CLIP2

Chr 7

CAP-Gly domain containing linker protein 2

Also known as: CLIP, CLIP-115, CYLN2, WBSCR3, WBSCR4, WSCR3, WSCR4

The protein links microtubules to dendritic lamellar bodies, specialized membranous organelles in neurons that are involved in brain-specific organelle transport. CLIP2 is hemizygously deleted in Williams syndrome, a multisystem developmental disorder caused by contiguous gene deletions at 7q11.23. This gene is extremely intolerant to loss-of-function variants (pLI ~1.0), suggesting that haploinsufficiency may contribute to the neurodevelopmental features observed in Williams syndrome.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.20
Clinical SummaryCLIP2
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.20LOEUF
pLI 1.000
Z-score 5.79
OE 0.09 (0.040.20)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.36Z-score
OE missense 0.74 (0.690.80)
493 obs / 663.8 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.09 (0.040.20)
00.351.4
Missense OE0.74 (0.690.80)
00.61.4
Synonymous OE1.05
01.21.6
LoF obs/exp: 4 / 46.7Missense obs/exp: 493 / 663.8Syn Z: -0.70
DN
0.4189th %ile
GOF
0.4480th %ile
LOF
0.71top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.20

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CLIP2 · 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

No active trials found for this gene.

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Clinical Literature
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