RRAGD

Summary

RRAGD (Ras related GTP binding D, HGNC:19903) is a protein-coding gene on chromosome 6q15, encoding Ras-related GTP-binding protein D (Q9NQL2). Guanine nucleotide-binding protein that plays a crucial role in the cellular response to amino acid availability through regulation of the mTORC1 signaling cascade.

RRAGD is a monomeric guanine nucleotide-binding protein, or G protein. By binding GTP or GDP, small G proteins act as molecular switches in numerous cell processes and signaling pathways.

Source: NCBI Gene 58528 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hypomagnesemia 7, renal, with or without dilated cardiomyopathy (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 34 total — 4 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 33
• MANE Select transcript: NM_021244

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19903
Approved symbol	RRAGD
Name	Ras related GTP binding D
Location	6q15
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP761H171, bA11D8.2.1
Ensembl gene	ENSG00000025039
Ensembl biotype	protein_coding
OMIM	608268
Entrez	58528

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000359203, ENST00000369415, ENST00000492783, ENST00000886443, ENST00000886444, ENST00000936138, ENST00000936139

RefSeq mRNA: 1 — MANE Select: NM_021244 NM_021244

CCDS: CCDS5022

Canonical transcript exons

ENST00000369415 — 7 exons

Exon	Start	End
ENSE00000760434	89372437	89372585
ENSE00001449984	89364616	89368207
ENSE00001449989	89411846	89412273
ENSE00001888083	89377671	89377813
ENSE00003498260	89379224	89379338
ENSE00003528533	89387295	89387590
ENSE00003559223	89380168	89380367

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 98.95.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.1663 / max 773.4901, expressed in 1275 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
74698	11.7375	1230
74696	2.8976	743
74697	1.0005	509
74695	0.5307	243

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
body of tongue	UBERON:0011876	98.95	gold quality
parotid gland	UBERON:0001831	98.82	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.68	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.21	gold quality
vastus lateralis	UBERON:0001379	98.19	gold quality
diaphragm	UBERON:0001103	98.14	gold quality
gluteal muscle	UBERON:0002000	98.12	gold quality
renal medulla	UBERON:0000362	98.02	gold quality
biceps brachii	UBERON:0001507	97.98	gold quality
skeletal muscle tissue	UBERON:0001134	97.94	gold quality
esophagus squamous epithelium	UBERON:0006920	97.83	gold quality
quadriceps femoris	UBERON:0001377	97.75	gold quality
triceps brachii	UBERON:0001509	97.55	gold quality
epithelium of esophagus	UBERON:0001976	97.42	gold quality
deltoid	UBERON:0001476	97.39	gold quality
tongue	UBERON:0001723	97.00	gold quality
pigmented layer of retina	UBERON:0001782	96.97	gold quality
muscle organ	UBERON:0001630	96.89	gold quality
gastrocnemius	UBERON:0001388	96.87	gold quality
pharyngeal mucosa	UBERON:0000355	96.86	gold quality
muscle of leg	UBERON:0001383	96.51	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.44	gold quality
caput epididymis	UBERON:0004358	96.43	gold quality
tibialis anterior	UBERON:0001385	96.25	gold quality
myocardium	UBERON:0002349	96.06	gold quality
islet of Langerhans	UBERON:0000006	96.04	gold quality
muscle tissue	UBERON:0002385	96.00	gold quality
heart right ventricle	UBERON:0002080	95.59	gold quality
left ventricle myocardium	UBERON:0006566	95.55	gold quality
vena cava	UBERON:0004087	95.52	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-ENAD-27	yes	11.19
E-ANND-3	yes	9.61
E-GEOD-83139	yes	8.64
E-ENAD-17	no	136.90

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

214 targeting RRAGD, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-1468-3P	99.96	72.74	3797

Literature-anchored findings (GeneRIF, showing 6)

• FLCN and its binding partners, FNIP1/2, are Rag-interacting proteins with GAP activity for RagC/D, but not RagA/B. (PMID:24095279)
• demonstrating a key role of RagD in promoting tumor growth (PMID:28619945)
• BC-LI-0186 binds to the RagD interacting site of LRS, thereby inhibiting lysosomal localization of LRS and mTORC1 activity. (PMID:28963468)
• Ras related GTP binding D promotes aerobic glycolysis of hepatocellular carcinoma. (PMID:33434687)
• mTOR-Activating Mutations in RRAGD Are Causative for Kidney Tubulopathy and Cardiomyopathy. (PMID:34607910)
• RagD auto-activating mutations impair MiT/TFE activity in kidney tubulopathy and cardiomyopathy syndrome. (PMID:37188688)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	rragd	ENSDARG00000006279
danio_rerio	rragca	ENSDARG00000069829
danio_rerio	rragcb	ENSDARG00000099049
mus_musculus	Rragd	ENSMUSG00000028278
rattus_norvegicus	Rragd	ENSRNOG00000007331
drosophila_melanogaster	RagC-D	FBGN0033272
caenorhabditis_elegans		WBGENE00012497

Paralogs (3): RRAGB (ENSG00000083750), RRAGC (ENSG00000116954), RRAGA (ENSG00000155876)

Protein

Protein identifiers

Ras-related GTP-binding protein D — Q9NQL2 (reviewed: Q9NQL2)

All UniProt accessions (1): Q9NQL2

UniProt curated annotations — full annotation on UniProt →

Function. Guanine nucleotide-binding protein that plays a crucial role in the cellular response to amino acid availability through regulation of the mTORC1 signaling cascade. Forms heterodimeric Rag complexes with RagA/RRAGA or RagB/RRAGB and cycles between an inactive GTP-bound and an active GDP-bound form: RagD/RRAGD is in its active form when GDP-bound RagD/RRAGD forms a complex with GTP-bound RagA/RRAGA (or RagB/RRAGB) and in an inactive form when GTP-bound RagD/RRAGD heterodimerizes with GDP-bound RagA/RRAGA (or RagB/RRAGB). In its active form, promotes the recruitment of mTORC1 to the lysosomes and its subsequent activation by the GTPase RHEB. This is a crucial step in the activation of the MTOR signaling cascade by amino acids. Also plays a central role in the non-canonical mTORC1 complex, which acts independently of RHEB and specifically mediates phosphorylation of MiT/TFE factors TFEB and TFE3: GDP-bound RagD/RRAGD mediates recruitment of MiT/TFE factors TFEB and TFE3.

Subunit / interactions. Forms a heterodimer with RRAGA in a sequence-independent manner and RRAGB. Heterodimerization stabilizes RRAG proteins. The GDP-bound form of RRAGD (in complex with the GTP-bound form of RRAGA or RRAGB), interacts with RPTOR, thereby promoting recruitment of mTORC1 to the lysosomes. Component of the lysosomal folliculin complex (LFC), composed of FLCN, FNIP1 (or FNIP2), RagA/RRAGA or RagB/RRAGB GDP-bound, RagC/RRAGC or RagD/RRAGD GTP-bound, and Ragulator. Interacts with NOL8. Interacts with SH3BP4; the interaction with this negative regulator is most probably direct, preferentially occurs with the inactive GDP-bound form of RRAGD and is negatively regulated by amino acids. The Rag heterodimer interacts with SLC38A9; the probable amino acid sensor. Interacts with SESN1, SESN2 and SESN3. The GDP-bound form interacts with TFEB. The GDP-bound form interacts with TFE3.

Subcellular location. Cytoplasm. Nucleus. Lysosome membrane.

Disease relevance. Hypomagnesemia 7, renal, with or without dilated cardiomyopathy (HOMG7) [MIM:620152] An autosomal dominant renal disease characterized by hypomagnesemia, hypokalemia, salt wasting, and nephrocalcinosis. A subset of patients develop severe dilated cardiomyopathy. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. The activation of RagD/RRAGD is mediated by a GTPase activating protein (GAP). In high-amino acid conditions, activated by GTPase activating protein FLCN that stimulates RRAGD GTPase activity to turn it into its active GDP-bound form. In response to amino acid depletion, the GATOR1 complex inactivates RagC/RRAGC by securing the GTP-bound inactive form.

Similarity. Belongs to the GTR/RAG GTP-binding protein family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NQL2-1	1	yes
Q9NQL2-2	2

RefSeq proteins (1): NP_067067* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006762	Gtr1_RagA	Family
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR039400	RagC/D	Family

Pfam: PF04670

Catalyzed reactions (Rhea), 1 shown:

• GTP + H2O = GDP + phosphate + H(+) (RHEA:19669)

UniProt features (53 total): binding site 28, helix 7, sequence variant 6, strand 6, compositionally biased region 2, chain 1, region of interest 1, splice variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2Q3F	X-RAY DIFFRACTION	2.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NQL2-F1	75.62	0.30

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (28): 74; 75; 75; 76; 76; 77; 77; 91; 91; 95; 97; 97 …

Mutagenesis-validated functional residues (1):

Position	Phenotype
121	decreased rptor-binding.

Function

Pathways and Gene Ontology

Reactome pathways

19 pathways

ID	Pathway
R-HSA-1632852	Macroautophagy
R-HSA-165159	MTOR signalling
R-HSA-166208	mTORC1-mediated signalling
R-HSA-380972	Energy dependent regulation of mTOR by LKB1-AMPK
R-HSA-5628897	TP53 Regulates Metabolic Genes
R-HSA-8943724	Regulation of PTEN gene transcription
R-HSA-9639288	Amino acids regulate mTORC1
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-162582	Signal Transduction
R-HSA-212436	Generic Transcription Pathway
R-HSA-2262752	Cellular responses to stress
R-HSA-3700989	Transcriptional Regulation by TP53
R-HSA-6807070	PTEN Regulation
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8953897	Cellular responses to stimuli
R-HSA-9006925	Intracellular signaling by second messengers
R-HSA-9612973	Autophagy
R-HSA-9711097	Cellular response to starvation

MSigDB gene sets: 442 (showing top): chr6q15, GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_RESPONSE_TO_ACID_CHEMICAL, MODULE_255, GOCC_VACUOLAR_MEMBRANE, GOBP_POSITIVE_REGULATION_OF_TOR_SIGNALING, MODULE_317, TGACCTY_ERR1_Q2, GOMF_GTPASE_BINDING, GOBP_CELLULAR_RESPONSE_TO_ACID_CHEMICAL, BROWNE_HCMV_INFECTION_12HR_UP, GGGTGGRR_PAX4_03

GO Biological Process (10): intracellular protein localization (GO:0008104), cellular response to starvation (GO:0009267), negative regulation of autophagy (GO:0010507), positive regulation of TOR signaling (GO:0032008), cellular response to amino acid stimulus (GO:0071230), cellular response to L-leucine (GO:0071233), positive regulation of TORC1 signaling (GO:1904263), cellular response to leucine starvation (GO:1990253), cellular response to amino acid starvation (GO:0034198), response to amino acid (GO:0043200)

GO Molecular Function (9): GTPase activity (GO:0003924), GTP binding (GO:0005525), GDP binding (GO:0019003), protein heterodimerization activity (GO:0046982), GTPase binding (GO:0051020), molecular adaptor activity (GO:0060090), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (9): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), lysosome (GO:0005764), lysosomal membrane (GO:0005765), centrosome (GO:0005813), cytosol (GO:0005829), Gtr1-Gtr2 GTPase complex (GO:1990131), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
Signal Transduction	2
MTOR signalling	2
Autophagy	1
Transcriptional Regulation by TP53	1
PTEN Regulation	1
Cellular response to starvation	1
Intracellular signaling by second messengers	1
RNA Polymerase II Transcription	1
Cellular responses to stimuli	1
Generic Transcription Pathway	1
PIP3 activates AKT signaling	1
Gene expression (Transcription)	1
Cellular responses to stress	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
guanyl ribonucleotide binding	2
binding	2
macromolecule localization	1
cellular response to nutrient levels	1
cellular response to stress	1
response to starvation	1
autophagy	1
negative regulation of catabolic process	1
regulation of autophagy	1
TOR signaling	1
regulation of TOR signaling	1
positive regulation of intracellular signal transduction	1
response to amino acid	1
cellular response to acid chemical	1
response to L-leucine	1
cellular response to amino acid stimulus	1
cellular response to nitrogen compound	1
cellular response to oxygen-containing compound	1
positive regulation of TOR signaling	1
TORC1 signaling	1
regulation of TORC1 signaling	1
cellular response to amino acid starvation	1
cellular response to starvation	1
response to amino acid starvation	1
response to acid chemical	1
ribonucleoside triphosphate phosphatase activity	1
purine ribonucleoside triphosphate binding	1
anion binding	1
protein dimerization activity	1
enzyme binding	1
molecular_function	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
lytic vacuole	1
lysosome	1

Protein interactions and networks

STRING

1050 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RRAGD	RRAGB	Q5VZM2	992
RRAGD	RRAGA	Q7L523	992
RRAGD	LARS1	Q9P2J5	961
RRAGD	RRAGC	Q9HB90	945
RRAGD	RHEB	Q15382	928
RRAGD	RPTOR	Q8N122	925
RRAGD	LARS2	Q15031	921
RRAGD	EFNA5	P52803	843
RRAGD	NOL8	Q76FK4	819
RRAGD	RPS6KB1	P23443	815
RRAGD	FLCN	Q8NFG4	777
RRAGD	TSC2	P49815	753
RRAGD	MLST8	Q9BVC4	749
RRAGD	NPRL2	Q8WTW4	716
RRAGD	WDR24	Q96S15	715

IntAct

63 interactions, top by confidence:

A	B	Type	Score
LAMTOR4	LAMTOR5	psi-mi:“MI:0914”(association)	0.960
LAMTOR5	LAMTOR4	psi-mi:“MI:0914”(association)	0.960
LAMTOR1	LAMTOR5	psi-mi:“MI:0914”(association)	0.870
LAMTOR2	LAMTOR5	psi-mi:“MI:0914”(association)	0.860
RRAGB	LAMTOR1	psi-mi:“MI:0914”(association)	0.840
RRAGD	RRAGA	psi-mi:“MI:0914”(association)	0.830
RRAGA	RRAGD	psi-mi:“MI:0915”(physical association)	0.830
RRAGD	RRAGA	psi-mi:“MI:0915”(physical association)	0.830
RRAGD	LAMTOR1	psi-mi:“MI:0914”(association)	0.790
LAMTOR2	RRAGB	psi-mi:“MI:0914”(association)	0.790
RRAGD	RRAGB	psi-mi:“MI:0914”(association)	0.740
RRAGD	RRAGB	psi-mi:“MI:0915”(physical association)	0.740
LAMTOR3	LAMTOR5	psi-mi:“MI:0914”(association)	0.730
RRAGA	LAMTOR5	psi-mi:“MI:0914”(association)	0.640

BioGRID (74): LAMTOR3 (Affinity Capture-MS), LAMTOR2 (Affinity Capture-MS), LAMTOR1 (Affinity Capture-MS), RRAGD (Affinity Capture-Western), LAMTOR2 (Affinity Capture-Western), LAMTOR3 (Affinity Capture-Western), LAMTOR1 (Affinity Capture-Western), RRAGB (Affinity Capture-Western), RRAGD (Affinity Capture-Western), RRAGD (Affinity Capture-MS), RRAGD (Affinity Capture-Western), RRAGD (Affinity Capture-MS), RRAGD (Affinity Capture-Western), NPRL2 (Affinity Capture-Western), RPTOR (Affinity Capture-Western)

ESM2 similar proteins: A2YFN7, B8AJT9, C7EXK4, D3K5L7, E1C6Q1, E2R222, O70133, O70496, O94973, O95544, P51798, P51799, P70704, P97834, P98200, Q0VCK5, Q10D38, Q13098, Q15645, Q304A0, Q3UA06, Q4PKH3, Q5JQD7, Q5XHZ9, Q5XIJ5, Q5ZJL4, Q61187, Q67UQ7, Q6DD70, Q6EPN6, Q6GL10, Q6IRE4, Q6NRT5, Q8L5Y9, Q99JW1, Q99K70, Q99LD4, Q9FLG2, Q9HB90, Q9HCX4

Diamond homologs: O74544, P53290, Q7TT45, Q99K70, Q9HB90, Q9NQL2, Q3SX43, Q63486, Q7L523, Q80X95, Q9Y7Z2

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
RRAGD	up-regulates	RPTOR	binding
RRAGD	up-regulates	mTORC1	binding
RRAGD	“form complex”	RAGAD	binding
RRAGD	“form complex”	RAGBD	binding
FLCN	“up-regulates activity”	RRAGD	“gtpase-activating protein”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 36 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
mTORC1-mediated signalling	9	133.8×	1e-15
Energy dependent regulation of mTOR by LKB1-AMPK	9	110.8×	4e-15
MTOR signalling	9	74.7×	1e-13
PTEN Regulation	9	64.2×	4e-13
Amino acids regulate mTORC1	9	56.4×	1e-12
Regulation of PTEN gene transcription	9	50.2×	3e-12
Cellular response to starvation	9	46.5×	5e-12
Autophagy	10	46.4×	4e-13

GO biological processes:

GO term	Partners	Fold	FDR
TORC1 signaling	6	137.6×	2e-10
positive regulation of TOR signaling	9	127.5×	2e-15
cellular response to amino acid stimulus	10	87.5×	2e-15
positive regulation of TORC1 signaling	9	76.0×	2e-13
intracellular protein localization	6	17.9×	6e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

34 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	1
Uncertain significance	20
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
1802636	NM_021244.5(RRAGD):c.227C>G (p.Ser76Trp)	Pathogenic
1802637	NM_021244.5(RRAGD):c.289A>C (p.Thr97Pro)	Pathogenic
3765496	NM_021244.5(RRAGD):c.230C>T (p.Ser77Phe)	Pathogenic
3765497	NM_021244.5(RRAGD):c.272C>T (p.Thr91Ile)	Pathogenic
1802633	NM_021244.5(RRAGD):c.227C>T (p.Ser76Leu)	Likely pathogenic

SpliceAI

1390 predictions. Top by Δscore:

Variant	Effect	Δscore
6:89377665:ACTT:A	donor_loss	1.0000
6:89377666:CTTA:C	donor_loss	1.0000
6:89377667:TTACC:T	donor_loss	1.0000
6:89377668:TACC:T	donor_loss	1.0000
6:89377669:A:AC	donor_gain	1.0000
6:89377669:AC:A	donor_gain	1.0000
6:89377669:ACC:A	donor_gain	1.0000
6:89377669:ACCCA:A	donor_loss	1.0000
6:89377670:C:CA	donor_loss	1.0000
6:89377670:C:CC	donor_gain	1.0000
6:89377670:CC:C	donor_gain	1.0000
6:89377670:CCC:C	donor_gain	1.0000
6:89377670:CCCAT:C	donor_gain	1.0000
6:89377809:GAATT:G	acceptor_gain	1.0000
6:89377810:AATT:A	acceptor_gain	1.0000
6:89377811:ATT:A	acceptor_gain	1.0000
6:89377812:TT:T	acceptor_gain	1.0000
6:89377812:TTC:T	acceptor_loss	1.0000
6:89377814:C:CA	acceptor_loss	1.0000
6:89377814:C:CC	acceptor_gain	1.0000
6:89377815:T:A	acceptor_loss	1.0000
6:89379216:TTAC:T	donor_loss	1.0000
6:89379217:TACT:T	donor_loss	1.0000
6:89379218:A:AC	donor_gain	1.0000
6:89379218:AC:A	donor_loss	1.0000
6:89379219:C:CC	donor_gain	1.0000
6:89379219:CTTA:C	donor_gain	1.0000
6:89379220:TTACT:T	donor_loss	1.0000
6:89379221:TA:T	donor_loss	1.0000
6:89379222:A:AC	donor_gain	1.0000

AlphaMissense

2683 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:89372481:A:G	L336P	1.000
6:89377758:G:T	A272E	1.000
6:89377759:C:G	A272P	1.000
6:89377770:T:A	K268I	1.000
6:89377788:A:G	L262P	1.000
6:89379240:A:G	L248P	1.000
6:89379290:G:C	S231R	1.000
6:89379290:G:T	S231R	1.000
6:89379291:C:A	S231I	1.000
6:89379292:T:G	S231R	1.000
6:89379306:A:T	I226K	1.000
6:89379321:A:C	I221R	1.000
6:89379321:A:T	I221K	1.000
6:89379323:G:C	S220R	1.000
6:89379323:G:T	S220R	1.000
6:89379325:T:G	S220R	1.000
6:89380272:T:A	K180N	1.000
6:89380272:T:G	K180N	1.000
6:89380273:T:A	K180I	1.000
6:89380274:T:C	K180E	1.000
6:89380274:T:G	K180Q	1.000
6:89380277:G:C	H179D	1.000
6:89387308:A:T	V144D	1.000
6:89387380:C:T	G120E	1.000
6:89387381:C:G	G120R	1.000
6:89387381:C:T	G120R	1.000
6:89387383:G:T	P119Q	1.000
6:89387389:T:G	D117A	1.000
6:89387390:C:G	D117H	1.000
6:89387449:G:A	T97I	1.000

dbSNP variants (sampled 300 via entrez): RS1000111903 (6:89369918 C>A,T), RS1000182784 (6:89397421 T>C), RS1000206787 (6:89403621 C>A,T), RS1000339659 (6:89393635 G>A,T), RS1000389892 (6:89401311 G>A), RS1000417343 (6:89384054 G>T), RS1000506101 (6:89375523 C>A), RS1000531678 (6:89389428 C>T), RS1000532888 (6:89380563 A>C), RS1000559487 (6:89367600 A>G), RS1000615956 (6:89382721 C>T), RS1000622300 (6:89375142 T>A,C), RS1000751969 (6:89382473 G>A), RS1000771939 (6:89406686 A>G), RS1000857370 (6:89393981 T>C)

Disease associations

OMIM: gene MIM:608268 | disease phenotypes: MIM:620152

GenCC curated gene-disease

Disease	Classification	Inheritance
hypomagnesemia 7, renal, with or without dilated cardiomyopathy	Strong	Autosomal dominant
inherited renal tubular disease	Strong	Autosomal dominant

Mondo (2): hypomagnesemia 7, renal, with or without dilated cardiomyopathy (MONDO:0859328), inherited renal tubular disease (MONDO:0015962)

Orphanet (0):

HPO phenotypes

33 total (30 of 33 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000103	Polyuria
HP:0000121	Nephrocalcinosis
HP:0000859	Increased circulating aldosterone concentration
HP:0001250	Seizure
HP:0001281	Tetany
HP:0001635	Congestive heart failure
HP:0001644	Dilated cardiomyopathy
HP:0001645	Sudden cardiac death
HP:0001698	Pericardial effusion
HP:0001942	Metabolic acidosis
HP:0001960	Hypokalemic metabolic alkalosis
HP:0002069	Bilateral tonic-clonic seizure
HP:0002150	Hypercalciuria
HP:0002487	Hyperkinetic movements
HP:0002829	Arthralgia
HP:0002900	Hypokalemia
HP:0002901	Hypocalcemia
HP:0002902	Hyponatremia
HP:0002917	Hypomagnesemia
HP:0003472	Hypocalcemic tetany
HP:0003527	Hyperprostaglandinuria
HP:0003593	Infantile onset
HP:0003621	Juvenile onset
HP:0003739	Myoclonic spasms
HP:0006559	Hepatic calcification
HP:0011038	Abnormal renal tubular resorption
HP:0011463	Childhood onset
HP:0012608	Hypermagnesiuria
HP:0012664	Reduced left ventricular ejection fraction

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST005984_46	Glomerular filtration rate	3.000000e-09
GCST005985_24	Creatinine levels	4.000000e-09
GCST008058_257	Estimated glomerular filtration rate	7.000000e-13

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

73 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases methylation, affects cotreatment, increases expression	9
trichostatin A	affects cotreatment, decreases expression, increases expression	3
Particulate Matter	affects cotreatment, decreases expression, increases abundance, increases expression	3
Panobinostat	decreases expression, affects cotreatment	2
Air Pollutants	increases abundance, increases expression, affects cotreatment, decreases expression	2
Cisplatin	affects expression, increases response to substance	2
Copper	affects binding, decreases expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Cyclosporine	increases expression	2
1-cyclopropyl-4-(4-((5-methyl-3-(3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-5-yl)-1H-pyrazol-1-yl)methyl)pyridin-2-yl)piperazine	decreases reaction, increases expression	1
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
sotorasib	decreases expression, affects cotreatment	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, decreases expression	1
propionaldehyde	increases expression	1
bisphenol A	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases abundance, decreases expression	1
butyraldehyde	increases expression	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
pentanal	increases expression	1
avobenzone	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, increases expression, affects cotreatment	1
2,2’,4,4’,5-brominated diphenyl ether	increases expression	1
ICG 001	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B3GB	Abcam HEK293T RRAGD KO	Transformed cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.