SLC14A2

protein-coding

solute carrier family 14 member 2, the group of Solute carrier family 14

Gene summary

The protein encoded by this gene belongs to the urea transporter family. In mammalian cells, urea is the chief end product of nitrogen catabolism, and plays an important role in the urinary concentration mechanism. This protein is expressed in the inner medulla of the kidney, and mediates rapid transepithelial urea transport across the inner medullary collecting duct. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2011]

MANE transcript

NM_007163.4

Inheritance

—

ClinVar variants

U:150B:6

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.73

Max pathogenic AF

—

Genomic locus

chr18:45,212,995-45,683,688

External References & Databases

Ensembl (ENSG00000132874)

Transcript & Mutation Effects

hg38 • Region Span ~470.7 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SLC14A2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 145

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_007163.4. 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			2 clinvar	2 clinvar		4
missense			144 clinvar	3 clinvar	1 clinvar	148
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	150	5	1	156

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 10 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_007163.4	RefSeq	NP_009094.3	19	MANE Select
ENST00000255226.11	Ensembl	ENSP00000255226.5	19	MANE Select
NM_001242692.2	RefSeq	NP_001229621.1	19	Standard
NM_001371319.1	RefSeq	NP_001358248.1	19	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
slc14a2	Danio rerio	Structure: urea transport Quality: decreased rate abnormal

Gene / Model

Organism

Observed Phenotype

slc14a2

Danio rerio

Structure: urea transport

Quality: decreased rate

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Polythiazide Action Pathway
Methyclothiazide Action Pathway
Bumetanide Action Pathway
Spironolactone Action Pathway
Eplerenone Action Pathway

Biological Process

urea transport
transmembrane transport
urea transmembrane transport

Molecular Function

urea transmembrane transporter activity
urea channel activity
cell adhesion molecule binding

Cellular Component

plasma membrane
integral component of plasma membrane
membrane
integral component of membrane
apical plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000255226
Coding exons: 19
Length: 470113
Individuals with no LoFs: 125523
Homozygous LoFs: 1
Heterozygous LoFs: 224
Defined: 125748
p: 0.000895

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.138	534	525	1.02	0.0000287	5958
Missense (PolyPhen)		139	152.95	0.90882		1766
Synonymous	-0.298	232	226	1.03	0.0000146	1890
Loss of Function	1.66	33	45.0	0.733	0.00000205	504

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0026	0.0026	notable
Latino/Admixed American	0.00055	0.00055	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0017	0.0016	notable
Finnish	0.0021	0.0020	notable
European (Non-Finnish)	0.00068	0.00067	rare
South Asian	0.00033	0.00033	rare
Other	0.00065	0.00065	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Specialized low-affinity vasopressin-regulated urea transporter. Mediates rapid transepithelial urea transport across the inner medullary collecting duct and plays a major role in the urinary concentrating mechanism. {ECO:0000269|PubMed:11502588, ECO:0000269|PubMed:8647271}.;

Recessive Scores

pRec: 0.179

Intolerance Scores

LoFtool: 0.877
RVIS EVS: 0.28
RVIS percentile EVS: 70.78

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.225

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High