SUN2

Chr 22

Sad1 and UNC84 domain containing 2

Also known as: UNC84B, rab5IP

NCBI Gene: 25777ENSG00000100242UniProt: Q9UH99

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]

585
ClinVar variants
17
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SUN2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
17 Pathogenic / Likely Pathogenic· 258 VUS of 585 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.65LOEUF
pLI 0.000
Z-score 3.48
OE 0.45 (0.32–0.65)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.95Z-score
OE missense 0.88 (0.81–0.95)
410 obs / 467.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.45 (0.32–0.65)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.88 (0.81–0.95)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.86
0≤1.21.6
LoF obs/exp: 21 / 46.7Missense obs/exp: 410 / 467.5Syn Z: 1.53

ClinVar Variant Classifications

585 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic1
VUS258
Likely Benign159
Benign30
Conflicting5
16
Pathogenic
1
Likely Pathogenic
258
VUS
159
Likely Benign
30
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
16
0
16
Likely Pathogenic
0
0
1
0
1
VUS
4
228
25
1
258
Likely Benign
0
16
54
89
159
Benign
0
10
14
6
30
Conflicting
—5
Total425411096469

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Elevated SUN1 promotes migratory cell polarity defects through mechanically coupling microtubules to the nuclear lamina.
Li Y et al.·Commun Biol
2025
Cytoplasmic keratins couple with and maintain nuclear envelope integrity in colonic epithelial cells.
Stenvall CA et al.·Mol Biol Cell
2022
Lamin A and the LINC complex act as potential tumor suppressors in Ewing Sarcoma.
Chiarini F et al.·Cell Death Dis
2022
Altered chromatin organization and SUN2 localization in mandibuloacral dysplasia are rescued by drug treatment.
Camozzi D et al.·Histochem Cell Biol
2012
Loss of the integral nuclear envelope protein SUN1 induces alteration of nucleoli.
Matsumoto A et al.·Nucleus
2016
LINC complex alterations in DMD and EDMD/CMT fibroblasts.
Taranum S et al.·Eur J Cell Biol
2012
Imbalanced nucleocytoskeletal connections create common polarity defects in progeria and physiological aging.
Chang W et al.·Proc Natl Acad Sci U S A
2019
Disruption of nesprin-1 produces an Emery Dreifuss muscular dystrophy-like phenotype in mice.
Puckelwartz MJ et al.·Hum Mol Genet
2009
Detection of SUN1 Splicing Variants at the mRNA and Protein Levels in Cancer.
Matsumoto A et al.·Methods Mol Biol
2018
Immunohistochemistry on a panel of Emery-Dreifuss muscular dystrophy samples reveals nuclear envelope proteins as inconsistent markers for pathology.
Le Thanh P et al.·Neuromuscul Disord
2017
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools