GAPVD1

protein-coding

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

Gene summary

Enables GTPase activating protein binding activity and guanyl-nucleotide exchange factor activity. Involved in regulation of protein transport. Located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_001282680.3

Inheritance

ClinVar variants

U:25B:33

Top phenotype

familial idiopathic steroid-resistant nephrotic syndrome

gnomAD constraint

pLI —, LoF o/e 0.05

Max pathogenic AF

—

Genomic locus

chr9:125,261,794-125,367,207

External References & Databases

Ensembl (ENSG00000165219)

Transcript & Mutation Effects

hg38 • Region Span ~105.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

familial idiopathic steroid-resistant nephrotic syndromeSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0019006

Submitter: Orphanet

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GAPVD1 variants in ClinVar

4 Conditions Cataloged

GAPVD1-related disorderTotal: 38

not providedTotal: 19

Autism spectrum disorderTotal: 1

GAPVD1-related Nephrotic syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001282680.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				22 clinvar	3 clinvar	25
missense			16 clinvar	5 clinvar	2 clinvar	23
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar	1 clinvar		2
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	0	0	25	28	5	58

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 118 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001282680.3	RefSeq	NP_001269609.1	25	MANE Select
ENST00000297933.11	Ensembl	ENSP00000297933.6	25	MANE Select
NM_001282679.2	RefSeq	NP_001269608.1	25	Standard
NM_001282681.3	RefSeq	NP_001269610.1	25	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Vesicle-mediated transport
Membrane Trafficking
Clathrin-mediated endocytosis
Rab regulation of trafficking
RAB GEFs exchange GTP for GDP on RABs

Biological Process

endocytosis
signal transduction
positive regulation of GTPase activity
regulation of protein transport
membrane organization

Molecular Function

guanyl-nucleotide exchange factor activity
GTPase activator activity
Rab guanyl-nucleotide exchange factor activity
GTPase activating protein binding
cadherin binding

Cellular Component

endosome
cytosol
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000394105
Coding exons: 26
Length: 105414
Individuals with no LoFs: 125741
Homozygous LoFs: 0
Heterozygous LoFs: 4
Defined: 125745
p: 0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.59	602	809	0.744	0.0000426	9777
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.115

Intolerance Scores

LoFtool: 0.0361
RVIS EVS: -0.86
RVIS percentile EVS: 10.95

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.958

Gene Damage Prediction

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