OPTB4
MCID: OST137
MIFTS: 44

Osteopetrosis, Autosomal Recessive 4 (OPTB4)

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 4

MalaCards integrated aliases for Osteopetrosis, Autosomal Recessive 4:

Name: Osteopetrosis, Autosomal Recessive 4 57 72 13 70
Autosomal Recessive Osteopetrosis 4 12 29 6 15
Optb4 57 12 20 72
Infantile Malignant Osteopetrosis 2 12 72
Osteopetrosis, Autosomal Recessive, Type 4 39
Autosomal Recessive Osteopetrosis Type 4 20
Osteopetrosis, Infantile Malignant 2 57
Osteopetrosis Autosomal Recessive 4 20
Osteopetrosis Infantile Malignant 2 20

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive


HPO:

31
osteopetrosis, autosomal recessive 4:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Osteopetrosis, Autosomal Recessive 4

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 4, also known as autosomal recessive osteopetrosis 4, is related to medullary sponge kidney and axial osteomalacia. An important gene associated with Osteopetrosis, Autosomal Recessive 4 is CLCN7 (Chloride Voltage-Gated Channel 7), and among its related pathways/superpathways are Metabolism and Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.. Affiliated tissues include bone and bone marrow, and related phenotypes are facial palsy and splenomegaly

Disease Ontology : 12 An osteopetrosis characterized by autosomal recessive inheritance that has material basis in homozygous or compound heterozygous mutation in the CLCN7 gene on chromosome 16p13.

UniProtKB/Swiss-Prot : 72 Osteopetrosis, autosomal recessive 4: 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: 611490 PS259700

Related Diseases for Osteopetrosis, Autosomal Recessive 4

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

(show all 35)
# Related Disease Score Top Affiliating Genes
1 medullary sponge kidney 10.3 ATP6V1B1 ATP6V0A4
2 axial osteomalacia 10.2 TCIRG1 CLCN7
3 fibrogenesis imperfecta ossium 10.2 TCIRG1 CLCN7
4 craniodiaphyseal dysplasia 10.2 TCIRG1 CLCN7
5 hereditary distal renal tubular acidosis 10.1 SLC4A1 ATP6V1B1 ATP6V0A4
6 distal renal tubular acidosis 10.1 SLC4A1 ATP6V1B1 ATP6V0A4
7 renal tubular acidosis, distal, 3, with or without sensorineural hearing loss 10.1 SLC4A1 ATP6V1B1 ATP6V0A4
8 autosomal recessive distal renal tubular acidosis 10.1 SLC4A1 ATP6V1B1 ATP6V0A4
9 nephrocalcinosis 10.0 SLC4A1 ATP6V1B1 ATP6V0A4
10 pseudohyperkalemia, familial, 2, due to red cell leak 10.0 SLC4A1 ABCB6
11 corneal dystrophy and perceptive deafness 10.0 SLC4A4 SLC4A1
12 nephrolithiasis 9.9 SLC4A1 ATP6V1B1 ATP6V0A4
13 osteopetrosis, autosomal recessive 2 9.9 TNFSF11 TCIRG1 CLCN7
14 osteopetrosis, autosomal dominant 2 9.9 TNFSF11 TCIRG1 CLCN7
15 autosomal recessive malignant osteopetrosis 9.9 TNFSF11 TCIRG1 CLCN7
16 osteopetrosis, autosomal recessive 8 9.9 TNFSF11 TCIRG1 CLCN7
17 pycnodysostosis 9.9 TNFSF11 TCIRG1 CLCN7
18 craniometaphyseal dysplasia, autosomal dominant 9.9 TNFSF11 TCIRG1 CLCN7
19 osteopetrosis, autosomal recessive 1 9.9 TCIRG1 IMPDH1 CLCN7 ATP6V1B1 ATP6V0A4
20 endosteal hyperostosis, autosomal dominant 9.9 TNFSF11 TCIRG1 CLCN7
21 bone remodeling disease 9.9 TNFSF11 TCIRG1 CLCN7
22 renal tubular transport disease 9.8 SLC4A4 SLC4A1 ATP6V1B1 ATP6V0A4
23 priapism 9.8 SLC4A1 HBB
24 metabolic acidosis 9.8 SLC4A4 SLC4A1 ATP6V1B1 ATP6V0A4
25 corneal degeneration 9.8 TGFBI SLC4A4
26 spherocytosis, type 4 9.8 SLC4A1 HBB
27 hereditary elliptocytosis 9.8 SLC4A1 HBB ATP6V1B1 ATP6V0A4
28 osteopetrosis 9.7 TNFSF11 TCIRG1 CLCN7 ATP6V1B1 ATP6V0A2
29 acute chest syndrome 9.6 HBB CD40LG
30 osteopetrosis, autosomal recessive 3 9.6 TCIRG1 SLC4A4 SLC4A1 CLCN7 ATP6V1B1 ATP6V0A4
31 osteoporosis 9.4 TNFSF11 TCIRG1 CLCN7 CD40LG CA8
32 renal tubular acidosis 9.4 TCIRG1 SLC4A4 SLC4A1 CLCN7 ATP6V1B1 ATP6V0A4
33 osteopetrosis, autosomal recessive 7 7.2 TNFSF11 TGFBI TCIRG1 SLC4A4 SLC4A1 PRKAG2
34 osteopetrosis, autosomal recessive 6 7.2 TNFSF11 TGFBI TCIRG1 SLC4A4 SLC4A1 PRKAG2
35 osteopetrosis, autosomal recessive 5 7.2 TNFSF11 TGFBI TCIRG1 SLC4A4 SLC4A1 PRKAG2

Graphical network of the top 20 diseases related to Osteopetrosis, Autosomal Recessive 4:



Diseases related to Osteopetrosis, Autosomal Recessive 4

Symptoms & Phenotypes for Osteopetrosis, Autosomal Recessive 4

Human phenotypes related to Osteopetrosis, Autosomal Recessive 4:

31 (show all 15)
# Description HPO Frequency HPO Source Accession
1 facial palsy 31 HP:0010628
2 splenomegaly 31 HP:0001744
3 hepatomegaly 31 HP:0002240
4 visual impairment 31 HP:0000505
5 optic atrophy 31 HP:0000648
6 anemia 31 HP:0001903
7 growth delay 31 HP:0001510
8 thrombocytopenia 31 HP:0001873
9 recurrent fractures 31 HP:0002757
10 petechiae 31 HP:0000967
11 reticulocytosis 31 HP:0001923
12 optic disc pallor 31 HP:0000543
13 osteopetrosis 31 HP:0011002
14 hepatosplenomegaly 31 HP:0001433
15 sclerotic vertebral endplates 31 HP:0004576

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Abdomen Spleen:
splenomegaly

Hematology:
anemia
thrombocytopenia
reticulocytosis

Head And Neck Eyes:
optic nerve atrophy
pale optic discs
visual impairment (early onset)

Skeletal:
severe osteopetrosis
segmentary osteosclerosis
generalized increased bone density
fractures with minor trauma
increased trabecular size
more
Skeletal Pelvis:
concentric arcs of sclerosis in iliac wings ('bone-within-bone' sign)

Skin Nails Hair Skin:
generalized petechiae

Abdomen Liver:
hepatomegaly

Growth Other:
growth retardation

Skeletal Spine:
increased bone density
sclerotic vertebral endplates ('rugger-jersey' spine)

Skeletal Skull:
sclerosis, particularly of the base of the skull

Skeletal Limbs:
increased bone density in epiphyseal growth plates of long bones

Neurologic Peripheral Nervous System:
bell palsy

Clinical features from OMIM®:

611490 (Updated 05-Apr-2021)

MGI Mouse Phenotypes related to Osteopetrosis, Autosomal Recessive 4:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 hematopoietic system MP:0005397 9.85 ABCB6 ATP6V0A2 CD40LG CLCN7 IMPDH1 SLC4A1
2 homeostasis/metabolism MP:0005376 9.7 ABCB6 ATP6V0A4 ATP6V1B1 CD40LG CLCN7 PRKAG2
3 immune system MP:0005387 9.32 ATP6V0A2 CD40LG CLCN7 IMPDH1 PRKAG2 SLC4A1

Drugs & Therapeutics for Osteopetrosis, Autosomal Recessive 4

Search Clinical Trials , NIH Clinical Center for Osteopetrosis, Autosomal Recessive 4

Genetic Tests for Osteopetrosis, Autosomal Recessive 4

Genetic tests related to Osteopetrosis, Autosomal Recessive 4:

# Genetic test Affiliating Genes
1 Autosomal Recessive Osteopetrosis 4 29 CLCN7

Anatomical Context for Osteopetrosis, Autosomal Recessive 4

MalaCards organs/tissues related to Osteopetrosis, Autosomal Recessive 4:

40
Bone, Bone Marrow

Publications for Osteopetrosis, Autosomal Recessive 4

Articles related to Osteopetrosis, Autosomal Recessive 4:

# Title Authors PMID Year
1
DNA-based diagnosis of malignant osteopetrosis by whole-genome scan using a single-nucleotide polymorphism microarray: standardization of molecular investigations of genetic diseases due to consanguinity. 6 57
17033731 2007
2
Albers-Schönberg disease (autosomal dominant osteopetrosis, type II) results from mutations in the ClCN7 chloride channel gene. 57 6
11741829 2001
3
Loss of the ClC-7 chloride channel leads to osteopetrosis in mice and man. 57 6
11207362 2001
4
Novel mutations of CLCN7 cause autosomal dominant osteopetrosis type II (ADOII) and intermediate autosomal recessive osteopetrosis (ARO) in seven Chinese families. 61
28975865 2017

Variations for Osteopetrosis, Autosomal Recessive 4

ClinVar genetic disease variations for Osteopetrosis, Autosomal Recessive 4:

6 (show all 15)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 CLCN7 NM_001287.6(CLCN7):c.1663C>T (p.Gln555Ter) SNV Pathogenic 6860 rs121434432 GRCh37: 16:1499283-1499283
GRCh38: 16:1449282-1449282
2 CLCN7 NM_001287.6(CLCN7):c.2285G>A (p.Arg762Gln) SNV Pathogenic 6861 rs121434433 GRCh37: 16:1497053-1497053
GRCh38: 16:1447052-1447052
3 CLCN7 NM_001287.6(CLCN7):c.2297T>C (p.Leu766Pro) SNV Pathogenic 6862 rs121434434 GRCh37: 16:1497041-1497041
GRCh38: 16:1447040-1447040
4 CLCN7 NM_001287.6(CLCN7):c.781A>T (p.Ile261Phe) SNV Pathogenic 6865 rs121434436 GRCh37: 16:1507296-1507296
GRCh38: 16:1457295-1457295
5 CLCN7 NM_001287.6(CLCN7):c.2299C>T (p.Arg767Trp) SNV Pathogenic 6863 rs121434435 GRCh37: 16:1497039-1497039
GRCh38: 16:1447038-1447038
6 CLCN7 NM_001287.6(CLCN7):c.643G>A (p.Gly215Arg) SNV Pathogenic 65635 rs397515539 GRCh37: 16:1509140-1509140
GRCh38: 16:1459139-1459139
7 CLCN7 NM_001287.6(CLCN7):c.2250+1G>T SNV Pathogenic 585308 rs1567263375 GRCh37: 16:1497392-1497392
GRCh38: 16:1447391-1447391
8 CLCN7 NM_001287.6(CLCN7):c.1617+119G>A SNV Pathogenic 827681 rs922106856 GRCh37: 16:1500379-1500379
GRCh38: 16:1450378-1450378
9 CLCN7 NM_001287.6(CLCN7):c.296A>G (p.Tyr99Cys) SNV Pathogenic 56890 rs387907576 GRCh37: 16:1511461-1511461
GRCh38: 16:1461460-1461460
10 CLCN7 NM_001287.6(CLCN7):c.839G>A (p.Arg280His) SNV Likely pathogenic 807386 rs1163577336 GRCh37: 16:1506191-1506191
GRCh38: 16:1456190-1456190
11 CLCN7 NM_001287.6(CLCN7):c.1682G>A (p.Arg561Gln) SNV Likely pathogenic 488379 rs757788894 GRCh37: 16:1499082-1499082
GRCh38: 16:1449081-1449081
12 CLCN7 NM_001287.6(CLCN7):c.641A>G (p.Asn214Ser) SNV Uncertain significance 545513 rs367567630 GRCh37: 16:1509142-1509142
GRCh38: 16:1459141-1459141
13 CLCN7 NM_001287.6(CLCN7):c.1165G>A (p.Gly389Arg) SNV Uncertain significance 545690 rs1555465003 GRCh37: 16:1503884-1503884
GRCh38: 16:1453883-1453883
14 CLCN7 NM_001287.6(CLCN7):c.2073+4C>T SNV Uncertain significance 626086 rs768190489 GRCh37: 16:1497652-1497652
GRCh38: 16:1447651-1447651
15 CLCN7 NM_001287.6(CLCN7):c.1252G>A (p.Val418Met) SNV Benign 65634 rs12926089 GRCh37: 16:1502857-1502857
GRCh38: 16:1452856-1452856

