TMEM38B
protein-codingtransmembrane protein 38B
Gene summary
This gene encodes an intracellular monovalent cation channel that functions in maintenance of intracellular calcium release. Mutations in this gene may be associated with autosomal recessive osteogenesis. [provided by RefSeq, Oct 2012]
- C9orf87
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~82.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0014029
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0014029
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0008148
Submitter: Orphanet
Clinical Genomic Database (CGD)
Manifestation: Musculoskeletal
Intervention: General
Rationale: 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
Comments: The use of bisphosphonates has been described in osteogenesis imperfecta, but it is unclear if an early (genomic) diagnosis would be advantageous
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TMEM38B variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_018112.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 42 | 1 | 44 | ||
| missense | 1 | 81 | 6 | 2 | 90 | |
| nonsense | 6 | 2 | 1 | 9 | ||
| start loss | 2 | 2 | ||||
| frameshift | 4 | 1 | 5 | |||
| splice donor/acceptor (+/-2bp) | 2 | 3 | 5 | |||
| Total | 6 | 9 | 89 | 48 | 3 | 155 |
Highest pathogenic variant AF is 0.00002292569
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060582.1 | 6 | MANE Select | |
| Ensembl | ENSP00000363824.3 | 6 | MANE Select | |
| Ensembl | ENSP00000363820.1 | 5 | Standard | |
| Ensembl | ENSP00000363820.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- potassium ion transmembrane transport
Molecular Function
- potassium channel activity
Cellular Component
- nucleus
- integral component of membrane
- nuclear membrane
- sarcoplasmic reticulum membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000374692
- Coding exons
- 6
- Length
- 82069
- Individuals with no LoFs
- 125732
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 16
- Defined
- 125748
- p
- 0.0000636
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.0505 | 158 | 156 | 1.01 | 0.00000714 | 1888 |
| Missense (PolyPhen) | 39 | 49.602 | 0.78625 | 644 | ||
| Synonymous | -0.836 | 68 | 59.8 | 1.14 | 0.00000310 | 568 |
| Loss of Function | 2.09 | 5 | 13.2 | 0.380 | 6.35e-7 | 151 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.00018 | 0.00018 | rare |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0.00030 | 0.00029 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Monovalent cation channel required for maintenance of rapid intracellular calcium release. May act as a potassium counter-ion channel that functions in synchronization with calcium release from intracellular stores. {ECO:0000250|UniProtKB:Q9DAV9}.;
- Disease
- DISEASE: Osteogenesis imperfecta 14 (OI14) [MIM:615066]: An autosomal recessive form of osteogenesis imperfecta, a connective tissue disorder characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI14 is characterized by variable degrees of severity of multiple fractures and osteopenia, with normal teeth, sclerae, and hearing. Fractures first occur prenatally or by age 6 years. {ECO:0000269|PubMed:23054245, ECO:0000269|PubMed:23316006}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.108
Intolerance Scores
- LoFtool
- 0.549
- RVIS EVS
- 0.22
- RVIS percentile EVS
- 68.27
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.641
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |