SCIN
protein-codingscinderin, the group of Gelsolin/villins
Gene summary
SCIN is a Ca(2+)-dependent actin-severing and -capping protein (Zunino et al., 2001 [PubMed 11568009]).[supplied by OMIM, May 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~89.6 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 SCIN variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001112706.3. 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 | 2 | 2 | ||||
| missense | 154 | 3 | 157 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 7 | 7 | ||||
| Total | 0 | 0 | 163 | 3 | 0 | 166 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001106177.1 | 16 | MANE Select | |
| Ensembl | ENSP00000297029.5 | 16 | MANE Select | |
| RefSeq | NP_149119.1 | 12 | Standard | |
| Ensembl | ENSP00000341375.5 | 13 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Fc gamma R-mediated phagocytosis - Homo sapiens (human)
- Regulation of actin cytoskeleton - Homo sapiens (human)
- Viral carcinogenesis - Homo sapiens (human)
- Endochondral Ossification
Biological Process
- negative regulation of cell population proliferation
- calcium ion regulated exocytosis
- regulation of chondrocyte differentiation
- sequestering of actin monomers
- positive regulation of apoptotic process
Molecular Function
- phosphatidylserine binding
- actin binding
- calcium ion binding
- 1-phosphatidylinositol binding
- phosphatidylinositol-4,5-bisphosphate binding
Cellular Component
- podosome
- cytoplasm
- plasma membrane
- brush border
- cell cortex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000297029
- Coding exons
- 16
- Length
- 83026
- Individuals with no LoFs
- 124497
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 141
- Defined
- 124638
- p
- 0.000566
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.771 | 404 | 363 | 1.11 | 0.0000183 | 4645 |
| Missense (PolyPhen) | 172 | 157.05 | 1.0952 | 1957 | ||
| Synonymous | -2.13 | 168 | 136 | 1.23 | 0.00000717 | 1326 |
| Loss of Function | -1.71 | 48 | 36.8 | 1.30 | 0.00000173 | 474 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00086 | 0.00071 | rare |
| Latino/Admixed American | 0.00072 | 0.00070 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00028 | 0.00028 | rare |
| Finnish | 0.00033 | 0.00032 | rare |
| European (Non-Finnish) | 0.00055 | 0.00054 | rare |
| South Asian | 0.0010 | 0.00098 | rare |
| Other | 0.00052 | 0.00050 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Ca(2+)-dependent actin filament-severing protein that has a regulatory function in exocytosis by affecting the organization of the microfilament network underneath the plasma membrane (PubMed:8547642, PubMed:26365202). Severing activity is inhibited by phosphatidylinositol 4,5-bis-phosphate (PIP2) (By similarity). In vitro, also has barbed end capping and nucleating activities in the presence of Ca(2+). Required for megakaryocyte differentiation, maturation, polyploidization and apoptosis with the release of platelet-like particles (PubMed:11568009). Plays a role in osteoclastogenesis (OCG) and actin cytoskeletal organization in osteoclasts (By similarity). Regulates chondrocyte proliferation and differentiation (By similarity). Inhibits cell proliferation and tumorigenesis. Signaling is mediated by MAPK, p38 and JNK pathways (PubMed:11568009). {ECO:0000250|UniProtKB:Q28046, ECO:0000250|UniProtKB:Q5ZIV9, ECO:0000250|UniProtKB:Q60604, ECO:0000269|PubMed:11568009, ECO:0000269|PubMed:26365202, ECO:0000269|PubMed:8547642}.;
Recessive Scores
- pRec
- 0.124
Intolerance Scores
- LoFtool
- 0.993
- RVIS EVS
- 1.22
- RVIS percentile EVS
- 93.24
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.714
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | Medium | High |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |