OPTB7
MCID: OST136
MIFTS: 45

Osteopetrosis, Autosomal Recessive 7 (OPTB7)

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

Aliases & Classifications for Osteopetrosis, Autosomal Recessive 7

MalaCards integrated aliases for Osteopetrosis, Autosomal Recessive 7:

Name: Osteopetrosis, Autosomal Recessive 7 58 76 13 74
Optb7 58 12 54 76
Autosomal Recessive Osteoclast-Poor Osteopetrosis with Hypogammaglobulinemia 12 54 60
Autosomal Recessive Osteopetrosis Type 7 12 54 60
Osteopetrosis Autosomal Recessive 7 54 30 6
Osteoclast-Poor Osteopetrosis with Hypogammaglobulinemia 12 76
Osteopetrosis-Hypogammaglobulinemia Syndrome 12 60
Autosomal Recessive Osteopetrosis 7 12 15
Osteopetrosis, Osteoclast-Poor, with Hypogammaglobulinemia 58
Osteopetrosis Osteoclast-Poor with Hypogammaglobulinemia 54
Osteopetrosis, Autosomal Recessive, Type 7 41

Characteristics:

Orphanet epidemiological data:

60
osteopetrosis-hypogammaglobulinemia syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide);

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
death in first years of life (in some patients)
hematopoietic stem cell transplantation can result in marked amelioration


HPO:

33
osteopetrosis, autosomal recessive 7:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0110946
OMIM 58 612301
MeSH 45 D010022
ICD10 34 Q78.2
ICD10 via Orphanet 35 Q78.2
UMLS via Orphanet 75 C2676766
Orphanet 60 ORPHA178389
MedGen 43 C2676766
UMLS 74 C2676766

Summaries for Osteopetrosis, Autosomal Recessive 7

NIH Rare Diseases : 54 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 7, also known as optb7, is related to osteopetrosis, autosomal recessive 2 and osteopetrosis. An important gene associated with Osteopetrosis, Autosomal Recessive 7 is TNFRSF11A (TNF Receptor Superfamily Member 11a), and among its related pathways/superpathways are Akt Signaling and Cytokine Signaling in Immune system. Affiliated tissues include bone, bone marrow and eye, and related phenotypes are decreased antibody level in blood and hydrocephalus

Disease Ontology : 12 An osteopetrosis characterized by autosomal recessive inheritance that has material basis in homozygous or compound heterozygous mutation in the TNFRSF11A gene on chromosome 18q21.

UniProtKB/Swiss-Prot : 76 Osteopetrosis, autosomal recessive 7: 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. OPTB7 is characterized by paucity of osteoclasts, suggesting a molecular defect in osteoclast development. OPTB7 is associated with hypogammaglobulinemia.

Description from OMIM: 612301

Related Diseases for Osteopetrosis, Autosomal Recessive 7

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 7 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 31)
# Related Disease Score Top Affiliating Genes
1 osteopetrosis, autosomal recessive 2 30.4 TNFRSF11A TNFSF11
2 osteopetrosis 29.7 CSF1 TNFRSF11A TNFSF11
3 agammaglobulinemia 10.3
4 polyarticular onset juvenile idiopathic arthritis 10.0 TNFRSF11A TNFSF11
5 hemophilic arthropathy 10.0 TNFRSF11A TNFSF11
6 breast leiomyosarcoma 10.0 TNFRSF11A TNFSF11
7 paget disease of bone 5, juvenile-onset 10.0 TNFRSF11A TNFSF11
8 familial expansile osteolysis 10.0 TNFRSF11A TNFSF11
9 multicentric carpotarsal osteolysis syndrome 10.0 TNFRSF11A TNFSF11
10 aneurysmal bone cysts 10.0 TNFRSF11A TNFSF11
11 periapical periodontitis 10.0 TNFRSF11A TNFSF11
12 tooth resorption 10.0 TNFRSF11A TNFSF11
13 ischemic bone disease 9.9 TNFRSF11A TNFSF11
14 root resorption 9.9 TNFRSF11A TNFSF11
15 multicentric reticulohistiocytosis 9.9 CSF1 TNFSF11
16 mandibular cancer 9.9 CSF1 TNFSF11
17 bone resorption disease 9.9 TNFRSF11A TNFSF11
18 pigmented villonodular synovitis 9.8 CSF1 TNFSF11
19 bone remodeling disease 9.8 TNFRSF11A TNFSF11
20 joint disorders 9.8 CSF1 TNFSF11
21 cherubism 9.8 CSF1 TNFSF11
22 endosteal hyperostosis, autosomal dominant 9.8 CSF1 TNFSF11
23 bone cancer 9.7 TNFRSF11A TNFSF11
24 langerhans cell histiocytosis 9.7 CSF1 TNFSF11
25 periodontal disease 9.6 TNFRSF11A TNFSF11
26 paget's disease of bone 9.5 CSF1 TNFRSF11A TNFSF11
27 giant cell tumor 9.5 CSF1 TNFRSF11A TNFSF11
28 arthritis 9.5 CSF1 TNFRSF11A TNFSF11
29 bone disease 9.5 CSF1 TNFRSF11A TNFSF11
30 osteoporosis 9.5 CSF1 TNFRSF11A TNFSF11
31 rheumatoid arthritis 9.4 CSF1 TNFRSF11A TNFSF11

Graphical network of the top 20 diseases related to Osteopetrosis, Autosomal Recessive 7:



Diseases related to Osteopetrosis, Autosomal Recessive 7

Symptoms & Phenotypes for Osteopetrosis, Autosomal Recessive 7

Human phenotypes related to Osteopetrosis, Autosomal Recessive 7:

33 (show all 20)
# Description HPO Frequency HPO Source Accession
1 decreased antibody level in blood 33 very rare (1%) HP:0004313
2 hydrocephalus 33 HP:0000238
3 nystagmus 33 HP:0000639
4 global developmental delay 33 HP:0001263
5 optic atrophy 33 HP:0000648
6 anemia 33 HP:0001903
7 progressive visual loss 33 HP:0000529
8 thrombocytopenia 33 HP:0001873
9 motor delay 33 HP:0001270
10 recurrent pneumonia 33 HP:0006532
11 proptosis 33 HP:0000520
12 generalized hypotonia 33 HP:0001290
13 osteopetrosis 33 HP:0011002
14 optic nerve compression 33 HP:0007807
15 dilation of lateral ventricles 33 HP:0006956
16 hypocalcemic seizures 33 HP:0002199
17 abnormal trabecular bone morphology 33 HP:0100671
18 multiple rib fractures 33 HP:0006640
19 psychomotor retardation 33 HP:0025356
20 increased head circumference 33 HP:0040194

Symptoms via clinical synopsis from OMIM:

58
Neurologic Central Nervous System:
hydrocephalus
motor delay
hypotonia
psychomotor retardation
seizures due to hypocalcemia
more
Abdomen Spleen:
splenomegaly

Hematology:
anemia
thrombocytopenia
reduced cellularity of bone marrow
reduced hematopoiesis in bone marrow

Respiratory:
recurrent infections

Immunology:
hypogammaglobulinemia

Skeletal:
increased bone density
increase of bony and cartilaginous trabeculae
significant reduction of medullary space
lack of osteoclasts in bone marrow
lack of multinucleated cells in bone marrow
more
Skeletal Skull:
increased head circumference
severe narrowing of optic foramina

Respiratory Nasopharynx:
bone hypertrophy in nasal cavity, resulting in protracted suffocation (in 1 patient)

Skeletal Spine:
thickened bone of vertebrae

Skeletal Hands:
alternating bands of radiodensity and lucency at metaphyses
increased bone density of diaphyses

Head And Neck Eyes:
nystagmus
optic nerve atrophy
vision loss
delayed visual evoked responses
exophthalmos (in 1 patient)

Abdomen Liver:
hepatomegaly

Laboratory Abnormalities:
hypocalcemia

Respiratory Lung:
recurrent pneumonia

Growth Other:
growth failure

Head And Neck Head:
increased head circumference

Head And Neck Nose:
olfactory nerve atrophy

Chest Ribs Sternum Clavicles And Scapulae:
thickened bone of ribs
multiple rib fractures (in 1 patient)

Skeletal Limbs:
femur fracture (in 1 patient)

Neurologic Peripheral Nervous System:
olfactory nerve atrophy due to bone compression
slow stimuli transmission in bilateral peripheral auditory pathways
chronic denervation and reinnervation (bulbar and limb musculature)

Clinical features from OMIM:

612301

GenomeRNAi Phenotypes related to Osteopetrosis, Autosomal Recessive 7 according to GeneCards Suite gene sharing:

27
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-142 9.28 CSF1 TNFSF11
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-145 9.28 TNFSF11
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-175 9.28 TNFSF11
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-180 9.28 CSF1 TNFSF11
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-84 9.28 CSF1
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-91 9.28 CSF1 TNFSF11

MGI Mouse Phenotypes related to Osteopetrosis, Autosomal Recessive 7:

47
# Description MGI Source Accession Score Top Affiliating Genes
1 craniofacial MP:0005382 9.5 CSF1 TNFRSF11A TNFSF11
2 integument MP:0010771 9.43 CSF1 TNFRSF11A TNFSF11
3 limbs/digits/tail MP:0005371 9.33 CSF1 TNFRSF11A TNFSF11
4 no phenotypic analysis MP:0003012 9.13 CSF1 TNFRSF11A TNFSF11
5 respiratory system MP:0005388 8.8 CSF1 TNFRSF11A TNFSF11

Drugs & Therapeutics for Osteopetrosis, Autosomal Recessive 7

Search Clinical Trials , NIH Clinical Center for Osteopetrosis, Autosomal Recessive 7

Genetic Tests for Osteopetrosis, Autosomal Recessive 7

Genetic tests related to Osteopetrosis, Autosomal Recessive 7:

# Genetic test Affiliating Genes
1 Osteopetrosis Autosomal Recessive 7 30 TNFRSF11A

Anatomical Context for Osteopetrosis, Autosomal Recessive 7

MalaCards organs/tissues related to Osteopetrosis, Autosomal Recessive 7:

42
Bone, Bone Marrow, Eye

Publications for Osteopetrosis, Autosomal Recessive 7

Articles related to Osteopetrosis, Autosomal Recessive 7:

# Title Authors Year
1
Central control of fever and female body temperature by RANKL/RANK. ( 19940926 )
2009
2
Human osteoclast-poor osteopetrosis with hypogammaglobulinemia due to TNFRSF11A (RANK) mutations. ( 18606301 )
2008
3
In vitro differentiation of CD14 cells from osteopetrotic subjects: contrasting phenotypes with TCIRG1, CLCN7, and attachment defects. ( 15231021 )
2004

Variations for Osteopetrosis, Autosomal Recessive 7

UniProtKB/Swiss-Prot genetic disease variations for Osteopetrosis, Autosomal Recessive 7:

76
# Symbol AA change Variation ID SNP ID
1 TNFRSF11A p.Gly53Arg VAR_046788 rs121908659
2 TNFRSF11A p.Arg129Cys VAR_046789 rs121908657
3 TNFRSF11A p.Arg170Gly VAR_046791 rs121908655
4 TNFRSF11A p.Cys175Arg VAR_046792 rs121908656
5 TNFRSF11A p.Ala244Ser VAR_046793 rs121908658

ClinVar genetic disease variations for Osteopetrosis, Autosomal Recessive 7:

6 (show all 12)
# Gene Variation Type Significance SNP ID Assembly Location
1 TNFRSF11A NM_003839.3(TNFRSF11A): c.508A> G (p.Arg170Gly) single nucleotide variant Pathogenic rs121908655 GRCh37 Chromosome 18, 60025561: 60025561
2 TNFRSF11A NM_003839.3(TNFRSF11A): c.508A> G (p.Arg170Gly) single nucleotide variant Pathogenic rs121908655 GRCh38 Chromosome 18, 62358328: 62358328
3 TNFRSF11A NM_003839.3(TNFRSF11A): c.523T> C (p.Cys175Arg) single nucleotide variant Pathogenic rs121908656 GRCh37 Chromosome 18, 60027189: 60027189
4 TNFRSF11A NM_003839.3(TNFRSF11A): c.523T> C (p.Cys175Arg) single nucleotide variant Pathogenic rs121908656 GRCh38 Chromosome 18, 62359956: 62359956
5 TNFRSF11A NM_003839.3(TNFRSF11A): c.385C> T (p.Arg129Cys) single nucleotide variant Uncertain significance rs121908657 GRCh37 Chromosome 18, 60021725: 60021725
6 TNFRSF11A NM_003839.3(TNFRSF11A): c.385C> T (p.Arg129Cys) single nucleotide variant Uncertain significance rs121908657 GRCh38 Chromosome 18, 62354492: 62354492
7 TNFRSF11A NM_003839.3(TNFRSF11A): c.730G> T (p.Ala244Ser) single nucleotide variant Pathogenic rs121908658 GRCh37 Chromosome 18, 60029026: 60029026
8 TNFRSF11A NM_003839.3(TNFRSF11A): c.730G> T (p.Ala244Ser) single nucleotide variant Pathogenic rs121908658 GRCh38 Chromosome 18, 62361793: 62361793
9 TNFRSF11A NM_003839.3(TNFRSF11A): c.157G> C (p.Gly53Arg) single nucleotide variant Pathogenic rs121908659 GRCh37 Chromosome 18, 60015482: 60015482
10 TNFRSF11A NM_003839.3(TNFRSF11A): c.157G> C (p.Gly53Arg) single nucleotide variant Pathogenic rs121908659 GRCh38 Chromosome 18, 62348249: 62348249
11 TNFRSF11A NM_003839.3(TNFRSF11A): c.718A> G (p.Lys240Glu) single nucleotide variant Uncertain significance rs148185533 GRCh37 Chromosome 18, 60029014: 60029014
12 TNFRSF11A NM_003839.3(TNFRSF11A): c.718A> G (p.Lys240Glu) single nucleotide variant Uncertain significance rs148185533 GRCh38 Chromosome 18, 62361781: 62361781

Expression for Osteopetrosis, Autosomal Recessive 7

Search GEO for disease gene expression data for Osteopetrosis, Autosomal Recessive 7.

Pathways for Osteopetrosis, Autosomal Recessive 7

Pathways related to Osteopetrosis, Autosomal Recessive 7 according to GeneCards Suite gene sharing:

(show all 15)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.83 CSF1 TNFRSF11A TNFSF11
2
Show member pathways
12.74 CSF1 TNFRSF11A TNFSF11
3
Show member pathways
12.67 CSF1 TNFRSF11A TNFSF11
4
Show member pathways
12 TNFRSF11A TNFSF11
5
Show member pathways
11.93 TNFRSF11A TNFSF11
6
Show member pathways
11.78 TNFRSF11A TNFSF11
7 11.74 TNFRSF11A TNFSF11
8 11.4 TNFRSF11A TNFSF11
9 11.24 CSF1 TNFRSF11A TNFSF11
10
Show member pathways
11.23 TNFRSF11A TNFSF11
11 11 CSF1 TNFSF11
12 10.91 TNFRSF11A TNFSF11
13 10.76 CSF1 TNFRSF11A TNFSF11
14 10.73 CSF1 TNFSF11
15 10.36 TNFRSF11A TNFSF11

GO Terms for Osteopetrosis, Autosomal Recessive 7

Biological processes related to Osteopetrosis, Autosomal Recessive 7 according to GeneCards Suite gene sharing:

(show all 14)
# Name GO ID Score Top Affiliating Genes
1 cytokine-mediated signaling pathway GO:0019221 9.54 CSF1 TNFSF11
2 positive regulation of NF-kappaB transcription factor activity GO:0051092 9.52 TNFRSF11A TNFSF11
3 positive regulation of DNA-binding transcription factor activity GO:0051091 9.51 TNFRSF11A TNFSF11
4 ossification GO:0001503 9.49 TNFRSF11A TNFSF11
5 tumor necrosis factor-mediated signaling pathway GO:0033209 9.48 TNFRSF11A TNFSF11
6 monocyte chemotaxis GO:0002548 9.46 TNFRSF11A TNFSF11
7 positive regulation of osteoclast differentiation GO:0045672 9.43 CSF1 TNFSF11
8 positive regulation of bone resorption GO:0045780 9.4 TNFRSF11A TNFSF11
9 mammary gland alveolus development GO:0060749 9.37 TNFRSF11A TNFSF11
10 TNFSF11-mediated signaling pathway GO:0071847 9.32 TNFRSF11A TNFSF11
11 osteoclast proliferation GO:0002158 9.26 CSF1 TNFSF11
12 positive regulation of ERK1 and ERK2 cascade via TNFSF11-mediated signaling GO:0071848 9.16 TNFRSF11A TNFSF11
13 positive regulation of fever generation by positive regulation of prostaglandin secretion GO:0071812 8.96 TNFRSF11A TNFSF11
14 osteoclast differentiation GO:0030316 8.8 CSF1 TNFRSF11A TNFSF11

Molecular functions related to Osteopetrosis, Autosomal Recessive 7 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytokine activity GO:0005125 8.62 CSF1 TNFSF11

Sources for Osteopetrosis, Autosomal Recessive 7

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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