RAB3GAP1

RAB3 GTPase activating protein catalytic subunit 1

Basic information

Region (hg38): 2:135052289-135176667

Links

ENSG00000115839 ∙ NCBI:22930 ∙ OMIM:602536 ∙ HGNC:17063 ∙ Uniprot:Q15042 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Warburg micro syndrome 1 (Definitive), mode of inheritance: AR
• cataract-intellectual disability-hypogonadism syndrome (Supportive), mode of inheritance: AR
• Warburg micro syndrome (Supportive), mode of inheritance: AR
• Warburg micro syndrome 1 (Strong), mode of inheritance: AR
• Warburg micro syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Warburg micro syndrome 1	AR	Endocrine; Ophthalmologic; Pharmacogenomic	The condition can include a risk of glaucoma, and early treatment may be beneficial; Medical care related to endocrine manifestations may be indicated; Agents that may contribute to glaucoma should be avoided	Craniofacial; Endocrine; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic	8249951; 10465117; 11237903; 15216543; 15696165; 18286824; 20512159; 22768674; 23420520; 30730599

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RAB3GAP1 gene.

• not provided (21 variants)
• Warburg micro syndrome 1 (17 variants)
• Inborn genetic diseases (3 variants)
• Warburg micro syndrome 1;Martsolf syndrome 2 (1 variants)
• Martsolf syndrome 2 (1 variants)
• RAB3GAP1-related disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RAB3GAP1 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			7	53	4	64
missense			128	8	4	140
nonsense	14	6	1			21
start loss						0
frameshift	11	5				16
inframe indel			4			4
splice donor/acceptor (+/-2bp)	7	6	1			14
splice region			9	15	2	26
non coding			28	81	45	154
Total	32	17	169	142	53

Highest pathogenic variant AF is 0.0000526

Variants in RAB3GAP1

This is a list of pathogenic ClinVar variants found in the RAB3GAP1 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-135052304-C-T		Warburg micro syndrome 1 • not specified • RAB3GAP1-related disorder	Uncertain significance (Jan 13, 2018)
2-135052312-C-T		Inborn genetic diseases	Uncertain significance (May 05, 2023)
2-135052314-GC-G		Martsolf syndrome • Martsolf syndrome 2	Pathogenic (May 01, 2013)
2-135052317-G-C		Inborn genetic diseases	Uncertain significance (Jun 16, 2024)
2-135052319-C-T			Likely benign (Jul 19, 2022)
2-135052326-G-C		RAB3GAP1-related disorder	Likely pathogenic (Sep 08, 2023)
2-135052328-G-C		Inborn genetic diseases	Uncertain significance (Jun 02, 2021)
2-135052329-A-G		not specified	Conflicting classifications of pathogenicity (Jul 25, 2022)
2-135052333-C-A			Likely benign (Jan 19, 2024)
2-135052333-C-T			Likely benign (Jul 16, 2022)
2-135052413-C-T			Likely benign (Jun 09, 2023)
2-135052417-C-T			Likely benign (Jun 26, 2023)
2-135052420-C-G			Likely benign (Aug 09, 2022)
2-135052432-C-G			Likely benign (Dec 06, 2023)
2-135052446-T-C		Warburg micro syndrome 1	Uncertain significance (Apr 28, 2017)
2-135052453-C-T			Likely benign (Oct 13, 2023)
2-135052454-A-G		not specified	Uncertain significance (Feb 28, 2017)
2-135052463-A-C		Warburg micro syndrome 1	Pathogenic (May 01, 2013)
2-135052479-G-A			Pathogenic/Likely pathogenic (Dec 13, 2023)
2-135052481-GAA-G			Pathogenic (Jun 03, 2022)
2-135052482-A-T		Warburg micro syndrome 1	Pathogenic (May 01, 2013)
2-135052493-A-T			Likely benign (Dec 31, 2019)
2-135052499-A-G			Likely benign (May 15, 2023)
2-135052500-T-A			Likely benign (Oct 05, 2023)
2-135052620-C-T			Likely benign (Apr 16, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RAB3GAP1	protein_coding	protein_coding	ENST00000442034	25	124130

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.45e-7	1.00	125652	0	96	125748	0.000382

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.18	440	516	0.853	0.0000269	6458
Missense in Polyphen		114	146.23	0.77959		1693
Synonymous	0.266	177	182	0.975	0.00000928	1877
Loss of Function	4.50	23	60.9	0.378	0.00000336	714

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000843	0.000843
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000272	0.000272
Finnish	0.000742	0.000739
European (Non-Finnish)	0.000405	0.000404
Middle Eastern	0.000272	0.000272
South Asian	0.000294	0.000294
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Probable catalytic subunit of a GTPase activating protein that has specificity for Rab3 subfamily (RAB3A, RAB3B, RAB3C and RAB3D). Rab3 proteins are involved in regulated exocytosis of neurotransmitters and hormones. Specifically converts active Rab3-GTP to the inactive form Rab3-GDP. Required for normal eye and brain development. May participate in neurodevelopmental processes such as proliferation, migration and differentiation before synapse formation, and non-synaptic vesicular release of neurotransmitters. {ECO:0000269|PubMed:10859313, ECO:0000269|PubMed:9030515}.
• Pathway: Vesicle-mediated transport;Membrane Trafficking;Rab regulation of trafficking;COPI-independent Golgi-to-ER retrograde traffic;Golgi-to-ER retrograde transport;RAB GEFs exchange GTP for GDP on RABs;Intra-Golgi and retrograde Golgi-to-ER traffic (Consensus)

Recessive Scores

• pRec: 0.149

Intolerance Scores

• loftool: 0.941
• rvis_EVS: 0.2
• rvis_percentile_EVS: 67.43

Haploinsufficiency Scores

• pHI: 0.421
• hipred: Y
• hipred_score: 0.528
• ghis: 0.536

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.673

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rab3gap1
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Gene ontology

• Biological process: brain development;positive regulation of gene expression;hypothalamus development;lipid droplet organization;camera-type eye development;regulation of GTPase activity;positive regulation of GTPase activity;regulation of short-term neuronal synaptic plasticity;excitatory postsynaptic potential;face morphogenesis;positive regulation of glutamate neurotransmitter secretion in response to membrane depolarization;establishment of protein localization to endoplasmic reticulum membrane;positive regulation of protein lipidation;regulation of calcium ion-dependent exocytosis of neurotransmitter;positive regulation of endoplasmic reticulum tubular network organization;positive regulation of autophagosome assembly
• Cellular component: endoplasmic reticulum membrane;Golgi apparatus;lipid droplet;cytosol;protein-containing complex;extracellular exosome;endoplasmic reticulum tubular network;postsynapse
• Molecular function: guanyl-nucleotide exchange factor activity;GTPase activator activity;protein binding;Rab guanyl-nucleotide exchange factor activity;Rab GTPase binding