OPTB6
MCID: OST134
MIFTS: 44

Osteopetrosis, Autosomal Recessive 6 (OPTB6)

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

Aliases & Classifications for Osteopetrosis, Autosomal Recessive 6

MalaCards integrated aliases for Osteopetrosis, Autosomal Recessive 6:

Name: Osteopetrosis, Autosomal Recessive 6 57 73 13 71
Autosomal Recessive Osteopetrosis 6 12 29 6 15
Optb6 57 12 20 73
Autosomal Recessive Osteopetrosis Intermediate Form 12 73
Osteopetrosis, Autosomal Recessive, Intermediate Form 57
Osteopetrosis Autosomal Recessive Intermediate Form 20
Autosomal Recessive Intermediate Osteopetrosis 58
Osteopetrosis, Autosomal Recessive, Type 6 39
Autosomal Recessive Osteopetrosis Type 6 20
Osteopetrosis Autosomal Recessive 6 20
Intermediate Osteopetrosis 58

Characteristics:

Orphanet epidemiological data:

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

OMIM®:

57 (Updated 05-Mar-2021)
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® 57 611497
OMIM Phenotypic Series 57 PS259700
MeSH 44 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

GARD : 20 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 autosomal recessive osteopetrosis 6, is related to pycnodysostosis and osteopetrosis. 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 Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds. Affiliated tissues include bone and bone marrow, and related phenotypes are back pain and recurrent fractures

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 42)
# Related Disease Score Top Affiliating Genes
1 pycnodysostosis 29.7 TNFSF11 TCIRG1 PLEKHM1 CLCN7
2 osteopetrosis 29.6 TNFSF11 TNF TCIRG1 PLEKHM1 CLCN7 ATP6V0A2
3 axial osteomalacia 10.3 TCIRG1 CLCN7
4 fibrogenesis imperfecta ossium 10.3 TCIRG1 CLCN7
5 medullary sponge kidney 10.3 ATP6V1B1 ATP6V0A4
6 craniodiaphyseal dysplasia 10.2 TCIRG1 PLEKHM1 CLCN7
7 hereditary distal renal tubular acidosis 10.1 SLC4A1 ATP6V1B1 ATP6V0A4
8 distal renal tubular acidosis 10.1 SLC4A1 ATP6V1B1 ATP6V0A4
9 renal tubular acidosis, distal, 3, with or without sensorineural hearing loss 10.1 SLC4A1 ATP6V1B1 ATP6V0A4
10 autosomal recessive distal renal tubular acidosis 10.1 SLC4A1 ATP6V1B1 ATP6V0A4
11 osteopetrosis, autosomal dominant 2 10.0 TNFSF11 TCIRG1 CLCN7
12 clcn7-related osteopetrosis 10.0
13 autosomal recessive malignant osteopetrosis 10.0 TNFSF11 TCIRG1 CLCN7
14 craniometaphyseal dysplasia, autosomal dominant 10.0 TNFSF11 TCIRG1 CLCN7
15 nephrocalcinosis 10.0 SLC4A1 ATP6V1B1 ATP6V0A4
16 endosteal hyperostosis, autosomal dominant 10.0 TNFSF11 TCIRG1 CLCN7
17 osteopetrosis, autosomal recessive 1 10.0 TCIRG1 IMPDH1 CLCN7 ATP6V1B1 ATP6V0A4
18 osteopetrosis, autosomal recessive 2 10.0 TNFSF11 TCIRG1 PLEKHM1 CLCN7
19 osteopetrosis, autosomal recessive 8 9.9 TNFSF11 TCIRG1 PLEKHM1 CLCN7
20 pustulosis palmaris et plantaris 9.9 TNF CD40LG
21 dental pulp necrosis 9.9 TNFSF11 TNF
22 gingival recession 9.9 TNFSF11 TNF
23 renal tubular transport disease 9.9 SLC4A4 SLC4A1 ATP6V1B1 ATP6V0A4
24 poikiloderma with neutropenia 9.9
25 bone resorption disease 9.9
26 overgrowth syndrome 9.9
27 metabolic acidosis 9.9 SLC4A4 SLC4A1 ATP6V1B1 ATP6V0A4
28 corneal degeneration 9.9 TGFBI SLC4A4
29 periapical periodontitis 9.9 TNFSF11 TNF
30 african tick-bite fever 9.8 TNF CD40LG
31 idiopathic neutropenia 9.8 TNF CD40LG
32 bone remodeling disease 9.8 TNFSF11 TNF TCIRG1 CLCN7
33 nephrolithiasis 9.7 SLC4A1 ATP6V1B1 ATP6V0A4
34 spondyloarthropathy 1 9.7 TNFSF11 TNF CD40LG
35 osteopetrosis, autosomal recessive 3 9.7 TCIRG1 SLC4A4 SLC4A1 CLCN7 ATP6V1B1 ATP6V0A4
36 autoimmune disease of musculoskeletal system 9.7 TNFSF11 TNF CD40LG
37 hereditary elliptocytosis 9.6 SLC4A1 HBB ATP6V1B1 ATP6V0A4
38 renal tubular acidosis 9.5 TCIRG1 SLC4A4 SLC4A1 CLCN7 ATP6V1B1 ATP6V0A4
39 osteoporosis 9.3 TNFSF11 TNF TCIRG1 CLCN7 CD40LG CA8
40 osteopetrosis, autosomal recessive 7 7.4 TNFSF11 TGFBI TCIRG1 SLC4A4 SLC4A1 PRKAG2
41 osteopetrosis, autosomal recessive 4 7.4 TNFSF11 TGFBI TCIRG1 SLC4A4 SLC4A1 PRKAG2
42 osteopetrosis, autosomal recessive 5 7.4 TNFSF11 TGFBI TCIRG1 SLC4A4 SLC4A1 PRKAG2

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 back pain 58 31 frequent (33%) Frequent (79-30%) HP:0003418
2 recurrent fractures 58 31 frequent (33%) Frequent (79-30%) HP:0002757
3 generalized osteosclerosis 58 31 frequent (33%) Frequent (79-30%) HP:0005789
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 abnormality of dental morphology 58 31 very rare (1%) Very rare (<4-1%) HP:0006482
13 osteomyelitis 58 31 very rare (1%) Very rare (<4-1%) HP:0002754
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 thrombocytopenia 58 Excluded (0%)
19 abnormality of bone mineral density 58 Very frequent (99-80%)
20 hypocalcemia 58 Excluded (0%)
21 abnormality of the nervous system 58 Occasional (29-5%)
22 osteopetrosis 31 HP:0011002
23 increased susceptibility to fractures 58 Frequent (79-30%)
24 dense metaphyseal bands 31 HP:0100959
25 cranial nerve compression 58 Very rare (<4-1%)

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
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 (Updated 05-Mar-2021)

MGI Mouse Phenotypes related to Osteopetrosis, Autosomal Recessive 6:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 hematopoietic system MP:0005397 10.15 ABCB6 ATP6V0A2 CD40LG CLCN7 IMPDH1 PLEKHM1
2 homeostasis/metabolism MP:0005376 10.1 ABCB6 ATP6V0A4 ATP6V1B1 CD40LG CLCN7 PRKAG2
3 immune system MP:0005387 10.03 ATP6V0A2 CD40LG CLCN7 IMPDH1 PLEKHM1 PRKAG2
4 integument MP:0010771 9.76 ABCB6 ATP6V0A2 CD40LG CLCN7 SLC4A1 SLC4A4
5 renal/urinary system MP:0005367 9.5 ATP6V0A4 ATP6V1B1 CD40LG CLCN7 PLEKHM1 SLC4A1
6 skeleton MP:0005390 9.28 ATP6V0A4 ATP6V1B1 CD40LG CLCN7 PLEKHM1 SLC4A4

Drugs & Therapeutics for Osteopetrosis, Autosomal Recessive 6

Search Clinical Trials , 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 Autosomal Recessive Osteopetrosis 6 29 PLEKHM1

Anatomical Context for Osteopetrosis, Autosomal Recessive 6

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

40
Bone, Bone Marrow

Publications for Osteopetrosis, Autosomal Recessive 6

Articles related to Osteopetrosis, Autosomal Recessive 6:

(show all 11)
# Title Authors PMID Year
1
Involvement of PLEKHM1 in osteoclastic vesicular transport and osteopetrosis in incisors absent rats and humans. 57 6
17404618 2007
2
Localization of the gene causing the osteopetrotic phenotype in the incisors absent (ia) rat on chromosome 10q32.1. 57
14969387 2004
3
Adult Osteosclerotic Metaphyseal Dysplasia With Progressive Osteonecrosis of the Jaws and Abnormal Bone Resorption Pattern Due to a LRRK1 Splice Site Mutation. 61
32119750 2020
4
Exome sequencing identifies CTSK mutations in patients originally diagnosed as intermediate osteopetrosis. 61
24269275 2014
5
Clinical considerations for prosthodontic rehabilitation of intermediate form of osteopetrosis: A report of two cases. 61
25737849 2012
6
Dental management in autosomal recessive (intermediate) osteopetrosis: a case report. 61
21462770 2010
7
Molecular and clinical heterogeneity in CLCN7-dependent osteopetrosis: report of 20 novel mutations. 61
19953639 2010
8
[Osteopetrosis. Classification, etiology, treatment options and implications for oral health]. 61
16385937 2005
9
Chloride channel ClCN7 mutations are responsible for severe recessive, dominant, and intermediate osteopetrosis. 61
14584882 2003
10
Cranial MR imaging of osteopetrosis. 61
10871023 2000
11
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>A SNV 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

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

(show all 14)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.06 TNF TCIRG1 PRKAG2 ATP6V1B1 ATP6V0A4 ATP6V0A2
2
Show member pathways
12.89 TCIRG1 SLC4A4 SLC4A1 CLCN7 ATP6V1B1 ATP6V0A4
3
Show member pathways
12.76 TNF TCIRG1 ATP6V1B1 ATP6V0A4 ATP6V0A2
4
Show member pathways
12.22 TCIRG1 CLCN7 ATP6V1B1 ATP6V0A4 ATP6V0A2
5 11.99 TNF TCIRG1 ATP6V0A4 ATP6V0A2
6 11.85 TCIRG1 ATP6V1B1 ATP6V0A4 ATP6V0A2
7 11.82 TCIRG1 ATP6V0A4 ATP6V0A2
8
Show member pathways
11.8 TCIRG1 SLC4A1 ATP6V1B1 ATP6V0A4 ATP6V0A2
9 11.7 TNFSF11 TNF CD40LG
10
Show member pathways
11.67 TCIRG1 ATP6V1B1 ATP6V0A4 ATP6V0A2
11
Show member pathways
11.58 TNFSF11 TNF CD40LG
12
Show member pathways
11.52 TNFSF11 TNF CD40LG
13 11.28 TNF HBB CD40LG
14 11.07 TNFSF11 TNF TCIRG1 ATP6V1B1 ATP6V0A4 ATP6V0A2

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 membrane GO:0016020 10.28 TNFSF11 TNF TCIRG1 SLC4A4 SLC4A1 PRKAG2
2 extracellular exosome GO:0070062 10.01 TGFBI SLC4A4 SLC4A1 HBB ATP6V1B1 ATP6V0A4
3 lysosomal membrane GO:0005765 9.72 TCIRG1 PLEKHM1 CLCN7 ATP6V0A4 ATP6V0A2
4 endosome membrane GO:0010008 9.65 TCIRG1 PLEKHM1 ATP6V0A4 ATP6V0A2 ABCB6
5 phagocytic vesicle membrane GO:0030670 9.54 TCIRG1 ATP6V0A4 ATP6V0A2
6 proton-transporting V-type ATPase, V0 domain GO:0033179 9.33 TCIRG1 ATP6V0A4 ATP6V0A2
7 vacuolar proton-transporting V-type ATPase, V0 domain GO:0000220 9.13 TCIRG1 ATP6V0A4 ATP6V0A2
8 vacuolar proton-transporting V-type ATPase complex GO:0016471 8.92 TCIRG1 ATP6V1B1 ATP6V0A4 ATP6V0A2

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

(show all 21)
# Name GO ID Score Top Affiliating Genes
1 ion transmembrane transport GO:0034220 9.85 TCIRG1 CLCN7 ATP6V1B1 ATP6V0A4 ATP6V0A2
2 tumor necrosis factor-mediated signaling pathway GO:0033209 9.76 TNFSF11 TNF CD40LG
3 regulation of macroautophagy GO:0016241 9.71 PRKAG2 ATP6V1B1 ATP6V0A2
4 ossification GO:0001503 9.71 TNFSF11 TCIRG1 ATP6V1B1 ATP6V0A4
5 insulin receptor signaling pathway GO:0008286 9.67 TCIRG1 ATP6V1B1 ATP6V0A4 ATP6V0A2
6 bicarbonate transport GO:0015701 9.65 SLC4A4 SLC4A1 HBB
7 proton transmembrane transport GO:1902600 9.65 TCIRG1 ATP6V1B1 ATP6V0A4 ATP6V0A2 ATP5F1A
8 osteoclast differentiation GO:0030316 9.61 TNFSF11 TNF TCIRG1
9 positive regulation of osteoclast differentiation GO:0045672 9.6 TNFSF11 TNF
10 positive regulation of bone resorption GO:0045780 9.59 TNFSF11 PLEKHM1
11 ion homeostasis GO:0050801 9.58 SLC4A4 SLC4A1
12 regulation of pH GO:0006885 9.57 ATP6V1B1 ATP6V0A4
13 regulation of osteoclast differentiation GO:0045670 9.56 TNFSF11 TNF
14 ion transport GO:0006811 9.56 TCIRG1 SLC4A4 SLC4A1 CLCN7 ATP6V1B1 ATP6V0A4
15 regulation of immunoglobulin production GO:0002637 9.55 TNF CD40LG
16 tooth eruption GO:0044691 9.52 TNFSF11 TCIRG1
17 pH reduction GO:0045851 9.51 TCIRG1 ATP6V1B1
18 vacuolar acidification GO:0007035 9.5 TCIRG1 ATP6V0A4 ATP6V0A2
19 osteoclast proliferation GO:0002158 9.49 TNFSF11 TCIRG1
20 transferrin transport GO:0033572 9.46 TCIRG1 ATP6V1B1 ATP6V0A4 ATP6V0A2
21 phagosome acidification GO:0090383 8.92 TCIRG1 ATP6V1B1 ATP6V0A4 ATP6V0A2

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 9.54 TCIRG1 ATP6V0A4 ATP6V0A2
2 chloride transmembrane transporter activity GO:0015108 9.46 SLC4A1 CLCN7
3 anion transmembrane transporter activity GO:0008509 9.43 SLC4A4 SLC4A1
4 inorganic anion exchanger activity GO:0005452 9.4 SLC4A4 SLC4A1
5 tumor necrosis factor receptor binding GO:0005164 9.33 TNFSF11 TNF CD40LG
6 hemoglobin binding GO:0030492 9.32 SLC4A1 HBB
7 adenyl ribonucleotide binding GO:0032559 9.26 PRKAG2 ATP5F1A
8 proton-transporting ATPase activity, rotational mechanism GO:0046961 9.13 TCIRG1 ATP6V0A4 ATP6V0A2
9 proton transmembrane transporter activity GO:0015078 8.92 TCIRG1 ATP6V1B1 ATP6V0A4 ATP6V0A2

Sources for Osteopetrosis, Autosomal Recessive 6

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
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
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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