Hypouricemia, renal 1

Summary

Hypouricemia, renal 1 (MONDO:0020728) is a disease caused by SLC22A12 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: SLC22A12 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 161

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hypouricemia, renal 1
Mondo ID	MONDO:0020728
OMIM	220150
UMLS	C0473219
MedGen	141632
GARD	0025226
Is cancer (heuristic)	no

Also known as: hypouricemia, renal, 1 · hypouricemia, renal, type 1 · RHUC1

Data availability: 161 ClinVar variants · 2 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 1

Related subtypes (1): hypouricemia, renal, 2

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

161 retrieved; paginated sample, class counts are floors:

104 uncertain significance, 20 conflicting classifications of pathogenicity, 8 pathogenic, 7 benign, 7 benign/likely benign, 6 likely pathogenic, 5 likely benign, 4 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1177307	NM_144585.4(SLC22A12):c.502G>A (p.Asp168Asn)	SLC22A12	Pathogenic	no assertion criteria provided
1908931	NM_144585.4(SLC22A12):c.1070G>A (p.Trp357Ter)	SLC22A12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2175414	NM_144585.4(SLC22A12):c.1429_1451del (p.Arg477fs)	SLC22A12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2501006	NM_144585.4(SLC22A12):c.1523G>A (p.Ser508Asn)	SLC22A12	Pathogenic	no assertion criteria provided
305239	NM_144585.4(SLC22A12):c.1145A>T (p.Gln382Leu)	SLC22A12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3512	NM_144585.4(SLC22A12):c.774G>A (p.Trp258Ter)	SLC22A12	Pathogenic	criteria provided, multiple submitters, no conflicts
3513	NM_144585.4(SLC22A12):c.650C>T (p.Thr217Met)	SLC22A12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3514	NM_144585.4(SLC22A12):c.894G>T (p.Glu298Asp)	SLC22A12	Pathogenic	no assertion criteria provided
3515	NM_144585.4(SLC22A12):c.1253T>G (p.Leu418Arg)	SLC22A12	Pathogenic	no assertion criteria provided
3516	NM_144585.4(SLC22A12):c.269G>A (p.Arg90His)	SLC22A12	Pathogenic	criteria provided, multiple submitters, no conflicts
3517	NM_144585.4(SLC22A12):c.1082G>T (p.Gly361Val)	SLC22A12	Pathogenic	no assertion criteria provided
3599964	NM_144585.4(SLC22A12):c.506+1G>A	SLC22A12	Pathogenic	criteria provided, multiple submitters, no conflicts
1515855	NM_144585.4(SLC22A12):c.507-8_511del	SLC22A12	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3599958	NM_144585.4(SLC22A12):c.259C>T (p.Gln87Ter)	SLC22A12	Likely pathogenic	criteria provided, single submitter
3599969	NM_144585.4(SLC22A12):c.536del (p.Ser179fs)	SLC22A12	Likely pathogenic	criteria provided, single submitter
3599974	NM_144585.4(SLC22A12):c.667G>T (p.Glu223Ter)	SLC22A12	Likely pathogenic	criteria provided, single submitter
4277583	NM_144585.4(SLC22A12):c.693del (p.Leu232fs)	SLC22A12	Likely pathogenic	criteria provided, single submitter
632166	NM_144585.4(SLC22A12):c.1216C>T (p.Arg406Cys)	SLC22A12	Likely pathogenic	criteria provided, single submitter
1086256	NM_144585.4(SLC22A12):c.679G>A (p.Ala227Thr)	SLC22A12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1919630	NM_144585.4(SLC22A12):c.918C>T (p.Asn306=)	SLC22A12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1983955	NM_144585.4(SLC22A12):c.371G>A (p.Arg124His)	SLC22A12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
305228	NM_144585.4(SLC22A12):c.-10A>C	SLC22A12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
305231	NM_144585.4(SLC22A12):c.327C>T (p.Ser109=)	SLC22A12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
305234	NM_144585.4(SLC22A12):c.564G>A (p.Thr188=)	SLC22A12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
305235	NM_144585.4(SLC22A12):c.570T>C (p.Ala190=)	SLC22A12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
305240	NM_144585.4(SLC22A12):c.1230C>T (p.Ala410=)	SLC22A12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
305242	NM_144585.4(SLC22A12):c.1254C>T (p.Leu418=)	SLC22A12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
305247	NM_144585.4(SLC22A12):c.1509G>A (p.Thr503=)	SLC22A12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
305248	NM_144585.4(SLC22A12):c.1572C>T (p.Pro524=)	SLC22A12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
305250	NM_144585.4(SLC22A12):c.1626G>A (p.Thr542=)	SLC22A12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
SLC22A12	Strong	Autosomal recessive	hypouricemia, renal 1	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC22A12	Orphanet:94088	Hereditary renal hypouricemia

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SLC22A12	HGNC:17989	ENSG00000197891	Q96S37	Solute carrier family 22 member 12	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC22A12	Solute carrier family 22 member 12	Electroneutral antiporter that translocates urate across the apical membrane of proximal tubular cells in exchange for monovalent organic or inorganic anions.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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	77.8×	0.013

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC22A12	Transporter	yes		MFS, MFS_dom, MFS_trans_sf

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
adult mammalian kidney	1
kidney	1
kidney epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC22A12	30	tissue_specific	marker	kidney epithelium, adult mammalian kidney, kidney

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLC22A12	1,033

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SLC22A12	Q96S37	28

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 9. Enrichment computed across 1 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 SLC22A12 causes renal hypouricemia 1 (RHUC1)	1	11420.0×	8e-04	SLC22A12
Organic anion transport by SLC22 transporters	1	2284.0×	0.002	SLC22A12
R-HSA-549132	1	761.3×	0.004	SLC22A12
SLC transporter disorders	1	203.9×	0.010	SLC22A12
R-HSA-425366	1	181.3×	0.010	SLC22A12
Disorders of transmembrane transporters	1	139.3×	0.011	SLC22A12
SLC-mediated transmembrane transport	1	59.2×	0.022	SLC22A12
Transport of small molecules	1	25.1×	0.045	SLC22A12
Disease	1	13.1×	0.076	SLC22A12

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
renal urate salt excretion	1	5617.3×	0.001	SLC22A12
urate transport	1	2407.4×	0.002	SLC22A12
urate metabolic process	1	1532.0×	0.002	SLC22A12
obsolete organic anion transport	1	802.5×	0.002	SLC22A12
cellular homeostasis	1	802.5×	0.002	SLC22A12
cellular response to insulin stimulus	1	170.2×	0.007	SLC22A12
monoatomic ion transport	1	156.0×	0.007	SLC22A12
response to xenobiotic stimulus	1	69.1×	0.014	SLC22A12

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
SLC22A12	BENZARONE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SLC22A12	13	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BENZARONE	4	SLC22A12
LESINURAD	4	SLC22A12
BENZBROMARONE	4	SLC22A12
SULFINPYRAZONE	4	SLC22A12
PROBENECID	4	SLC22A12
FENOFIBRIC ACID	4	SLC22A12
SHR-4640	3	SLC22A12
DOTINURAD	3	SLC22A12
ARHALOFENATE	2	SLC22A12
PF-05089771	2	SLC22A12
VERINURAD	2	SLC22A12
PULIGINURAD	2	SLC22A12
EPAMINURAD	1	SLC22A12

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SLC22A12	108	Binding:108

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
SLC22A12	108

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

13 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)
BENZARONE	4	SLC22A12
LESINURAD	4	SLC22A12
BENZBROMARONE	4	SLC22A12
SULFINPYRAZONE	4	SLC22A12
PROBENECID	4	SLC22A12
FENOFIBRIC ACID	4	SLC22A12
SHR-4640	3	SLC22A12
DOTINURAD	3	SLC22A12
ARHALOFENATE	2	SLC22A12
PF-05089771	2	SLC22A12
VERINURAD	2	SLC22A12
PULIGINURAD	2	SLC22A12
EPAMINURAD	1	SLC22A12

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	SLC22A12
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.