SNIP1
protein-codingSmad nuclear interacting protein 1, the group of Spliceosomal P complex
Gene summary
This gene encodes a protein that contains a coiled-coil motif and C-terminal forkhead-associated (FHA) domain. The encoded protein functions as a transcriptional coactivator that increases c-Myc activity and inhibits transforming growth factor beta (TGF-beta) and nuclear factor kappa-B (NF-kB) signaling. The encoded protein also regulates the stability of cyclin D1 mRNA, and may play a role in cell proliferation and cancer progression. Mutations in this gene are a cause of psychomotor retardation, epilepsy, and craniofacial dysmorphism (PMRED). [provided by RefSeq, Mar 2012]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~19.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0013787
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0013787
Submitter: G2P
Inheritance Pattern: Unknown
Disease ID:MONDO:0013787
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0013787
Submitter: Illumina
Clinical Genomic Database (CGD)
Manifestation: Craniofacial; Musculoskeletal; 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 SNIP1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_024700.4. 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 | 60 | 3 | 63 | |||
| missense | 1 | 156 | 12 | 1 | 170 | |
| nonsense | 1 | 7 | 8 | |||
| start loss | 0 | |||||
| frameshift | 4 | 4 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 2 | 168 | 72 | 4 | 246 |
Highest pathogenic variant AF is 0.000009293104
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_078976.2 | 4 | MANE Select | |
| Ensembl | ENSP00000296215.5 | 4 | MANE Select | |
| Ensembl | ENSP00000492185.1 | 3 | Standard | |
| Ensembl | ENSP00000805089.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- TGF-Ncore
- TGF-beta Signaling Pathway
- TGF_beta_Receptor
- Regulation of nuclear SMAD2/3 signaling
Biological Process
- regulation of transcription, DNA-templated
- I-kappaB kinase/NF-kappaB signaling
- production of miRNAs involved in gene silencing by miRNA
Molecular Function
- RNA binding
- mRNA binding
- protein binding
Cellular Component
- nucleus
- nucleoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000296215
- Coding exons
- 4
- Length
- 19854
- Individuals with no LoFs
- 125737
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 11
- Defined
- 125748
- p
- 0.0000437
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.24 | 201 | 257 | 0.783 | 0.0000163 | 2559 |
| Missense (PolyPhen) | 33 | 61.892 | 0.53319 | 607 | ||
| Synonymous | 1.26 | 79 | 94.6 | 0.835 | 0.00000539 | 809 |
| Loss of Function | 3.10 | 4 | 18.3 | 0.218 | 0.00000124 | 178 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000059 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000063 | 0.000062 | rare |
| South Asian | 0.000040 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Down-regulates NF-kappa-B signaling by competing with RELA for CREBBP/EP300 binding. Involved in the microRNA (miRNA) biogenesis. May be involved in cyclin-D1/CCND1 mRNA stability through the SNARP complex which associates with both the 3'end of the CCND1 gene and its mRNA. {ECO:0000269|PubMed:11567019, ECO:0000269|PubMed:15378006, ECO:0000269|PubMed:18632581, ECO:0000269|PubMed:18794151}.;
- Disease
- DISEASE: Psychomotor retardation, epilepsy, and craniofacial dysmorphism (PMRED) [MIM:614501]: A disease characterized by severe psychomotor retardation, intractable seizures, dysmorphic features, and a lumpy skull surface. Patients are hypotonic and have poor feeding in the neonatal period. {ECO:0000269|PubMed:22279524}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.0973
Intolerance Scores
- LoFtool
- 0.251
- RVIS EVS
- 0.13
- RVIS percentile EVS
- 63.2
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.998
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |