OPTB6
MCID: OST134
MIFTS: 42

Osteopetrosis, Autosomal Recessive 6 (OPTB6)

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 6

MalaCards integrated aliases for Osteopetrosis, Autosomal Recessive 6:

Name: Osteopetrosis, Autosomal Recessive 6 56 73 13 71
Optb6 56 12 52 73
Osteopetrosis Autosomal Recessive 6 52 29 6
Autosomal Recessive Osteopetrosis Intermediate Form 12 73
Autosomal Recessive Osteopetrosis 6 12 15
Osteopetrosis, Autosomal Recessive, Intermediate Form 56
Osteopetrosis Autosomal Recessive Intermediate Form 52
Autosomal Recessive Intermediate Osteopetrosis 58
Osteopetrosis, Autosomal Recessive, Type 6 39
Autosomal Recessive Osteopetrosis Type 6 52
Intermediate Osteopetrosis 58

Characteristics:

Orphanet epidemiological data:

58
intermediate osteopetrosis
Inheritance: Autosomal recessive; Age of onset: Childhood; Age of death: any age;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
based on report of 1 patient (last curated august 2018)
younger homozygous sib showed only dense metaphyseal bands in femur


HPO:

31
osteopetrosis, autosomal recessive 6:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare bone diseases
Developmental anomalies during embryogenesis


External Ids:

Disease Ontology 12 DOID:0110945
OMIM 56 611497
OMIM Phenotypic Series 56 PS259700
MeSH 43 D010022
ICD10 via Orphanet 33 Q78.2
UMLS via Orphanet 72 C0432261 C1969093
Orphanet 58 ORPHA210110
MedGen 41 C1969093
UMLS 71 C1969093

Summaries for Osteopetrosis, Autosomal Recessive 6

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 6, also known as optb6, is related to osteopetrosis and pycnodysostosis. An important gene associated with Osteopetrosis, Autosomal Recessive 6 is PLEKHM1 (Pleckstrin Homology And RUN Domain Containing M1), and among its related pathways/superpathways are Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins. and Insulin receptor recycling. The drugs Antiviral Agents and Anti-Infective Agents have been mentioned in the context of this disorder. Affiliated tissues include bone, bone marrow and eye, and related phenotypes are generalized osteosclerosis and back pain

Disease Ontology : 12 An osteopetrosis characterized by autosomal recessive inheritance of that has material basis in mutation in the PLEKHM1 gene on chromosome 17q21.31.

UniProtKB/Swiss-Prot : 73 Osteopetrosis, autosomal recessive 6: 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.

More information from OMIM: 611497 PS259700

Related Diseases for Osteopetrosis, Autosomal Recessive 6

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

(show all 30)
# Related Disease Score Top Affiliating Genes
1 osteopetrosis 30.2 TCIRG1 PLEKHM1 CLCN7
2 pycnodysostosis 29.7 TCIRG1 PLEKHM1 CLCN7
3 autosomal recessive malignant osteopetrosis 10.1 TCIRG1 CLCN7
4 axial osteomalacia 10.1 TCIRG1 CLCN7
5 fibrogenesis imperfecta ossium 10.1 TCIRG1 CLCN7
6 clcn7-related osteopetrosis 10.1
7 osteopetrosis, autosomal dominant 2 10.0 TCIRG1 CLCN7
8 craniometaphyseal dysplasia, autosomal dominant 10.0 TCIRG1 CLCN7
9 medullary sponge kidney 10.0 ATP6V1B1 ATP6V0A4
10 hereditary distal renal tubular acidosis 10.0 ATP6V1B1 ATP6V0A4
11 distal renal tubular acidosis 10.0 ATP6V1B1 ATP6V0A4
12 renal tubular acidosis, distal, autosomal recessive 9.9 ATP6V1B1 ATP6V0A4
13 poikiloderma with neutropenia 9.9
14 bone resorption disease 9.9
15 overgrowth syndrome 9.9
16 osteopetrosis, autosomal recessive 8 9.9 TCIRG1 PLEKHM1 CLCN7
17 osteopetrosis, autosomal recessive 2 9.9 TCIRG1 PLEKHM1 CLCN7
18 craniodiaphyseal dysplasia 9.9 TCIRG1 PLEKHM1 CLCN7
19 bone remodeling disease 9.8 TCIRG1 CLCN7
20 renal tubular transport disease 9.8 ATP6V1B1 ATP6V0A4
21 osteopetrosis, autosomal recessive 5 9.8 TCIRG1 CLCN7 ATP6V1B1
22 auditory system disease 9.7 ATP6V1B1 ATP6V0A4
23 endosteal hyperostosis, autosomal dominant 9.7 TCIRG1 CLCN7
24 nephrocalcinosis 9.6 CLCN7 ATP6V1B1 ATP6V0A4
25 nephrolithiasis, calcium oxalate 9.6 CLCN7 ATP6V1B1 ATP6V0A4
26 osteopetrosis, autosomal recessive 3 9.4 TCIRG1 CLCN7 ATP6V1B1 ATP6V0A4
27 renal tubular acidosis 9.4 TCIRG1 CLCN7 ATP6V1B1 ATP6V0A4
28 osteopetrosis, autosomal recessive 7 9.3 TCIRG1 IMPDH1 ATP6V1B1 ATP6V0A4
29 osteopetrosis, autosomal recessive 1 9.0 TCIRG1 IMPDH1 CLCN7 ATP6V1B1 ATP6V0A4
30 osteopetrosis, autosomal recessive 4 8.3 TCIRG1 IMPDH1 CLCN7 ATP6V1B1 ATP6V0A4 ATP5F1A

Graphical network of the top 20 diseases related to Osteopetrosis, Autosomal Recessive 6:



Diseases related to Osteopetrosis, Autosomal Recessive 6

Symptoms & Phenotypes for Osteopetrosis, Autosomal Recessive 6

Human phenotypes related to Osteopetrosis, Autosomal Recessive 6:

58 31 (show all 25)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 generalized osteosclerosis 58 31 frequent (33%) Frequent (79-30%) HP:0005789
2 back pain 58 31 frequent (33%) Frequent (79-30%) HP:0003418
3 recurrent fractures 58 31 frequent (33%) Frequent (79-30%) HP:0002757
4 sandwich appearance of vertebral bodies 58 31 frequent (33%) Frequent (79-30%) HP:0004618
5 erlenmeyer flask deformity of the femurs 58 31 frequent (33%) Frequent (79-30%) HP:0004975
6 cortical sclerosis 58 31 frequent (33%) Frequent (79-30%) HP:0005652
7 osteosclerosis of the base of the skull 58 31 frequent (33%) Frequent (79-30%) HP:0005746
8 anemia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001903
9 elevated alkaline phosphatase 58 31 occasional (7.5%) Occasional (29-5%) HP:0003155
10 dental malocclusion 58 31 very rare (1%) Very rare (<4-1%) HP:0000689
11 visual impairment 58 31 very rare (1%) Very rare (<4-1%) HP:0000505
12 osteomyelitis 58 31 very rare (1%) Very rare (<4-1%) HP:0002754
13 abnormality of dental morphology 58 31 very rare (1%) Very rare (<4-1%) HP:0006482
14 hepatosplenomegaly 58 31 very rare (1%) Very rare (<4-1%) HP:0001433
15 chronic infection 58 31 very rare (1%) Very rare (<4-1%) HP:0031035
16 optic atrophy from cranial nerve compression 58 31 very rare (1%) Very rare (<4-1%) HP:0007958
17 abnormality of the dentition 58 Very rare (<4-1%)
18 abnormality of the nervous system 58 Occasional (29-5%)
19 thrombocytopenia 58 Excluded (0%)
20 hypocalcemia 58 Excluded (0%)
21 abnormality of bone mineral density 58 Very frequent (99-80%)
22 increased susceptibility to fractures 58 Frequent (79-30%)
23 osteopetrosis 31 HP:0011002
24 cranial nerve compression 58 Very rare (<4-1%)
25 dense metaphyseal bands 31 HP:0100959

Symptoms via clinical synopsis from OMIM:

56
Skeletal Spine:
band-like sclerosis of vertebral endplates ('rugger-jersey' spine)

Skeletal Limbs:
nonhomogeneous sclerosis of metadiaphyses (distal femora, tibiae, and fibulae, and proximal fibulae and tibiae)
'erlenmeyer flask' deformity of distal femora and proximal tibiae

Skeletal Pelvis:
cortical sclerosis of pelvic bones

Clinical features from OMIM:

611497

Drugs & Therapeutics for Osteopetrosis, Autosomal Recessive 6

Drugs for Osteopetrosis, Autosomal Recessive 6 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Antiviral Agents Phase 2
2 Anti-Infective Agents Phase 2
3 interferons Phase 2
4 Interferon-gamma Phase 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Open-label Early Phase 2 Study With a Single Arm of Interferon Gamma-1b Treatment of Osteopetrosis Completed NCT02666768 Phase 2 Interferon gamma-1b

Search NIH Clinical Center for Osteopetrosis, Autosomal Recessive 6

Genetic Tests for Osteopetrosis, Autosomal Recessive 6

Genetic tests related to Osteopetrosis, Autosomal Recessive 6:

# Genetic test Affiliating Genes
1 Osteopetrosis Autosomal Recessive 6 29 PLEKHM1

Anatomical Context for Osteopetrosis, Autosomal Recessive 6

MalaCards organs/tissues related to Osteopetrosis, Autosomal Recessive 6:

40
Bone, Bone Marrow, Eye, Kidney, Liver

Publications for Osteopetrosis, Autosomal Recessive 6

Articles related to Osteopetrosis, Autosomal Recessive 6:

# Title Authors PMID Year
1
Involvement of PLEKHM1 in osteoclastic vesicular transport and osteopetrosis in incisors absent rats and humans. 56 6
17404618 2007
2
Localization of the gene causing the osteopetrotic phenotype in the incisors absent (ia) rat on chromosome 10q32.1. 56
14969387 2004
3
Exome sequencing identifies CTSK mutations in patients originally diagnosed as intermediate osteopetrosis. 61
24269275 2014
4
Clinical considerations for prosthodontic rehabilitation of intermediate form of osteopetrosis: A report of two cases. 61
25737849 2012
5
Dental management in autosomal recessive (intermediate) osteopetrosis: a case report. 61
21462770 2010
6
Molecular and clinical heterogeneity in CLCN7-dependent osteopetrosis: report of 20 novel mutations. 61
19953639 2010
7
[Osteopetrosis. Classification, etiology, treatment options and implications for oral health]. 61
16385937 2005
8
Chloride channel ClCN7 mutations are responsible for severe recessive, dominant, and intermediate osteopetrosis. 61
14584882 2003
9
Cranial MR imaging of osteopetrosis. 61
10871023 2000
10
Association of intermediate osteopetrosis with poikiloderma. 61
10320533 1999

Variations for Osteopetrosis, Autosomal Recessive 6

ClinVar genetic disease variations for Osteopetrosis, Autosomal Recessive 6:

6 ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 PLEKHM1 NM_014798.3(PLEKHM1):c.296+1G>ASNV Pathogenic 922 rs786205055 17:43555265-43555265 17:45477899-45477899

Expression for Osteopetrosis, Autosomal Recessive 6

Search GEO for disease gene expression data for Osteopetrosis, Autosomal Recessive 6.

Pathways for Osteopetrosis, Autosomal Recessive 6

GO Terms for Osteopetrosis, Autosomal Recessive 6

Cellular components related to Osteopetrosis, Autosomal Recessive 6 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 lysosome GO:0005764 9.58 TCIRG1 PLEKHM1 CLCN7
2 apical plasma membrane GO:0016324 9.54 TCIRG1 ATP6V1B1 ATP6V0A4
3 endosome membrane GO:0010008 9.5 TCIRG1 PLEKHM1 ATP6V0A4
4 lysosomal membrane GO:0005765 9.46 TCIRG1 PLEKHM1 CLCN7 ATP6V0A4
5 phagocytic vesicle membrane GO:0030670 9.43 TCIRG1 ATP6V0A4
6 proton-transporting V-type ATPase, V0 domain GO:0033179 9.26 TCIRG1 ATP6V0A4
7 vacuolar proton-transporting V-type ATPase, V0 domain GO:0000220 8.96 TCIRG1 ATP6V0A4
8 vacuolar proton-transporting V-type ATPase complex GO:0016471 8.8 TCIRG1 ATP6V1B1 ATP6V0A4

Biological processes related to Osteopetrosis, Autosomal Recessive 6 according to GeneCards Suite gene sharing:

(show all 15)
# Name GO ID Score Top Affiliating Genes
1 ion transmembrane transport GO:0034220 9.67 TCIRG1 CLCN7 ATP6V1B1 ATP6V0A4
2 ion transport GO:0006811 9.65 TCIRG1 CLCN7 ATP6V1B1 ATP6V0A4 ATP5F1A
3 ossification GO:0001503 9.61 TCIRG1 ATP6V1B1 ATP6V0A4
4 insulin receptor signaling pathway GO:0008286 9.58 TCIRG1 ATP6V1B1 ATP6V0A4
5 macroautophagy GO:0016236 9.55 TCIRG1 PRKAG2
6 regulation of macroautophagy GO:0016241 9.54 PRKAG2 ATP6V1B1
7 ATP metabolic process GO:0046034 9.52 ATP6V1B1 ATP5F1A
8 excretion GO:0007588 9.51 ATP6V1B1 ATP6V0A4
9 ATP biosynthetic process GO:0006754 9.49 PRKAG2 ATP5F1A
10 regulation of pH GO:0006885 9.48 ATP6V1B1 ATP6V0A4
11 vacuolar acidification GO:0007035 9.46 TCIRG1 ATP6V0A4
12 transferrin transport GO:0033572 9.33 TCIRG1 ATP6V1B1 ATP6V0A4
13 pH reduction GO:0045851 9.32 TCIRG1 ATP6V1B1
14 phagosome acidification GO:0090383 9.13 TCIRG1 ATP6V1B1 ATP6V0A4
15 proton transmembrane transport GO:1902600 8.92 TCIRG1 ATP6V1B1 ATP6V0A4 ATP5F1A

Molecular functions related to Osteopetrosis, Autosomal Recessive 6 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ATPase binding GO:0051117 9.32 TCIRG1 ATP6V0A4
2 ADP binding GO:0043531 9.26 PRKAG2 ATP5F1A
3 proton-transporting ATPase activity, rotational mechanism GO:0046961 9.16 TCIRG1 ATP6V0A4
4 adenyl ribonucleotide binding GO:0032559 8.96 PRKAG2 ATP5F1A
5 proton transmembrane transporter activity GO:0015078 8.8 TCIRG1 ATP6V1B1 ATP6V0A4

Sources for Osteopetrosis, Autosomal Recessive 6

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
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