TCN1
protein-codingtranscobalamin 1
Gene summary
This gene encodes a member of the vitamin B12-binding protein family. This family of proteins, alternatively referred to as R binders, is expressed in various tissues and secretions. This protein is a major constituent of secondary granules in neutrophils and facilitates the transport of cobalamin into cells. [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:0008659
Submitter: PanelApp Australia
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TCN1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001062.4. 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 | 33 | 2 | 35 | |||
| missense | 92 | 10 | 1 | 103 | ||
| nonsense | 3 | 3 | ||||
| start loss | 0 | |||||
| frameshift | 4 | 1 | 5 | |||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 7 | 0 | 92 | 44 | 3 | 146 |
Highest pathogenic variant AF is 0.00006939359
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001053.2 | 9 | MANE Select | |
| Ensembl | ENSP00000257264.3 | 9 | MANE Select |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Vitamin B12 Metabolism
- Neutrophil degranulation
- Innate Immune System
- Immune System
- Cobalamin (Cbl, vitamin B12) transport and metabolism
Biological Process
- cobalt ion transport
- cobalamin metabolic process
- cobalamin transport
- neutrophil degranulation
Molecular Function
- cobalamin binding
Cellular Component
- extracellular region
- extracellular space
- specific granule lumen
- tertiary granule lumen
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000257264
- Coding exons
- 9
- Length
- 13776
- Individuals with no LoFs
- 125722
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 18
- Defined
- 125740
- p
- 0.0000716
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -1.08 | 262 | 217 | 1.21 | 0.0000118 | 2843 |
| Missense (PolyPhen) | 83 | 64.849 | 1.2799 | 937 | ||
| Synonymous | 0.302 | 84 | 87.6 | 0.959 | 0.00000534 | 815 |
| Loss of Function | -0.906 | 23 | 18.8 | 1.23 | 8.22e-7 | 253 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00018 | 0.00018 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00033 | 0.00033 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000044 | 0.000044 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Binds vitamin B12 with femtomolar affinity and protects it from the acidic environment of the stomach.;
Recessive Scores
- pRec
- 0.145
Intolerance Scores
- LoFtool
- 0.955
- RVIS EVS
- -0.04
- RVIS percentile EVS
- 50.45
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.00706
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |