RGN
protein-codingregucalcin
Gene summary
The protein encoded by this gene is a highly conserved, calcium-binding protein, that is preferentially expressed in the liver and kidney. It may have an important role in calcium homeostasis. Studies in rat indicate that this protein may also play a role in aging, as it shows age-associated down-regulation. This gene is part of a gene cluster on chromosome Xp11.3-Xp11.23. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~15.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to RGN variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_152869.4. 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 | 7 | 1 | 8 | |||
| missense | 57 | 1 | 1 | 59 | ||
| nonsense | 6 | 6 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 7 | 7 | ||||
| Total | 0 | 0 | 78 | 2 | 1 | 81 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_690608.1 | 6 | MANE Select | |
| Ensembl | ENSP00000380365.1 | 6 | MANE Select | |
| RefSeq | NP_001269777.1 | 6 | Standard | |
| RefSeq | NP_001269778.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Ascorbate and aldarate metabolism - Homo sapiens (human)
- Pentose phosphate pathway - Homo sapiens (human)
Biological Process
- kidney development
- negative regulation of protein kinase activity
- cellular calcium ion homeostasis
- spermatogenesis
- aging
Molecular Function
- gluconolactonase activity
- calcium ion binding
- zinc ion binding
- enzyme regulator activity
Cellular Component
- nucleus
- cytoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000397180
- Coding exons
- 6
- Length
- 14938
- Individuals with no LoFs
- 125711
- Homozygous LoFs
- 12
- Heterozygous LoFs
- 21
- Defined
- 125744
- p
- 0.000131
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.913 | 138 | 111 | 1.24 | 0.00000868 | 1939 |
| Missense (PolyPhen) | 43 | 37.541 | 1.1454 | 642 | ||
| Synonymous | 0.190 | 41 | 42.6 | 0.963 | 0.00000344 | 578 |
| Loss of Function | 1.60 | 4 | 9.23 | 0.433 | 6.54e-7 | 177 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00015 | 0.00012 | rare |
| Latino/Admixed American | 0.00018 | 0.00014 | rare |
| Ashkenazi Jewish | 0.00081 | 0.00060 | rare |
| East Asian | 0.00015 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00016 | 0.00011 | rare |
| South Asian | 0.00027 | 0.00016 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Gluconolactonase with low activity towards other sugar lactones, including gulonolactone and galactonolactone. Can also hydrolyze diisopropyl phosphorofluoridate and phenylacetate (in vitro). Calcium-binding protein. Modulates Ca(2+) signaling, and Ca(2+)-dependent cellular processes and enzyme activities (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.344
Intolerance Scores
- LoFtool
- 0.396
- RVIS EVS
- 0.02
- RVIS percentile EVS
- 55.22
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.908
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |