SUN2

Chr 22

Sad1 and UNC84 domain containing 2

Also known as: UNC84B, rab5IP

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]

OMIMResearchGenerating clinical summary…
DNmechanismLOEUF 0.65
Clinical SummarySUN2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.65LOEUF
pLI 0.000
Z-score 3.48
OE 0.45 (0.320.65)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
0.95Z-score
OE missense 0.88 (0.810.95)
410 obs / 467.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.45 (0.320.65)
00.351.4
Missense OE?0.88 (0.810.95)
00.61.4
Synonymous OE?0.86
01.21.6
LoF obs/exp: 21 / 46.7Missense obs/exp: 410 / 467.5Syn Z: 1.53

This gene — mechanism propensity

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

0 submitted variants 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.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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