ITM2B
integral membrane protein 2B, the group of BRICHOS domain containing
Basic information
Region (hg38): 13:48232612-48270357
Links
Phenotypes
GenCC
Source:
- ABri amyloidosis (Strong), mode of inheritance: AD
- ABri amyloidosis (Supportive), mode of inheritance: AD
- ADan amyloidosis (Supportive), mode of inheritance: AD
- retinal dystrophy with inner retinal dysfunction and ganglion cell anomalies (Supportive), mode of inheritance: AD
- retinal dystrophy with inner retinal dysfunction and ganglion cell anomalies (Limited), mode of inheritance: AD
- retinal dystrophy with inner retinal dysfunction and ganglion cell anomalies (Limited), mode of inheritance: AD
- retinal dystrophy with inner retinal dysfunction and ganglion cell anomalies (Limited), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Cerebral amyloid angiopathy, ITM2B-related, 1; Cerebral amyloid angiopathy, ITM2B-related, 2; Retinal dystrophy with inner retinal dysfunction and ganglion cell abnormalities | AD | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Audiologic/Otolaryngologic; Neurologic; Ophthalmologic | 21610757; 7086452; 2364266; 10391242; 10781099; 11557758; 21048150; 24026677 |
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (138 variants)
- Inborn_genetic_diseases (24 variants)
- ITM2B-related_disorder (6 variants)
- ABri_amyloidosis (3 variants)
- ADan_amyloidosis (3 variants)
- not_specified (3 variants)
- Retinal_dystrophy_with_inner_retinal_dysfunction_and_ganglion_cell_anomalies (2 variants)
- Optic_atrophy (1 variants)
- Vascular_dementia (1 variants)
- Hereditary_ataxia (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the ITM2B gene is commonly pathogenic or not. These statistics are base on transcript: NM_000021999.5. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 36 | 40 | ||||
| missense | 87 | 93 | ||||
| nonsense | 1 | |||||
| start loss | 0 | |||||
| frameshift | 6 | |||||
| splice donor/acceptor (+/-2bp) | 1 | |||||
| Total | 2 | 0 | 94 | 40 | 5 |
Highest pathogenic variant AF is 6.9137644e-7
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| ITM2B | protein_coding | protein_coding | ENST00000378565 | 6 | 29770 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.626 | 0.373 | 125705 | 0 | 8 | 125713 | 0.0000318 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.04 | 107 | 142 | 0.754 | 0.00000708 | 1754 |
| Missense in Polyphen | 24 | 41.217 | 0.58229 | 504 | ||
| Synonymous | 0.871 | 41 | 48.7 | 0.841 | 0.00000238 | 484 |
| Loss of Function | 2.64 | 2 | 11.8 | 0.170 | 5.59e-7 | 159 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000618 | 0.0000616 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000327 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Plays a regulatory role in the processing of the amyloid-beta A4 precursor protein (APP) and acts as an inhibitor of the amyloid-beta peptide aggregation and fibrils deposition. Plays a role in the induction of neurite outgrowth. Functions as a protease inhibitor by blocking access of secretases to APP cleavage sites.; FUNCTION: Bri23 peptide prevents aggregation of APP amyloid-beta protein 42 into toxic oligomers.;
- Disease
- DISEASE: Cerebral amyloid angiopathy, ITM2B-related 1 (CAA-ITM2B1) [MIM:176500]: A disorder characterized by amyloid deposition in the walls of cerebral blood vessels and neurodegeneration in the central nervous system. Cerebral amyloid angiopathy, non-neuritic and perivascular plaques and neurofibrillary tangles are the predominant pathological lesions. Clinical features include progressive mental deterioration, spasticity and muscular rigidity. {ECO:0000269|PubMed:10391242, ECO:0000269|PubMed:10526337, ECO:0000269|PubMed:14656991}. Note=The disease is caused by mutations affecting the gene represented in this entry. A single base substitution at the stop codon of ITM2B generates a 277-residue precursor that is cleaved at the normal furin processing site to generate the ABri amyloidogenic peptide (PubMed:10391242). ABri accumulates in the brain and produces amyloid fibrils responsible for neuronal dysfunction and dementia. ABri peptide variant forms fibrils in vitro (PubMed:10526337). {ECO:0000269|PubMed:10391242, ECO:0000269|PubMed:10526337}.; DISEASE: Cerebral amyloid angiopathy, ITM2B-related 2 (CAA-ITM2B2) [MIM:117300]: A disorder characterized by amyloid deposition in the walls of the blood vessels of the cerebrum, choroid plexus, cerebellum, spinal cord and retina. Plaques and neurofibrillary tangles are observed in the hippocampus. Clinical features include progressive ataxia, dementia, cataracts and deafness. {ECO:0000269|PubMed:10781099, ECO:0000269|PubMed:14656991, ECO:0000269|PubMed:16091362}. Note=The disease is caused by mutations affecting the gene represented in this entry. A decamer duplication in the 3' region of ITM2B results in the production of the ADan amyloidogenic peptide (PubMed:10781099). ADan is generated by cleavage of the mutated precursor at the normal furin processing site. ADan accumulates in the brain and produces amyloid fibrils responsible for neuronal dysfunction and dementia. {ECO:0000269|PubMed:10781099}.; DISEASE: Retinal dystrophy with inner retinal dysfunction and ganglion cell abnormalities (RDGCA) [MIM:616079]: An autosomal dominant retinal dystrophy characterized by inner retinal dysfunction in association with ganglion cell abnormalities. Clinical features include mild photophobia, progressive loss of central vision, night blindness, and hyperreflectivity of nerve and ganglion cell layers. {ECO:0000269|PubMed:24026677}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- IL2
(Consensus)
Recessive Scores
- pRec
- 0.315
Intolerance Scores
- loftool
- 0.474
- rvis_EVS
- -0.14
- rvis_percentile_EVS
- 42.88
Haploinsufficiency Scores
- pHI
- 0.229
- hipred
- Y
- hipred_score
- 0.825
- ghis
- 0.556
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.506
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Itm2b
- Phenotype
- nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan);
Gene ontology
- Biological process
- nervous system development;negative regulation of amyloid precursor protein biosynthetic process;cellular protein metabolic process
- Cellular component
- Golgi membrane;extracellular region;extracellular space;Golgi apparatus;plasma membrane;endosome membrane;membrane;Golgi-associated vesicle membrane;integral component of organelle membrane;intracellular membrane-bounded organelle;extracellular exosome
- Molecular function
- amyloid-beta binding;protein binding;ATP binding