Hypouricemia, renal, 2

Summary

Hypouricemia, renal, 2 (MONDO:0012793) is a disease caused by SLC2A9 (GenCC Strong), with 3 cohort genes.

At a glance

• Causal gene: SLC2A9 (GenCC Strong)
• Cohort genes: 3
• ClinVar variants: 103

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hypouricemia, renal, 2
Mondo ID	MONDO:0012793
MeSH	C567426
OMIM	612076
UMLS	C2677549
MedGen	436974
GARD	0015541
Is cancer (heuristic)	no

Also known as: hypouricemia, renal, 2 · hypouricemia, renal, type 2 · RHUC2 · uric acid concentration, serum, QTL 2

Data availability: 103 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › urinary system disorder › kidney disorder › renal tubule disorder › inherited renal tubular disease › hereditary renal hypouricemia › hypouricemia, renal › hypouricemia, renal, 2

Related subtypes (1): hypouricemia, renal 1

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

103 retrieved; paginated sample, class counts are floors:

39 uncertain significance, 22 benign, 19 benign/likely benign, 7 conflicting classifications of pathogenicity, 6 likely pathogenic, 4 pathogenic, 4 likely benign, 2 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
217419	NM_001001290.1(SLC2A9):c.595_727del	LOC129992239	Pathogenic	no assertion criteria provided
1027407	NM_020041.3(SLC2A9):c.593G>A (p.Arg198His)	SLC2A9	Pathogenic	no assertion criteria provided
217418	NM_020041.3(SLC2A9):c.224T>G (p.Leu75Arg)	SLC2A9	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
217422	NC_000004.12:g.(?9826223)(9908346_9920384)del	SLC2A9	Pathogenic	no assertion criteria provided
350238	NM_020041.3(SLC2A9):c.354dup (p.Ile119fs)	SLC2A9	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4598	NM_020041.3(SLC2A9):c.1235C>G (p.Pro412Arg)	SLC2A9	Pathogenic	no assertion criteria provided
217421	NM_020041.3(SLC2A9):c.374C>T (p.Thr125Met)	SLC2A9	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3359196	NM_020041.3(SLC2A9):c.570T>G (p.Ser190Arg)	SLC2A9	Likely pathogenic	no assertion criteria provided
3359197	NM_020041.3(SLC2A9):c.1202C>T (p.Thr401Met)	SLC2A9	Likely pathogenic	no assertion criteria provided
3767964	NM_020041.3(SLC2A9):c.1557dup (p.Ala520fs)	SLC2A9	Likely pathogenic	criteria provided, single submitter
830032	NM_020041.3(SLC2A9):c.1343C>T (p.Pro448Leu)	SLC2A9	Likely pathogenic	no assertion criteria provided
3780618	NM_020041.3(SLC2A9):c.151-1G>A	SLC2A9-AS3	Likely pathogenic	criteria provided, single submitter
1049499	NM_020041.3(SLC2A9):c.646G>A (p.Gly216Arg)	SLC2A9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1504763	NM_020041.3(SLC2A9):c.1518C>G (p.Thr506=)	SLC2A9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
350211	NM_020041.3(SLC2A9):c.898C>T (p.Arg300Cys)	SLC2A9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
4596	NM_020041.3(SLC2A9):c.1138C>T (p.Arg380Trp)	SLC2A9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
4597	NM_020041.3(SLC2A9):c.592C>T (p.Arg198Cys)	SLC2A9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
829962	NM_020041.3(SLC2A9):c.759G>A (p.Pro253=)	SLC2A9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
904605	NM_020041.3(SLC2A9):c.727G>A (p.Val243Ile)	SLC2A9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1017579	NM_020041.3(SLC2A9):c.538G>A (p.Val180Ile)	SLC2A9	Uncertain significance	criteria provided, multiple submitters, no conflicts
1928845	NM_020041.3(SLC2A9):c.1339C>T (p.Arg447Trp)	SLC2A9	Uncertain significance	criteria provided, multiple submitters, no conflicts
2069944	NM_020041.3(SLC2A9):c.1369G>A (p.Val457Ile)	SLC2A9	Uncertain significance	criteria provided, multiple submitters, no conflicts
2148495	NM_020041.3(SLC2A9):c.541G>A (p.Ala181Thr)	SLC2A9	Uncertain significance	criteria provided, single submitter
217420	NM_020041.3(SLC2A9):c.511C>T (p.Arg171Cys)	SLC2A9	Uncertain significance	criteria provided, single submitter
2436013	NM_020041.3(SLC2A9):c.94G>A (p.Ala32Thr)	SLC2A9	Uncertain significance	criteria provided, single submitter
2436015	NM_020041.3(SLC2A9):c.1105G>A (p.Val369Ile)	SLC2A9	Uncertain significance	criteria provided, single submitter
2446002	NM_020041.3(SLC2A9):c.929C>A (p.Ala310Asp)	SLC2A9	Uncertain significance	criteria provided, single submitter
2506947	NM_020041.3(SLC2A9):c.684G>A (p.Glu228=)	SLC2A9	Uncertain significance	criteria provided, single submitter
2506948	NM_020041.3(SLC2A9):c.731T>A (p.Val244Asp)	SLC2A9	Uncertain significance	criteria provided, single submitter
3065291	NM_020041.3(SLC2A9):c.611_613dup (p.Val204_Thr205insMet)	SLC2A9	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
SLC2A9	Strong	Autosomal recessive	hypouricemia, renal, 2	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC2A9	Orphanet:94088	Hereditary renal hypouricemia

Cohort genes → proteins

3 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SLC2A9	HGNC:13446	ENSG00000109667	Q9NRM0	Solute carrier family 2, facilitated glucose transporter member 9	gencc,clinvar
SLC2A9-AS1	HGNC:40636	ENSG00000250413		SLC2A9 antisense RNA 1	clinvar
SLC2A9-AS3	HGNC:59109	ENSG00000250413		SLC2A9 antisense RNA 3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC2A9	Solute carrier family 2, facilitated glucose transporter member 9	High-capacity urate transporter, which may play a role in the urate reabsorption by proximal tubules.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.33

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Transporter	1	25.9×	0.076
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC2A9	Transporter	yes		Sugar/inositol_transpt, MFS_sugar_transport-like, Sugar_transporter_CS
SLC2A9-AS1	Other/Unknown	no
SLC2A9-AS3	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

3 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
colonic epithelium	2
male germ line stem cell (sensu Vertebrata) in testis	2
right uterine tube	2
buccal mucosa cell	1
monocyte	1
mononuclear cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC2A9	182	broad	marker	buccal mucosa cell, monocyte, mononuclear cell
SLC2A9-AS1	118	tissue_specific	marker	colonic epithelium, male germ line stem cell (sensu Vertebrata) in testis, right uterine tube
SLC2A9-AS3	118	tissue_specific	marker	colonic epithelium, male germ line stem cell (sensu Vertebrata) in testis, right uterine tube

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLC2A9	1,285
SLC2A9-AS1	0
SLC2A9-AS3	0

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 2

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SLC2A9	Q9NRM0	7

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 3 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective SLC2A9 causes hypouricemia renal 2 (RHUC2)	1	11420.0×	2e-04	SLC2A9
Cellular hexose transport	1	543.8×	0.002	SLC2A9

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
urate transport	1	2407.4×	0.001	SLC2A9
fructose transmembrane transport	1	2106.5×	0.001	SLC2A9
urate metabolic process	1	1532.0×	0.001	SLC2A9
hexose transmembrane transport	1	1404.3×	0.001	SLC2A9
dehydroascorbic acid transport	1	1203.7×	0.001	SLC2A9
D-glucose transmembrane transport	1	936.2×	0.001	SLC2A9
obsolete D-glucose import	1	842.6×	0.001	SLC2A9

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 2

Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SLC2A9	1	3
SLC2A9-AS1	0	0
SLC2A9-AS3	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CURCUMIN	3	SLC2A9

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
SLC2A9	13	Binding:11, Functional:2

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

1 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
CURCUMIN	3	SLC2A9

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	1	SLC2A9
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	SLC2A9-AS1, SLC2A9-AS3

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
SLC2A9-AS1	0	—
SLC2A9-AS3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.