MCID: OST001
MIFTS: 63

Osteopetrosis

Categories: Blood diseases, Bone diseases, Cancer diseases, Ear diseases, Eye diseases, Fetal diseases, Genetic diseases, Immune diseases, Liver diseases, Nephrological diseases, Neuronal diseases, Rare diseases
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Aliases & Classifications for Osteopetrosis

MalaCards integrated aliases for Osteopetrosis:

Name: Osteopetrosis 11 19 42 75 28 53 5 14 36 71 75 31 33
Albers-Schonberg Disease 11 19 75
Marble Bone Disease 19 42 33
Osteopetroses 19 42 5
Osteopetrosis and Related Disorders 19 58
Congenital Osteopetrosis 42 71
Marble Bones 19 33
Albers-Schonberg Osteopetrosis 19
Albers-Schoenberg Disease 19
Osteosclerosis Fragilis 19
Marble Bone 11
Ivory Bones 33

Characteristics:


Inheritance:

Osteopetrosis and Related Disorders: Autosomal dominant,Autosomal recessive,X-linked recessive 58

Age Of Onset:

Osteopetrosis and Related Disorders: All ages 58

Classifications:

Orphanet: 58  
Rare bone diseases
Developmental anomalies during embryogenesis


External Ids:

Disease Ontology 11 DOID:13533
ICD9CM 34 756.52
MeSH 43 D010022
NCIt 49 C26840
SNOMED-CT 68 205500005
ICD10 31 Q78.2
MESH via Orphanet 44 D010022
ICD10 via Orphanet 32 Q78.2
UMLS via Orphanet 72 C0029454
Orphanet 58 ORPHA2781
ICD11 33 1498426606
UMLS 71 C0029454 C3645711

Summaries for Osteopetrosis

MedlinePlus Genetics: 42 Osteopetrosis is a bone disease that makes bones abnormally dense and prone to breakage (fracture). Researchers have described several major types of osteopetrosis, which are usually distinguished by their pattern of inheritance: autosomal dominant, autosomal recessive, or X-linked. The different types of the disorder can also be distinguished by the severity of their signs and symptoms.Autosomal dominant osteopetrosis (ADO), which is also called Albers-Schönberg disease, is typically the mildest type of the disorder. Some affected individuals have no symptoms. In these people, the unusually dense bones may be discovered by accident when an x-ray is done for another reason. In affected individuals who develop signs and symptoms, the major features of the condition include multiple bone fractures, abnormal side-to-side curvature of the spine (scoliosis) or other spinal abnormalities, arthritis in the hips, and a bone infection called osteomyelitis. These problems usually become apparent in late childhood or adolescence.Autosomal recessive osteopetrosis (ARO) is a more severe form of the disorder that becomes apparent in early infancy. Affected individuals have a high risk of bone fracture resulting from seemingly minor bumps and falls. Their abnormally dense skull bones pinch nerves in the head and face (cranial nerves), often resulting in vision loss, hearing loss, and paralysis of facial muscles. Dense bones can also impair the function of bone marrow, preventing it from producing new blood cells and immune system cells. As a result, people with severe osteopetrosis are at risk of abnormal bleeding, a shortage of red blood cells (anemia), and recurrent infections. In the most severe cases, these bone marrow abnormalities can be life-threatening in infancy or early childhood.Other features of autosomal recessive osteopetrosis can include slow growth and short stature, dental abnormalities, and an enlarged liver and spleen (hepatosplenomegaly). Depending on the genetic changes involved, people with severe osteopetrosis can also have brain abnormalities, intellectual disability, or recurrent seizures (epilepsy).A few individuals have been diagnosed with intermediate autosomal osteopetrosis (IAO), a form of the disorder that can have either an autosomal dominant or an autosomal recessive pattern of inheritance. The signs and symptoms of this condition become noticeable in childhood and include an increased risk of bone fracture and anemia. People with this form of the disorder typically do not have life-threatening bone marrow abnormalities. However, some affected individuals have had abnormal calcium deposits (calcifications) in the brain, intellectual disability, and a form of kidney disease called renal tubular acidosis.Rarely, osteopetrosis can have an X-linked pattern of inheritance. In addition to abnormally dense bones, the X-linked form of the disorder is characterized by abnormal swelling caused by a buildup of fluid (lymphedema) and a condition called anhydrotic ectodermal dysplasia that affects the skin, hair, teeth, and sweat glands. Affected individuals also have a malfunctioning immune system (immunodeficiency), which allows severe, recurrent infections to develop. Researchers often refer to this condition as OL-EDA-ID, an acronym derived from each of the major features of the disorder.

MalaCards based summary: Osteopetrosis, also known as albers-schonberg disease, is related to osteopetrosis, autosomal recessive 7 and osteopetrosis, autosomal recessive 5. An important gene associated with Osteopetrosis is CLCN7 (Chloride Voltage-Gated Channel 7), and among its related pathways/superpathways are Innate Immune System and Akt Signaling. The drugs Busulfan and Alemtuzumab have been mentioned in the context of this disorder. Affiliated tissues include bone, bone marrow and spleen, and related phenotypes are growth/size/body region and limbs/digits/tail

GARD: 19 Osteopetrosis refers to a group of rare, inherited skeletal disorders characterized by increased bone density and abnormal bone growth. Symptoms and severity can vary greatly, ranging from neonatal onset with serious complications (such as bone marrow failure) to the incidental finding of osteopetrosis on X-ray. Depending on severity and age of onset, features may include fractures, short stature, compressive neuropathies (pressure on the nerves), hypocalcemia with attendant tetanic seizures, and pancytopenia. In rare cases, there may be neurological impairment or involvement of other body systems. Osteopetrosis may be caused by genetic changes in at least 10 genes. Inheritance can be autosomal recessive, autosomal dominant, or X-linked recessive with the most severe forms being autosomal recessive.

Orphanet: 58 Osteopetrosis, also known as marble bone disease, is a descriptive term that refers to a group of rare, heritable disorders of the skeleton characterized by increased bone density on radiographs.

Disease Ontology: 11 An osteosclerosis that has material basis in lack of bone resorption which results in abnormally hard and brittle bones.

Wikipedia: 75 Osteopetrosis, literally "stone bone", also known as marble bone disease or Albers-Schönberg disease, is... more...

Related Diseases for Osteopetrosis

Diseases in the Osteopetrosis family:

Osteopetrosis, Autosomal Dominant 2 Osteopetrosis, Autosomal Recessive 1
Osteopetrosis, Autosomal Recessive 2 Osteopetrosis, Autosomal Recessive 5
Osteopetrosis, Autosomal Recessive 3 Osteopetrosis, Autosomal Dominant 1
Osteopetrosis, Autosomal Recessive 4 Osteopetrosis, Autosomal Recessive 6
Osteopetrosis, Autosomal Recessive 7 Osteopetrosis, Autosomal Recessive 8
Osteopetrosis, Autosomal Dominant 3 Clcn7-Related Osteopetrosis
Autosomal Recessive Malignant Osteopetrosis

Diseases related to Osteopetrosis via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 466)
# Related Disease Score Top Affiliating Genes
1 osteopetrosis, autosomal recessive 7 33.3 TNFRSF11A TCIRG1 CLCN7
2 osteopetrosis, autosomal recessive 5 33.2 TCIRG1 OSTM1 CLCN7
3 osteopetrosis, autosomal recessive 6 33.2 TNFSF11 TCIRG1 PLEKHM1 CLCN7
4 osteopetrosis, autosomal recessive 3 33.2 TCIRG1 OSTM1 LRRK1 CLCN7 CA2
5 osteopetrosis, autosomal dominant 1 33.2 TNFRSF11A LRP5 CLCN7
6 osteopetrosis, autosomal recessive 1 33.2 TCIRG1 CLCN7
7 osteopetrosis, autosomal dominant 2 33.1 TNFSF11 TCIRG1 OSTM1 LRP5 CTSK CLCN7
8 osteopetrosis, autosomal recessive 4 33.1 TCIRG1 OSTM1 CLCN7
9 osteopetrosis, autosomal recessive 8 33.0 TCIRG1 SNX10 CLCN7
10 autosomal recessive malignant osteopetrosis 32.7 TNFSF11 TCIRG1 SNX10 CLCN7
11 osteopetrosis, autosomal recessive 2 32.7 TNFSF11 TNFRSF11A TCIRG1 SNX10 PLEKHM1 OSTM1
12 pycnodysostosis 31.8 TNFSF11 TCIRG1 SNX10 PLEKHM1 OSTM1 MITF
13 osteomyelitis 31.6 TNFSF11 TNFRSF11A CTSK ACP5
14 endosteal hyperostosis, autosomal dominant 31.4 TNFSF11 TCIRG1 OSTM1 LRP5 CTSK CLCN7
15 bone disease 31.3 TRAF6 TNFSF11 TNFRSF11A SRC OSTM1 LRP5
16 dysosteosclerosis 30.7 TNFRSF11A TCIRG1 CSF1R
17 osteochondrodysplasia 30.6 TNFSF11 TCIRG1 OSTM1 LRP5 CTSK CLCN7
18 craniometaphyseal dysplasia, autosomal dominant 30.6 TNFSF11 TNFRSF11A TCIRG1 OSTM1 CLCN7 ACP5
19 sclerosteosis 30.6 TNFSF11 LRP5 CTSK ACP5
20 mammary paget's disease 30.5 TRAF6 TNFSF11 TNFRSF11A CTSK ACP5
21 paget's disease of bone 30.4 TRAF6 TNFSF11 TNFRSF11A CTSK ACP5
22 periodontitis 30.4 TNFSF11 CTSK ACP5
23 brittle bone disorder 30.4 TNFSF11 TNFRSF11A LRP5 CTSK CLCN7 ACP5
24 van buchem disease 30.1 TNFSF11 LRP5 CTSK
25 familial expansile osteolysis 30.1 TNFSF11 TNFRSF11A CTSK ACP5
26 bone giant cell tumor 30.0 TNFSF11 CTSK CSF1 ACP5
27 connective tissue disease 30.0 TRAF6 TNFSF11 SRC CTSK CSF1 ACP5
28 osteoporosis 29.9 TRAF6 TNFSF11 TNFRSF11A TCIRG1 SRC LRP5
29 rheumatoid arthritis 29.8 TRAF6 TNFSF11 TNFRSF11A CTSK CSF1R CSF1
30 osteopetrosis, autosomal dominant 3 11.6
31 ectodermal dysplasia and immunodeficiency 1 11.5
32 coloboma, osteopetrosis, microphthalmia, macrocephaly, albinism, and deafness 11.4
33 osteopetrosis and infantile neuroaxonal dystrophy 11.3
34 infantile osteopetrosis with neuroaxonal dysplasia 11.2
35 csf1r-related brain malformation and osteopetrosis 11.1
36 clcn7-related osteopetrosis 11.0
37 raine syndrome 10.9
38 contractures, pterygia, and spondylocarpotarsal fusion syndrome 1a 10.8
39 renal tubular acidosis 10.5
40 axial osteomalacia 10.4 TCIRG1 OSTM1 CLCN7
41 fibrogenesis imperfecta ossium 10.4 TCIRG1 OSTM1 CLCN7
42 3-methylglutaconic aciduria, type iii 10.4
43 rickets 10.4
44 hydrocephalus 10.4
45 multiple cranial nerve palsy 10.4 CLCN7 CA2
46 synovitis 10.4 TNFSF11 CSF1 ACP5
47 aplastic anemia 10.4
48 periapical periodontitis 10.4 TNFSF11 CTSK ACP5
49 paget disease of bone 5, juvenile-onset 10.4 TNFSF11 TNFRSF11A
50 pancytopenia 10.4

Graphical network of the top 20 diseases related to Osteopetrosis:



Diseases related to Osteopetrosis

Symptoms & Phenotypes for Osteopetrosis

GenomeRNAi Phenotypes related to Osteopetrosis according to GeneCards Suite gene sharing:

25
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 no effect GR00402-S-1 10.15 ACP5 CA2 CLCN7 CSF1 CSF1R CSK
2 no effect GR00402-S-2 10.15 ACP5 CA2 CSF1 CSK IKBKG LRP5

MGI Mouse Phenotypes related to Osteopetrosis:

45 (show all 19)
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 10.48 CA2 CLCN7 CSF1 CSF1R CSK CTSK
2 limbs/digits/tail MP:0005371 10.45 ACP5 CLCN7 CSF1 CSF1R CTSK LRP5
3 homeostasis/metabolism MP:0005376 10.44 CA2 CLCN7 CSF1 CSF1R CTSK IKBKG
4 immune system MP:0005387 10.43 ACP5 CA2 CLCN7 CSF1 CSF1R CSK
5 craniofacial MP:0005382 10.37 CLCN7 CSF1 CSF1R CSK CTSK LRP5
6 endocrine/exocrine gland MP:0005379 10.36 CA2 CSF1 CSF1R CSK CTSK IKBKG
7 behavior/neurological MP:0005386 10.33 CLCN7 CSF1 CSF1R CSK CTSK IKBKG
8 cellular MP:0005384 10.32 CLCN7 CSF1 CSF1R CSK CTSK IKBKG
9 nervous system MP:0003631 10.3 CA2 CLCN7 CSF1 CSF1R CSK CTSK
10 normal MP:0002873 10.27 CLCN7 CSF1R CSK IKBKG LRP5 MITF
11 skeleton MP:0005390 10.25 ACP5 CA2 CLCN7 CSF1 CSF1R CTSK
12 pigmentation MP:0001186 10.13 CLCN7 IKBKG LRP5 MITF OSTM1 SRC
13 hematopoietic system MP:0005397 10.13 ACP5 CLCN7 CSF1 CSF1R CSK CTSK
14 no phenotypic analysis MP:0003012 10.11 CSF1 CSF1R MITF RAB7A TCIRG1 TNFRSF11A
15 reproductive system MP:0005389 10.07 CA2 CSF1 CSF1R CTSK IKBKG MITF
16 vision/eye MP:0005391 10.03 CLCN7 CSF1 CSK LRP5 LRRK1 MITF
17 respiratory system MP:0005388 10.01 CA2 CLCN7 CSF1 CSK CTSK SRC
18 mortality/aging MP:0010768 9.89 CA2 CLCN7 CSF1 CSF1R CSK IKBKG
19 integument MP:0010771 9.32 CLCN7 CSF1 CSF1R IKBKG MITF OSTM1

Drugs & Therapeutics for Osteopetrosis

Drugs for Osteopetrosis (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show top 50) (show all 59)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Busulfan Approved, Investigational Phase 2, Phase 3 55-98-1 2478
2
Alemtuzumab Approved, Investigational Phase 2, Phase 3 216503-57-0
3
Fludarabine Approved Phase 2, Phase 3 75607-67-9, 21679-14-1 30751 657237
4
Cyclophosphamide Approved, Investigational Phase 2, Phase 3 50-18-0, 6055-19-2 2907
5
Methotrexate Approved Phase 2, Phase 3 1959-05-2, 59-05-2 4112 126941
6
Miconazole Approved, Investigational, Vet_approved Phase 2, Phase 3 22916-47-8 4189
7
Clotrimazole Approved, Vet_approved Phase 2, Phase 3 23593-75-1 2812
8
Folic acid Approved, Nutraceutical, Vet_approved Phase 2, Phase 3 59-30-3 6037
9
Calcitriol Approved, Nutraceutical Phase 3 32222-06-3 5280453
10 Immunologic Factors Phase 2, Phase 3
11 Cyclosporins Phase 2, Phase 3
12 Folic Acid Antagonists Phase 2, Phase 3
13 Folate Phase 2, Phase 3
14 Vitamin B9 Phase 2, Phase 3
15 Calcineurin Inhibitors Phase 2, Phase 3
16 Vitamin B Complex Phase 2, Phase 3
17 Antifungal Agents Phase 2, Phase 3
18 Thymoglobulin Phase 2, Phase 3
19 Dermatologic Agents Phase 2, Phase 3
20 Alkylating Agents Phase 2, Phase 3
21 Antineoplastic Agents, Alkylating Phase 2, Phase 3
22 Antimetabolites Phase 2, Phase 3
23 Antineoplastic Agents, Immunological Phase 2, Phase 3
24 Immunosuppressive Agents Phase 2, Phase 3
25 Antiviral Agents Phase 3
26 Anti-Infective Agents Phase 3
27 interferons Phase 3
28 Interferon-gamma Phase 3
29 Antirheumatic Agents Phase 2, Phase 3
30 Trace Elements Phase 3
31 Vasoconstrictor Agents Phase 3
32 Micronutrients Phase 3
33
Adenosine Approved, Investigational Phase 2 58-61-7 60961
34
Rituximab Approved Phase 2 174722-31-7
35
Thiotepa Approved, Investigational Phase 2 52-24-4 5453
36
Celecoxib Approved, Investigational Phase 2 169590-42-5 2662
37
Acetylcysteine Approved, Investigational Phase 2 616-91-1 581 12035
38
Tocopherol Approved, Investigational Phase 2 1406-66-2
39
Clofarabine Approved, Investigational Phase 2 123318-82-1 119182
40
Lenograstim Approved, Investigational Phase 2 135968-09-1
41
DL-alpha-Tocopherol Approved, Experimental, Investigational, Nutraceutical, Vet_approved Phase 2 59-02-9, 10191-41-0 2116 14985
42
Lipoic acid Approved, Investigational, Nutraceutical Phase 2 1200-22-2 864 6112
43
Tocotrienol Investigational Phase 2 6829-55-6 9929901
44 Antilymphocyte Serum Phase 2
45 Vitamins Phase 2
46 Alpha-lipoic Acid Phase 2
47 N-monoacetylcystine Phase 2
48 Tocotrienols Phase 2
49 Tocopherols Phase 2
50 Liver Extracts Phase 2

Interventional clinical trials:

(show all 18)
# Name Status NCT ID Phase Drugs
1 Hematopoietic Stem Cell Transplantation for Malignant Infantile Osteopetrosis Unknown status NCT01087398 Phase 2, Phase 3 Busulfan, Cyclophosphamide, Thymoglobulin, Fludarabine (Conditioning regimen);Cyclosporin, Methotrexate (GVHD prophylaxis)
2 Risk-Adapted Allogeneic Stem Cell Transplantation For Mixed Donor Chimerism In Patients With Selected Non-Malignant Diseases Unknown status NCT01019876 Phase 2, Phase 3 Fludarabine;Cyclophosphamide;Cyclophosphamide 40;Cyclophosphamide 30
3 Allogeneic Hematopoietic Stem Cell Transplantation For Severe Osteopetrosis Completed NCT00775931 Phase 2, Phase 3 Campath-1H;Cyclophosphamide;Busulfan;Fludarabine monophosphate
4 Phase III Randomized Study of Interferon Gamma in Children With Severe, Congenital Osteopetrosis Completed NCT00004402 Phase 3 calcitriol;interferon gamma
5 Phase 2a Study of Interferon Gamma-1b for the Treatment of Autosomal Dominant Type 2 Osteopetrosis Completed NCT02584608 Phase 2 ACTIMMUNE
6 Open-label Early Phase 2 Study With a Single Arm of Interferon Gamma-1b Treatment of Osteopetrosis Completed NCT02666768 Phase 2 Interferon gamma-1b
7 Phase I/II Trial Of Hematopoietic Stem Cell Transplant (HSCT) For Children With A Genetic Disease Of Blood Cells Without An HLA-Matched Sibling Donor Completed NCT00730314 Phase 1, Phase 2
8 MT2013-31: Allogeneic Hematopoietic Cell Transplantation for Inherited Metabolic Disorders and Severe Osteopetrosis Following Conditioning With Busulfan (Therapeutic Drug Monitoring), Fludarabine +/- ATG Recruiting NCT02171104 Phase 2 IMD Preparative Regimen;Osteopetrosis Only Preparative Regimen;Osteopetrosis Haploidentical Only Preparative Regimen;cALD SR-A (Standard-Risk, Regimen A);cALD SR-B (Standard-Risk, Regimen B);cALD HR-D (High-Risk, Regimen C);cALD HR-D (High-Risk, Regimen D)
9 Phase I/II Study of CaspaCIDe® T Cells From an HLA-Partially Matched Family Donor After Negative Selection of TCR αβ+T Cells in Pediatric Patients Affected by Hematological Disorders Active, not recruiting NCT03301168 Phase 1, Phase 2 Rimiducid
10 Phase II Extension Study of CaspaCIDe T Cells (BPX-501) From an HLA-partially Matched Family Donor After Negative Selection of TCR αβ+T Cells in Pediatric Patients Affected by Hematological Disorders Active, not recruiting NCT02065869 Phase 2 rimiducid
11 Reduced Intensity Allogeneic Transplantation For Severe Osteopetrosis Incorporating A Second Cd34 Selected Graft Terminated NCT00638820 Phase 2 Campath, Busulfan, Clofarabine
12 A Phase II Study Using the CliniMACS® Device for CD34+ Cell Selection and T Cell Depletion for Graft-versus-Host Disease Prophylaxis in Alternative Donor Stem Cell Transplant Recipients Terminated NCT00968864 Phase 2
13 A Phase I Clinical Trial for Gene Therapy in Infantile Malignant Osteopetrosis (IMO) to Evaluate the Safety and Preliminary Efficacy of Autologous CD34+ Enriched Cells Transduced With a LV Vector Encoding the TCIRG1 Gene Terminated NCT04525352 Phase 1
14 Effect of 12 Months Treatment With rhPTH on Calcium Balance, Bone Turnover, Bone Mineral Density, and Bone Micro-architecture in Patients With Fractures Associated With Low Bone Turnover and Sclerosing Bone Disorders Terminated NCT00145886 Phase 1 rhPTH
15 Post-Marketing Surveillance Study of Actimmune (Interferon Gamma-1b) in Patients With Severe Malignant Osteopetrosis Completed NCT00043329 Actimmune Registry
16 Clinical Assessment of Patients With High Bone Mass Due to Mutation in Low Density Lipoprotein l Receptor 5 Completed NCT01199094
17 An Expanded Access Study of the Feasibility of Using the CliniMACS® Device for CD34+ Cell Selection and T Cell Depletion for Graft-versus-Host Disease Prophylaxis in Alternative Donor Stem Cell Transplant Recipients No longer available NCT01200017
18 Allogeneic Hematopoietic Stem Cell Transplantation for Children Affected With Malignant Osteopetrosis: A Pilot Study Terminated NCT00145587 Systemic chemotherapy and antibodies

Search NIH Clinical Center for Osteopetrosis

Inferred drug relations via UMLS 71 / NDF-RT 50 :


Interferon gamma-1b

Cell-based therapeutics:


LifeMap Discovery
Data from LifeMap, the Embryonic Development and Stem Cells Database
Read about Osteopetrosis cell therapies at LifeMap Discovery.

Genetic Tests for Osteopetrosis

Genetic tests related to Osteopetrosis:

# Genetic test Affiliating Genes
1 Osteopetrosis 28

Anatomical Context for Osteopetrosis

Organs/tissues related to Osteopetrosis:

MalaCards : Bone, Bone Marrow, Spleen, Brain, Liver, Kidney, Skin

Publications for Osteopetrosis

Articles related to Osteopetrosis:

(show top 50) (show all 2737)
# Title Authors PMID Year
1
Albers-Schönberg disease (autosomal dominant osteopetrosis, type II) results from mutations in the ClCN7 chloride channel gene. 53 62 5
11741829 2001
2
TCIRG1 Transgenic Rescue of Osteoclast Function Using Induced Pluripotent Stem Cells Derived from Patients with Infantile Malignant Autosomal Recessive Osteopetrosis. 62 5
31567691 2019
3
TCIRG1 and SNX10 gene mutations in the patients with autosomal recessive osteopetrosis. 62 5
30898715 2019
4
CLCN7 and TCIRG1 mutations in a single family: Evidence for digenic inheritance of osteopetrosis. 62 5
30431110 2019
5
MiT family translocation renal cell carcinoma after malignant infantile osteopetrosis in childhood: a case report. 62 5
31949762 2018
6
Autosomal recessive osteopetrosis type I: description of pathogenic variant of TCIRG1 gene. 62 5
30084437 2018
7
Ophthalmic phenotype of TCIRG1 gene mutations in Chinese infantile malignant osteopetrosis. 62 5
30539151 2018
8
Identification of TCIRG1 and CLCN7 gene mutations in a patient with autosomal recessive osteopetrosis. 62 5
24535484 2014
9
A novel CLCN7 mutation resulting in a most severe form of autosomal recessive osteopetrosis. 62 5
19238435 2009
10
A single-center experience in 20 patients with infantile malignant osteopetrosis. 62 5
19507210 2009
11
Effects of human a3 and a4 mutations that result in osteopetrosis and distal renal tubular acidosis on yeast V-ATPase expression and activity. 62 5
16840787 2006
12
TCIRG1-dependent recessive osteopetrosis: mutation analysis, functional identification of the splicing defects, and in vitro rescue by U1 snRNA. 62 5
15300850 2004
13
Chloride channel ClCN7 mutations are responsible for severe recessive, dominant, and intermediate osteopetrosis. 62 5
14584882 2003
14
Mapping of autosomal dominant osteopetrosis type II (Albers-Schönberg disease) to chromosome 16p13.3. 62 5
11468688 2001
15
The mutational spectrum of human malignant autosomal recessive osteopetrosis. 62 5
11532986 2001
16
Mutations in the a3 subunit of the vacuolar H(+)-ATPase cause infantile malignant osteopetrosis. 62 5
10942435 2000
17
Defects in TCIRG1 subunit of the vacuolar proton pump are responsible for a subset of human autosomal recessive osteopetrosis. 62 5
10888887 2000
18
Elevated serum levels of creatine kinase BB in autosomal dominant osteopetrosis type II--a family study. 62 5
1516225 1992
19
The resorptive apparatus of osteoclasts supports lysosomotropism and increases potency of basic versus non-basic inhibitors of cathepsin K. 53 62
20097319 2010
20
Molecular and clinical heterogeneity in CLCN7-dependent osteopetrosis: report of 20 novel mutations. 53 62
19953639 2010
21
Characteristics of ClC7 Cl- channels and their inhibition in mutant (G215R) associated with autosomal dominant osteopetrosis type II in native osteoclasts and hClcn7 gene-expressing cells. 53 62
19543743 2009
22
Carbonic anhydrase II deficiency a novel mutation. 53 62
19556665 2009
23
NF-kappaB functions in osteoclasts. 53 62
18992710 2009
24
CLCN7 polymorphisms and bone mineral density in healthy premenopausal white women and in white men. 53 62
18755304 2008
25
Rare gross deletion in T-cell immune regulator-1 gene in Iranian family with infantile malignant osteopetrosis. 53 62
18946580 2008
26
Human osteoclast-poor osteopetrosis with hypogammaglobulinemia due to TNFRSF11A (RANK) mutations. 53 62
18606301 2008
27
Osteoclast-poor human osteopetrosis due to mutations in the gene encoding RANKL. 53 62
17632511 2007
28
The retinoblastoma protein is an essential mediator of osteogenesis that links the p204 protein to the Cbfa1 transcription factor thereby increasing its activity. 53 62
17439944 2007
29
Autosomal dominant osteopetrosis: clinical severity and natural history of 94 subjects with a chloride channel 7 gene mutation. 53 62
17164308 2007
30
Novel pycnodysostosis mouse model uncovers cathepsin K function as a potential regulator of osteoclast apoptosis and senescence. 53 62
17210673 2007
31
Interleukin-7 partially rescues B-lymphopoiesis in osteopetrotic oc/oc mice through the engagement of B220+ CD11b+ progenitors. 53 62
16797412 2006
32
Carbonic anhydrase II in the developing and adult human brain. 53 62
16825953 2006
33
Establishment and characterization of new osteoclast progenitor cell lines derived from osteopetrotic and wild type mice. 53 62
16503212 2006
34
Polymorphisms in the CLCN7 gene modulate bone density in postmenopausal women and in patients with autosomal dominant osteopetrosis type II. 53 62
16368748 2006
35
Clinical and molecular findings in a family with the carbonic anhydrase II deficiency syndrome. 53 62
16382316 2006
36
Limited rescue of osteoclast-poor osteopetrosis after successful engraftment by cord blood from an unrelated donor. 53 62
16294279 2005
37
Polymorphisms of the CLCN7 gene are associated with BMD in women. 53 62
16234969 2005
38
Marble brain disease in two Saudi Arabian siblings. 53 62
16156988 2005
39
[Osteopetrosis with carbonic anhydrase II deficiency: report of 24 cases]. 53 62
16220698 2005
40
[Osteoprotegerin--a neutralizing receptor, protector of bones and a potential antiresorptive agent]. 53 62
16296579 2005
41
Intrafamilial phenotypic variability of osteopetrosis due to chloride channel 7 (CLCN7) mutations. 53 62
15633192 2005
42
Loss of the chloride channel ClC-7 leads to lysosomal storage disease and neurodegeneration. 53 62
15706348 2005
43
Carbonic anhydrase II deficiency: a rare autosomal recessive disorder of osteopetrosis, renal tubular acidosis, and cerebral calcification. 53 62
15701991 2005
44
Immunohistochemical evaluation of microphthalmia-associated transcription factor expression in giant cell lesions. 53 62
15205688 2004
45
Carbonic anhydrase II deficiency syndrome (osteopetrosis with renal tubular acidosis and brain calcification): novel mutations in CA2 identified by direct sequencing expand the opportunity for genotype-phenotype correlation. 53 62
15300855 2004
46
Severe malignant osteopetrosis caused by a GL gene mutation. 53 62
15177004 2004
47
Characterization of osteoclasts from patients harboring a G215R mutation in ClC-7 causing autosomal dominant osteopetrosis type II. 53 62
15111300 2004
48
Mitf and Tfe3: members of a b-HLH-ZIP transcription factor family essential for osteoclast development and function. 53 62
15050900 2004
49
Src kinase activity is essential for osteoclast function. 53 62
14739300 2004
50
Role for osteoprotegerin in rheumatoid inflammation. 53 62
14769514 2004

Variations for Osteopetrosis

ClinVar genetic disease variations for Osteopetrosis:

5 (show top 50) (show all 214)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 CLCN7 NM_001287.6(CLCN7):c.2274C>G (p.Phe758Leu) SNV Pathogenic
1684675 GRCh37: 16:1497064-1497064
GRCh38: 16:1447063-1447063
2 CLCN7 NM_001287.6(CLCN7):c.2066del (p.Lys689fs) DEL Pathogenic
1685637 GRCh37: 16:1497663-1497663
GRCh38: 16:1447662-1447662
3 CLCN7 NM_001287.6(CLCN7):c.1562G>C (p.Gly521Ala) SNV Pathogenic
1685638 GRCh37: 16:1500553-1500553
GRCh38: 16:1450552-1450552
4 CLCN7 NM_001287.6(CLCN7):c.952T>C (p.Phe318Leu) SNV Pathogenic
1012215 rs2038825509 GRCh37: 16:1505761-1505761
GRCh38: 16:1455760-1455760
5 TCIRG1 NM_006019.4(TCIRG1):c.504-6C>A SNV Pathogenic
1217234 GRCh37: 11:67810832-67810832
GRCh38: 11:68043365-68043365
6 CLCN7 NM_001287.6(CLCN7):c.2385_2386del (p.Gly796fs) MICROSAT Pathogenic
1371048 GRCh37: 16:1496664-1496665
GRCh38: 16:1446663-1446664
7 CLCN7 NM_001287.6(CLCN7):c.2299C>T (p.Arg767Trp) SNV Pathogenic
6863 rs121434435 GRCh37: 16:1497039-1497039
GRCh38: 16:1447038-1447038
8 CLCN7 NM_001287.6(CLCN7):c.857G>A (p.Arg286Gln) SNV Pathogenic
438670 rs760956030 GRCh37: 16:1506173-1506173
GRCh38: 16:1456172-1456172
9 CLCN7 NM_001287.6(CLCN7):c.856C>T (p.Arg286Trp) SNV Pathogenic
1068483 GRCh37: 16:1506174-1506174
GRCh38: 16:1456173-1456173
10 TCIRG1 NM_006019.4(TCIRG1):c.1674-1G>A SNV Pathogenic
189246 rs139617644 GRCh37: 11:67816547-67816547
GRCh38: 11:68049080-68049080
11 TCIRG1 NM_006019.4(TCIRG1):c.1213G>A (p.Gly405Arg) SNV Pathogenic
5463 rs137853150 GRCh37: 11:67814947-67814947
GRCh38: 11:68047480-68047480
12 TCIRG1 NM_006019.4(TCIRG1):c.2008C>T (p.Arg670Ter) SNV Pathogenic
551284 rs371263807 GRCh37: 11:67817250-67817250
GRCh38: 11:68049783-68049783
13 CLCN7 NM_001287.6(CLCN7):c.643G>A (p.Gly215Arg) SNV Pathogenic
65635 rs397515539 GRCh37: 16:1509140-1509140
GRCh38: 16:1459139-1459139
14 TCIRG1 NM_006019.4(TCIRG1):c.1549G>A (p.Asp517Asn) SNV Likely Pathogenic
975009 rs369264588 GRCh37: 11:67815434-67815434
GRCh38: 11:68047967-68047967
15 CLCN7 NM_001287.6(CLCN7):c.296A>G (p.Tyr99Cys) SNV Likely Pathogenic
56890 rs387907576 GRCh37: 16:1511461-1511461
GRCh38: 16:1461460-1461460
16 CLCN7 NM_001287.6(CLCN7):c.994A>G (p.Met332Val) SNV Likely Pathogenic
1526273 GRCh37: 16:1505239-1505239
GRCh38: 16:1455238-1455238
17 CLCN7 NM_001287.6(CLCN7):c.1077C>A (p.Asn359Lys) SNV Likely Pathogenic
1334479 GRCh37: 16:1505156-1505156
GRCh38: 16:1455155-1455155
18 TCIRG1 NM_006019.4(TCIRG1):c.1024G>T (p.Glu342Ter) SNV Likely Pathogenic
555504 rs1159666762 GRCh37: 11:67812428-67812428
GRCh38: 11:68044961-68044961
19 CLCN7 NM_001287.6(CLCN7):c.1841T>G (p.Leu614Arg) SNV Likely Pathogenic
867226 rs1064794323 GRCh37: 16:1498724-1498724
GRCh38: 16:1448723-1448723
20 CLCN7 NM_001287.6(CLCN7):c.739-18G>A SNV Uncertain Significance
1029299 rs371893553 GRCh37: 16:1507356-1507356
GRCh38: 16:1457355-1457355
21 OSTM1 NM_014028.4(OSTM1):c.*2370dup DUP Uncertain Significance
354939 rs58798743 GRCh37: 6:108363618-108363619
GRCh38: 6:108042414-108042415
22 CLCN7 NM_001287.6(CLCN7):c.2073+4C>T SNV Uncertain Significance
626086 rs768190489 GRCh37: 16:1497652-1497652
GRCh38: 16:1447651-1447651
23 CLCN7 NM_001287.6(CLCN7):c.1207C>T (p.Arg403Ter) SNV Uncertain Significance
631745 rs200789982 GRCh37: 16:1503842-1503842
GRCh38: 16:1453841-1453841
24 CLCN7 NM_001287.6(CLCN7):c.*359A>G SNV Uncertain Significance
884259 rs762306226 GRCh37: 16:1496273-1496273
GRCh38: 16:1446272-1446272
25 CLCN7 NM_001287.6(CLCN7):c.*614G>A SNV Uncertain Significance
317929 rs886051694 GRCh37: 16:1496018-1496018
GRCh38: 16:1446017-1446017
26 CLCN7 NM_001287.6(CLCN7):c.2150G>A (p.Arg717His) SNV Uncertain Significance
317945 rs886051699 GRCh37: 16:1497493-1497493
GRCh38: 16:1447492-1447492
27 CLCN7 NM_001287.6(CLCN7):c.*510G>C SNV Uncertain Significance
888485 rs527600278 GRCh37: 16:1496122-1496122
GRCh38: 16:1446121-1446121
28 CLCN7 NM_001287.6(CLCN7):c.2014-5T>C SNV Uncertain Significance
888540 rs1032878925 GRCh37: 16:1497720-1497720
GRCh38: 16:1447719-1447719
29 CLCN7 NM_001287.6(CLCN7):c.*24C>T SNV Uncertain Significance
886291 rs1361452118 GRCh37: 16:1496608-1496608
GRCh38: 16:1446607-1446607
30 CLCN7 NM_001287.6(CLCN7):c.*9C>T SNV Uncertain Significance
886292 rs773825294 GRCh37: 16:1496623-1496623
GRCh38: 16:1446622-1446622
31 CLCN7 NM_001287.6(CLCN7):c.1524G>A (p.Thr508=) SNV Uncertain Significance
886348 rs150009847 GRCh37: 16:1500591-1500591
GRCh38: 16:1450590-1450590
32 CLCN7 NM_001287.6(CLCN7):c.1332C>T (p.Gly444=) SNV Uncertain Significance
886350 rs749075927 GRCh37: 16:1502777-1502777
GRCh38: 16:1452776-1452776
33 CLCN7 NM_001287.6(CLCN7):c.521T>C (p.Phe174Ser) SNV Uncertain Significance
886406 rs752298744 GRCh37: 16:1510492-1510492
GRCh38: 16:1460491-1460491
34 CLCN7 NM_001287.6(CLCN7):c.*1623G>T SNV Uncertain Significance
887168 rs1451036503 GRCh37: 16:1495009-1495009
GRCh38: 16:1445008-1445008
35 CLCN7 NM_001287.6(CLCN7):c.*1607G>T SNV Uncertain Significance
887169 rs941409246 GRCh37: 16:1495025-1495025
GRCh38: 16:1445024-1445024
36 CLCN7 NM_001287.6(CLCN7):c.*1573G>A SNV Uncertain Significance
887170 rs890063151 GRCh37: 16:1495059-1495059
GRCh38: 16:1445058-1445058
37 CLCN7 NM_001287.6(CLCN7):c.*671T>C SNV Uncertain Significance
887232 rs1427445361 GRCh37: 16:1495961-1495961
GRCh38: 16:1445960-1445960
38 CLCN7 NM_001287.6(CLCN7):c.*632C>G SNV Uncertain Significance
887233 rs751460368 GRCh37: 16:1496000-1496000
GRCh38: 16:1445999-1445999
39 CLCN7 NM_001287.6(CLCN7):c.2402C>T (p.Ser801Leu) SNV Uncertain Significance
887290 rs184833329 GRCh37: 16:1496648-1496648
GRCh38: 16:1446647-1446647
40 CLCN7 NM_001287.6(CLCN7):c.2124G>A (p.Leu708=) SNV Uncertain Significance
887292 rs2038669299 GRCh37: 16:1497519-1497519
GRCh38: 16:1447518-1447518
41 CLCN7 NM_001287.6(CLCN7):c.1138G>A (p.Ala380Thr) SNV Uncertain Significance
887343 rs553977226 GRCh37: 16:1504427-1504427
GRCh38: 16:1454426-1454426
42 CLCN7 NM_001287.6(CLCN7):c.286-7C>A SNV Uncertain Significance
887412 rs1191046309 GRCh37: 16:1511478-1511478
GRCh38: 16:1461477-1461477
43 CLCN7 NM_001287.6(CLCN7):c.285+8T>C SNV Uncertain Significance
887413 rs2038938204 GRCh37: 16:1511596-1511596
GRCh38: 16:1461595-1461595
44 CLCN7 NM_001287.6(CLCN7):c.838C>T (p.Arg280Cys) SNV Uncertain Significance
887536 rs1395527274 GRCh37: 16:1506192-1506192
GRCh38: 16:1456191-1456191
45 CLCN7 NM_001287.6(CLCN7):c.130G>A (p.Ala44Thr) SNV Uncertain Significance
887594 rs528173586 GRCh37: 16:1524846-1524846
GRCh38: 16:1474845-1474845
46 CLCN7 NM_001287.6(CLCN7):c.*1368G>A SNV Uncertain Significance
888425 rs376131222 GRCh37: 16:1495264-1495264
GRCh38: 16:1445263-1445263
47 CLCN7 NM_001287.6(CLCN7):c.*1330C>T SNV Uncertain Significance
888426 rs2038617678 GRCh37: 16:1495302-1495302
GRCh38: 16:1445301-1445301
48 TNFRSF11A NM_003839.4(TNFRSF11A):c.*626_*627insCC INSERT Uncertain Significance
327749 rs886054093 GRCh37: 18:60052892-60052893
GRCh38: 18:62385659-62385660
49 TNFRSF11A NM_003839.4(TNFRSF11A):c.*321del DEL Uncertain Significance
327744 rs886054088 GRCh37: 18:60052588-60052588
GRCh38: 18:62385355-62385355
50 TNFRSF11A NM_003839.4(TNFRSF11A):c.*320dup DUP Uncertain Significance
327742 rs552069161 GRCh37: 18:60052576-60052577
GRCh38: 18:62385343-62385344

Expression for Osteopetrosis

Search GEO for disease gene expression data for Osteopetrosis.

Pathways for Osteopetrosis

Pathways related to Osteopetrosis according to GeneCards Suite gene sharing:

(show all 18)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.82 TRAF6 TNFSF11 TNFRSF11A TCIRG1 SRC RAB7A
2
Show member pathways
13.26 TRAF6 TNFSF11 TNFRSF11A SRC IKBKG CSF1R
3
Show member pathways
13.09 TRAF6 TNFSF11 TNFRSF11A SRC IKBKG CSK
4
Show member pathways
12.48 IKBKG SRC TNFRSF11A TNFSF11 TRAF6
5
Show member pathways
12.42 TRAF6 TNFSF11 TNFRSF11A SRC MITF IKBKG
6 12.39 TRAF6 TNFSF11 TNFRSF11A IKBKG
7
Show member pathways
11.94 IKBKG SRC TNFRSF11A TNFSF11 TRAF6
8 11.55 TRAF6 IKBKG CSK
9
Show member pathways
11.49 TRAF6 TNFSF11 TNFRSF11A IKBKG
10 11.48 SRC CSF1R CSF1
11 11.4 TRAF6 TNFSF11 TNFRSF11A PLEKHM1 LRP5 CTSK
12 11.37 TNFSF11 CSF1R CSF1
13 11.32 TNFSF11 TNFRSF11A CA2
14
Show member pathways
11.31 SRC CSF1R CSF1
15 11.27 IKBKG SRC TRAF6
16 11.13 TNFSF11 TNFRSF11A LRP5
17 11.12 SRC CSK CSF1R CSF1
18 10.32 TRAF6 TNFSF11 TNFRSF11A TCIRG1 SNX10 RAB7A

GO Terms for Osteopetrosis

Cellular components related to Osteopetrosis according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 endosome membrane GO:0010008 9.76 TRAF6 TCIRG1 SNX10 RAB7A PLEKHM1
2 lysosome GO:0005764 9.44 TCIRG1 SRC RAB7A PLEKHM1 OSTM1 CTSK
3 CSF1-CSF1R complex GO:1990682 9.26 CSF1R CSF1

Biological processes related to Osteopetrosis according to GeneCards Suite gene sharing:

(show all 32)
# Name GO ID Score Top Affiliating Genes
1 positive regulation of NF-kappaB transcription factor activity GO:0051092 10.23 TRAF6 TNFSF11 TNFRSF11A IKBKG
2 peptidyl-tyrosine phosphorylation GO:0018108 10.21 CSF1R CSK LRRK1 SRC
3 positive regulation of DNA-binding transcription factor activity GO:0051091 10.19 TRAF6 TNFSF11 TNFRSF11A LRP5
4 I-kappaB kinase/NF-kappaB signaling GO:0007249 10.13 TRAF6 TNFSF11 IKBKG
5 response to mechanical stimulus GO:0009612 10.11 TNFRSF11A SRC CSF1
6 tumor necrosis factor-mediated signaling pathway GO:0033209 10.1 TRAF6 TNFSF11 TNFRSF11A
7 ossification GO:0001503 10.1 TRAF6 TNFSF11 TNFRSF11A TCIRG1 CSF1
8 response to interleukin-1 GO:0070555 10.04 SRC TNFRSF11A TRAF6
9 cellular response to cytokine stimulus GO:0071345 10.03 TRAF6 TCIRG1 CSF1R
10 positive regulation of osteoclast differentiation GO:0045672 10.01 TRAF6 TNFSF11 CSF1
11 odontogenesis GO:0042476 9.97 CSF1 SRC TCIRG1
12 regulation of bone resorption GO:0045124 9.95 SRC CSF1R
13 cellular response to zinc ion starvation GO:0034224 9.95 TNFRSF11A CTSK
14 branching involved in mammary gland duct morphogenesis GO:0060444 9.95 SRC LRP5 CSF1
15 transepithelial chloride transport GO:0030321 9.94 OSTM1 CLCN7
16 microglial cell proliferation GO:0061518 9.93 CSF1 CSF1R
17 osteoclast development GO:0036035 9.93 TNFSF11 SRC LRRK1
18 phagosome acidification GO:0090383 9.92 TCIRG1 RAB7A
19 positive regulation of macrophage proliferation GO:0120041 9.91 CSF1R CSF1
20 establishment of vesicle localization GO:0051650 9.91 IKBKG RAB7A TCIRG1
21 osteoclast differentiation GO:0030316 9.91 CSF1 CSF1R MITF OSTM1 SNX10 TCIRG1
22 TNFSF11-mediated signaling pathway GO:0071847 9.89 TNFSF11 TNFRSF11A
23 positive regulation of intracellular signal transduction GO:1902533 9.89 TNFSF11 SRC LRRK1
24 positive regulation of bone resorption GO:0045780 9.86 PLEKHM1 SRC TNFRSF11A TNFSF11
25 macrophage colony-stimulating factor signaling pathway GO:0038145 9.85 CSF1R CSF1
26 tooth eruption GO:0044691 9.85 TNFSF11 TCIRG1 SNX10
27 positive regulation of fever generation by positive regulation of prostaglandin secretion GO:0071812 9.83 TNFRSF11A TNFSF11
28 positive regulation of ERK1 and ERK2 cascade via TNFSF11-mediated signaling GO:0071848 9.81 TNFRSF11A TNFSF11
29 osteoclast proliferation GO:0002158 9.8 TNFSF11 TCIRG1 CSF1
30 mammary gland duct morphogenesis GO:0060603 9.77 LRP5 CSF1R
31 bone remodeling GO:0046849 9.63 TRAF6 SNX10 MITF LRP5
32 bone resorption GO:0045453 9.58 ACP5 CTSK LRRK1 RAB7A SNX10 SRC

Molecular functions related to Osteopetrosis according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 tumor necrosis factor receptor superfamily binding GO:0032813 8.92 TRAF6 TNFSF11

Sources for Osteopetrosis

2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 08-Dec-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
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