SUN2
protein-codingSad1 and UNC84 domain containing 2, the group of SUN family
Gene summary
SUN1 (MIM 607723) and SUN2 are inner nuclear membrane (INM) proteins that play a major role in nuclear-cytoplasmic connection by formation of a 'bridge' across the nuclear envelope, known as the LINC complex, via interaction with the conserved luminal KASH domain of nesprins (e.g., SYNE1; MIM 608441) located in the outer nuclear membrane (ONM). The LINC complex provides a direct connection between the nuclear lamina and the cytoskeleton, which contributes to nuclear positioning and cellular rigidity (summary by Haque et al., 2010 [PubMed 19933576]).[supplied by OMIM, Nov 2010]
- UNC84B
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~60.9 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 SUN2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_015374.3. 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 | 120 | 10 | 132 | ||
| missense | 267 | 21 | 8 | 296 | ||
| nonsense | 7 | 7 | ||||
| start loss | 0 | |||||
| frameshift | 2 | 2 | ||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 283 | 141 | 18 | 442 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_056189.1 | 17 | MANE Select | |
| Ensembl | ENSP00000508608.1 | 17 | MANE Select | |
| RefSeq | NP_001186508.1 | 17 | Standard | |
| RefSeq | NP_001186509.1 | 17 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- nuclear envelope organization
- mitotic spindle organization
- nuclear migration
- nucleokinesis involved in cell motility in cerebral cortex radial glia guided migration
- positive regulation of cell migration
Molecular Function
- protein binding
- lamin binding
- microtubule binding
- identical protein binding
- protein membrane anchor
Cellular Component
- nuclear chromosome, telomeric region
- condensed nuclear chromosome
- nuclear envelope
- integral component of nuclear inner membrane
- endosome membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000405018
- Coding exons
- 17
- Length
- 59419
- Individuals with no LoFs
- 125690
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 57
- Defined
- 125748
- p
- 0.000231
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.945 | 410 | 468 | 0.877 | 0.0000314 | 4716 |
| Missense (PolyPhen) | 125 | 164.42 | 0.76025 | 1616 | ||
| Synonymous | 1.53 | 178 | 206 | 0.865 | 0.0000146 | 1526 |
| Loss of Function | 3.48 | 21 | 46.7 | 0.450 | 0.00000259 | 449 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.00029 | 0.00029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.00091 | 0.00083 | rare |
| European (Non-Finnish) | 0.00016 | 0.00015 | rare |
| South Asian | 0.00030 | 0.00026 | rare |
| Other | 0.00066 | 0.00065 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: As a component of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex, involved in the connection between the nuclear lamina and the cytoskeleton. The nucleocytoplasmic interactions established by the LINC complex play an important role in the transmission of mechanical forces across the nuclear envelope and in nuclear movement and positioning. Specifically, SYNE2 and SUN2 assemble in arrays of transmembrane actin- associated nuclear (TAN) lines which are bound to F-actin cables and couple the nucleus to retrograde actin flow during actin- dependent nuclear movement. Required for interkinetic nuclear migration (INM) and essential for nucleokinesis and centrosome- nucleus coupling during radial neuronal migration in the cerebral cortex and during glial migration. Required for nuclear migration in retinal photoreceptor progenitors implicating association with cytoplasmic dynein-dynactin and kinesin motor complexes, and probably B-type lamins; SUN1 and SUN2 seem to act redundantly. The SUN1/2:KASH5 LINC complex couples telomeres to microtubules during meiosis; SUN1 and SUN2 seem to act at least partial redundantly. Anchors chromosome movement in the prophase of meiosis and is involved in selective gene expression of coding and non-coding RNAs needed for gametogenesis. Required for telomere attachment to nuclear envelope and gametogenesis. May also function on endocytic vesicles as a receptor for RAB5-GDP and participate in the activation of RAB5. {ECO:0000250|UniProtKB:Q8BJS4, ECO:0000269|PubMed:18396275, ECO:0000305}.;
Recessive Scores
- pRec
- 0.118
Intolerance Scores
- LoFtool
- 0.897
- RVIS EVS
- 0.05
- RVIS percentile EVS
- 57.54
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.539
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |