OPTB1
MCID: OST126
MIFTS: 51

Osteopetrosis, Autosomal Recessive 1 (OPTB1)

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 1

MalaCards integrated aliases for Osteopetrosis, Autosomal Recessive 1:

Name: Osteopetrosis, Autosomal Recessive 1 57 72 13 70
Autosomal Recessive Osteopetrosis 1 12 29 6 15
Optb1 57 12 20 72
Autosomal Recessive Albers-Schonberg Disease 12 72
Infantile Malignant Osteopetrosis 72 70
Albers-Schonberg Disease, Autosomal Recessive 57
Osteopetrosis, Autosomal Recessive, Type 1 39
Autosomal Recessive Osteopetrosis Type 1 20
Osteopetrosis, Infantile Malignant 1 57
Infantile Malignant Osteopetrosis 1 12
Osteopetrosis Autosomal Recessive 1 20
Osteopetrosis Infantile Malignant 1 20
Marble Bones, Autosomal Recessive 57
Marble Bones Autosomal Recessive 20

Characteristics:

OMIM®:

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

Miscellaneous:
genetic heterogeneity (see )


HPO:

31
osteopetrosis, autosomal recessive 1:
Inheritance autosomal recessive inheritance heterogeneous


Classifications:



Summaries for Osteopetrosis, Autosomal Recessive 1

OMIM® : 57 Osteopetrosis (OPT) is a life-threatening disease caused by subnormal osteoclast function, with an incidence of 1 in 250,000 births. The disease usually manifests in the first few months of life with macrocephaly and frontal bossing, resulting in a characteristic facial appearance. Defective bone remodeling of the skull results in choanal stenosis with concomitant respiratory problems and feeding difficulties, which are the first clinical manifestation of disease. The expanding bone encroaches on neural foramina, leading to blindness, deafness, and facial palsy. Complete visual loss invariably occurs in all untreated patients, and hearing loss is estimated to affect 78% of patients with OPT. Tooth eruption defects and severe dental caries are common. Calcium feedback hemostasis is impaired, and children with OPT are at risk of developing hypocalcemia with attendant tetanic seizures and secondary hyperparathyroidism. The most severe complication of OPT, limiting survival, is bone marrow insufficiency. The abnormal expansion of cortical and trabecular bone physically limits the availability of medullary space for hematopoietic activity, leading to life-threatening cytopenia and secondary expansion of extramedullary hematopoiesis at sites such as the liver and spleen (summary by Aker et al., 2012). (259700) (Updated 05-Apr-2021)

MalaCards based summary : Osteopetrosis, Autosomal Recessive 1, also known as autosomal recessive osteopetrosis 1, is related to autosomal recessive malignant osteopetrosis and osteopetrosis, autosomal recessive 5, and has symptoms including ophthalmoplegia An important gene associated with Osteopetrosis, Autosomal Recessive 1 is TCIRG1 (T Cell Immune Regulator 1, ATPase H+ Transporting V0 Subunit A3), and among its related pathways/superpathways are Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds and PI3K-Akt signaling pathway. The drugs Levoleucovorin and leucovorin have been mentioned in the context of this disorder. Affiliated tissues include bone, bone marrow and spleen, and related phenotypes are macrocephaly and failure to thrive

Disease Ontology : 12 An osteopetrosis characterized by autosomal recessive inheritance that has material basis in homozygous or compound heterozygous mutation in the TCIRG1 gene on chromosome 11q13.2.

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.

UniProtKB/Swiss-Prot : 72 Osteopetrosis, autosomal recessive 1: 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.

Related Diseases for Osteopetrosis, Autosomal Recessive 1

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

(show top 50) (show all 62)
# Related Disease Score Top Affiliating Genes
1 autosomal recessive malignant osteopetrosis 32.1 TCIRG1 CLCN7
2 osteopetrosis, autosomal recessive 5 30.8 TCIRG1 IMPDH1 CLCN7 ATP6V1B1 ATP6V0A4
3 osteopetrosis 30.8 TCIRG1 CLCN7 ATP6V1B1
4 osteopetrosis, autosomal recessive 4 30.5 TCIRG1 IMPDH1 CLCN7 ATP6V1B1 ATP6V0A4
5 autosomal recessive disease 10.3
6 bone resorption disease 10.3
7 thrombocytopenia 10.3
8 yemenite deaf-blind hypopigmentation syndrome 10.2
9 graft-versus-host disease 10.2
10 clcn7-related osteopetrosis 10.2
11 branchiootic syndrome 1 10.1
12 pancytopenia 10.1
13 pathologic nystagmus 10.1
14 pulmonary hypertension, primary, 1 10.0
15 silver-russell syndrome 1 10.0
16 strabismus 10.0
17 myelofibrosis 10.0
18 3-methylglutaconic aciduria, type iii 10.0
19 juvenile myelomonocytic leukemia 10.0
20 choanal atresia, posterior 10.0
21 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 10.0
22 pulmonary hypertension 10.0
23 hypophosphatemia 10.0
24 bone disease 10.0
25 hepatic veno-occlusive disease 10.0
26 osteomyelitis 10.0
27 osteomalacia 10.0
28 rickets 10.0
29 respiratory failure 10.0
30 diarrhea 10.0
31 agammaglobulinemia 10.0
32 retinal degeneration 10.0
33 mechanical strabismus 10.0
34 diencephalic syndrome 10.0
35 homologous wasting disease 10.0
36 hypotonia 10.0
37 axial osteomalacia 10.0 TCIRG1 CLCN7
38 fibrogenesis imperfecta ossium 10.0 TCIRG1 CLCN7
39 osteopetrosis, autosomal recessive 2 9.9 TCIRG1 CLCN7
40 craniodiaphyseal dysplasia 9.9 TCIRG1 CLCN7
41 osteopetrosis, autosomal dominant 2 9.9 TCIRG1 CLCN7
42 osteopetrosis, autosomal recessive 8 9.9 TCIRG1 CLCN7
43 pycnodysostosis 9.9 TCIRG1 CLCN7
44 craniometaphyseal dysplasia, autosomal dominant 9.9 TCIRG1 CLCN7
45 endosteal hyperostosis, autosomal dominant 9.9 TCIRG1 CLCN7
46 bone remodeling disease 9.8 TCIRG1 CLCN7
47 hereditary distal renal tubular acidosis 9.8 ATP6V1B1 ATP6V0A4
48 distal renal tubular acidosis 9.8 ATP6V1B1 ATP6V0A4
49 medullary sponge kidney 9.8 ATP6V1B1 ATP6V0A4
50 renal tubular acidosis, distal, 3, with or without sensorineural hearing loss 9.8 ATP6V1B1 ATP6V0A4

Graphical network of the top 20 diseases related to Osteopetrosis, Autosomal Recessive 1:



Diseases related to Osteopetrosis, Autosomal Recessive 1

Symptoms & Phenotypes for Osteopetrosis, Autosomal Recessive 1

Human phenotypes related to Osteopetrosis, Autosomal Recessive 1:

31 (show all 25)
# Description HPO Frequency HPO Source Accession
1 macrocephaly 31 HP:0000256
2 failure to thrive 31 HP:0001508
3 frontal bossing 31 HP:0002007
4 nystagmus 31 HP:0000639
5 facial palsy 31 HP:0010628
6 hydrocephalus 31 HP:0000238
7 hearing impairment 31 HP:0000365
8 splenomegaly 31 HP:0001744
9 hepatomegaly 31 HP:0002240
10 carious teeth 31 HP:0000670
11 optic atrophy 31 HP:0000648
12 blindness 31 HP:0000618
13 anemia 31 HP:0001903
14 tetany 31 HP:0001281
15 osteomyelitis 31 HP:0002754
16 ophthalmoparesis 31 HP:0000597
17 coxa vara 31 HP:0002812
18 osteopetrosis 31 HP:0011002
19 pancytopenia 31 HP:0001876
20 pathologic fracture 31 HP:0002756
21 flared metaphysis 31 HP:0003015
22 elevated alkaline phosphatase 31 HP:0003155
23 facial paralysis 31 HP:0007209
24 sandwich appearance of vertebral bodies 31 HP:0004618
25 seizure 31 HP:0001250

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Head And Neck Head:
macrocephaly

Head And Neck Face:
frontal bossing
facial paralysis

Neurologic Central Nervous System:
hydrocephalus
cranial nerve palsies
seizures (tetany)

Abdomen Liver:
hepatomegaly

Skeletal:
osteomyelitis
pathologic fractures
uniformly dense skeleton
bone-within-bone appearance

Laboratory Abnormalities:
elevated alkaline phosphatase
elevated serum phosphorus
low serum calcium

Head And Neck Ears:
deafness

Skeletal Skull:
thick, dense skull
narrowness of neural and vascular foramina

Growth Weight:
failure to thrive

Head And Neck Eyes:
nystagmus
optic atrophy
blindness
extraocular muscle paralysis

Abdomen Spleen:
splenomegaly

Hematology:
anemia
pancytopenia

Skeletal Pelvis:
coxa vara

Skeletal Spine:
sandwich appearance of vertebral bodies

Head And Neck Teeth:
dental caries
distorted primary molars

Skeletal Limbs:
splayed metaphyses

Clinical features from OMIM®:

259700 (Updated 05-Apr-2021)

UMLS symptoms related to Osteopetrosis, Autosomal Recessive 1:


ophthalmoplegia

Drugs & Therapeutics for Osteopetrosis, Autosomal Recessive 1

Drugs for Osteopetrosis, Autosomal Recessive 1 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Levoleucovorin Approved, Investigational Phase 1 68538-85-2 149436
2
leucovorin Approved Phase 1 58-05-9 6006

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 A Phase I Clinical Trial for Gene Therapy in Infantile Malignant Osteopetrosis (IMO) to Evaluate the Safety and Preliminary Efficacy of Autologous CD34+ Enriched Cells Transduced With a LV Vector Encoding the TCIRG1 Gene Recruiting NCT04525352 Phase 1

Search NIH Clinical Center for Osteopetrosis, Autosomal Recessive 1

Genetic Tests for Osteopetrosis, Autosomal Recessive 1

Genetic tests related to Osteopetrosis, Autosomal Recessive 1:

# Genetic test Affiliating Genes
1 Autosomal Recessive Osteopetrosis 1 29 TCIRG1

Anatomical Context for Osteopetrosis, Autosomal Recessive 1

MalaCards organs/tissues related to Osteopetrosis, Autosomal Recessive 1:

40
Bone, Bone Marrow, Spleen, Brain, Neutrophil

Publications for Osteopetrosis, Autosomal Recessive 1

Articles related to Osteopetrosis, Autosomal Recessive 1:

(show top 50) (show all 115)
# Title Authors PMID Year
1
Mutations in the a3 subunit of the vacuolar H(+)-ATPase cause infantile malignant osteopetrosis. 61 57 6
10942435 2000
2
Defects in TCIRG1 subunit of the vacuolar proton pump are responsible for a subset of human autosomal recessive osteopetrosis. 6 57 61
10888887 2000
3
A phenocopy of CAII deficiency: a novel genetic explanation for inherited infantile osteopetrosis with distal renal tubular acidosis. 6 57
12566520 2003
4
Identification of novel mutation in autosomal recessive infantile malignant osteopetrosis. 61 6
24101165 2014
5
Infantile malignant osteopetrosis. 61 6
23721911 2013
6
Novel mutation of TCIRG1 and clinical pictures of two infantile malignant osteopetrosis patients. 6 61
21042819 2011
7
A single-center experience in 20 patients with infantile malignant osteopetrosis. 6 61
19507210 2009
8
Novel mutations in the TCIRG1 gene encoding the a3 subunit of the vacuolar proton pump in patients affected by infantile malignant osteopetrosis. 61 6
12552563 2003
9
Allogeneic bone-marrow transplantation in infantile malignant osteopetrosis. 61 57
6131166 1983
10
Successful bone-marrow transplantation for infantile malignant osteopetrosis. 57 61
6986555 1980
11
Genetic Diagnosis Using Whole Exome Analysis in Two Cases with Malignant Osteopetrosis of Infancy. 6
26777052 2015
12
Buried in the Middle but Guilty: Intronic Mutations in the TCIRG1 Gene Cause Human Autosomal Recessive Osteopetrosis. 6
25829125 2015
13
A founder mutation in the TCIRG1 gene causes osteopetrosis in the Ashkenazi Jewish population. 6
24989235 2015
14
RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease. 6
25525159 2015
15
Identification of TCIRG1 and CLCN7 gene mutations in a patient with autosomal recessive osteopetrosis. 6
24535484 2014
16
Malignant infantile osteopetrosis: case report with review of literature. 6
25018813 2014
17
Autosomal recessive osteopetrosis: report of 41 novel mutations in the TCIRG1 gene and diagnostic implications. 6
22231430 2012
18
An SNX10 mutation causes malignant osteopetrosis of infancy. 57
22499339 2012
19
Characterization of a novel Alu-Alu recombination-mediated genomic deletion in the TCIRG1 gene in five osteopetrotic patients. 6
18715141 2009
20
TCIRG1-dependent recessive osteopetrosis: mutation analysis, functional identification of the splicing defects, and in vitro rescue by U1 snRNA. 6
15300850 2004
21
Hematopoietic cells and osteoblasts are derived from a common marrow progenitor after bone marrow transplantation. 57
15282377 2004
22
Genotype-phenotype relationship in human ATP6i-dependent autosomal recessive osteopetrosis. 6
12507890 2003
23
Molecular genetics of too much bone. 57
12351574 2002
24
The mutational spectrum of human malignant autosomal recessive osteopetrosis. 6
11532986 2001
25
Human autosomal recessive osteopetrosis maps to 11q13, a position predicted by comparative mapping of the murine osteosclerosis (oc) mutation. 57
9700194 1998
26
Demonstration of an osteoblast defect in two cases of human malignant osteopetrosis. Correction of the phenotype after bone marrow transplant. 57
8878435 1996
27
Long-term treatment of osteopetrosis with recombinant human interferon gamma. 57
7753137 1995
28
Prenatal diagnosis of autosomal recessive osteopetrosis, infantile type, by X-ray evaluation. 57
7644439 1995
29
Bone marrow transplantation for autosomal recessive osteopetrosis. A report from the Working Party on Inborn Errors of the European Bone Marrow Transplantation Group. 57
7996361 1994
30
Syndrome of infantile osteopetrosis and Hirschsprung disease in seven children born to four consanguineous unions in two families. 57
8291528 1993
31
Combination macrophage-colony stimulating factor and interferon-gamma administration ameliorates the osteopetrotic condition in microphthalmic (mi/mi) mice. 57
8479820 1993
32
Recombinant human interferon gamma therapy for osteopetrosis. 57
1320672 1992
33
Circulating macrophage colony-stimulating factor is not reduced in malignant osteopetrosis. 57
1577090 1992
34
Partial correction of the phagocyte defect in patients with X-linked chronic granulomatous disease by subcutaneous interferon gamma. 57
2838754 1988
35
Osteopetrosis. A genetic and epidemiological study. 57
3829443 1987
36
Neutrophil defect associated with malignant infantile osteopetrosis. 57
3021878 1986
37
Bone-marrow transplantation for immunodeficiencies and osteopetrosis: European survey, 1968-1985. 57
2877234 1986
38
Treatment of congenital osteopetrosis with high-dose calcitriol. 57
6546410 1984
39
Marrow transplantation for juvenile osteopetrosis. 57
7015858 1981
40
Osteopetrosis in children: a report of 26 cases. 57
874663 1977
41
Bone resorption restored in osteopetrotic mice by transplants of normal bone marrow and spleen cells. 57
1105786 1975
42
Spleen cells transmit osteopetrosis in mice. 57
1198094 1975
43
Therapeutic studies in osteopetrosis. Report of 4 cases. 57
5378349 1969
44
Retinal atrophy in osteopetrosis. 57
4170880 1968
45
Malignant congenital osteopetrosis resulting from a consanguineous marriage. 57
13985134 1962
46
Studies on osteopetrosis. 1. Clinical report of three cases with genetic considerations. 57
13532685 1958
47
About the genetics of the simple recessive forms of marble bone disease and two corresponding family trees from Switzerland. 57
18865120 1948
48
Gene therapy for infantile malignant osteopetrosis: review of pre-clinical research and proof-of-concept for phenotypic reversal. 61
33575431 2021
49
SNX10 gene mutation in infantile malignant osteopetrosis: A case report and literature review. 61
33678645 2021
50
Generation of gene-corrected functional osteoclasts from osteopetrotic induced pluripotent stem cells. 61
32414402 2020

Variations for Osteopetrosis, Autosomal Recessive 1

ClinVar genetic disease variations for Osteopetrosis, Autosomal Recessive 1:

6 (show top 50) (show all 250)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 TCIRG1 NM_006019.4(TCIRG1):c.922del (p.Gln308fs) Deletion Pathogenic 5459 rs1554996130 GRCh37: 11:67811712-67811712
GRCh38: 11:68044245-68044245
2 TCIRG1 NM_006019.4(TCIRG1):c.1392C>A (p.Cys464Ter) SNV Pathogenic 5460 rs137853149 GRCh37: 11:67815200-67815200
GRCh38: 11:68047733-68047733
3 TCIRG1 NM_006019.4(TCIRG1):c.1674G>A (p.Val558=) SNV Pathogenic 5461 rs745971874 GRCh37: 11:67816548-67816548
GRCh38: 11:68049081-68049081
4 TCIRG1 NM_006019.4(TCIRG1):c.1331G>T (p.Arg444Leu) SNV Pathogenic 5464 rs137853151 GRCh37: 11:67815139-67815139
GRCh38: 11:68047672-68047672
5 TCIRG1 NM_006019.3(TCIRG1):c.649_674del (p.Met217Terfs) Deletion Pathogenic 5465 GRCh37: 11:67811056-67811081
GRCh38: 11:68043587-68043612
6 TCIRG1 NM_006019.4(TCIRG1):c.630+2T>C SNV Pathogenic 551426 rs1392364437 GRCh37: 11:67810966-67810966
GRCh38: 11:68043499-68043499
7 TCIRG1 NM_006019.4(TCIRG1):c.2236C>T (p.Gln746Ter) SNV Pathogenic 553240 rs748659068 GRCh37: 11:67817721-67817721
GRCh38: 11:68050254-68050254
8 TCIRG1 NM_006019.4(TCIRG1):c.1276C>T (p.Arg426Ter) SNV Pathogenic 557398 rs1489993984 GRCh37: 11:67815010-67815010
GRCh38: 11:68047543-68047543
9 TCIRG1 NM_006019.4(TCIRG1):c.2236+1G>A SNV Pathogenic 558226 rs1475338876 GRCh37: 11:67817722-67817722
GRCh38: 11:68050255-68050255
10 TCIRG1 NM_006019.4(TCIRG1):c.1114C>T (p.Gln372Ter) SNV Pathogenic 830066 rs776436008 GRCh37: 11:67812518-67812518
GRCh38: 11:68045051-68045051
11 TCIRG1 NM_006019.4(TCIRG1):c.553del (p.Leu185fs) Deletion Pathogenic 978470 GRCh37: 11:67810886-67810886
GRCh38: 11:68043419-68043419
12 TCIRG1 NM_006019.4(TCIRG1):c.1674-1G>A SNV Pathogenic 189246 rs139617644 GRCh37: 11:67816547-67816547
GRCh38: 11:68049080-68049080
13 TCIRG1 NM_006019.4(TCIRG1):c.2008C>T (p.Arg670Ter) SNV Pathogenic 551284 rs371263807 GRCh37: 11:67817250-67817250
GRCh38: 11:68049783-68049783
14 TCIRG1 NM_006019.4(TCIRG1):c.1213G>C (p.Gly405Arg) SNV Pathogenic/Likely pathogenic 552227 rs137853150 GRCh37: 11:67814947-67814947
GRCh38: 11:68047480-68047480
15 TCIRG1 NM_006019.4(TCIRG1):c.1213G>A (p.Gly405Arg) SNV Pathogenic/Likely pathogenic 5463 rs137853150 GRCh37: 11:67814947-67814947
GRCh38: 11:68047480-68047480
16 TCIRG1 NM_006019.4(TCIRG1):c.1559G>A (p.Trp520Ter) SNV Likely pathogenic 371557 rs1057517365 GRCh37: 11:67816350-67816350
GRCh38: 11:68048883-68048883
17 TCIRG1 NM_006019.4(TCIRG1):c.205C>T (p.Gln69Ter) SNV Likely pathogenic 552024 rs1554995009 GRCh37: 11:67810118-67810118
GRCh38: 11:68042651-68042651
18 TCIRG1 NM_006019.4(TCIRG1):c.242del (p.Pro81fs) Deletion Likely pathogenic 551450 rs1208311085 GRCh37: 11:67810151-67810151
GRCh38: 11:68042684-68042684
19 TCIRG1 NM_006019.4(TCIRG1):c.1555-2A>C SNV Likely pathogenic 551487 rs758977199 GRCh37: 11:67816344-67816344
GRCh38: 11:68048877-68048877
20 TCIRG1 NM_006019.4(TCIRG1):c.557_570del (p.Leu186fs) Deletion Likely pathogenic 551799 rs1554995522 GRCh37: 11:67810885-67810898
GRCh38: 11:68043418-68043431
21 TCIRG1 NM_006019.4(TCIRG1):c.979C>T (p.Arg327Ter) SNV Likely pathogenic 550832 rs749361897 GRCh37: 11:67811770-67811770
GRCh38: 11:68044303-68044303
22 TCIRG1 NM_006019.4(TCIRG1):c.1435_1438dup (p.Ala480fs) Duplication Likely pathogenic 550871 rs1554998061 GRCh37: 11:67815241-67815242
GRCh38: 11:68047774-68047775
23 TCIRG1 NM_006019.4(TCIRG1):c.1889_1890dup (p.Val631fs) Duplication Likely pathogenic 551059 rs1554999516 GRCh37: 11:67817129-67817130
GRCh38: 11:68049662-68049663
24 TCIRG1 NM_006019.4(TCIRG1):c.1118del (p.Gly373fs) Deletion Likely pathogenic 552720 rs1269558164 GRCh37: 11:67812520-67812520
GRCh38: 11:68045053-68045053
25 TCIRG1 NM_006019.4(TCIRG1):c.346C>T (p.Gln116Ter) SNV Likely pathogenic 552835 rs1338631330 GRCh37: 11:67810259-67810259
GRCh38: 11:68042792-68042792
26 TCIRG1 NM_006019.4(TCIRG1):c.807+1G>T SNV Likely pathogenic 553582 rs1458295257 GRCh37: 11:67811375-67811375
GRCh38: 11:68043908-68043908
27 TCIRG1 NM_006019.4(TCIRG1):c.-5+1G>T SNV Likely pathogenic 553850 rs917505107 GRCh37: 11:67806587-67806587
GRCh38: 11:68039120-68039120
28 TCIRG1 NM_006019.4(TCIRG1):c.1306-1G>A SNV Likely pathogenic 554018 rs1554997884 GRCh37: 11:67815113-67815113
GRCh38: 11:68047646-68047646
29 TCIRG1 NM_006019.4(TCIRG1):c.2415-2A>G SNV Likely pathogenic 554390 rs1555000376 GRCh37: 11:67818206-67818206
GRCh38: 11:68050739-68050739
30 TCIRG1 NM_006019.4(TCIRG1):c.1554+1G>T SNV Likely pathogenic 554456 rs1439348400 GRCh37: 11:67815440-67815440
GRCh38: 11:68047973-68047973
31 TCIRG1 NM_006019.4(TCIRG1):c.466C>T (p.Gln156Ter) SNV Likely pathogenic 554751 rs1554995330 GRCh37: 11:67810461-67810461
GRCh38: 11:68042994-68042994
32 TCIRG1 NM_006019.4(TCIRG1):c.2450dup (p.Tyr818fs) Duplication Likely pathogenic 694391 rs1590819834 GRCh37: 11:67818240-67818241
GRCh38: 11:68050773-68050774
33 TCIRG1 NM_006019.4(TCIRG1):c.674del (p.Gly225fs) Deletion Likely pathogenic 804459 rs1590804397 GRCh37: 11:67811078-67811078
GRCh38: 11:68043611-68043611
34 TCIRG1 NM_006019.4(TCIRG1):c.2415-1G>C SNV Likely pathogenic 804460 rs1590819770 GRCh37: 11:67818207-67818207
GRCh38: 11:68050740-68050740
35 TCIRG1 NM_006019.4(TCIRG1):c.1887+1G>C SNV Likely pathogenic 558282 rs1554999205 GRCh37: 11:67816762-67816762
GRCh38: 11:68049295-68049295
36 TCIRG1 NM_006019.4(TCIRG1):c.503+1G>A SNV Likely pathogenic 558548 rs1554995381 GRCh37: 11:67810499-67810499
GRCh38: 11:68043032-68043032
37 TCIRG1 NM_006019.4(TCIRG1):c.1305+2T>C SNV Likely pathogenic 557548 rs1554997818 GRCh37: 11:67815041-67815041
GRCh38: 11:68047574-68047574
38 TCIRG1 NM_006019.4(TCIRG1):c.713+1G>C SNV Likely pathogenic 557878 rs774308815 GRCh37: 11:67811121-67811121
GRCh38: 11:68043654-68043654
39 TCIRG1 NM_006019.4(TCIRG1):c.487C>T (p.Gln163Ter) SNV Likely pathogenic 557925 rs1385741705 GRCh37: 11:67810482-67810482
GRCh38: 11:68043015-68043015
40 TCIRG1 NM_006019.4(TCIRG1):c.690_706dup (p.Thr236fs) Duplication Likely pathogenic 557128 rs1554995706 GRCh37: 11:67811094-67811095
GRCh38: 11:68043627-68043628
41 TCIRG1 NM_006019.4(TCIRG1):c.479_480delinsT (p.Gly160fs) Indel Likely pathogenic 558012 rs1554995350 GRCh37: 11:67810474-67810475
GRCh38: 11:68043007-68043008
42 TCIRG1 NM_006019.4(TCIRG1):c.630+1G>T SNV Likely pathogenic 555046 rs1554995582 GRCh37: 11:67810965-67810965
GRCh38: 11:68043498-68043498
43 TCIRG1 NM_006019.4(TCIRG1):c.713+1G>T SNV Likely pathogenic 555158 rs774308815 GRCh37: 11:67811121-67811121
GRCh38: 11:68043654-68043654
44 TCIRG1 NM_006019.4(TCIRG1):c.1891del (p.Val631fs) Deletion Likely pathogenic 555837 rs1300297240 GRCh37: 11:67817132-67817132
GRCh38: 11:68049665-68049665
45 TCIRG1 NM_006019.4(TCIRG1):c.480dup (p.Pro161fs) Duplication Likely pathogenic 556585 rs1554995341 GRCh37: 11:67810469-67810470
GRCh38: 11:68043002-68043003
46 TCIRG1 NM_006019.4(TCIRG1):c.1385dup (p.Asn462fs) Duplication Likely pathogenic 556717 rs1554997997 GRCh37: 11:67815191-67815192
GRCh38: 11:68047724-68047725
47 TCIRG1 NM_006019.4(TCIRG1):c.117+4A>T SNV Likely pathogenic 5462 rs751881962 GRCh37: 11:67808859-67808859
GRCh38: 11:68041392-68041392
48 TCIRG1 NM_006019.4(TCIRG1):c.1684C>T (p.Gln562Ter) SNV Likely pathogenic 995579 GRCh37: 11:67816558-67816558
GRCh38: 11:68049091-68049091
49 TCIRG1 NM_006019.4(TCIRG1):c.1024G>T (p.Glu342Ter) SNV Likely pathogenic 555504 rs1159666762 GRCh37: 11:67812428-67812428
GRCh38: 11:68044961-68044961
50 TCIRG1 NM_006019.4(TCIRG1):c.1800C>T (p.Ala600=) SNV Conflicting interpretations of pathogenicity 305811 rs145144233 GRCh37: 11:67816674-67816674
GRCh38: 11:68049207-68049207

UniProtKB/Swiss-Prot genetic disease variations for Osteopetrosis, Autosomal Recessive 1:

72
# Symbol AA change Variation ID SNP ID
1 TCIRG1 p.Gly405Arg VAR_019569 rs137853150
2 TCIRG1 p.Arg444Leu VAR_019570 rs137853151
3 TCIRG1 p.Ala141Pro VAR_020988
4 TCIRG1 p.Asp517Asn VAR_020990 rs369264588
5 TCIRG1 p.Pro775Arg VAR_020991

Expression for Osteopetrosis, Autosomal Recessive 1

Search GEO for disease gene expression data for Osteopetrosis, Autosomal Recessive 1.

Pathways for Osteopetrosis, Autosomal Recessive 1

Pathways related to Osteopetrosis, Autosomal Recessive 1 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.8 TCIRG1 CLCN7 ATP6V1B1 ATP6V0A4
2
Show member pathways
12.42 TCIRG1 ATP6V1B1 ATP6V0A4
3
Show member pathways
11.95 TCIRG1 ATP6V1B1 ATP6V0A4
4 11.71 TCIRG1 ATP6V0A4
5 11.61 TCIRG1 ATP6V1B1 ATP6V0A4
6 11.54 TCIRG1 ATP6V0A4
7
Show member pathways
11.45 TCIRG1 ATP6V1B1 ATP6V0A4
8
Show member pathways
11.42 TCIRG1 CLCN7 ATP6V1B1 ATP6V0A4
9 11.1 TCIRG1 ATP6V1B1 ATP6V0A4

GO Terms for Osteopetrosis, Autosomal Recessive 1

Cellular components related to Osteopetrosis, Autosomal Recessive 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 apical plasma membrane GO:0016324 9.5 TCIRG1 ATP6V1B1 ATP6V0A4
2 lysosomal membrane GO:0005765 9.43 TCIRG1 CLCN7 ATP6V0A4
3 phagocytic vesicle membrane GO:0030670 9.37 TCIRG1 ATP6V0A4
4 proton-transporting V-type ATPase, V0 domain GO:0033179 9.16 TCIRG1 ATP6V0A4
5 vacuolar proton-transporting V-type ATPase, V0 domain GO:0000220 8.96 TCIRG1 ATP6V0A4
6 vacuolar proton-transporting V-type ATPase complex GO:0016471 8.8 TCIRG1 ATP6V1B1 ATP6V0A4

Biological processes related to Osteopetrosis, Autosomal Recessive 1 according to GeneCards Suite gene sharing:

(show all 12)
# Name GO ID Score Top Affiliating Genes
1 ion transport GO:0006811 9.73 TCIRG1 CLCN7 ATP6V1B1 ATP6V0A4
2 proton transmembrane transport GO:1902600 9.58 TCIRG1 ATP6V1B1 ATP6V0A4
3 ossification GO:0001503 9.54 TCIRG1 ATP6V1B1 ATP6V0A4
4 sensory perception of sound GO:0007605 9.51 ATP6V1B1 ATP6V0A4
5 excretion GO:0007588 9.49 ATP6V1B1 ATP6V0A4
6 regulation of pH GO:0006885 9.48 ATP6V1B1 ATP6V0A4
7 vacuolar acidification GO:0007035 9.46 TCIRG1 ATP6V0A4
8 ion transmembrane transport GO:0034220 9.46 TCIRG1 CLCN7 ATP6V1B1 ATP6V0A4
9 insulin receptor signaling pathway GO:0008286 9.43 TCIRG1 ATP6V1B1 ATP6V0A4
10 pH reduction GO:0045851 9.32 TCIRG1 ATP6V1B1
11 transferrin transport GO:0033572 9.13 TCIRG1 ATP6V1B1 ATP6V0A4
12 phagosome acidification GO:0090383 8.8 TCIRG1 ATP6V1B1 ATP6V0A4

Molecular functions related to Osteopetrosis, Autosomal Recessive 1 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 1

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
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