NPHL2
MCID: DNT020
MIFTS: 63

Dent Disease 1 (NPHL2)

Categories: Bone diseases, Endocrine diseases, Eye diseases, Fetal diseases, Genetic diseases, Nephrological diseases, Rare diseases

Aliases & Classifications for Dent Disease 1

MalaCards integrated aliases for Dent Disease 1:

Name: Dent Disease 1 57 12 72 44 70
Dent Disease 57 12 73 25 20 43 58 36 13 54 44 15
Dent's Disease 12 73 20 43 29 6 70
Dent Disease Type 1 58 29 6
Dent Disease 2 12 44 70
Low-Molecular-Weight Proteinuria with Hypercalciuria and Nephrocalcinosis 20 58
Renal Fanconi Syndrome with Nephrocalcinosis and Renal Stones 20 58
X-Linked Recessive Hypercalciuric Hypophosphatemic Rickets 20 58
X-Linked Recessive Nephrolithiasis 20 58
Nephrolithiasis 2 57 72
Dent Syndrome 20 58
Dents Disease 20 43
Nphl2 57 72
Nephrolithiasis-Hypercalciuria X-Linked Recessive 72
Nephrolithiasis, Hypercalciuric, X-Linked 57
X-Linked Hypercalciuric Nephrolithiasis 36
Urolithiasis, Hypercalciuric, X-Linked 57
Nephrolithiasis, X-Linked Recessive 6
Nephrolithiasis 2; Nphl2 57
Nephrolithiasis, Type 2 39
Nephrolithiasis Type 1 58
Dent Disease, Type 1 39

Characteristics:

Orphanet epidemiological data:

58
dent disease
Inheritance: X-linked recessive; Age of onset: Childhood; Age of death: adult;
dent disease type 1
Inheritance: X-linked recessive; Age of onset: Childhood; Age of death: adult;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
x-linked recessive

Miscellaneous:
variable phenotypic severity
female carriers may have asymptomatic proteinuria, hypercalciuria, or hypophosphatemia only
part of 'dent disease complex'
see also x-linked nephrocalcinosis , x-linked recessive hypophosphatemic rickets , and low-molecular-weight proteinuria with nephrocalcinosis
see also dent disease 2


HPO:

31
dent disease 1:
Inheritance x-linked recessive inheritance


Classifications:

Orphanet: 58  
Rare renal diseases
Rare bone diseases
Rare endocrine diseases
Developmental anomalies during embryogenesis


External Ids:

Disease Ontology 12 DOID:0050699
OMIM® 57 300009
OMIM Phenotypic Series 57 PS300009
NCIt 50 C123260
SNOMED-CT 67 444645005 717789008
MESH via Orphanet 45 C538212 C545036 D057973
ICD10 via Orphanet 33 N25.8
UMLS via Orphanet 71 C0403720 C0878681 C1839874 more
MedGen 41 C1848336
UMLS 70 C0878681 C1845167 C1848336

Summaries for Dent Disease 1

MedlinePlus Genetics : 43 Dent disease is a chronic kidney disorder that occurs almost exclusively in males. In affected individuals, kidney problems result from damage to structures called proximal tubules. Signs and symptoms of this condition appear in early childhood and worsen over time.The most frequent sign of Dent disease is the presence of an abnormally large amount of proteins in the urine (tubular proteinuria). Other common signs of the disorder include excess calcium in the urine (hypercalciuria), calcium deposits in the kidneys (nephrocalcinosis), and kidney stones (nephrolithiasis). Kidney stones can cause abdominal pain and blood in the urine (hematuria). In most affected males, progressive kidney problems lead to end-stage renal disease (ESRD) in early to mid-adulthood. ESRD is a life-threatening failure of kidney function that occurs when the kidneys are no longer able to filter fluids and waste products from the body effectively.Some people with Dent disease develop rickets, a bone disorder that results when the levels of vitamin D and certain minerals (including calcium) in the blood become too low. Rickets can be associated with weakening and softening of the bones, bone pain, bowed legs, and difficulty walking.Researchers have described two forms of Dent disease, which are distinguished by their genetic cause and pattern of signs and symptoms. Both forms of Dent disease (type 1 and type 2) are characterized by the features described above, but Dent disease 2 can also be associated with abnormalities unrelated to kidney function. These additional signs and symptoms include mild intellectual disability, weak muscle tone (hypotonia), and clouding of the lens of the eyes (cataract) that is described as subclinical because it does not impair vision. Some researchers consider Dent disease 2 to be a mild variant of a similar disorder called Lowe syndrome.

MalaCards based summary : Dent Disease 1, also known as dent disease, is related to hypophosphatemic rickets, x-linked recessive and proteinuria, chronic benign, and has symptoms including bone pain An important gene associated with Dent Disease 1 is CLCN5 (Chloride Voltage-Gated Channel 5), and among its related pathways/superpathways are Inositol phosphate metabolism and Phosphatidylinositol signaling system. The drugs Hydrochlorothiazide and Sodium Chloride Symporter Inhibitors have been mentioned in the context of this disorder. Affiliated tissues include kidney, bone and cortex, and related phenotypes are aminoaciduria and hematuria

Disease Ontology : 12 A renal tubular transport disease that is characterized by tubular proteinuria, hypercalciuria, calcium nephrolithiasis, nephrocalcinosis and chronic kidney failure and has material basis in X-linked recessive inheritance of mutations in the CLCN5 gene or OCRL1 gene.

GARD : 20 Dent disease is a chronic kidney disease that primarily affects males. While symptoms and severity vary, they usually begin in childhood and worsen over time. The most common feature of Dent disease is proteinuria ( protein in the urine). Other common features include excess calcium in the urine ( hypercalciuria ); calcium deposits in the kidneys ( nephrocalcinosis ); and kidney stones. Less common features include rickets and mildy short stature. Progressive kidney problems often lead to kidney failure by early to mid-adulthood. There are two forms of Dent disease which are distinguished based on their genetic causes. Both forms are inherited in an X-linked recessive manner. Dent disease type 1 is caused by a mutation in the CLCN5 gene. Dent disease type 2 is caused by a mutation in the OCRL gene. Males with this form are also at increased risk for mild intellectual disability and hypotonia. Treatment is based on the symptoms present, aiming to delay progression of kidney disease and improve quality of life.

OMIM® : 57 The term 'X-linked hypercalciuric nephrolithiasis' comprises several related forms of hereditary renal tubular disorders caused by mutations in the CLCN5 gene, including Dent disease, X-linked recessive nephrolithiasis (310468), X-linked recessive hypophosphatemic rickets (300554), and low molecular weight proteinuria (308990). Although these disorders are allelic and are all characterized by progressive proximal renal tubulopathy with hypercalciuria, low molecular weight proteinuria, and nephrocalcinosis, they vary in degree of severity and were originally reported as separate disorders. Some have considered these disorders as phenotypic variants of a single disease, referred to as the 'Dent disease complex' (Scheinman, 1998; Gambaro et al., 2004). Scheinman et al. (1999) provided a comprehensive review of genetic disorders of renal electrolyte transport. (300009) (Updated 05-Apr-2021)

KEGG : 36 X-linked hypercalciuric nephrolithiasis (XLHN) includes four syndromes: X-linked recessive nephrolithiasis with renal failure, Dent disease, X-linked recessive hypophosphatemic rickets, and Low molecular weight proteinuria with hypercalciuria and nephrocalcinosis. These syndromes differ in degree from each other, but common themes include proximal tubular reabsorptive failure, nephrolithiasis, nephrocalcinosis, progressive renal insufficiency, and in some cases rickets. They were reported independently, but mutations in the chloride channel gene CLCN5 have been identified in all four syndromes.

UniProtKB/Swiss-Prot : 72 Nephrolithiasis 2: An X-linked recessive renal disease belonging to the 'Dent disease complex', a group of disorders characterized by proximal renal tubular defect, hypercalciuria, nephrocalcinosis, and renal insufficiency. The spectrum of phenotypic features is remarkably similar in the various disorders, except for differences in the severity of bone deformities and renal impairment. Nephrolithiasis type 2 patients manifest hypercalciuria, hypophosphatemia, aminoaciduria, nephrocalcinosis and nephrolithiasis, renal insufficiency leading to renal failure in adulthood, rickets (33% of patients) and osteomalacia.

Wikipedia : 73 Dent's disease (or Dent disease) is a rare X-linked recessive inherited condition that affects the... more...

GeneReviews: NBK99494

Related Diseases for Dent Disease 1

Diseases in the Dent Disease 1 family:

Dent Disease 2

Diseases related to Dent Disease 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 104)
# Related Disease Score Top Affiliating Genes
1 hypophosphatemic rickets, x-linked recessive 32.3 SLC34A3 SLC34A1 OCRL CLCN5
2 proteinuria, chronic benign 31.0 LRP2 CUBN CLCNKB CLCN5
3 rickets 30.9 SLC34A3 SLC34A1 OCRL CLCN5
4 dent disease 2 30.8 OCRL INPP5B
5 nephrolithiasis, calcium oxalate 30.6 SLC34A1 SLC12A1 CLCN5
6 renal tubular acidosis 30.4 SLC9A3 OCRL CLCN7
7 osteomalacia 30.4 SLC34A3 SLC34A1 CLCN5
8 aminoaciduria 30.4 SLC34A1 OCRL CLCN5
9 hypokalemia 30.4 SLC12A1 KCNJ1 CLCNKB BSND
10 lowe oculocerebrorenal syndrome 30.2 RAB5A PHETA1 OCRL LRP2 INPP5B CLCN5
11 hypercalciuria, absorptive, 2 30.2 SLC34A3 KCNJ1 CLCN5
12 hypophosphatemia 30.2 SLC34A3 SLC34A1 OCRL CLCN5
13 idiopathic hypercalciuria 30.2 SLC34A3 CLCN5
14 nephrocalcinosis 30.2 SLC34A3 SLC34A1 SLC12A1 OCRL KCNJ1 CLCNKB
15 gitelman syndrome 29.9 SLC12A1 KCNJ1 CLCNKB CLCNKA BSND
16 nephrolithiasis 29.8 SLC34A3 SLC34A1 SLC12A1 LRP2 KCNJ1 CLCNKB
17 fanconi syndrome 29.8 SLC9A3 SLC34A3 SLC34A1 OCRL LRP2 INPP5B
18 cystic fibrosis 29.7 SLC9A3 KCNJ1 CLCN5 CLCN4 CLCN3
19 bartter disease 28.7 SLC9A3 SLC34A3 SLC34A1 SLC12A1 KCNJ1 CLCNKB
20 proteinuria, low molecular weight, with hypercalciuria and nephrocalcinosis 11.3
21 x-linked nephrolithiasis type i 11.3
22 nephrolithiasis, x-linked recessive, with renal failure 11.2
23 familial primary hypomagnesemia with hypercalciuria and nephrocalcinosis 11.0
24 fanconi-like syndrome 10.4 LRP2 CUBN
25 intestinal impaction 10.3 SLC9A3 CLCN4
26 orofaciodigital syndrome x 10.3 CLCNKA BSND
27 congenital intrinsic factor deficiency 10.3 LRP2 CUBN
28 dental abscess 10.3 SLC34A3 CLCN7
29 hereditary hypophosphatemic rickets 10.3 SLC34A3 SLC34A1
30 bartter syndrome, type 4b, neonatal, with sensorineural deafness 10.3 CLCNKB CLCNKA
31 infantile bartter syndrome with sensorineural deafness 10.3 CLCNKB CLCNKA BSND
32 donnai-barrow syndrome 10.3 OCRL LRP2 CUBN CLCN5
33 fanconi renotubular syndrome 2 10.3 SLC34A3 SLC34A1
34 x-linked recessive disease 10.3 OCRL INPP5B CLCN5
35 nephrolithiasis/osteoporosis, hypophosphatemic, 1 10.3 SLC34A3 SLC34A1
36 bartter syndrome, type 4a, neonatal, with sensorineural deafness 10.3 KCNJ1 CLCNKB BSND
37 diabetes insipidus 10.3 SLC12A1 CLCNKB CLCNKA
38 hypophosphatemic rickets with hypercalciuria, hereditary 10.2 SLC34A3 SLC34A1
39 arthrogryposis, distal, type 3 10.2 SLC12A1 KCNJ1 CLCNKB
40 hypomagnesemia 5, renal, with or without ocular involvement 10.2 SLC12A1 KCNJ1 BSND
41 bartter syndrome, type 1, antenatal 10.2 SLC12A1 KCNJ1
42 antenatal bartter syndrome 10.2 SLC12A1 KCNJ1 BSND
43 bartter syndrome, type 2, antenatal 10.2 SLC12A1 KCNJ1
44 ureteral obstruction 10.2 SLC9A3 SLC12A1 LRP2 CLCN5
45 seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance 10.1 SLC12A1 KCNJ1 CLCNKB BSND
46 liddle syndrome 1 10.1 SLC12A1 KCNJ1 CLCNKB BSND
47 hidradenitis suppurativa 10.1
48 hidradenitis 10.1
49 cataract 10.1
50 urolithiasis 10.1

Graphical network of the top 20 diseases related to Dent Disease 1:



Diseases related to Dent Disease 1

Symptoms & Phenotypes for Dent Disease 1

Human phenotypes related to Dent Disease 1:

58 31 (show all 48)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 aminoaciduria 58 31 hallmark (90%) Very frequent (99-80%) HP:0003355
2 hematuria 58 31 hallmark (90%) Very frequent (99-80%) HP:0000790
3 nephrolithiasis 58 31 hallmark (90%) Very frequent (99-80%) HP:0000787
4 hypercalciuria 58 31 hallmark (90%) Very frequent (99-80%) HP:0002150
5 recurrent fractures 58 31 hallmark (90%) Very frequent (99-80%) HP:0002757
6 chronic kidney disease 58 31 hallmark (90%) Very frequent (99-80%) HP:0012622
7 glycosuria 58 31 hallmark (90%) Very frequent (99-80%) HP:0003076
8 hyperphosphaturia 58 31 hallmark (90%) Very frequent (99-80%) HP:0003109
9 renal hypophosphatemia 58 31 hallmark (90%) Very frequent (99-80%) HP:0008732
10 low-molecular-weight proteinuria 58 31 hallmark (90%) Very frequent (99-80%) HP:0003126
11 renal tubular atrophy 58 31 hallmark (90%) Very frequent (99-80%) HP:0000092
12 focal segmental glomerulosclerosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0000097
13 renal phosphate wasting 58 31 hallmark (90%) Very frequent (99-80%) HP:0000117
14 hyperuricosuria 58 31 hallmark (90%) Very frequent (99-80%) HP:0003149
15 tubulointerstitial fibrosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0005576
16 non-acidotic proximal tubulopathy 58 31 hallmark (90%) Very frequent (99-80%) HP:0005574
17 high serum calcitriol 31 hallmark (90%) HP:0031415
18 elevated serum creatine kinase 58 31 frequent (33%) Frequent (79-30%) HP:0003236
19 abdominal pain 58 31 frequent (33%) Frequent (79-30%) HP:0002027
20 nephrocalcinosis 58 31 frequent (33%) Frequent (79-30%) HP:0000121
21 bone pain 58 31 frequent (33%) Frequent (79-30%) HP:0002653
22 cataract 58 31 occasional (7.5%) Occasional (29-5%) HP:0000518
23 rickets 58 31 occasional (7.5%) Occasional (29-5%) HP:0002748
24 intellectual disability, mild 58 31 occasional (7.5%) Occasional (29-5%) HP:0001256
25 osteomalacia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002749
26 mild global developmental delay 58 31 occasional (7.5%) Occasional (29-5%) HP:0011342
27 metaphyseal irregularity 58 31 occasional (7.5%) Occasional (29-5%) HP:0003025
28 bowing of the legs 58 31 occasional (7.5%) Occasional (29-5%) HP:0002979
29 delayed epiphyseal ossification 58 31 occasional (7.5%) Occasional (29-5%) HP:0002663
30 thin bony cortex 58 31 occasional (7.5%) Occasional (29-5%) HP:0002753
31 sparse bone trabeculae 58 31 occasional (7.5%) Occasional (29-5%) HP:0002752
32 bulging epiphyses 58 31 occasional (7.5%) Occasional (29-5%) HP:0003013
33 enlargement of the wrists 58 31 occasional (7.5%) Occasional (29-5%) HP:0003020
34 enlargement of the ankles 58 31 occasional (7.5%) Occasional (29-5%) HP:0003029
35 hypotonia 31 occasional (7.5%) HP:0001252
36 proximal tubulopathy 58 31 Very frequent (99-80%) HP:0000114
37 muscular hypotonia 58 Occasional (29-5%)
38 short stature 31 HP:0004322
39 proteinuria 58 Very frequent (99-80%)
40 hypophosphatemia 31 HP:0002148
41 renal insufficiency 58 Very frequent (99-80%)
42 abnormality of the lower limb 58 Occasional (29-5%)
43 femoral bowing 31 HP:0002980
44 tibial bowing 31 HP:0002982
45 fibular bowing 31 HP:0010502
46 microscopic hematuria 31 HP:0002907
47 enlarged epiphyses 58 Occasional (29-5%)
48 increased serum 1,25-dihydroxyvitamin d3 58 Very frequent (99-80%)

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Growth Height:
short stature

Genitourinary Kidneys:
nephrocalcinosis
nephrolithiasis
proximal renal tubule defect
decreased renal tubular phosphate reabsorption
renal insufficiency, progressive
more
Skeletal Limbs:
bowing of the legs
enlargement of the wrists
enlargement of the ankles
delayed opacification of the epiphyses
widened, distorted epiphyses
more
Laboratory Abnormalities:
hypophosphatemia
aminoaciduria
hypercalciuria
glycosuria
microscopic hematuria
more
Skeletal:
osteomalacia
bone pain
thin bony cortex
sparse bone trabeculae
increased fractures
more
Growth Other:
poor growth

Clinical features from OMIM®:

300009 (Updated 05-Apr-2021)

UMLS symptoms related to Dent Disease 1:


bone pain

GenomeRNAi Phenotypes related to Dent Disease 1 according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00221-A-3 9.86 APPL1
2 Decreased viability GR00221-A-4 9.86 APPL1
3 Decreased viability GR00240-S-1 9.86 CLCN1 SLC34A3
4 Decreased viability GR00249-S 9.86 CLCN3 CLCN7 KCNJ1 SLC12A1
5 Decreased viability GR00381-A-1 9.86 APPL1 SLC34A3
6 Decreased viability GR00386-A-1 9.86 CLCN4 LRP2 SLC34A3 SLC9A3
7 Decreased viability GR00402-S-2 9.86 CLCN7 SLC12A1
8 shRNA abundance <= 50% GR00343-S 9.28 CLCN3 CLCN7 CLCNKB INPP5B KCNJ1 OCRL

MGI Mouse Phenotypes related to Dent Disease 1:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 10.3 APPL1 BSND CLCN1 CLCN3 CLCN4 CLCN5
2 growth/size/body region MP:0005378 10.24 APPL1 BSND CLCN1 CLCN3 CLCN5 CLCN7
3 mortality/aging MP:0010768 10.07 APPL1 BSND CLCN1 CLCN3 CLCN7 CLCNKA
4 renal/urinary system MP:0005367 10.06 BSND CLCN3 CLCN4 CLCN5 CLCN7 CLCNKA
5 reproductive system MP:0005389 9.61 CLCN1 CLCN3 CLCNKA INPP5B LRP2 OCRL
6 skeleton MP:0005390 9.32 CLCN1 CLCN3 CLCN5 CLCN7 CLCNKA CUBN

Drugs & Therapeutics for Dent Disease 1

Drugs for Dent Disease 1 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 9)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Hydrochlorothiazide Approved, Vet_approved Phase 2, Phase 3 58-93-5 3639
2 Sodium Chloride Symporter Inhibitors Phase 2, Phase 3
3 Antihypertensive Agents Phase 2, Phase 3
4 diuretics Phase 2, Phase 3
5 potassium phosphate Phase 1, Phase 2
6 Phosphorus Supplement Phase 1, Phase 2
7
Bisphenol A Experimental 80-05-7 6623
8 Endocrine Disruptors
9 Noni

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Pharmacodynamic Evaluation of the ANTICALCIURIC Effect of Hydrochlorothiazide in Dent's Disease Terminated NCT00638482 Phase 2, Phase 3 Hydrochlorothiazide
2 Role Of Phosphorus And FGF 23 In Patients With Dent Disease Completed NCT02016235 Phase 1, Phase 2 Phosphorus Supplement
3 Screening for Dent Disease Mutations in Patients With Proteinuria Completed NCT01783795
4 Systematic Review of Clinical Biopsies of Dent Disease Patients Completed NCT02022189
5 Evaluation of the Release of Monomers From Composite Bonding Resins in Orthodontics Recruiting NCT04459013
6 Prospective Research Rare Kidney Stones (ProRKS) Recruiting NCT02780297
7 Rare Kidney Stone Consortium Registry for Hereditary Kidney Stone Diseases Recruiting NCT00588562
8 Rare Kidney Stone Consortium Biobank, Rare Diseases Clinical Research Network Recruiting NCT02026388
9 Assessment of Health-related Quality of Life in Rare Kidney Stone Formers in the Rare Kidney Stone Consortium Recruiting NCT02124395

Search NIH Clinical Center for Dent Disease 1

Cochrane evidence based reviews: dent disease

Genetic Tests for Dent Disease 1

Genetic tests related to Dent Disease 1:

# Genetic test Affiliating Genes
1 Dent Disease Type 1 29 CLCN5
2 Dent's Disease 29

Anatomical Context for Dent Disease 1

MalaCards organs/tissues related to Dent Disease 1:

40
Kidney, Bone, Cortex, Bone Marrow, Skin

Publications for Dent Disease 1

Articles related to Dent Disease 1:

