OPTB4
MCID: OST137
MIFTS: 26

Osteopetrosis, Autosomal Recessive 4 (OPTB4)

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 4

MalaCards integrated aliases for Osteopetrosis, Autosomal Recessive 4:

Name: Osteopetrosis, Autosomal Recessive 4 58 76 13 74
Optb4 58 12 54 76
Osteopetrosis Autosomal Recessive 4 54 30 6
Autosomal Recessive Osteopetrosis 4 12 15
Infantile Malignant Osteopetrosis 2 12 76
Osteopetrosis, Autosomal Recessive, Type 4 41
Autosomal Recessive Osteopetrosis Type 4 54
Osteopetrosis, Infantile Malignant 2 58
Osteopetrosis Infantile Malignant 2 54

Characteristics:

OMIM:

58
Inheritance:
autosomal recessive


HPO:

33
osteopetrosis, autosomal recessive 4:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Osteopetrosis, Autosomal Recessive 4

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 4, is also known as optb4. An important gene associated with Osteopetrosis, Autosomal Recessive 4 is CLCN7 (Chloride Voltage-Gated Channel 7). Affiliated tissues include bone and bone marrow, and related phenotypes are facial palsy and anemia

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 : 76 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.

Description from OMIM: 611490

Related Diseases for Osteopetrosis, Autosomal Recessive 4

Symptoms & Phenotypes for Osteopetrosis, Autosomal Recessive 4

Human phenotypes related to Osteopetrosis, Autosomal Recessive 4:

33 (show all 6)
# Description HPO Frequency HPO Source Accession
1 facial palsy 33 HP:0010628
2 anemia 33 HP:0001903
3 reticulocytosis 33 HP:0001923
4 recurrent fractures 33 HP:0002757
5 osteopetrosis 33 HP:0011002
6 hepatosplenomegaly 33 HP:0001433

Symptoms via clinical synopsis from OMIM:

58
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

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

27
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Synthetic lethal with MLN4924 (a NAE inhibitor) GR00250-A-1 9.23 CLCN7 F2
2 Synthetic lethal with MLN4924 (a NAE inhibitor) GR00250-A-2 9.23 CLCN7 F2

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 Osteopetrosis Autosomal Recessive 4 30 CLCN7

Anatomical Context for Osteopetrosis, Autosomal Recessive 4

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

42
Bone, Bone Marrow

Publications for Osteopetrosis, Autosomal Recessive 4

Variations for Osteopetrosis, Autosomal Recessive 4

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

76 (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

ClinVar genetic disease variations for Osteopetrosis, Autosomal Recessive 4:

