SLC22A12

protein-coding

solute carrier family 22 member 12, the group of Solute carrier family 22

Gene summary

The protein encoded by this gene is a member of the organic anion transporter (OAT) family, and it acts as a urate transporter to regulate urate levels in blood. This protein is an integral membrane protein primarily found in epithelial cells of the proximal tubule of the kidney. An elevated level of serum urate, hyperuricemia, is associated with increased incidences of gout, and mutations in this gene cause renal hypouricemia type 1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2013]

MANE transcript

NM_144585.4

Inheritance

ClinVar variants

P:27U:156B:68

Top phenotype

Hypouricemia, renal 1

gnomAD constraint

pLI —, LoF o/e 0.9

Max pathogenic AF

—

Genomic locus

chr11:64,590,641-64,602,353

External References & Databases

Ensembl (ENSG00000197891)

Transcript & Mutation Effects

hg38 • Region Span ~11.7 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hereditary renal hypouricemiaSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009071

Submitter: Orphanet

hypouricemia, renal 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0020728

Submitter: Labcorp Genetics (formerly Invitae)

hypouricemia, renal 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0020728

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Hypouricemia, renal 1AR

Manifestation: Renal

Intervention: Renal

Rationale: The condition may be asymptomatic, but a minority of individuals can be affected by nephrolithiasis and/or exercise-induce acute renal failure, and preventive measures can be beneficial

Refs: 12024214; 14655203; 18492088

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SLC22A12 variants in ClinVar

6 Conditions Cataloged

not providedTotal: 166

Dalmatian hypouricemiaTotal: 138

Inborn genetic diseasesTotal: 60

SLC22A12-related disorderTotal: 27

not specifiedTotal: 16

Familial renal hypouricemiaTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_144585.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			8 clinvar	60 clinvar	2 clinvar	70
missense	6 clinvar	6 clinvar	147 clinvar	6 clinvar		165
nonsense	2 clinvar	3 clinvar				5
start loss						0
frameshift	1 clinvar	6 clinvar	1 clinvar			8
splice donor/acceptor (+/-2bp)	1 clinvar	2 clinvar				3
Total	10	17	156	66	2	251

Highest pathogenic variant AF is 0.00038181708

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_144585.4	RefSeq	NP_653186.2	10	MANE Select
ENST00000377574.6	Ensembl	ENSP00000366797.1	10	MANE Select
NM_001276326.2	RefSeq	NP_001263255.1	10	Standard
NM_001276327.2	RefSeq	NP_001263256.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Uricosurics Pathway, Pharmacodynamics
Organic anion transport
Transport of bile salts and organic acids, metal ions and amine compounds
SLC-mediated transmembrane transport
Transport of small molecules

Biological Process

urate transport
cellular homeostasis
response to drug
urate metabolic process
transmembrane transport

Molecular Function

urate transmembrane transporter activity
PDZ domain binding

Cellular Component

plasma membrane
integral component of membrane
apical plasma membrane
brush border membrane
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000377574
Coding exons: 10
Length: 11708
Individuals with no LoFs: 125602
Homozygous LoFs: 2
Heterozygous LoFs: 144
Defined: 125748
p: 0.000581

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.372	315	334	0.943	0.0000226	3499
Missense (PolyPhen)		82	100.27	0.81779		1149
Synonymous	-0.901	167	153	1.09	0.0000109	1237
Loss of Function	0.437	21	23.3	0.902	0.00000120	227

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00044	0.00043	rare
Latino/Admixed American	0.00023	0.00023	rare
Ashkenazi Jewish	0.00080	0.00079	rare
East Asian	0.0046	0.0045	notable
Finnish	0.00017	0.00014	rare
European (Non-Finnish)	0.00022	0.00022	rare
South Asian	0.00040	0.00036	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Required for efficient urate re-absorption in the kidney. Regulates blood urate levels. Mediates saturable urate uptake by facilitating the exchange of urate against organic anions. {ECO:0000269|PubMed:12024214}.;

Recessive Scores

pRec: 0.141

Intolerance Scores

LoFtool: 0.166
RVIS EVS: -1.15
RVIS percentile EVS: 6.23

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.863

Gene Damage Prediction

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