SHROOM2
protein-codingshroom family member 2, the group of PDZ domain containing|Shroom family
Gene summary
This gene represents the human homolog of Xenopus laevis apical protein (APX) gene, which is implicated in amiloride-sensitive sodium channel activity. It is expressed in endothelial cells and facilitates the formation of a contractile network within endothelial cells. Depletion of this gene results in an increase in endothelial sprouting, migration, and angiogenesis. This gene is highly expressed in the retina, and is a strong candidate for ocular albinism type 1 syndrome. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2016]
- APXL
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~163.0 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 SHROOM2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001649.4. 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 | 15 | 18 | 8 | 41 | ||
| missense | 1 | 248 | 39 | 12 | 300 | |
| nonsense | 6 | 6 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 11 | 11 | ||||
| Total | 0 | 1 | 280 | 57 | 20 | 358 |
Highest pathogenic variant AF is 0.003266677
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001640.1 | 10 | MANE Select | |
| Ensembl | ENSP00000370299.3 | 10 | MANE Select | |
| RefSeq | NP_001307592.1 | 5 | Standard | |
| RefSeq | NP_001307593.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- cell morphogenesis
- lens morphogenesis in camera-type eye
- actin filament organization
- brain development
- eye pigment granule organization
Molecular Function
- actin binding
- protein binding
- beta-catenin binding
- ligand-gated sodium channel activity
- actin filament binding
Cellular Component
- cytoskeleton
- microtubule
- plasma membrane
- adherens junction
- cell-cell adherens junction
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000380913
- Coding exons
- 10
- Length
- 162988
- Individuals with no LoFs
- 125715
- Homozygous LoFs
- 12
- Heterozygous LoFs
- 20
- Defined
- 125747
- p
- 0.000127
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.325 | 710 | 686 | 1.03 | 0.0000640 | 10382 |
| Missense (PolyPhen) | 212 | 230.97 | 0.91786 | 3531 | ||
| Synonymous | -1.26 | 347 | 319 | 1.09 | 0.0000320 | 3426 |
| Loss of Function | 3.70 | 11 | 34.5 | 0.319 | 0.00000258 | 611 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00016 | 0.00012 | rare |
| Latino/Admixed American | 0.00062 | 0.00049 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000065 | 0.000046 | rare |
| European (Non-Finnish) | 0.000089 | 0.000062 | rare |
| South Asian | 0.00027 | 0.00016 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May be involved in endothelial cell morphology changes during cell spreading. In the retinal pigment epithelium, may regulate the biogenesis of melanosomes and promote their association with the apical cell surface by inducing gamma-tubulin redistribution (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.139
Intolerance Scores
- LoFtool
- 0.446
- RVIS EVS
- 1.53
- RVIS percentile EVS
- 95.54
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0858
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |