SUN2

Chr 22

Sad1 and UNC84 domain containing 2

Also known as: UNC84B, rab5IP

NCBI Gene: 25777ENSG00000100242UniProt: Q9UH99OMIM: 613569

SUN2 encodes an inner nuclear membrane protein that forms the LINC complex by bridging the nuclear envelope to connect the nuclear lamina with the cytoskeleton, playing essential roles in nuclear positioning, nuclear migration during brain development, and telomere attachment during meiosis. Mutations cause autosomal recessive neuronal migration disorders affecting cerebral cortex development. This gene is highly constrained against loss-of-function variants in the general population.

GeneReviewsOMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.65
Clinical Summary— SUN2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
5 unique Pathogenic / Likely Pathogenic· 274 VUS of 500 total submissions
Explore recent and relevant literature in Research Assistant →
📖
GeneReview available — SUN2
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.65LOEUF
pLI 0.000
Z-score 3.48
OE 0.45 (0.32–0.65)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.95Z-score
OE missense 0.88 (0.81–0.95)
410 obs / 467.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.45 (0.32–0.65)
0≤0.351.4
Missense OE0.88 (0.81–0.95)
0≤0.61.4
Synonymous OE0.86
0≤1.21.6
LoF obs/exp: 21 / 46.7Missense obs/exp: 410 / 467.5Syn Z: 1.53
DN
0.6647th %ile
GOF
0.4282th %ile
LOF
0.3356th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

500 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4
Likely Pathogenic1
VUS274
Likely Benign176
Benign22
Conflicting7
4
Pathogenic
1
Likely Pathogenic
274
VUS
176
Likely Benign
22
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
4
0
4
Likely Pathogenic
0
0
1
0
1
VUS
7
253
13
1
274
Likely Benign
0
15
53
108
176
Benign
0
3
13
6
22
Conflicting
—7
Total727184115484

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SUN2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients