OPTB2
MCID: OST129
MIFTS: 47

Osteopetrosis, Autosomal Recessive 2 (OPTB2)

Categories: Blood diseases, Bone diseases, Eye diseases, Fetal diseases, Genetic diseases, Immune diseases, Nephrological diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Osteopetrosis, Autosomal Recessive 2

MalaCards integrated aliases for Osteopetrosis, Autosomal Recessive 2:

Name: Osteopetrosis, Autosomal Recessive 2 57 75 13
Optb2 57 12 53 75
Osteopetrosis Autosomal Recessive 2 53 29 6
Osteopetrosis, Mild Autosomal Recessive Form 57 73
Autosomal Recessive Osteopetrosis 2 12 15
Osteoclast-Poor Osteopetrosis 12 75
Mild Autosomal Recessive Form Osteopetrosis 12
Osteopetrosis, Autosomal Recessive, Type 2 40
Autosomal Recessive Osteopetrosis Type 2 53
Osteopetrosis, Osteoclast-Poor 57
Osteopetrosis Osteoclast-Poor 53

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive
also a mild dominant form and a lethal recessive form


HPO:

32
osteopetrosis, autosomal recessive 2:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Osteopetrosis, Autosomal Recessive 2

NIH Rare Diseases : 53 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 life-threatening 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 life-threatening pancytopenia. In rare cases, there may be neurological impairment or involvement of other body systems. Osteopetrosis may be caused by mutations in at least 10 genes. Inheritance can be autosomal recessive, autosomal dominant, or X-linked recessive with the most severe forms being autosomal recessive. Management depends on the specific symptoms and severity and may include vitamin D supplements, various medications, and/or surgery. Adult osteopetrosis requires no treatment by itself, but complications may require intervention.

MalaCards based summary : Osteopetrosis, Autosomal Recessive 2, also known as optb2, is related to osteopetrosis, autosomal recessive 7 and osteopetrosis. An important gene associated with Osteopetrosis, Autosomal Recessive 2 is TNFSF11 (TNF Superfamily Member 11), and among its related pathways/superpathways are Innate Immune System and Development Angiotensin activation of ERK. Affiliated tissues include bone, bone marrow and eye, and related phenotypes are genu valgum and mandibular prognathia

Disease Ontology : 12 An osteopetrosis characterized by autosomal recessive inheritance that has material basis in homozygous mutation in the TNFSF11 gene on chromosome 13q14.

UniProtKB/Swiss-Prot : 75 Osteopetrosis, autosomal recessive 2: A rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. Osteopetrosis occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood. Recessive osteopetrosis commonly manifests in early infancy with macrocephaly, feeding difficulties, evolving blindness and deafness, bone marrow failure, severe anemia, and hepatosplenomegaly. Deafness and blindness are generally thought to represent effects of pressure on nerves. OPTB2 is characterized by paucity of osteoclasts, suggesting a molecular defect in osteoclast development.

Description from OMIM: 259710

Related Diseases for Osteopetrosis, Autosomal Recessive 2

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, Autosomal Recessive 2 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 22)
# Related Disease Score Top Affiliating Genes
1 osteopetrosis, autosomal recessive 7 32.8 TNFSF11 TNFRSF11A
2 osteopetrosis 30.6 TNFSF11 TNFRSF11A CLCN7
3 bone resorption disease 30.2 TNFSF11 TNFRSF11A CYP27A1
4 autosomal recessive malignant osteopetrosis 10.2 TNFSF11 CLCN7
5 polyarticular onset juvenile idiopathic arthritis 10.2 TNFSF11 TNFRSF11A
6 breast leiomyosarcoma 10.2 TNFSF11 TNFRSF11A
7 hemophilic arthropathy 10.2 TNFSF11 TNFRSF11A
8 paget disease of bone 5, juvenile-onset 10.2 TNFSF11 TNFRSF11A
9 familial expansile osteolysis 10.2 TNFRSF11A TNFSF11
10 multicentric carpotarsal osteolysis syndrome 10.1 TNFRSF11A TNFSF11
11 aneurysmal bone cysts 10.1 TNFRSF11A TNFSF11
12 periapical periodontitis 10.1 TNFRSF11A TNFSF11
13 tooth resorption 10.1 TNFRSF11A TNFSF11
14 ischemic bone disease 10.1 TNFRSF11A TNFSF11
15 root resorption 10.1 TNFRSF11A TNFSF11
16 osteopetrosis, autosomal dominant 2 10.1 CLCN7 TNFSF11
17 endosteal hyperostosis, autosomal dominant 10.1 CLCN7 TNFSF11
18 periodontal disease 10.0 TNFSF11 TNFRSF11A DEFB1
19 bone disease 10.0 CLCN7 TNFRSF11A TNFSF11
20 giant cell tumor 10.0 TNFRSF11A TNFSF11
21 bone cancer 9.9 TNFRSF11A TNFSF11
22 bone remodeling disease 9.9 TNFSF11 TNFRSF11A CYP27A1 CLCN7

Graphical network of the top 20 diseases related to Osteopetrosis, Autosomal Recessive 2:



Diseases related to Osteopetrosis, Autosomal Recessive 2

Symptoms & Phenotypes for Osteopetrosis, Autosomal Recessive 2

Symptoms via clinical synopsis from OMIM:

57
Skel:
genu valgum
osteosclerosis
multiple fractures
osteomyelitis, especially of the mandible

Heme:
anemia
pancytopenia
thrombocytopenia
extramedullary hematopoiesis

G I:
hepatosplenomegaly

Mandible:
mandibular prognathism

Teeth:
dental anomalies
dental caries
deciduous teeth retention
tooth crown malformation

Eyes:
optic atrophy
early blindness

Skull:
cranial hyperostosis

Limbs:
diaphyseal sclerosis

Neuro:
normal intelligence
facial paralysis due to cranial nerve vii compression

Nose:
chronic rhinitis due to narrow nasal airway


Clinical features from OMIM:

259710

Human phenotypes related to Osteopetrosis, Autosomal Recessive 2:

32 (show all 18)
# Description HPO Frequency HPO Source Accession
1 genu valgum 32 HP:0002857
2 mandibular prognathia 32 HP:0000303
3 carious teeth 32 HP:0000670
4 optic atrophy 32 HP:0000648
5 blindness 32 HP:0000618
6 anemia 32 HP:0001903
7 pancytopenia 32 HP:0001876
8 thrombocytopenia 32 HP:0001873
9 recurrent fractures 32 HP:0002757
10 mandibular osteomyelitis 32 HP:0007626
11 cranial hyperostosis 32 HP:0004437
12 osteopetrosis 32 HP:0011002
13 persistence of primary teeth 32 HP:0006335
14 hepatosplenomegaly 32 HP:0001433
15 facial paralysis 32 HP:0007209
16 extramedullary hematopoiesis 32 HP:0001978
17 diaphyseal sclerosis 32 HP:0003034
18 chronic rhinitis due to narrow nasal airway 32 HP:0004499

GenomeRNAi Phenotypes related to Osteopetrosis, Autosomal Recessive 2 according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased Salmonella enterica Typhimurium binding GR00133-A-3 9.16 CYP27A1 ITGAV
2 Decreased Salmonella enterica Typhimurium effector injection GR00133-A-4 8.96 CYP27A1 ITGAV
3 Decreased Salmonella enterica Typhimurium membrane closure GR00133-A-6 8.62 CYP27A1 ITGAV

MGI Mouse Phenotypes related to Osteopetrosis, Autosomal Recessive 2:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 craniofacial MP:0005382 9.35 CLCN7 ITGAV TNFRSF11A TNFSF11 TRAF6
2 hematopoietic system MP:0005397 9.17 CLCN7 CYP27A1 ITGAV RPS19BP1 TNFRSF11A TNFSF11

Drugs & Therapeutics for Osteopetrosis, Autosomal Recessive 2

Search Clinical Trials , NIH Clinical Center for Osteopetrosis, Autosomal Recessive 2

Genetic Tests for Osteopetrosis, Autosomal Recessive 2

Genetic tests related to Osteopetrosis, Autosomal Recessive 2:

# Genetic test Affiliating Genes
1 Osteopetrosis Autosomal Recessive 2 29 TNFSF11

Anatomical Context for Osteopetrosis, Autosomal Recessive 2

MalaCards organs/tissues related to Osteopetrosis, Autosomal Recessive 2:

41
Bone, Bone Marrow, Eye

Publications for Osteopetrosis, Autosomal Recessive 2

Articles related to Osteopetrosis, Autosomal Recessive 2:

# Title Authors Year
1
A comparison of osteoclast-rich and osteoclast-poor osteopetrosis in adult mice sheds light on the role of the osteoclast in coupling bone resorption and bone formation. ( 24838599 )
2014
2
Human osteoclast-poor osteopetrosis with hypogammaglobulinemia due to TNFRSF11A (RANK) mutations. ( 18606301 )
2008
3
Limited rescue of osteoclast-poor osteopetrosis after successful engraftment by cord blood from an unrelated donor. ( 16294279 )
2005

Variations for Osteopetrosis, Autosomal Recessive 2

UniProtKB/Swiss-Prot genetic disease variations for Osteopetrosis, Autosomal Recessive 2:

75
# Symbol AA change Variation ID SNP ID
1 TNFSF11 p.Met199Lys VAR_037424 rs121909072

ClinVar genetic disease variations for Osteopetrosis, Autosomal Recessive 2:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 TNFSF11 TNFSF11, 5-BP DEL, IVS7+4 deletion Pathogenic
2 TNFSF11 NM_033012.3(TNFSF11): c.377T> A (p.Met126Lys) single nucleotide variant Pathogenic rs121909072 GRCh37 Chromosome 13, 43180696: 43180696
3 TNFSF11 NM_033012.3(TNFSF11): c.377T> A (p.Met126Lys) single nucleotide variant Pathogenic rs121909072 GRCh38 Chromosome 13, 42606560: 42606560
4 TNFSF11 NM_033012.3(TNFSF11): c.609_610delCG (p.Val204Trpfs) deletion Pathogenic rs863223288 GRCh37 Chromosome 13, 43180928: 43180929
5 TNFSF11 NM_033012.3(TNFSF11): c.609_610delCG (p.Val204Trpfs) deletion Pathogenic rs863223288 GRCh38 Chromosome 13, 42606792: 42606793

Expression for Osteopetrosis, Autosomal Recessive 2

Search GEO for disease gene expression data for Osteopetrosis, Autosomal Recessive 2.

Pathways for Osteopetrosis, Autosomal Recessive 2

Pathways related to Osteopetrosis, Autosomal Recessive 2 according to GeneCards Suite gene sharing:

(show all 14)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.66 DEFB1 DEFB105A DEFB105B ITGAV TNFRSF11A TNFSF11
2
Show member pathways
12.56 ITGAV TNFRSF11A TNFSF11 TRAF6
3 12.23 TNFRSF11A TNFSF11 TRAF6
4
Show member pathways
12.15 ITGAV TNFRSF11A TNFSF11 TRAF6
5
Show member pathways
12.05 TNFRSF11A TNFSF11 TRAF6
6
Show member pathways
11.99 DEFB1 DEFB105A DEFB105B
7
Show member pathways
11.86 TNFRSF11A TNFSF11 TRAF6
8 11.85 TNFRSF11A TNFSF11 TRAF6
9 11.54 TNFRSF11A TNFSF11 TRAF6
10 11.16 TNFRSF11A TNFSF11
11 11.11 TNFRSF11A TNFSF11 TRAF6
12
Show member pathways
10.66 TNFRSF11A TNFSF11 TRAF6
13 10.57 TNFRSF11A TNFSF11
14 10.3 ITGAV TNFSF11

GO Terms for Osteopetrosis, Autosomal Recessive 2

Biological processes related to Osteopetrosis, Autosomal Recessive 2 according to GeneCards Suite gene sharing:

(show all 17)
# Name GO ID Score Top Affiliating Genes
1 defense response to bacterium GO:0042742 9.72 DEFB1 DEFB105A DEFB105B
2 positive regulation of NF-kappaB transcription factor activity GO:0051092 9.63 TNFRSF11A TNFSF11 TRAF6
3 defense response GO:0006952 9.61 DEFB1 DEFB105A DEFB105B
4 monocyte chemotaxis GO:0002548 9.57 TNFRSF11A TNFSF11
5 positive regulation of JUN kinase activity GO:0043507 9.56 TNFRSF11A TRAF6
6 response to interleukin-1 GO:0070555 9.54 TNFRSF11A TRAF6
7 positive regulation of DNA-binding transcription factor activity GO:0051091 9.54 TNFRSF11A TNFSF11 TRAF6
8 ERK1 and ERK2 cascade GO:0070371 9.52 ITGAV TNFSF11
9 bone resorption GO:0045453 9.51 TNFSF11 TRAF6
10 ossification GO:0001503 9.5 TNFRSF11A TNFSF11 TRAF6
11 positive regulation of osteoclast differentiation GO:0045672 9.49 TNFSF11 TRAF6
12 positive regulation of bone resorption GO:0045780 9.48 TNFRSF11A TNFSF11
13 mammary gland alveolus development GO:0060749 9.4 TNFRSF11A TNFSF11
14 TNFSF11-mediated signaling pathway GO:0071847 9.26 TNFRSF11A TNFSF11
15 positive regulation of ERK1 and ERK2 cascade via TNFSF11-mediated signaling GO:0071848 9.16 TNFRSF11A TNFSF11
16 positive regulation of fever generation by positive regulation of prostaglandin secretion GO:0071812 8.96 TNFRSF11A TNFSF11
17 osteoclast differentiation GO:0030316 8.8 TNFRSF11A TNFSF11 TRAF6

Molecular functions related to Osteopetrosis, Autosomal Recessive 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 tumor necrosis factor receptor binding GO:0005164 8.62 TNFSF11 TRAF6

Sources for Osteopetrosis, Autosomal Recessive 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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