(show top 50) (show all 251)
# Title Authors PMID Year
1
Evidence for genetic heterogeneity in Dent's disease. 57 25 6 54
15086899 2004
2
Novel mutations of the CLCN5 gene including a complex allele and A 5' UTR mutation in Dent disease 1. 57 6 61 54
19673950 2009
3
A common molecular basis for three inherited kidney stone diseases. 6 57 54
8559248 1996
4
From Lowe syndrome to Dent disease: correlations between mutations of the OCRL1 gene and clinical and biochemical phenotypes. 6 61 25
21031565 2011
5
Truncating mutations in the chloride/proton ClC-5 antiporter gene in Seven Jewish Israeli families with Dent's 1 disease. 54 6 25
19546586 2009
6
CLCN5 chloride-channel mutations in six new North American families with X-linked nephrolithiasis. 54 25 6
9734595 1998
7
Dent's disease manifesting as focal glomerulosclerosis: Is it the tip of the iceberg? 6 25
19806368 2009
8
Renal manifestations of Dent disease and Lowe syndrome. 61 6 54
18038239 2008
9
OCRL1 mutations in patients with Dent disease phenotype in Japan. 61 54 6
17384968 2007
10
Novel OCRL1 mutations in patients with the phenotype of Dent disease. 61 54 6
17162149 2006
11
Dent Disease with mutations in OCRL1. 54 6 61
15627218 2005
12
Examination of megalin in renal tubular epithelium from patients with Dent disease. 61 54 6
15052463 2004
13
X-linked hypercalciuric nephrolithiasis: clinical syndromes and chloride channel mutations. 25 57
9452994 1998
14
Idiopathic low molecular weight proteinuria associated with hypercalciuric nephrocalcinosis in Japanese children is due to mutations of the renal chloride channel (CLCN5). 6 25
9062355 1997
15
Dent's disease; a familial proximal renal tubular syndrome with low-molecular-weight proteinuria, hypercalciuria, nephrocalcinosis, metabolic bone disease, progressive renal failure and a marked male predominance. 25 57
7922301 1994
16
Digenic mutations of human OCRL paralogs in Dent's disease type 2 associated with Chiari I malformation. 61 6
28018608 2016
17
Japanese Dent disease has a wider clinical spectrum than Dent disease in Europe/USA: genetic and clinical studies of 86 unrelated patients with low-molecular-weight proteinuria. 6 61
24081861 2014
18
Novel OCRL mutations in patients with Dent-2 disease. 6 61
27625797 2012
19
Novel CLCN5 mutations in patients with Dent's disease result in altered ion currents or impaired exchanger processing. 6 54
19657328 2009
20
Phenotype and genotype of Dent's disease in three Chinese boys. 54 6
19076289 2009
21
OCRL1 mutations in Dent 2 patients suggest a mechanism for phenotypic variability. 54 61 25
19390221 2009
22
Mutational analysis of CLC-5, cofilin and CLC-4 in patients with Dent's disease. 54 6
19546591 2009
23
Molecular analysis of the CLCN5 gene in Dent's disease: first mutation identified in a patient from South America. 54 6
18184518 2007
24
Phenotypic and genetic heterogeneity in Dent's disease--the results of an Italian collaborative study. 6 54
16822791 2006
25
Functional evaluation of Dent's disease-causing mutations: implications for ClC-5 channel trafficking and internalization. 6 54
15895257 2005
26
Phenotype and genotype of Dent's disease in three Korean boys. 6 54
15719255 2005
27
The Alu insertion in the CLCN5 gene of a patient with Dent's disease leads to exon 11 skipping. 54 6
16041495 2005
28
De novo insertion of an Alu sequence in the coding region of the CLCN5 gene results in Dent's disease. 6 54
14569459 2003
29
Novel truncating mutations in the ClC-5 chloride channel gene in patients with Dent's disease. 54 6
12637640 2003
30
Identification of two novel mutations in the CLCN5 gene in Japanese patients with familial idiopathic low molecular weight proteinuria (Japanese Dent's disease). 6 54
11136179 2001
31
Characterization of renal chloride channel (CLCN5) mutations in Dent's disease. 6 54
10906159 2000
32
Clinical and genetic studies of CLCN5 mutations in Japanese families with Dent's disease. 6 54
10916075 2000
33
Renal chloride channel, CLCN5, mutations in Dent's disease. 6 54
10469281 1999
34
Mutations in CLCN5 chloride channel in Japanese patients with low molecular weight proteinuria. 54 6
9596078 1998
35
A second family with XLRH displays the mutation S244L in the CLCN5 gene. 54 6
9187673 1997
36
Genetic mapping in the Xp11.2 region of a new form of X-linked hypophosphatemic rickets. 6 61
7915957 1993
37
A comparison of splicing assays to detect an intronic variant of the OCRL gene in Lowe syndrome. 6
28803024 2017
38
Glomerular Pathology in Dent Disease and Its Association with Kidney Function. 25 61
27697782 2016
39
Observations of a large Dent disease cohort. 61 25
27342959 2016
40
Dent Disease in Chinese Children and Findings from Heterozygous Mothers: Phenotypic Heterogeneity, Fetal Growth, and 10 Novel Mutations. 25 61
27174143 2016
41
Hereditary causes of kidney stones and chronic kidney disease. 25 61
23334384 2013
42
Heterogeneity in the processing of CLCN5 mutants related to Dent disease. 25 61
21305656 2011
43
Dent's disease. 25 61
20946626 2010
44
Locus heterogeneity of Dent's disease: OCRL1 and TMEM27 genes in patients with no CLCN5 mutations. 54 25
19582483 2009
45
Dent-2 disease: a mild variant of Lowe syndrome. 25 61
19559295 2009
46
Effect of hydrochlorothiazide on urinary calcium excretion in dent disease: an uncontrolled trial. 61 25
18976849 2008
47
Dent disease presenting as partial Fanconi syndrome and hypercalciuria. 25 61
18235437 2008
48
Growth hormone improves growth rate and preserves renal function in Dent disease. 61 25
18540256 2008
49
Hypothesis: Dent disease is an underrecognized cause of focal glomerulosclerosis. 61 25
17702731 2007
50
Recent advances in understanding the clinical and genetic heterogeneity of Dent's disease. 6
16861240 2006

Variations for Dent Disease 1

ClinVar genetic disease variations for Dent Disease 1:

