EIEE49) [MIM:617281]: A form of epileptic encephalopathy, a heterogeneous group of severe childhood onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. EIEE49 is a severe autosomal recessive form characterized by onset of seizures in the neonatal period, global developmental delay, intellectual disability, and additionally cerebral calcifications and coarse facial features. {ECO:0000269|PubMed:27431290, ECO:0000269|PubMed:27866705}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Vesicle-mediated transport;Membrane Trafficking;Rab regulation of trafficking;RAB GEFs exchange GTP for GDP on RABs (Consensus)

Recessive Scores

• pRec: 0.107

Intolerance Scores

• loftool: 0.395
• rvis_EVS: -1.37
• rvis_percentile_EVS: 4.45

Haploinsufficiency Scores

• pHI: 0.304
• hipred: Y
• hipred_score: 0.610
• ghis: 0.549

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.847

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dennd5a

Gene ontology

• Biological process: negative regulation of neuron projection development;retrograde transport, endosome to Golgi
• Cellular component: Golgi membrane;trans-Golgi network;cytosol;retromer complex
• Molecular function: Rab guanyl-nucleotide exchange factor activity