UniProtKB/Swiss-Prot genetic disease variations for Osteopetrosis, Autosomal Recessive 4:

72 (show all 20)
# Symbol AA change Variation ID SNP ID
1 CLCN7 p.Arg762Gln VAR_017838 rs121434433
2 CLCN7 p.Leu766Pro VAR_017839 rs121434434
3 CLCN7 p.Arg767Trp VAR_017840 rs121434435
4 CLCN7 p.Gly240Arg VAR_020998 rs136048051
5 CLCN7 p.Pro249Arg VAR_020999
6 CLCN7 p.Met332Val VAR_021001
7 CLCN7 p.Arg526Trp VAR_021004 rs123308526
8 CLCN7 p.Leu614Pro VAR_021005 rs106479432
9 CLCN7 p.Ser744Phe VAR_021007 rs132093233
10 CLCN7 p.Arg767Gln VAR_021008 rs772579858
11 CLCN7 p.Ile261Phe VAR_037427 rs121434436
12 CLCN7 p.Leu132Pro VAR_064637
13 CLCN7 p.Asn214Ser VAR_064638 rs367567630
14 CLCN7 p.Arg403Gln VAR_064641 rs765444328
15 CLCN7 p.Gly521Arg VAR_064642 rs368190250
16 CLCN7 p.Arg526Gln VAR_064643 rs139329533
17 CLCN7 p.Leu549Pro VAR_064644
18 CLCN7 p.Leu651Pro VAR_064645
19 CLCN7 p.Arg762Trp VAR_064647 rs149059853
20 CLCN7 p.Arg767Pro VAR_064648

Expression for Osteopetrosis, Autosomal Recessive 4

Search GEO for disease gene expression data for Osteopetrosis, Autosomal Recessive 4.

Pathways for Osteopetrosis, Autosomal Recessive 4

Pathways related to Osteopetrosis, Autosomal Recessive 4 according to GeneCards Suite gene sharing:

(show all 11)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.76 TCIRG1 SLC4A1 PRKAG2 IMPDH1 HBB CA8
2
Show member pathways
13.07 TCIRG1 PRKAG2 ATP6V1B1 ATP6V0A4 ATP6V0A2 ATP5F1A
3
Show member pathways
12.69 TCIRG1 SLC4A4 SLC4A1 CLCN7 ATP6V1B1 ATP6V0A4
4
Show member pathways
12.15 TCIRG1 CLCN7 ATP6V1B1 ATP6V0A4 ATP6V0A2
5
Show member pathways
12 TCIRG1 SLC4A1 ATP6V1B1 ATP6V0A4 ATP6V0A2
6 11.91 TCIRG1 ATP6V0A4 ATP6V0A2
7 11.85 TCIRG1 ATP6V1B1 ATP6V0A4 ATP6V0A2
8
Show member pathways
11.74 TCIRG1 ATP6V1B1 ATP6V0A4 ATP6V0A2
9 11.72 TCIRG1 ATP6V0A4 ATP6V0A2
10
Show member pathways
11.04 SLC4A1 HBB
11 10.99 TNFSF11 TCIRG1 ATP6V1B1 ATP6V0A4 ATP6V0A2

