CAMLG
protein-codingcalcium modulating ligand, the group of Guided entry of tail-anchored proteins complex subunits
Gene summary
The immunosuppressant drug cyclosporin A blocks a calcium-dependent signal from the T-cell receptor (TCR) that normally leads to T-cell activation. When bound to cyclophilin B, cyclosporin A binds and inactivates the key signaling intermediate calcineurin. The protein encoded by this gene functions similarly to cyclosporin A, binding to cyclophilin B and acting downstream of the TCR and upstream of calcineurin by causing an influx of calcium. This integral membrane protein appears to be a new participant in the calcium signal transduction pathway, implicating cyclophilin B in calcium signaling, even in the absence of cyclosporin. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~13.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0859357
Submitter: ClinGen
CAMLG was first reported in relation to autosomal recessive Congenital Disorder of Glycosylation, type IIz (MONDO:0859357) in 2022 (Wilson M et al., 2022; PMID: 35262690). CDG2z is a disorder characterized by poor overall growth, severe global developmental delay, seizures, contractures, hypotonia, and brain imaging abnormalities. This gene forms an ER membrane receptor that enables cytoplasmically facing tail-anchored (TA) proteins to be integrated within the lipid bilayer. 35 variants (e.g., synonymous, missense, in-frame indel, nonsense) have been reported in humans by ClinVar. Evidence supporting this gene-disease relationship includes case-level data and experimental data. One variant has been reported in 1 probands in 1 publication (Wilson M et al., 2022; PMID: 35262690), are included in this curation. Limited evidence was available in the literature. This gene-disease relationship is also supported by non-human model organisms and a rescue in non-human model organisms (Tran D et al., 2014, PMID:24392163; Vilardi F et al., 2003, PMID:12919676). In summary, there is limited evidence to support the relationship between CAMLG and Congenital Disorder of Glycosylation, type IIz. This has been demonstrated in both the research and clinical diagnostic settings. This classification was approved by the ClinGen Congenital Disorder of Glycosylation GCEP on the meeting date September 18, 2024 (SOP Version 10).
Inheritance Pattern: AR
Disease ID:MONDO:0859357
Submitter: Ambry Genetics
Clinical Genomic Database (CGD)
Manifestation: Biochemical; Neurologic
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
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CAMLG variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001745.4. 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 | 0 | |||||
| missense | 34 | 34 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 36 | 0 | 0 | 36 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001736.1 | 4 | MANE Select | |
| Ensembl | ENSP00000297156.2 | 4 | MANE Select | |
| Ensembl | ENSP00000427331.1 | 3 | Standard | |
| Ensembl | ENSP00000427331.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Prolactin
Biological Process
- receptor recycling
- defense response
- signal transduction
- epidermal growth factor receptor signaling pathway
- viral process
Molecular Function
- protein binding
Cellular Component
- endoplasmic reticulum
- membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000297156
- Coding exons
- 4
- Length
- 13657
- Individuals with no LoFs
- 125732
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 15
- Defined
- 125747
- p
- 0.0000596
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.645 | 142 | 165 | 0.859 | 0.00000861 | 1901 |
| Missense (PolyPhen) | 58 | 63.95 | 0.90696 | 807 | ||
| Synonymous | 0.182 | 67 | 68.9 | 0.972 | 0.00000388 | 605 |
| Loss of Function | 1.52 | 7 | 12.9 | 0.542 | 7.63e-7 | 145 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000053 | 0.000053 | rare |
| South Asian | 0.00014 | 0.00013 | rare |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Likely involved in the mobilization of calcium as a result of the TCR/CD3 complex interaction. Binds to cyclophilin B.;
Recessive Scores
- pRec
- 0.195
Intolerance Scores
- LoFtool
- 0.663
- RVIS EVS
- -0.38
- RVIS percentile EVS
- 27.69
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.843
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |