OPTB7
MCID: OST136
MIFTS: 43

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 56 73 13 71
Optb7 56 12 52 73
Autosomal Recessive Osteoclast-Poor Osteopetrosis with Hypogammaglobulinemia 12 52 58
Autosomal Recessive Osteopetrosis Type 7 12 52 58
Osteopetrosis Autosomal Recessive 7 52 29 6
Osteoclast-Poor Osteopetrosis with Hypogammaglobulinemia 12 73
Osteopetrosis-Hypogammaglobulinemia Syndrome 12 58
Autosomal Recessive Osteopetrosis 7 12 15
Osteopetrosis, Osteoclast-Poor, with Hypogammaglobulinemia 56
Osteopetrosis Osteoclast-Poor with Hypogammaglobulinemia 52
Osteopetrosis, Autosomal Recessive, Type 7 39

Characteristics:

Orphanet epidemiological data:

58
osteopetrosis-hypogammaglobulinemia syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide);

OMIM:

56
Inheritance:
autosomal recessive

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


HPO:

31
osteopetrosis, autosomal recessive 7:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare bone diseases
Developmental anomalies during embryogenesis
Rare immunological diseases


External Ids:

Disease Ontology 12 DOID:0110946
OMIM 56 612301
OMIM Phenotypic Series 56 PS259700
MeSH 43 D010022
ICD10 32 Q78.2
ICD10 via Orphanet 33 Q78.2
UMLS via Orphanet 72 C2676766
Orphanet 58 ORPHA178389
MedGen 41 C2676766
UMLS 71 C2676766

Summaries for Osteopetrosis, Autosomal Recessive 7

NIH Rare Diseases : 52 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 and immune deficiency disease. An important gene associated with Osteopetrosis, Autosomal Recessive 7 is TNFRSF11A (TNF Receptor Superfamily Member 11a), and among its related pathways/superpathways are Innate Immune System and PI3K-Akt signaling pathway. Affiliated tissues include bone, bone marrow and eye, and related phenotypes are decreased antibody level in blood and nystagmus

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 : 73 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.

More information from OMIM: 612301 PS259700

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 22)
# Related Disease Score Top Affiliating Genes
1 osteopetrosis 30.4 TNFRSF11A TCIRG1
2 immune deficiency disease 10.3
3 osteopetrosis, autosomal recessive 2 10.3
4 bone disease 10.3
5 agammaglobulinemia 10.3
6 clcn7-related osteopetrosis 10.3
7 medullary sponge kidney 9.8 ATP6V1B1 ATP6V0A4
8 hereditary distal renal tubular acidosis 9.8 ATP6V1B1 ATP6V0A4
9 bone remodeling disease 9.8 TNFRSF11A TCIRG1
10 distal renal tubular acidosis 9.8 ATP6V1B1 ATP6V0A4
11 osteopetrosis, autosomal recessive 5 9.8 TCIRG1 ATP6V1B1
12 renal tubular acidosis, distal, autosomal recessive 9.8 ATP6V1B1 ATP6V0A4
13 renal tubular transport disease 9.7 ATP6V1B1 ATP6V0A4
14 auditory system disease 9.7 ATP6V1B1 ATP6V0A4
15 metabolic acidosis 9.6 ATP6V1B1 ATP6V0A4
16 nephrocalcinosis 9.5 ATP6V1B1 ATP6V0A4
17 osteopetrosis, autosomal recessive 3 9.4 TCIRG1 ATP6V1B1 ATP6V0A4
18 renal tubular acidosis 9.4 TCIRG1 ATP6V1B1 ATP6V0A4
19 nephrolithiasis, calcium oxalate 9.4 ATP6V1B1 ATP6V0A4
20 osteopetrosis, autosomal recessive 4 8.8 TCIRG1 IMPDH1 ATP6V1B1 ATP6V0A4
21 osteopetrosis, autosomal recessive 1 8.8 TCIRG1 IMPDH1 ATP6V1B1 ATP6V0A4
22 osteopetrosis, autosomal recessive 6 8.8 TCIRG1 IMPDH1 ATP6V1B1 ATP6V0A4

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:

31 (show all 24)
# Description HPO Frequency HPO Source Accession
1 decreased antibody level in blood 31 very rare (1%) HP:0004313
2 nystagmus 31 HP:0000639
3 hydrocephalus 31 HP:0000238
4 global developmental delay 31 HP:0001263
5 splenomegaly 31 HP:0001744
6 hepatomegaly 31 HP:0002240
7 optic atrophy 31 HP:0000648
8 anemia 31 HP:0001903
9 generalized hypotonia 31 HP:0001290
10 progressive visual loss 31 HP:0000529
11 growth delay 31 HP:0001510
12 thrombocytopenia 31 HP:0001873
13 motor delay 31 HP:0001270
14 proptosis 31 HP:0000520
15 recurrent pneumonia 31 HP:0006532
16 osteopetrosis 31 HP:0011002
17 optic nerve compression 31 HP:0007807
18 dilation of lateral ventricles 31 HP:0006956
19 increased head circumference 31 HP:0040194
20 hypocalcemic seizures 31 HP:0002199
21 psychomotor retardation 31 HP:0025356
22 abnormal trabecular bone morphology 31 HP:0100671
23 multiple rib fractures 31 HP:0006640
24 femur fracture 31 HP:0031846

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Eyes:
nystagmus
vision loss
optic nerve atrophy
delayed visual evoked responses
exophthalmos (in 1 patient)

Abdomen Spleen:
splenomegaly

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

Respiratory:
recurrent infections

Head And Neck Head:
increased head circumference

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
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

Neurologic Central Nervous System:
hydrocephalus
motor delay
psychomotor retardation
hypotonia
seizures due to hypocalcemia
more
Abdomen Liver:
hepatomegaly

Laboratory Abnormalities:
hypocalcemia

Respiratory Lung:
recurrent pneumonia

Skeletal Skull:
increased head circumference
severe narrowing of optic foramina

Growth Other:
growth failure

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

MGI Mouse Phenotypes related to Osteopetrosis, Autosomal Recessive 7:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 skeleton MP:0005390 9.26 ATP6V0A4 ATP6V1B1 TCIRG1 TNFRSF11A
2 taste/olfaction MP:0005394 8.62 ATP6V0A4 ATP6V1B1

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 29 TNFRSF11A

Anatomical Context for Osteopetrosis, Autosomal Recessive 7

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

40
Bone, Bone Marrow, Eye, Kidney, Liver

Publications for Osteopetrosis, Autosomal Recessive 7

Articles related to Osteopetrosis, Autosomal Recessive 7:

# Title Authors PMID Year
1
Central control of fever and female body temperature by RANKL/RANK. 56 6
19940926 2009
2
Human osteoclast-poor osteopetrosis with hypogammaglobulinemia due to TNFRSF11A (RANK) mutations. 56 6
18606301 2008
3
In vitro differentiation of CD14 cells from osteopetrotic subjects: contrasting phenotypes with TCIRG1, CLCN7, and attachment defects. 56 6
15231021 2004
4
TNFRSF11A-Associated Dysosteosclerosis: A Report of the Second Case and Characterization of the Phenotypic Spectrum. 61
31163101 2019
5
Dysosteosclerosis is also caused by TNFRSF11A mutation. 61
29568001 2018

Variations for Osteopetrosis, Autosomal Recessive 7

ClinVar genetic disease variations for Osteopetrosis, Autosomal Recessive 7:

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 TNFRSF11A NM_003839.4(TNFRSF11A):c.508A>G (p.Arg170Gly)SNV Pathogenic 6301 rs121908655 18:60025561-60025561 18:62358328-62358328
2 TNFRSF11A NM_003839.4(TNFRSF11A):c.523T>C (p.Cys175Arg)SNV Pathogenic 6302 rs121908656 18:60027189-60027189 18:62359956-62359956
3 TNFRSF11A NM_003839.4(TNFRSF11A):c.730G>T (p.Ala244Ser)SNV Pathogenic 6304 rs121908658 18:60029026-60029026 18:62361793-62361793
4 TNFRSF11A NM_003839.4(TNFRSF11A):c.157G>C (p.Gly53Arg)SNV Pathogenic 6305 rs121908659 18:60015482-60015482 18:62348249-62348249
5 TNFRSF11A NM_003839.4(TNFRSF11A):c.718A>G (p.Lys240Glu)SNV Uncertain significance 287370 rs148185533 18:60029014-60029014 18:62361781-62361781
6 TNFRSF11A NM_003839.4(TNFRSF11A):c.385C>T (p.Arg129Cys)SNV Uncertain significance 6303 rs121908657 18:60021725-60021725 18:62354492-62354492

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

73
# 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

Expression for Osteopetrosis, Autosomal Recessive 7

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

Pathways for Osteopetrosis, Autosomal Recessive 7

GO Terms for Osteopetrosis, Autosomal Recessive 7

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

# Name GO ID Score Top Affiliating Genes
1 apical plasma membrane GO:0016324 9.43 TCIRG1 ATP6V1B1 ATP6V0A4
2 phagocytic vesicle membrane GO:0030670 9.32 TCIRG1 ATP6V0A4
3 proton-transporting V-type ATPase, V0 domain GO:0033179 9.16 TCIRG1 ATP6V0A4
4 vacuolar proton-transporting V-type ATPase, V0 domain GO:0000220 8.96 TCIRG1 ATP6V0A4
5 vacuolar proton-transporting V-type ATPase complex GO:0016471 8.8 TCIRG1 ATP6V1B1 ATP6V0A4

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

(show all 13)
# Name GO ID Score Top Affiliating Genes
1 ion transport GO:0006811 9.69 TCIRG1 ATP6V1B1 ATP6V0A4
2 ion transmembrane transport GO:0034220 9.63 TCIRG1 ATP6V1B1 ATP6V0A4
3 proton transmembrane transport GO:1902600 9.54 TCIRG1 ATP6V1B1 ATP6V0A4
4 sensory perception of sound GO:0007605 9.52 ATP6V1B1 ATP6V0A4
5 insulin receptor signaling pathway GO:0008286 9.5 TCIRG1 ATP6V1B1 ATP6V0A4
6 osteoclast differentiation GO:0030316 9.49 TNFRSF11A TCIRG1
7 excretion GO:0007588 9.48 ATP6V1B1 ATP6V0A4
8 regulation of pH GO:0006885 9.43 ATP6V1B1 ATP6V0A4
9 vacuolar acidification GO:0007035 9.4 TCIRG1 ATP6V0A4
10 transferrin transport GO:0033572 9.33 TCIRG1 ATP6V1B1 ATP6V0A4
11 pH reduction GO:0045851 9.26 TCIRG1 ATP6V1B1
12 phagosome acidification GO:0090383 9.13 TCIRG1 ATP6V1B1 ATP6V0A4
13 ossification GO:0001503 8.92 TNFRSF11A TCIRG1 ATP6V1B1 ATP6V0A4

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

# Name GO ID Score Top Affiliating Genes
1 ATPase binding GO:0051117 9.16 TCIRG1 ATP6V0A4
2 proton-transporting ATPase activity, rotational mechanism GO:0046961 8.96 TCIRG1 ATP6V0A4
3 proton transmembrane transporter activity GO:0015078 8.8 TCIRG1 ATP6V1B1 ATP6V0A4

Sources for Osteopetrosis, Autosomal Recessive 7

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
Content
Loading form....