RAB3GAP2

RAB3 GTPase activating non-catalytic protein subunit 2, the group of Small nucleolar RNA protein coding host genes|MicroRNA protein coding host genes

Basic information

Region (hg38): 1:220148293-220272529

Links

ENSG00000118873 ∙ NCBI:25782 ∙ OMIM:609275 ∙ HGNC:17168 ∙ Uniprot:Q9H2M9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Martsolf 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
• autosomal recessive spastic paraplegia type 69 (Supportive), mode of inheritance: AR
• Warburg micro syndrome 2 (Strong), mode of inheritance: AR
• Warburg micro syndrome (Definitive), mode of inheritance: AR
• RAB18 deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Warburg micro syndrome 2; Martsolf 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	677168; 16532399; 20967465

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RAB3GAP2 gene.

• Warburg_micro_syndrome_2 (466 variants)
• Martsolf_syndrome (456 variants)
• not_provided (156 variants)
• Inborn_genetic_diseases (137 variants)
• not_specified (48 variants)
• RAB3GAP2-related_disorder (30 variants)
• Martsolf_syndrome_1 (19 variants)
• Warburg_micro_syndrome (4 variants)
• Microcephaly (3 variants)
• Amenorrhea (3 variants)
• Esophageal_atresia/tracheoesophageal_fistula (1 variants)
• Developmental_cataract (1 variants)
• Neurodevelopmental_delay (1 variants)
• See_cases (1 variants)
• Persistent_pupillary_membrane (1 variants)
• Microphthalmia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RAB3GAP2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000012414.4. 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			8	135	1	144
missense	3	4	308	20	3	338
nonsense	8	4				12
start loss			1			1
frameshift	9	7	2			18
splice donor/acceptor (+/-2bp)	2	8	2			12
Total	22	23	321	155	4

Highest pathogenic variant AF is 0.0000111534

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RAB3GAP2	protein_coding	protein_coding	ENST00000358951	35	124162

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.987	0.0133	125708	0	40	125748	0.000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.868	645	710	0.908	0.0000352	9119
Missense in Polyphen		158	222.27	0.71086		2812
Synonymous	1.05	238	259	0.917	0.0000134	2637
Loss of Function	6.85	16	83.6	0.191	0.00000426	987

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000431	0.000424
Ashkenazi Jewish	0.000106	0.0000992
East Asian	0.000273	0.000272
Finnish	0.00	0.00
European (Non-Finnish)	0.000177	0.000176
Middle Eastern	0.000273	0.000272
South Asian	0.000164	0.000163
Other	0.000180	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Regulatory 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. Rab3 GTPase-activating complex 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:9733780}.
• Disease: DISEASE: Warburg micro syndrome 2 (WARBM2) [MIM:614225]: A rare syndrome characterized by microcephaly, microphthalmia, microcornia, congenital cataracts, optic atrophy, cortical dysplasia, in particular corpus callosum hypoplasia, severe mental retardation, spastic diplegia, and hypogonadism. {ECO:0000269|PubMed:20967465}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Vesicle-mediated transport;Membrane Trafficking;Effects of Botulinum toxin;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: 0.121

Intolerance Scores

• loftool: 0.420
• rvis_EVS: -1.08
• rvis_percentile_EVS: 7.28

Haploinsufficiency Scores

• pHI: 0.640
• hipred: N
• hipred_score: 0.480
• ghis: 0.673

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.919

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rab3gap2

Gene ontology

• Biological process: intracellular protein transport;regulation of GTPase activity;positive regulation of GTPase activity;establishment of protein localization to endoplasmic reticulum membrane;positive regulation of protein lipidation;positive regulation of endoplasmic reticulum tubular network organization;positive regulation of autophagosome assembly
• Cellular component: endoplasmic reticulum membrane;cytosol;plasma membrane;protein-containing complex
• Molecular function: GTPase activator activity;protein binding;enzyme activator activity;Rab guanyl-nucleotide exchange factor activity;Rab GTPase binding;enzyme regulator activity;protein heterodimerization activity