RRAGD

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

Basic information

Region (hg38): 6:89364616-89412273

Links

ENSG00000025039 ∙ NCBI:58528 ∙ OMIM:608268 ∙ HGNC:19903 ∙ Uniprot:Q9NQL2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypomagnesemia 7, renal, with or without dilated cardiomyopathy (Moderate), mode of inheritance: AD
• hypomagnesemia 7, renal, with or without dilated cardiomyopathy (Strong), mode of inheritance: AD

ClinVar

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

• not provided (1 variants)
• HYPOMAGNESEMIA 7, RENAL, WITH DILATED CARDIOMYOPATHY (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RRAGD 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						0
missense	1	1	10			12
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	1	1	10	0	0

Variants in RRAGD

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

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

Position	Type	Phenotype	Significance	ClinVar
6-89368122-C-G		Inborn genetic diseases	Uncertain significance (Jun 29, 2023)
6-89379237-T-A		Inborn genetic diseases	Uncertain significance (Sep 07, 2022)
6-89380166-A-G			Uncertain significance (Apr 07, 2024)
6-89380239-T-G		Inborn genetic diseases	Uncertain significance (Oct 29, 2024)
6-89380270-A-G		Inborn genetic diseases	Uncertain significance (Jun 13, 2023)
6-89387306-T-G			Uncertain significance (Sep 29, 2023)
6-89387347-T-C		Inborn genetic diseases	Uncertain significance (Mar 15, 2024)
6-89387383-G-A		HYPOMAGNESEMIA 7, RENAL, WITH DILATED CARDIOMYOPATHY	Pathogenic (Dec 08, 2022)
6-89387383-G-C		HYPOMAGNESEMIA 7, RENAL, WITH DILATED CARDIOMYOPATHY	Pathogenic (Nov 01, 2021)
6-89387440-A-C		Hypomagnesemia 7, renal, with or without dilated cardiomyopathy	Likely pathogenic (Dec 05, 2023)
6-89387450-T-G		HYPOMAGNESEMIA 7, RENAL, WITHOUT DILATED CARDIOMYOPATHY	Pathogenic (Dec 08, 2022)
6-89387452-C-T		Inborn genetic diseases	Uncertain significance (Sep 17, 2021)
6-89387512-G-A		Hypomagnesemia 7, renal, with or without dilated cardiomyopathy • RRAGD-related disorder	Pathogenic (Dec 08, 2022)
6-89387512-G-C		HYPOMAGNESEMIA 7, RENAL, WITHOUT DILATED CARDIOMYOPATHY	Pathogenic (Dec 08, 2022)
6-89411861-C-A		Inborn genetic diseases	Uncertain significance (Aug 22, 2023)
6-89411887-T-C		Inborn genetic diseases	Uncertain significance (Jan 18, 2022)
6-89411893-C-A		Inborn genetic diseases	Uncertain significance (Nov 21, 2023)
6-89411911-A-G		Inborn genetic diseases	Uncertain significance (Jan 31, 2023)
6-89411925-A-C		Inborn genetic diseases	Uncertain significance (Feb 16, 2023)
6-89411938-T-A		Inborn genetic diseases	Uncertain significance (Oct 11, 2024)
6-89411957-C-T		Inborn genetic diseases	Uncertain significance (Aug 13, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RRAGD	protein_coding	protein_coding	ENST00000369415	7	47635

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.820	0.180	125725	0	1	125726	0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.20	119	208	0.571	0.0000103	2671
Missense in Polyphen		18	61.372	0.2933		758
Synonymous	1.13	65	77.7	0.837	0.00000427	730
Loss of Function	3.03	2	14.4	0.139	6.51e-7	202

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000879	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
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}.
• 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: 0.105

Intolerance Scores

• loftool: 0.0712
• rvis_EVS: -0.05
• rvis_percentile_EVS: 49.76

Haploinsufficiency Scores

• pHI: 0.211
• hipred: Y
• hipred_score: 0.715
• ghis: 0.517

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.838

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rragd

Gene ontology

• Biological process: cell cycle arrest;cellular response to starvation;regulation of autophagy;regulation of macroautophagy;positive regulation of TOR signaling;cellular protein localization;cellular response to amino acid stimulus;cellular response to leucine;positive regulation of TORC1 signaling;cellular response to leucine starvation
• Cellular component: nucleus;nucleoplasm;cytoplasm;lysosome;centrosome;cytosol;EGO complex;Gtr1-Gtr2 GTPase complex
• Molecular function: GTPase activity;protein binding;GTP binding;GDP binding;protein heterodimerization activity;GTPase binding