6 (show top 50) (show all 196)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 CLCN5 NM_001127898.4(CLCN5):c.1727G>A (p.Gly576Glu) SNV Pathogenic 11801 rs151340625 GRCh37: X:49853524-49853524
GRCh38: X:50088867-50088867
2 CLCN5 NM_001127898.4(CLCN5):c.380G>T (p.Gly127Val) SNV Pathogenic 11806 rs151340629 GRCh37: X:49837208-49837208
GRCh38: X:50072553-50072553
3 CLCN5 NM_001127898.4(CLCN5):c.1047G>A (p.Trp349Ter) SNV Pathogenic 11796 rs151340620 GRCh37: X:49851017-49851017
GRCh38: X:50086360-50086360
4 CLCN5 NM_001127898.4(CLCN5):c.1047G>A (p.Trp349Ter) SNV Pathogenic 11796 rs151340620 GRCh37: X:49851017-49851017
GRCh38: X:50086360-50086360
5 CLCN5 NM_001127898.4(CLCN5):c.2152C>T (p.Arg718Ter) SNV Pathogenic 11797 rs151340621 GRCh37: X:49855335-49855335
GRCh38: X:50090678-50090678
6 CLCN5 NM_001127898.4(CLCN5):c.809T>G (p.Leu270Arg) SNV Pathogenic 11798 rs151340622 GRCh37: X:49846380-49846380
GRCh38: X:50081723-50081723
7 CLCN5 NM_001127898.4(CLCN5):c.1768T>C (p.Ser590Pro) SNV Pathogenic 11799 rs151340623 GRCh37: X:49854796-49854796
GRCh38: X:50090139-50090139
8 CLCN5 NM_001127898.4(CLCN5):c.1238G>A (p.Trp413Ter) SNV Pathogenic 11803 rs151340627 GRCh37: X:49851208-49851208
GRCh38: X:50086551-50086551
9 CLCN5 NM_001127898.4(CLCN5):c.2295del (p.Met766fs) Deletion Pathogenic 11804 rs1569540520 GRCh37: X:49855476-49855476
GRCh38: X:50090819-50090819
10 CLCN5 NM_001127898.4(CLCN5):c.1049G>C (p.Arg350Pro) SNV Pathogenic 11805 rs151340628 GRCh37: X:49851019-49851019
GRCh38: X:50086362-50086362
11 CLCN5 CLCN5, ALU INS, EX11 Insertion Pathogenic 11807 GRCh37:
GRCh38:
12 CLCN5 NM_001127898.4(CLCN5):c.989G>T (p.Gly330Val) SNV Pathogenic 11808 rs151340630 GRCh37: X:49850692-49850692
GRCh38: X:50086035-50086035
13 CLCN5 NM_001127898.4(CLCN5):c.1557+1G>T SNV Pathogenic 18451 rs1569540382 GRCh37: X:49851528-49851528
GRCh38: X:50086871-50086871
14 OCRL OCRL, ARG476TRP SNV Pathogenic 29971 GRCh37:
GRCh38:
15 OCRL I526T SNV Pathogenic 29972 GRCh37:
GRCh38:
16 OCRL OCRL, 2-BP DEL, 166TT Deletion Pathogenic 29973 GRCh37:
GRCh38:
17 CLCN5 NM_001127898.4(CLCN5):c.1230C>A (p.Asn410Lys) SNV Pathogenic 40980 rs273585646 GRCh37: X:49851200-49851200
GRCh38: X:50086543-50086543
18 CLCN5 NM_001127898.4(CLCN5):c.1747G>A (p.Gly583Arg) SNV Pathogenic 40981 rs273585647 GRCh37: X:49854775-49854775
GRCh38: X:50090118-50090118
19 CLCN5 NM_001127898.4(CLCN5):c.1847A>G (p.Lys616Arg) SNV Pathogenic 40982 rs273585649 GRCh37: X:49854875-49854875
GRCh38: X:50090218-50090218
20 CLCN5 NM_001127898.4(CLCN5):c.1849T>G (p.Trp617Gly) SNV Pathogenic 40983 rs273585650 GRCh37: X:49854877-49854877
GRCh38: X:50090220-50090220
21 CLCN5 NM_001127898.4(CLCN5):c.884T>C (p.Leu295Pro) SNV Pathogenic 40984 rs273585645 GRCh37: X:49846455-49846455
GRCh38: X:50081798-50081798
22 CLCN5 NM_001127898.4(CLCN5):c.1025A>G (p.Tyr342Cys) SNV Pathogenic 40985 rs273585644 GRCh37: X:49850995-49850995
GRCh38: X:50086338-50086338
23 CLCN5 NM_001127898.4(CLCN5):c.1044G>C (p.Leu348Phe) SNV Pathogenic 40986 rs273585648 GRCh37: X:49851014-49851014
GRCh38: X:50086357-50086357
24 OCRL NM_000276.4(OCRL):c.1436A>G (p.Tyr479Cys) SNV Pathogenic 10860 rs137853262 GRCh37: X:128701310-128701310
GRCh38: X:129567333-129567333
25 CLCN5 NM_001127898.4(CLCN5):c.310C>T (p.Arg104Ter) SNV Pathogenic 207994 rs797044808 GRCh37: X:49834680-49834680
GRCh38: X:50070025-50070025
26 CLCN5 NM_001127898.4(CLCN5):c.1046G>A (p.Trp349Ter) SNV Pathogenic 207995 rs797044809 GRCh37: X:49851016-49851016
GRCh38: X:50086359-50086359
27 CLCN5 NM_001127898.4(CLCN5):c.1609C>T (p.Arg537Ter) SNV Pathogenic 207997 rs797044811 GRCh37: X:49853406-49853406
GRCh38: X:50088749-50088749
28 CLCN5 NG_007159.3:g.(?_162979)_(164232_?)del Deletion Pathogenic 208001 GRCh37: X:49845251-49846504
GRCh38: X:50080594-50081847
29 CLCN5 NM_001127898.4(CLCN5):c.2393_2415del (p.Val798fs) Deletion Pathogenic 208002 rs797044815 GRCh37: X:49856814-49856836
GRCh38: X:50092157-50092179
30 overlap with 9 genes NC_000023.11:g.(?_49922616)_(50099235_?)del Deletion Pathogenic 208003 GRCh37:
GRCh38: X:49922616-50099235
31 overlap with 9 genes NC_000023.11:g.(?_49922616)_(50099235_?)del Deletion Pathogenic 208004 GRCh37:
GRCh38: X:49922616-50099235
32 overlap with 9 genes NC_000023.11:g.(?_49922616)_(50099235_?)del Deletion Pathogenic 208005 GRCh37:
GRCh38: X:49922616-50099235
33 CLCN5 Variation Pathogenic 208006 GRCh37:
GRCh38:
34 CLCN5 Variation Pathogenic 208007 GRCh37:
GRCh38:
35 OCRL NM_000276.3:c.2140_*2286del Deletion Pathogenic 208012 GRCh37:
GRCh38:
36 OCRL NG_008638.1:g.(5550_9683)_(13328_22050)del Deletion Pathogenic 208013 GRCh37:
GRCh38:
37 CLCN5 NM_001127898.4(CLCN5):c.1676G>A (p.Trp559Ter) SNV Pathogenic 438798 rs1557194353 GRCh37: X:49853473-49853473
GRCh38: X:50088816-50088816
38 CLCN5 NM_001127898.4(CLCN5):c.344G>A (p.Trp115Ter) SNV Pathogenic 560969 rs1569540047 GRCh37: X:49837172-49837172
GRCh38: X:50072517-50072517
39 CLCN5 NM_001127898.4(CLCN5):c.1396G>C (p.Asp466His) SNV Pathogenic 586983 rs1569540369 GRCh37: X:49851366-49851366
GRCh38: X:50086709-50086709
40 OCRL NM_000276.4(OCRL):c.2464C>T (p.Arg822Ter) SNV Pathogenic 641377 rs1602819835 GRCh37: X:128722985-128722985
GRCh38: X:129589008-129589008
41 CLCN5 NM_001127898.4(CLCN5):c.1851G>T (p.Trp617Cys) SNV Pathogenic 930215 GRCh37: X:49854879-49854879
GRCh38: X:50090222-50090222
42 CLCN5 NM_001127898.4(CLCN5):c.1768dup (p.Ser590fs) Duplication Pathogenic 932731 GRCh37: X:49854793-49854794
GRCh38: X:50090136-50090137
43 CLCN5 NM_001127898.4(CLCN5):c.1771_1772del (p.Leu591fs) Microsatellite Pathogenic 932943 GRCh37: X:49854796-49854797
GRCh38: X:50090139-50090140
44 CLCN5 NM_001127898.4(CLCN5):c.477_478dup (p.Cys160fs) Microsatellite Pathogenic 932945 GRCh37: X:49840507-49840508
GRCh38: X:50075852-50075853
45 CLCN5 NM_001127898.4(CLCN5):c.2236del (p.Thr746fs) Deletion Pathogenic 932946 GRCh37: X:49855419-49855419
GRCh38: X:50090762-50090762
46 OCRL NM_000276.4(OCRL):c.2078C>T (p.Pro693Leu) SNV Pathogenic 932947 GRCh37: X:128710492-128710492
GRCh38: X:129576515-129576515
47 CLCN5 NM_001127898.4(CLCN5):c.1176del (p.Phe392fs) Deletion Pathogenic 932948 GRCh37: X:49851146-49851146
GRCh38: X:50086489-50086489
48 CLCN5 NM_001127898.4(CLCN5):c.1810T>A (p.Tyr604Asn) SNV Pathogenic 973833 GRCh37: X:49854838-49854838
GRCh38: X:50090181-50090181
49 OCRL NM_000276.4(OCRL):c.1245-1083G>A SNV Pathogenic 975017 GRCh37: X:128698666-128698666
GRCh38: X:129564689-129564689
50 CLCN5 NM_001127898.4(CLCN5):c.1441A>T (p.Lys481Ter) SNV Pathogenic 975058 GRCh37: X:49851411-49851411
GRCh38: X:50086754-50086754

UniProtKB/Swiss-Prot genetic disease variations for Dent Disease 1:

72 (show all 28)
# Symbol AA change Variation ID SNP ID
1 CLCN5 p.Gly127Val VAR_001616 rs151340629
2 CLCN5 p.Leu270Arg VAR_001617 rs151340622
3 CLCN5 p.Gly582Arg VAR_001621
4 CLCN5 p.Ser590Pro VAR_001622 rs151340623
5 CLCN5 p.Glu597Asp VAR_001623
6 CLCN5 p.Gly249Asp VAR_065591
7 CLCN5 p.Ser273Leu VAR_065592
8 CLCN5 p.Gly282Ala VAR_065593
9 CLCN5 p.Cys289Arg VAR_065594
10 CLCN5 p.Cys291Arg VAR_065595
11 CLCN5 p.Leu295Pro VAR_065596 rs273585645
12 CLCN5 p.Gly330Val VAR_065597 rs151340630
13 CLCN5 p.Glu337Ala VAR_065598
14 CLCN5 p.Ser340Gly VAR_065600
15 CLCN5 p.Ser340Arg VAR_065601
16 CLCN5 p.Tyr342Cys VAR_065602 rs273585644
17 CLCN5 p.Phe343Leu VAR_065603
18 CLCN5 p.Leu348Phe VAR_065604 rs273585648
19 CLCN5 p.Asn410Lys VAR_065605 rs273585646
20 CLCN5 p.Gly532Asp VAR_065606
21 CLCN5 p.Leu539Pro VAR_065607
22 CLCN5 p.Gly583Glu VAR_065608
23 CLCN5 p.Gly583Arg VAR_065609 rs273585647
24 CLCN5 p.Arg586Trp VAR_065610 rs797044812
25 CLCN5 p.Ser615Asn VAR_065612
26 CLCN5 p.Lys616Glu VAR_065613
27 CLCN5 p.Trp617Gly VAR_065614 rs273585650
28 CLCN5 p.Thr727Ser VAR_065615 rs144207967

Expression for Dent Disease 1

Search GEO for disease gene expression data for Dent Disease 1.

Pathways for Dent Disease 1

Pathways related to Dent Disease 1 according to KEGG:

36
# Name Kegg Source Accession
1 Inositol phosphate metabolism hsa00562
2 Phosphatidylinositol signaling system hsa04070

Pathways related to Dent Disease 1 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.06 SLC9A3 SLC34A3 SLC34A1 SLC12A1 CLCNKB CLCNKA
2
Show member pathways
12.39 SLC12A1 CLCN7 CLCN5 CLCN4 CLCN3 CLCN1
3
Show member pathways
12.35 CLCNKB CLCNKA CLCN7 CLCN5 CLCN4 CLCN3
4 11.32 SLC9A3 SLC34A3 SLC34A1
5
Show member pathways
11.26 CLCNKB CLCNKA CLCN7 CLCN5 CLCN4 CLCN3
6 10.82 SLC12A1 KCNJ1 CLCNKB CLCNKA BSND
7 10.71 OCRL INPP5B

GO Terms for Dent Disease 1

Cellular components related to Dent Disease 1 according to GeneCards Suite gene sharing:

(show all 24)
# Name GO ID Score Top Affiliating Genes
1 membrane GO:0016020 10.41 SLC9A3 SLC34A3 SLC34A1 SLC12A1 RAB5A OCRL
2 integral component of membrane GO:0016021 10.37 SLC9A3 SLC34A3 SLC34A1 SLC12A1 LRP2 KCNJ1
3 integral component of plasma membrane GO:0005887 10.16 SLC34A1 CLCNKB CLCNKA CLCN5 CLCN4 CLCN3
4 Golgi apparatus GO:0005794 10.14 PHETA1 OCRL LRP2 INPP5B CUBN CLCN5
5 plasma membrane GO:0005886 10.09 SLC9A3 SLC34A3 SLC34A1 SLC12A1 RAB5A OCRL
6 cytoplasmic vesicle GO:0031410 10.07 RAB5A PHETA1 OCRL INPP5B CLCN7 CLCN3
7 lysosome GO:0005764 9.99 OCRL LRP2 CUBN CLCN7 CLCN4 CLCN3
8 apical plasma membrane GO:0016324 9.95 SLC9A3 SLC34A3 SLC34A1 SLC12A1 LRP2 CUBN
9 lysosomal membrane GO:0005765 9.93 LRP2 CUBN CLCN7 CLCN5 CLCN4 CLCN3
10 early endosome GO:0005769 9.91 RAB5A PHETA1 OCRL CLCN5 CLCN4 CLCN3
11 early endosome membrane GO:0031901 9.88 RAB5A OCRL INPP5B CLCN4 CLCN3 APPL1
12 endosome membrane GO:0010008 9.87 RAB5A OCRL CUBN CLCN5 CLCN4 CLCN3
13 synaptic vesicle GO:0008021 9.85 RAB5A CLCN5 CLCN4 CLCN3
14 recycling endosome GO:0055037 9.79 PHETA1 CLCN4 CLCN3
15 apical part of cell GO:0045177 9.79 LRP2 CUBN CLCN5
16 phagocytic vesicle GO:0045335 9.77 RAB5A CLCN3 APPL1
17 phagocytic vesicle membrane GO:0030670 9.77 RAB5A OCRL INPP5B
18 clathrin-coated pit GO:0005905 9.76 OCRL LRP2 CUBN
19 endocytic vesicle GO:0030139 9.75 RAB5A LRP2 CUBN
20 chloride channel complex GO:0034707 9.74 CLCNKB CLCNKA CLCN1
21 brush border GO:0005903 9.65 SLC9A3 SLC34A3 SLC34A1 LRP2 CUBN
22 early phagosome GO:0032009 9.61 RAB5A APPL1
23 endosome GO:0005768 9.36 SLC34A1 RAB5A PHETA1 OCRL LRP2 INPP5B
24 brush border membrane GO:0031526 9.35 SLC9A3 SLC34A3 SLC34A1 LRP2 CUBN

Biological processes related to Dent Disease 1 according to GeneCards Suite gene sharing:

(show all 19)
# Name GO ID Score Top Affiliating Genes
1 transmembrane transport GO:0055085 10.02 SLC9A3 SLC34A3 SLC12A1 CLCNKB CLCNKA CLCN7
2 ion transport GO:0006811 9.93 SLC9A3 SLC34A3 SLC34A1 SLC12A1 KCNJ1 CLCNKB
3 ion transmembrane transport GO:0034220 9.91 SLC12A1 KCNJ1 CLCNKB CLCNKA CLCN7 CLCN5
4 endocytosis GO:0006897 9.83 RAB5A LRP2 CUBN CLCN5
5 regulation of ion transmembrane transport GO:0034765 9.8 KCNJ1 CLCNKB CLCNKA CLCN1
6 sodium ion transport GO:0006814 9.78 SLC9A3 SLC34A3 SLC34A1 SLC12A1
7 membrane organization GO:0061024 9.76 RAB5A OCRL LRP2
8 proton transmembrane transport GO:1902600 9.73 SLC9A3 CLCN5 CLCN4 CLCN3
9 sodium ion transmembrane transport GO:0035725 9.71 SLC9A3 SLC34A3 SLC34A1 SLC12A1
10 excretion GO:0007588 9.67 KCNJ1 CLCNKB CLCNKA CLCN5
11 sodium ion import across plasma membrane GO:0098719 9.58 SLC9A3 SLC34A1
12 regulation of pH GO:0006885 9.57 SLC9A3 CLCN3
13 inositol phosphate dephosphorylation GO:0046855 9.56 OCRL INPP5B
14 chloride transport GO:0006821 9.56 CLCNKB CLCNKA CLCN7 CLCN5 CLCN4 CLCN3
15 vitamin D metabolic process GO:0042359 9.55 LRP2 CUBN
16 phosphate ion transport GO:0006817 9.54 SLC34A3 SLC34A1
17 cellular phosphate ion homeostasis GO:0030643 9.51 SLC34A3 SLC34A1
18 sodium-dependent phosphate transport GO:0044341 9.46 SLC34A3 SLC34A1
19 chloride transmembrane transport GO:1902476 9.28 SLC12A1 CLCNKB CLCNKA CLCN7 CLCN5 CLCN4

Molecular functions related to Dent Disease 1 according to GeneCards Suite gene sharing:

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 symporter activity GO:0015293 9.67 SLC34A3 SLC34A1 SLC12A1
2 voltage-gated ion channel activity GO:0005244 9.67 KCNJ1 CLCNKB CLCNKA CLCN1
3 PDZ domain binding GO:0030165 9.65 SLC9A3 SLC34A1 CLCN3
4 antiporter activity GO:0015297 9.65 SLC9A3 CLCN7 CLCN5 CLCN4 CLCN3
5 chloride channel activity GO:0005254 9.56 CLCNKB CLCNKA CLCN7 CLCN5 CLCN4 CLCN3
6 sodium:phosphate symporter activity GO:0005436 9.46 SLC34A3 SLC34A1
7 solute:proton antiporter activity GO:0015299 9.46 SLC9A3 CLCN5 CLCN4 CLCN3
8 phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity GO:0004439 9.43 OCRL INPP5B
9 inositol-1,4,5-trisphosphate 5-phosphatase activity GO:0052658 9.4 OCRL INPP5B
10 inositol phosphate phosphatase activity GO:0052745 9.32 OCRL INPP5B
11 voltage-gated chloride channel activity GO:0005247 9.17 CLCNKB CLCNKA CLCN7 CLCN5 CLCN4 CLCN3

Sources for Dent Disease 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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