GAPVD1

GTPase activating protein and VPS9 domains 1, the group of VPS9 domain containing

Basic information

Region (hg38): 9:125261793-125367207

Links

ENSG00000165219 ∙ NCBI:26130 ∙ OMIM:611714 ∙ HGNC:23375 ∙ Uniprot:Q14C86 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• familial idiopathic steroid-resistant nephrotic syndrome (Supportive), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GAPVD1 gene.

• not provided (18 variants)
• GAPVD1-related condition (3 variants)
• GAPVD1-related Nephrotic syndrome (1 variants)
• Autism spectrum disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GAPVD1 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				2	4	6
missense			4	1	1	6
nonsense						0
start loss						0
frameshift				1		1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					10	10
Total	0	0	4	4	15

Variants in GAPVD1

This is a list of pathogenic ClinVar variants found in the GAPVD1 region.

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

Position	Type	Phenotype	Significance	ClinVar
9-125301963-CTT-C		GAPVD1-related disorder	Benign (Jan 09, 2020)
9-125302062-T-C			Likely benign (Sep 01, 2022)
9-125302132-C-T		GAPVD1-related disorder	Uncertain significance (Nov 20, 2023)
9-125302154-A-G		GAPVD1-related disorder	Likely benign (Jun 07, 2019)
9-125302394-T-G			Benign (May 05, 2021)
9-125302647-G-A			Benign/Likely benign (Jun 01, 2023)
9-125302818-C-T		GAPVD1-related disorder	Likely benign (Jan 10, 2020)
9-125305017-T-C			Benign (May 12, 2021)
9-125305116-C-T		GAPVD1-related disorder	Likely benign (Nov 06, 2023)
9-125305140-G-A			Benign (May 04, 2021)
9-125307424-C-A		FAM157B-related disorder	Benign (May 04, 2021)
9-125307554-G-A		GAPVD1-related disorder	Likely benign (Jul 21, 2019)
9-125307598-G-A			Benign (May 17, 2021)
9-125307821-A-G		GAPVD1-related disorder	Benign (May 03, 2019)
9-125307868-C-T			Uncertain significance (Nov 02, 2021)
9-125307897-G-T		GAPVD1-related disorder	Likely benign (Mar 07, 2022)
9-125307948-G-C			Benign (May 11, 2021)
9-125312444-T-C		GAPVD1-related disorder	Likely benign (Mar 16, 2021)
9-125312470-G-A		GAPVD1-related disorder	Uncertain significance (Dec 19, 2022)
9-125312528-T-C		FAM157B-related disorder	Benign (Jul 18, 2019)
9-125321310-A-C			Benign (May 11, 2021)
9-125321521-G-A		GAPVD1-related disorder	Uncertain significance (Aug 25, 2023)
9-125323754-T-C			Benign (May 17, 2021)
9-125323822-T-C		GAPVD1-related disorder	Likely benign (Jun 04, 2021)
9-125323933-A-G		GAPVD1-related disorder	Benign (Feb 03, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GAPVD1	protein_coding	protein_coding	ENST00000394105	26	105414

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	1.62e-9	125741	0	4	125745	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.59	602	809	0.744	0.0000426	9777
Missense in Polyphen		244	386.68	0.63101		4668
Synonymous	-0.449	295	285	1.03	0.0000145	2891
Loss of Function	7.50	4	73.3	0.0546	0.00000404	855

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000123	0.000123
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000185	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts both as a GTPase-activating protein (GAP) and a guanine nucleotide exchange factor (GEF), and participates in various processes such as endocytosis, insulin receptor internalization or LC2A4/GLUT4 trafficking. Acts as a GEF for the Ras-related protein RAB31 by exchanging bound GDP for free GTP, leading to regulate LC2A4/GLUT4 trafficking. In the absence of insulin, it maintains RAB31 in an active state and promotes a futile cycle between LC2A4/GLUT4 storage vesicles and early endosomes, retaining LC2A4/GLUT4 inside the cells. Upon insulin stimulation, it is translocated to the plasma membrane, releasing LC2A4/GLUT4 from intracellular storage vesicles. Also involved in EGFR trafficking and degradation, possibly by promoting EGFR ubiquitination and subsequent degradation by the proteasome. Has GEF activity for Rab5 and GAP activity for Ras. {ECO:0000269|PubMed:16410077}.
• Pathway: Vesicle-mediated transport;Membrane Trafficking;Clathrin-mediated endocytosis;Rab regulation of trafficking;RAB GEFs exchange GTP for GDP on RABs (Consensus)

Recessive Scores

• pRec: 0.115

Intolerance Scores

• loftool: 0.0361
• rvis_EVS: -0.86
• rvis_percentile_EVS: 10.95

Haploinsufficiency Scores

• pHI: 0.656
• hipred: Y
• hipred_score: 0.768
• ghis: 0.593

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.958

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gapvd1

Gene ontology

• Biological process: endocytosis;signal transduction;positive regulation of GTPase activity;regulation of protein transport;membrane organization
• Cellular component: endosome;cytosol;membrane
• Molecular function: guanyl-nucleotide exchange factor activity;GTPase activator activity;Rab guanyl-nucleotide exchange factor activity;GTPase activating protein binding;cadherin binding