DENND1A

DENN domain containing 1A, the group of MicroRNA protein coding host genes|DENN domain containing

Basic information

Region (hg38): 9:123379654-123930152

Previous symbols: [ "KIAA1608" ]

Links

ENSG00000119522 ∙ NCBI:57706 ∙ OMIM:613633 ∙ HGNC:29324 ∙ Uniprot:Q8TEH3 ∙ 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 DENND1A gene.

• not_specified (135 variants)
• not_provided (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DENND1A gene is commonly pathogenic or not. These statistics are base on transcript: NM_001352964.2. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2	1	3
missense			130	4	1	135
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	130	6	2

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DENND1A	protein_coding	protein_coding	ENST00000373624	22	550499

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000235	125733	0	15	125748	0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.26	493	578	0.852	0.0000354	6479
Missense in Polyphen		148	212.04	0.69797		2423
Synonymous	-1.37	276	249	1.11	0.0000171	2094
Loss of Function	5.60	5	45.9	0.109	0.00000237	524

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000910	0.0000904
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.0000538	0.0000527
Middle Eastern	0.000163	0.000163
South Asian	0.000165	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Guanine nucleotide exchange factor (GEF) regulating clathrin-mediated endocytosis through RAB35 activation. Promotes the exchange of GDP to GTP, converting inactive GDP-bound RAB35 into its active GTP-bound form. Regulates clathrin-mediated endocytosis of synaptic vesicles and mediates exit from early endosomes (PubMed:20154091, PubMed:20937701). Binds phosphatidylinositol-phosphates (PtdInsPs), with some preference for PtdIns(3)P (By similarity). {ECO:0000250|UniProtKB:Q8K382, ECO:0000269|PubMed:20154091, ECO:0000269|PubMed:20937701}.
• Disease: DISEASE: Note=Genetic variants in DENND1A may play a role in susceptibility to polycystic ovary syndrome (PCOS), the most common endocrine disease among premenopausal women. PCOS is a complex disorder characterized by infertility, hirsutism, obesity, various menstrual disturbances, and enlarged ovaries studded with atretic follicles. {ECO:0000269|PubMed:22180642, ECO:0000269|PubMed:23208300, ECO:0000269|PubMed:24086769, ECO:0000269|PubMed:25626177}.
• Pathway: Vesicle-mediated transport;Membrane Trafficking;Rab regulation of trafficking;RAB GEFs exchange GTP for GDP on RABs (Consensus)

Recessive Scores

• pRec: 0.0838

Intolerance Scores

• loftool: 0.256
• rvis_EVS: -1.46
• rvis_percentile_EVS: 3.86

Haploinsufficiency Scores

• pHI: 0.119
• hipred: Y
• hipred_score: 0.605
• ghis: 0.510

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.619

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dennd1a

Gene ontology

• Biological process: endocytosis;protein transport;endocytic recycling;regulation of Rab protein signal transduction;positive regulation of GTPase activity;synaptic vesicle endocytosis
• Cellular component: nucleoplasm;cytosol;cell junction;clathrin-coated vesicle;dendrite;clathrin-coated vesicle membrane;presynaptic membrane;neuronal cell body;intracellular membrane-bounded organelle
• Molecular function: Rab guanyl-nucleotide exchange factor activity;SH3 domain binding;Rab GTPase binding;phosphatidylinositol-3-phosphate binding;phosphatidylinositol phosphate binding