GO Terms for Osteopetrosis, Autosomal Recessive 4

Cellular components related to Osteopetrosis, Autosomal Recessive 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular exosome GO:0070062 9.92 TGFBI SLC4A4 SLC4A1 HBB ATP6V1B1 ATP6V0A4
2 lysosomal membrane GO:0005765 9.71 TCIRG1 CLCN7 ATP6V0A4 ATP6V0A2
3 endosome membrane GO:0010008 9.67 TCIRG1 ATP6V0A4 ATP6V0A2 ABCB6
4 phagocytic vesicle membrane GO:0030670 9.43 TCIRG1 ATP6V0A4 ATP6V0A2
5 proton-transporting V-type ATPase, V0 domain GO:0033179 9.33 TCIRG1 ATP6V0A4 ATP6V0A2
6 vacuolar proton-transporting V-type ATPase, V0 domain GO:0000220 9.13 TCIRG1 ATP6V0A4 ATP6V0A2
7 vacuolar proton-transporting V-type ATPase complex GO:0016471 8.92 TCIRG1 ATP6V1B1 ATP6V0A4 ATP6V0A2

Biological processes related to Osteopetrosis, Autosomal Recessive 4 according to GeneCards Suite gene sharing:

(show all 23)
# Name GO ID Score Top Affiliating Genes
1 ion transmembrane transport GO:0034220 9.83 TCIRG1 CLCN7 ATP6V1B1 ATP6V0A4 ATP6V0A2
2 ossification GO:0001503 9.71 TNFSF11 TCIRG1 ATP6V1B1 ATP6V0A4
3 regulation of macroautophagy GO:0016241 9.7 PRKAG2 ATP6V1B1 ATP6V0A2
4 insulin receptor signaling pathway GO:0008286 9.67 TCIRG1 ATP6V1B1 ATP6V0A4 ATP6V0A2
5 proton transmembrane transport GO:1902600 9.65 TCIRG1 ATP6V1B1 ATP6V0A4 ATP6V0A2 ATP5F1A
6 bicarbonate transport GO:0015701 9.63 SLC4A4 SLC4A1 HBB
7 osteoclast differentiation GO:0030316 9.61 TNFSF11 TCIRG1
8 excretion GO:0007588 9.61 ATP6V1B1 ATP6V0A4
9 ATP biosynthetic process GO:0006754 9.6 PRKAG2 ATP5F1A
10 calcium ion homeostasis GO:0055074 9.59 TNFSF11 ATP6V1B1
11 regulation of intracellular pH GO:0051453 9.58 SLC4A4 SLC4A1
12 anion transport GO:0006820 9.58 SLC4A4 SLC4A1
13 inorganic anion transport GO:0015698 9.57 SLC4A4 SLC4A1
14 bone resorption GO:0045453 9.56 TNFSF11 TCIRG1
15 ion homeostasis GO:0050801 9.55 SLC4A4 SLC4A1
16 regulation of pH GO:0006885 9.54 ATP6V1B1 ATP6V0A4
17 tooth eruption GO:0044691 9.51 TNFSF11 TCIRG1
18 vacuolar acidification GO:0007035 9.5 TCIRG1 ATP6V0A4 ATP6V0A2
19 pH reduction GO:0045851 9.49 TCIRG1 ATP6V1B1
20 osteoclast proliferation GO:0002158 9.48 TNFSF11 TCIRG1
21 transferrin transport GO:0033572 9.46 TCIRG1 ATP6V1B1 ATP6V0A4 ATP6V0A2
22 phagosome acidification GO:0090383 9.26 TCIRG1 ATP6V1B1 ATP6V0A4 ATP6V0A2
23 ion transport GO:0006811 9.23 TCIRG1 SLC4A4 SLC4A1 CLCN7 ATP6V1B1 ATP6V0A4

Molecular functions related to Osteopetrosis, Autosomal Recessive 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ATPase binding GO:0051117 9.5 TCIRG1 ATP6V0A4 ATP6V0A2
2 tumor necrosis factor receptor binding GO:0005164 9.46 TNFSF11 CD40LG
3 chloride transmembrane transporter activity GO:0015108 9.43 SLC4A1 CLCN7
4 anion transmembrane transporter activity GO:0008509 9.4 SLC4A4 SLC4A1
5 inorganic anion exchanger activity GO:0005452 9.37 SLC4A4 SLC4A1
6 hemoglobin binding GO:0030492 9.26 SLC4A1 HBB
7 adenyl ribonucleotide binding GO:0032559 9.16 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 4

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-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
Content
Loading form....