RNPC3
protein-codingRNA binding region (RNP1, RRM) containing 3, the group of RNA binding motif containing|U11/U12 di-snRNP
Gene summary
Two types of spliceosomes catalyze splicing of pre-mRNAs. The major U2-type spliceosome is found in all eukaryotes and removes U2-type introns, which represent more than 99% of pre-mRNA introns. The minor U12-type spliceosome is found in some eukaryotes and removes U12-type introns, which are rare and have distinct splice consensus signals. The U12-type spliceosome consists of several small nuclear RNAs and associated proteins. This gene encodes a 65K protein that is a component of the U12-type spliceosome. This protein contains two RNA recognition motifs (RRMs), suggesting that it may contact one of the small nuclear RNAs of the minor spliceosome. [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 ~29.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0009876
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0032569
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0032569
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0032569
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0032569
Submitter: Ambry Genetics
Clinical Genomic Database (CGD)
Manifestation: Craniofacial; Endocrine; Neurologic
Intervention: Endocrine
Rationale: Individuals may have multiple hormonal deficiencies (eg, GH hormone deficiency, hypothyroidism), and awareness may allow prompt management to treat with relevant hormonal therapeutics
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to RNPC3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_017619.4. 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 | 1 | 7 | 8 | |||
| missense | 4 | 74 | 2 | 1 | 81 | |
| nonsense | 3 | 3 | ||||
| start loss | 0 | |||||
| frameshift | 2 | 1 | 2 | 5 | ||
| splice donor/acceptor (+/-2bp) | 1 | 1 | 2 | |||
| Total | 10 | 2 | 77 | 9 | 1 | 99 |
Highest pathogenic variant AF is 0.0000514605
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060089.1 | 14 | MANE Select | |
| Ensembl | ENSP00000391432.1 | 14 | MANE Select | |
| Ensembl | ENSP00000437278.1 | 14 | Standard | |
| Ensembl | ENSP00000437278.1 | 14 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| rnpc3 | Danio rerio | Structure: intestinal epithelium Quality: surface feature shape abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Metabolism of RNA
- mRNA Splicing - Minor Pathway
- mRNA Splicing
- Processing of Capped Intron-Containing Pre-mRNA
Biological Process
- mRNA splicing, via spliceosome
- RNA splicing
Molecular Function
- U12 snRNA binding
- pre-mRNA intronic binding
Cellular Component
- nucleus
- nucleoplasm
- U12-type spliceosomal complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000533099
- Coding exons
- 14
- Length
- 29549
- Individuals with no LoFs
- 124530
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 10
- Defined
- 124540
- p
- 0.0000401
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.990 | 178 | 219 | 0.812 | 0.0000107 | 3359 |
| Missense (PolyPhen) | 46 | 65.113 | 0.70646 | 929 | ||
| Synonymous | 0.227 | 74 | 76.5 | 0.967 | 0.00000373 | 960 |
| Loss of Function | 2.49 | 10 | 22.8 | 0.438 | 0.00000115 | 390 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000065 | 0.000065 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000080 | 0.000080 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Participates in pre-mRNA U12-dependent splicing, performed by the minor spliceosome which removes U12-type introns. U12-type introns comprises less than 1% of all non-coding sequences. Binds to the 3'-stem-loop of m(7)G-capped U12 snRNA. {ECO:0000269|PubMed:16096647, ECO:0000269|PubMed:19447915}.;
Intolerance Scores
- LoFtool
- 0.697
- RVIS EVS
- -0.01
- RVIS percentile EVS
- 52.85
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.802
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |