1. Gene
  2. SLC12A3 - solute carrier family 12 member 3 Gene

SLC12A3 - solute carrier family 12 member 3 Gene

Homo sapiens

Also known as NCC; TSC; NCCT

Gene ID: 6559 | Gene type: protein coding

About SLC12A3

Cytogenetic location: 16q13 Genomic coordinates (GRCh38): 16:56,865,207-56,915,850 (from NCBI)

This gene has 6 transcripts (splice variants), 203 orthologues, 8 paralogues and is associated with 2 phenotypes. Restricted expression toward kidney (RPKM 65.2).

Summary

This gene encodes a renal thiazide-sensitive sodium-chloride cotransporter that is important for electrolyte homeostasis. This cotransporter mediates sodium and chloride reabsorption in the distal convoluted tubule. Mutations in this gene cause Gitelman syndrome, a disease similar to Bartter's syndrome, that is characterized by hypokalemic alkalosis combined with hypomagnesemia, low urinary calcium, and increased Renin activity associated with normal blood pressure. This cotransporter is the target for thiazide diuretics that are used for treating high blood pressure. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

SLC12A3 Products(4)

mRNA Protein Name
NM_000339.3 NP_000330.3 solute carrier family 12 member 3 isoform 1
NM_001126107.2 NP_001119579.2 solute carrier family 12 member 3 isoform 2
NM_001126108.2 NP_001119580.2 solute carrier family 12 member 3 isoform 3
NM_001410896.1 NP_001397825.1 solute carrier family 12 member 3 isoform 4
Gene Ontology
  • Molecular Function
  • Biological Process
  • Cellular Component
Molecular Function GO Annotation Evidence Reference Source
enables protein binding IPI
IPI: Inferred from physical interaction
22406640 GOA
enables sodium:chloride symporter activity IDA
IDA: Inferred from direct assay
18270262 GOA
Biological Process GO Annotation Evidence Reference Source
involved in renal sodium ion absorption IDA
IDA: Inferred from direct assay
18270262 GOA
Cellular Component GO Annotation Evidence Reference Source
located in apical plasma membrane IDA
IDA: Inferred from direct assay
21397062 GOA
located in extracellular exosome IDA
IDA: Inferred from direct assay
21082674 GOA
is active in plasma membrane IDA
IDA: Inferred from direct assay
22009145 GOA
EXP: Inferred from Experiment IDA: Inferred from direct assay IPI: Inferred from physical interaction IMP: Inferred from mutant phenotype IGI: Inferred from genetic interaction IEP: Inferred from expression pattern

SLC12A3 Protein Structure

AA_permease_N

AA_permease_N: Amino acid permease N-terminal (46 - 112)

AA_permease

AA_permease: Amino acid permease (141 - 646)

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  • 1021 a.a.
Protein Preferred Names Protein Names

solute carrier family 12 member 3

Na-Cl cotransporter

Related Diseases

Diseases Alias
Gitelman Syndrome

Familial Hypokalemia-Hypomagnesemia

Hypomagnesemia-Hypokalemia, Primary Renotubular, With Hypocalciuria

Potassium And Magnesium Depletion

GTLMNS

Gitelman'S Syndrome

Gs

Hypokalemia-Hypomagnesemia, Primary Renotubular, With Hypocalciuria

Tubular Hypomagnesemia-Hypokalemia With Hypocalcuria

Bartter Syndrome Gitelman Variant

Bartter Syndrome Hypocalciuric Variant

Primary Renotubular Hypomagnesemia-Hypokalemia With Hypocalciuria

Hypokalemia

Potassium Deficiency

Potassium Deficiency Disorder

Hypopotassemia

Potassium

Potassium [K] Deficiency

Hypokalaemic Syndrome

Hypopotassaemia

Hypopotassaemia Syndrome

Hypokalaemic

Potassium Depletion

Bartter Disease

Bartter Syndrome

Bartter'S Syndrome

Aldosteronism With Hyperplasia Of The Adrenal Cortex

Hypokalemic Alkalosis With Hypercalciuria

Potassium Wasting

Juxtaglomerular Hyperplasia With Secondary Aldosteronism

Renal Tubular Normotensive Hypokalemic Alkalosis With Hypercalciuria

Salt-Losing Tubular Disorder, Henle'S Loop Type

Salt-Wasting Tubulopathy, Henle'S Loop Type

Bartters Syndrome

Chondrocalcinosis

Pseudogout

Calcium Pyrophosphate Deposition Disease

Familial Chondrocalcinosis

Chondrocalcinosis Nos

Cppd - [Calcium Pyrophosphate Deposition Disease]

Cpdd - [Calcium Pyrophosphate Deposition Disease]

Chondrocalcinosis, Due To Pyrophosphate Crystals, Involving Unspecified Site

Chondrocalcinosis, Cause Unspecified

Chondrocalcinosis Due To Pyrophosphate Crystals

Chondrocalcinosis Articularis

Calcium Pyrophosphate Arthritis And Periarthritis

Bartter Syndrome, Type 3

Bartter Disease Type 3

BARTS3

Bartter Syndrome Type 3

Bartter Syndrome, Classic

Classic Bartter Syndrome

Bartter Syndrome Classic

Bartter Syndrome Type Iii

Bartter Syndrome 3

Renal Tubular Transport Disease

Renal Tubular Transport, Inborn Errors

Inborn Renal Tubular Transport Disorder

Arthrogryposis, Distal, Type 3

Gordon Syndrome

DA3

Distal Arthrogryposis Type 3

Arthrogryposis Multiplex Congenita, Distal, Type Iia

Camptodactyly, Cleft Palate, And Clubfoot

Camptodactyly-Cleft Palate-Clubfoot Syndrome

Distal Arthrogryposis Multiplex Congenita Type Iia

Arthrogryposis Distal Type 3

Distal Arthrogryposis Type Iia

Arthrogryposis, Distal, 3

Pseudohypoaldosteronism, Type Ii

Pseudohypoaldosteronism
Conn'S Syndrome

Cushing Syndrome

Hyperaldosteronism

Primary Hyperaldosteronism

Hypercortisolism

Primary Aldosteronism

Cushing'S Syndrome

Adrenal Gland Hyperfunction

Conn Syndrome

Hyperadrenalism

Ectopic Acth Syndrome

Hyperadrenocorticism

Cushing Disease

Cushing'S Disease

Adrenal Cortex Adenoma

Corticotroph Pituitary Adenoma

Pituitary Corticotroph Micro-Adenoma

Pituitary-Dependent Cushing Syndrome

Pituitary Acth Hypersecretion

Acth Syndrome, Ectopic

Acth-Secreting Pituitary Adenoma

Adrenal Hyperfunction Resulting From Pituitary Acth Excess

Ectopic Adrenocorticotropic Hormone Syndrome

Nodular Primary Adrenocortical Dysplasia

Pituitary Dependent Cushing Syndrome

Pituitary Cushing Syndrome

Pituitary-Dependant Cushing Syndrome

Pituitary-Dependant Hypercortisolism

Pituitary-Dependant Hypercortisolism Disorder

Aldosteronism Primary

Acth Syndrome Ectopic

Adrenal Cushing'S Syndrome

Adrenal Cortical Adenoma

Cushing Syndrome Nos

Cortisol Hypersecretion

Corticoadrenal Hypersecretion

Cushing Syndrome Secondary To Ectopic Acth-Secretion

Ectopic Cushing Syndrome

Hypercortisolism Due To Nonpituitary Tumour

Ectopic Acth - [Adrenocorticotropic Hormone] Secretion

Ectopic Acth - [Adrenocorticotropic Hormone] Secretion Causing Cushing Syndrome

Idiopathic Aldosteronism

Aldosteronism

Primary Aldosteronism Due To Bilateral Adrenal Hyperplasia

Primary Aldosteronism Due To Adrenal Hyperplasia

Nephrocalcinosis

Hypercalcemic Nephropathy

Seizures, Sensorineural Deafness, Ataxia, Mental Retardation, And Electrolyte Imbalance

Sesame Syndrome

East Syndrome

SESAMES

Epilepsy, Ataxia, Sensorineural Deafness And Tubulopathy

Seizures, Sensorineural Deafness, Ataxia, Mental Retardation And Electrolyte Imbalance

Epilepsy-Ataxia-Sensorineural Deafness-Tubulopathy Syndrome

Seizures-Sensorineural Deafness-Ataxia-Intellectual Disability-Electrolyte Imbalance Syndrome

Epilepsy, Ataxia, Sensorineural Deafness, And Tubulopathy

Seizures - Sensorineural Deafness - Ataxia - Intellectual Disability - Electrolyte Imbalance

Epilepsy-Ataxia-Sensorineural Hearing Loss-Tubulopathy Syndrome

Seizures-Sensorineural Hearing Loss-Ataxia-Intellectual Disability-Electrolyte Imbalance Syndrome

Seizures, Sensorineural Deafness, Ataxia, Intellectual Disability, And Electrolyte Imbalance

Epilepsy Ataxia Sensorineural Deafness And Tubulopathy

Seizures, Sensorineural Deafness, Ataxia, Intellectual Disability, And Electrolyte Imbalance Syndrome

Bartter Syndrome, Type 1, Antenatal

Hyperprostaglandin E Syndrome 1

Bartter Disease Type 1

BARTS1

Bartter Syndrome, Type 1

Bartter Syndrome Type 1

Hypokalemic Alkalosis With Hypercalciuria Antenatal 1

Hypokalemic Alkalosis With Hypercalciuria 1, Antenatal

Bartter Syndrome Type 1 Antenatal

Hypokalemic Alkalosis With Hypercalciuria 1 Antenatal

Bartter Syndrome Antenatal Type 1

Antenatal Bartter Syndrome Type 1

Bartter Syndrome Type I

Bartter Syndrome 1, Antenatal

Abs1

Antenatal Bartter Syndrome 1

Bs1

Bartter Syndrome, Antenatal Type 1

Antley-Bixler Syndrome With Genital Anomalies And Disordered Steroidogenesis

Pendred Syndrome

Goiter-Deafness Syndrome

Deafness With Goiter

PDS

Thyroid Dyshormonogenesis 2b

Tdh2b

Autosomal Recessive Sensorineural Hearing Impairment And Goiter

Pendred'S Syndrome

Thyroid Hormonogenesis, Genetic Defect In, 2b

Hypothyroidism, Congenital, Due To Dyshormonogenesis, 2b

Congenital Hypothyroidism Due To Dyshormonogenesis 2b

Genetic Defect In Thyroid Hormonogenesis 2b

Autosomal Recessive Sensorineural Hearing Impairment, Enlarged Vestibular Aqueduct, And Goiter

Goiter-Hearing Loss Syndrome

Goitre-Deafness Syndrome

Goitre Deafness

Hypertension, Essential

Essential Hypertension

Hypertension

High Blood Pressure

Hypertension, Essential, Susceptibility To

Hypertensive Disease

Primary Hypertension

EHT

Hypertension, Salt-Sensitive Essential, Susceptibility To

Hyperpiesia

Idiopathic Hypertension

Hypertensive Disorder

Hypertension, Essential, Susceptibility To, 3

Hypertension, Essential 3

Hypertension, Essential, Salt-Sensitive

Hypertension, Essential, Susceptibility To, 6

Hypertension, Essential 6

Hypertension, Salt-Sensitive Essential

Hypertension, Susceptibility To

Hypertension, Essential, Susceptibility To, 4

Hypertension, Essential 4

Hypertension, Essential, Susceptibility To, 2

Hypertension, Essential 2

Hypertension, Essential, Susceptibility To, 1

Hypertension, Essential 1

Hypertension, Essential, Susceptibility To, 5

Hypertension, Essential 5

Htn

Vascular Hypertensive Disorder

Systemic Primary Arterial Hypertension

Hbp - [High Blood Pressure]

Systemic Arterial Hypertensive Disorder

Elevated Blood Pressure

Arterial Hypertension Nos

Hypertension Nos

Benign Hypertension

Systemic Arterial Hypertension

Systemic Hypertension

Artery Htn

Benign Htn

Vascular Htn

Vascular Hypertension

Cholesterol Hypertension

Cholesterol Htn

Idiopathic Htn

Malignant Hypertension

Malignant Htn

Raised Blood Pressure

Cardiovascular Hypertension

Primary Htn - [Hypertension]

High Arterial Tension

High Blood Pressure Disorder

Ht - [Hypertension]

Htn - [Hypertension]

Hypertensive Vascular Disease

Hypertensive Vascular Degeneration

Mineral Metabolism Disease

Mineral Metabolism Disorder

Disorder Of Mineral Metabolism

Dipsogenic Diabetes Insipidus

Primary Polydipsia

Doid:0081058

Psychogenic Polydipsia

Thyroid Dyshormonogenesis 6

TDH6

Genetic Defect In Thyroid Hormonogenesis 6

Thyroid Hormonogenesis, Genetic Defect In, 6

Hypothyroidism, Congenital, Due To Dyshormonogenesis, 6

Chdh6

Congenital Hypothyroidism Due To Dyshormonogenesis Type 6

Kidney Disease

Renal Failure

Kidney Failure

Kidney Diseases

Nephropathy

Abnormality Of The Kidney

Impaired Renal Function Disease

Renal Anomaly

Kidney Dysfunction

Renal Disease

Nephropathies

Renal Failure Adverse Event

Abnormal Renal Function

Agenesis Of The Corpus Callosum With Peripheral Neuropathy

Andermann Syndrome

Charlevoix Disease

ACCPN

Polyneuropathy, Sensorimotor, With Or Without Agenesis Of The Corpus Callosum

Corpus Callosum, Agenesis Of, With Neuronopathy

Corpus Callosum Agenesis-Neuronopathy Syndrome

Agenesis Of Corpus Callosum With Neuronopathy

Agenesis Of Corpus Callosum With Peripheral Neuropathy

Agenesis Of Corpus Callosum With Polyneuropathy

Corpus Callosum Agenesis Neuronopathy

Hmsn/Acc

Hereditary Motor And Sensory Neuropathy With Agenesis Of The Corpus Callosum

Agenesis Of The Corpus Callosum, With Peripheral Neuropathy

Andermann'S Syndrome

Agenesis, Corpus Callosum, With Peripheral Neuropathy

Familial Periodic Paralysis

Genetic Periodic Paralysis

Paralyses, Familial Periodic

Hypokalemic Periodic Paralysis, Type 1

Hypokalemic Periodic Paralysis

Hokpp

Hypopp

Westphall Disease

HOKPP1

Familial Hypokalemic Periodic Paralysis

Familial Periodic Paralysis

Westphal Disease

Hypokalemic Periodic Paralysis Type 1

Hypokalemic Familial Periodic Paralysis

Periodic Hypokalemic Paralysis

Periodic Paralysis I

Hypokpp

Primary Hypokalemic Periodic Paralysis

Periodic Paralysis Hypokalemic 1

Paralysis, Hypokalemic, Periodic

Paralysis, Hypokalemic, Periodic, Type 1

Apparent Mineralocorticoid Excess

Cortisol 11-Beta-Ketoreductase Deficiency

Apparent Mineralocorticoid Excess Syndrome

AME

Ame1

11-Beta-Hydroxysteroid Dehydrogenase Deficiency Type 2

Ulick Syndrome

Mineralocorticoid Excess Syndrome, Apparent

Syndrome Of Apparent Mineralocorticoid Excess

Ame 1

11 Beta Hydroxysteroid Dehydrogenase Type 2 Deficiency

Liddle Syndrome 1

Liddle Syndrome

Pseudoaldosteronism

Liddle'S Syndrome

LIDLS1

Lidls

Pseudohyperaldosteronism

Pseudoprimary Hyperaldosteronism

Pseudohyperaldosteronism Type 1

Liddles Syndrome

Hypomagnesemia 3, Renal

HOMG3

Renal Hypomagnesemia 3

Fhhnc Without Severe Ocular Involvement

Renal Hypomagnesemia Type 3

Hypomagnesemia, Primary, Due To Defect In Renal Tubular Transport Of Magnesium

Hypomagnesemia, Isolated Renal

Hypomagnesemia, Familial, With Hypercalciuria And Nephrocalcinosis

Familial Primary Hypomagnesemia With Hypercalciuria And Nephrocalcinosis Without Severe Ocular Involvement

Isolated Renal Hypomagnesemia

Primary Hypomagnesemia Due To Defect In Renal Tubular Transport Of Magnesium

Primary Hypomagnesemia With Hypercalciuria And Nephrocalcinosis Without Severe Ocular Involvement

Hypomagnesemia 3

Familial Hypomagnesemia With Hypercalciuria And Nephrocalcinosis

Fhhnc

Hhn

Renal Hypomagnesemia Hypercalciuria Nephrocalcinosis

Hypomagnesemia, Type 3, Renal

Primary Hypomagnesemia

Miliaria Rubra

Miliaria

Prickly Heat

Miliaria Crystallina

Renal Tubular Acidosis

Acidosis Renal Tubular

Acidosis, Renal Tubular

Lightwood-Albright Syndrome

Lightwood Syndrome

Idiopathic Infantile Hypercalcemia - Mild Form

Kidney Tubular Acidosis

Renal Tubule Acidosis

Kidney Acidosis

Renal Acidosis

Renal Hyperchloremic Acidosis

Rta - [Renal Tubular Acidosis]

Miliaria

Eccrine Miliaria

Heat Rash

Sweat Rash

Sweat Retention Syndrome

Nephrogenic Diabetes Insipidus

Vasopressin-Resistant Diabetes Insipidus

Diabetes Insipidus, Nephrogenic

Diabetes Insipidus Nephrogenic

Congenital Nephrogenic Diabetes Insipidus

Adh Resistant Diabetes Insipidus

Diabetes Insipidus Nephrogenic X-Linked

Diabetes Insipidus Nephrogenic Type 1

Adh-Resistant Diabetes Insipidus

Diabetes Insipidus Renalis

Ndi

Renal Diabetes Insipidus

Familial Nephrogenic Diabetes

Antidiuretic-Hormone-Resistant Diabetes Insipidus

Adiuretin-Resistant Diabetes Insipidus

Ndi - [Nephrogenic Diabetes Insipidus]

Diabetes Tenuifluus

Adh - [Antidiuretic-Hormone] Resistant Diabetes Insipidus

Hereditary Nephrogenic Diabetes Insipidus

Familial Nephrogenic Diabetes Insipidus

Primary Nephrogenic Diabetes Insipidus

Adrenal Gland Disease

Adrenal Gland Diseases

Adrenal Gland Disorders

Osteoporosis

Postmenopausal Osteoporosis

Osteoporosis, Postmenopausal

Bone Mineral Density Quantitative Trait Locus

Bmnd

Osteoporosis, Involutional

Osteoporosis, Susceptibility To

Osteoporosis, Postmenopausal, Susceptibility

Bone Mineral Density Variation Qtl, Osteoporosis

OSTEOP

Involutional Osteoporosis

Senile Osteoporosis

Osteoporosis Postmenopausal

Bone Mineral Density, Quantitative Trait Locus

Osteoporosis, Senile

Idiopathic Osteoporosis

Bone Rarefaction Nos

Type 1 Osteoporosis

Polyhydramnios
Distal Arthrogryposis

Arthrogryposis Multiplex Congenita

Arthrogryposis

Congenital Multiple Arthrogryposis

Congenital Arthromyodysplasia

Fibrous Ankylosis Of Multiple Joints

Guerin-Stern Syndrome

Guérin-Stern Syndrome

Myodystrophia Fetalis Deformans

Otto Syndrome

Rocher-Sheldon Syndrome

Rossi Syndrome

Amc

Multiple Congenital Arthrogryposis

Arthrogryposis Syndrome

Arthrogryposis, Distal

Distal Arthrogryposis Syndrome

Freeman-Sheldon Syndrome

Arthrogryposis, Distal, Type 2b

Congenital Multiplex Arthrogryposis

Amyoplasia Congenita

Congenital Amyoplasia

Amc - [Arthrogryposis Multiplex Congenita]

Cakut

Renal Or Urinary Tract Malformation

Congenital Anomalies Of Kidney And Urinary Tract

Congenital Anomaly Of Kidney And Urinary Tract

Congenital Anomalies Of The Kidney And Urinary Tract

Kidney And Urinary Tract, Anomalies, Congenital

Renal Hypodysplasia, Nonsyndromic, 1

Autosomal Dominant Polycystic Kidney Disease

Polycystic Kidney Disease, Adult Type

Adpkd

Polycystic Kidney Diseases

Polycystic Kidney, Autosomal Dominant

Congenital Biliary Ectasias

Polycystic Kidney And Hepatic Disease 1

Polycystic Kidney Disease, Autosomal Dominant

Kidney, Polycystic, Disease, Autosomal Dominant

Adult Polycystic Kidney Disease

Polycystic Kidney, Adult Type

Apckd - [Autosomal Polycystic Kidney Disease]

Diseases Alias
Waldenstroem'S Macroglobulinemia

Waldenstroem'S Macroglobulinemia

Waldenstroem'S Macroglobulinemia

Macroglobulinemia Of Waldenstrom

Lymphoplasmacytic Lymphoma With Igm Gammopathy

Lymphoplasmacytic Lymphoma

Waldenstroem'S Macroglobulinemia

Waldenstroem'S Macroglobulinemia

Macroglobulinemia Of Waldenstrom

Lymphoplasmacytic Lymphoma With Igm Gammopathy

Lymphoplasmacytic Lymphoma

Orthologs Information

Species Symbol Source ID
Rattus norvegicus SLC12A3 RGD RGD:3686
Felis catus SLC12A3 VGNC VGNC:65189
Mus musculus SLC12A3 MGD MGI:108114
Bos taurus SLC12A3 VGNC VGNC:34666
Macaca mulatta SLC12A3 VGNC VGNC:77387
Canis familiaris SLC12A3 VGNC VGNC:46220
Others SLC12A3 NCBI