RRAGC

Ras related GTP binding C, the group of Ras related GTP binding proteins

Basic information

Region (hg38): 1:38838198-38859772

Links

ENSG00000116954

∙ NCBI:64121 ∙ OMIM:608267 ∙ HGNC:19902 ∙ Uniprot:Q9HB90 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

Long-Olsen-Distelmaier syndrome (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Long-Olsen-Distelmaier syndrome	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Cardiovascular; Neurologic; Ophthalmologic	27234373; 37057673

ClinVar

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

Inborn_genetic_diseases (29 variants)
Long-Olsen-Distelmaier_syndrome (4 variants)
RRAGC-related_condition (1 variants)
See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RRAGC gene is commonly pathogenic or not. These statistics are base on transcript: NM_000022157.4. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar		1
missense	3 clinvar	1 clinvar	29 clinvar			33
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	3	1	29	1	0

Highest pathogenic variant AF is 0.0000065672816

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RRAGC	protein_coding	protein_coding	ENST00000373001	7	21626

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.975	0.0246	125742	0	6	125748	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.46	113	215	0.527	0.00000996	2660
Missense in Polyphen		15	44.978	0.3335		595
Synonymous	0.623	76	83.2	0.913	0.00000440	736
Loss of Function	3.45	1	15.8	0.0633	7.48e-7	206

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000579	0.0000579
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.000163	0.000163
South Asian	0.0000364	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Guanine nucleotide-binding protein forming heterodimeric Rag complexes required for the amino acid-induced relocalization of mTORC1 to the lysosomes and its subsequent activation by the GTPase RHEB. This is a crucial step in the activation of the TOR signaling cascade by amino acids. {ECO:0000269|PubMed:20381137, ECO:0000269|PubMed:27234373}.;
Disease: DISEASE: Note=RRAGC mutations have been found in a patient with idiopathic dilated cardiomyopathy with ventricular dilation and systolic dysfunction, bilateral cataracts, and mild facial dysmorphisms. {ECO:0000269|PubMed:27234373}.;
Pathway: mTOR signaling pathway - Homo sapiens (human);Autophagy - animal - Homo sapiens (human);Target Of Rapamycin (TOR) Signaling;Signal Transduction;Gene expression (Transcription);Generic Transcription Pathway;RNA Polymerase II Transcription;mTORC1-mediated signalling;Energy dependent regulation of mTOR by LKB1-AMPK;mTOR signalling;TP53 Regulates Metabolic Genes;Macroautophagy;Cellular responses to external stimuli;Regulation of PTEN gene transcription;PTEN Regulation;PIP3 activates AKT signaling;Transcriptional Regulation by TP53;Intracellular signaling by second messengers;mTOR signaling pathway (Consensus)

Recessive Scores

pRec: 0.117

Intolerance Scores

loftool: 0.175
rvis_EVS: -0.23
rvis_percentile_EVS: 36.86

Haploinsufficiency Scores

pHI: 0.372
hipred: Y
hipred_score: 0.765
ghis: 0.608

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.990

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Rragc
Phenotype

Gene ontology

Biological process: transcription, DNA-templated;apoptotic process;cell cycle arrest;small GTPase mediated signal transduction;RNA splicing;cellular response to starvation;regulation of autophagy;regulation of macroautophagy;regulation of TOR signaling;positive regulation of TOR signaling;cellular response to amino acid starvation;cellular protein localization;response to amino acid;cellular response to amino acid stimulus;regulation of TORC1 signaling
Cellular component: nucleus;cytoplasm;lysosome;cytosol;EGO complex;intracellular membrane-bounded organelle;Gtr1-Gtr2 GTPase complex
Molecular function: magnesium ion binding;GTPase activity;protein binding;GTP binding;GDP binding;protein heterodimerization activity;GTPase binding