6 (show all 24)
# Gene Variation Type Significance SNP ID Assembly Location
1 CLCN7 NM_001287.5(CLCN7): c.1663C> T (p.Gln555Ter) single nucleotide variant Pathogenic rs121434432 GRCh37 Chromosome 16, 1499283: 1499283
2 CLCN7 NM_001287.5(CLCN7): c.1663C> T (p.Gln555Ter) single nucleotide variant Pathogenic rs121434432 GRCh38 Chromosome 16, 1449282: 1449282
3 CLCN7 NM_001287.5(CLCN7): c.2285G> A (p.Arg762Gln) single nucleotide variant Pathogenic rs121434433 GRCh37 Chromosome 16, 1497053: 1497053
4 CLCN7 NM_001287.5(CLCN7): c.2285G> A (p.Arg762Gln) single nucleotide variant Pathogenic rs121434433 GRCh38 Chromosome 16, 1447052: 1447052
5 CLCN7 NM_001287.5(CLCN7): c.2297T> C (p.Leu766Pro) single nucleotide variant Pathogenic rs121434434 GRCh37 Chromosome 16, 1497041: 1497041
6 CLCN7 NM_001287.5(CLCN7): c.2297T> C (p.Leu766Pro) single nucleotide variant Pathogenic rs121434434 GRCh38 Chromosome 16, 1447040: 1447040
7 CLCN7 NM_001287.5(CLCN7): c.2299C> T (p.Arg767Trp) single nucleotide variant Pathogenic rs121434435 GRCh37 Chromosome 16, 1497039: 1497039
8 CLCN7 NM_001287.5(CLCN7): c.2299C> T (p.Arg767Trp) single nucleotide variant Pathogenic rs121434435 GRCh38 Chromosome 16, 1447038: 1447038
9 CLCN7 NM_001287.5(CLCN7): c.781A> T (p.Ile261Phe) single nucleotide variant Pathogenic rs121434436 GRCh37 Chromosome 16, 1507296: 1507296
10 CLCN7 NM_001287.5(CLCN7): c.781A> T (p.Ile261Phe) single nucleotide variant Pathogenic rs121434436 GRCh38 Chromosome 16, 1457295: 1457295
11 CLCN7 NM_001287.5(CLCN7): c.296A> G (p.Tyr99Cys) single nucleotide variant Likely pathogenic rs387907576 GRCh37 Chromosome 16, 1511461: 1511461
12 CLCN7 NM_001287.5(CLCN7): c.296A> G (p.Tyr99Cys) single nucleotide variant Likely pathogenic rs387907576 GRCh38 Chromosome 16, 1461460: 1461460
13 CLCN7 NM_001287.5(CLCN7): c.1252G> A (p.Val418Met) single nucleotide variant Benign/Likely benign rs12926089 GRCh37 Chromosome 16, 1502857: 1502857
14 CLCN7 NM_001287.5(CLCN7): c.1252G> A (p.Val418Met) single nucleotide variant Benign/Likely benign rs12926089 GRCh38 Chromosome 16, 1452856: 1452856
15 CLCN7 NM_001287.5(CLCN7): c.643G> A (p.Gly215Arg) single nucleotide variant Pathogenic rs397515539 GRCh37 Chromosome 16, 1509140: 1509140
16 CLCN7 NM_001287.5(CLCN7): c.643G> A (p.Gly215Arg) single nucleotide variant Pathogenic rs397515539 GRCh38 Chromosome 16, 1459139: 1459139
17 CLCN7 NM_001114331.2(CLCN7): c.1610G> A (p.Arg537Gln) single nucleotide variant Likely pathogenic rs757788894 GRCh37 Chromosome 16, 1499082: 1499082
18 CLCN7 NM_001114331.2(CLCN7): c.1610G> A (p.Arg537Gln) single nucleotide variant Likely pathogenic rs757788894 GRCh38 Chromosome 16, 1449081: 1449081
19 CLCN7 NM_001287.5(CLCN7): c.641A> G (p.Asn214Ser) single nucleotide variant Uncertain significance rs367567630 GRCh38 Chromosome 16, 1459141: 1459141
20 CLCN7 NM_001287.5(CLCN7): c.641A> G (p.Asn214Ser) single nucleotide variant Uncertain significance rs367567630 GRCh37 Chromosome 16, 1509142: 1509142
21 CLCN7 NM_001287.5(CLCN7): c.1165G> A (p.Gly389Arg) single nucleotide variant Uncertain significance rs1555465003 GRCh38 Chromosome 16, 1453883: 1453883
22 CLCN7 NM_001287.5(CLCN7): c.1165G> A (p.Gly389Arg) single nucleotide variant Uncertain significance rs1555465003 GRCh37 Chromosome 16, 1503884: 1503884
23 CLCN7 NM_001287.5(CLCN7): c.2250+1G> T single nucleotide variant Pathogenic GRCh38 Chromosome 16, 1447391: 1447391
24 CLCN7 NM_001287.5(CLCN7): c.2250+1G> T single nucleotide variant Pathogenic GRCh37 Chromosome 16, 1497392: 1497392

Expression for Osteopetrosis, Autosomal Recessive 4

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

Pathways for Osteopetrosis, Autosomal Recessive 4

GO Terms for Osteopetrosis, Autosomal Recessive 4

Sources for Osteopetrosis, Autosomal Recessive 4

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