CLIP2

Chr 7

CAP-Gly domain containing linker protein 2

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

NCBI Gene: 7461ENSG00000106665UniProt: Q9UDT6

The protein encoded by this gene belongs to the family of cytoplasmic linker proteins, which have been proposed to mediate the interaction between specific membranous organelles and microtubules. This protein was found to associate with both microtubules and an organelle called the dendritic lamellar body. This gene is hemizygously deleted in Williams syndrome, a multisystem developmental disorder caused by the deletion of contiguous genes at 7q11.23. Alternative splicing of this gene generates 2 transcript variants. [provided by RefSeq, Jul 2008]

343
ClinVar variants
164
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— CLIP2
⚡
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.
📋
ClinVar Variants
164 Pathogenic / Likely Pathogenic· 142 VUS of 343 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.20LOEUF
pLI 1.000
Z-score 5.79
OE 0.09 (0.04–0.20)
Highly constrained

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

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.
2.36Z-score
OE missense 0.74 (0.69–0.80)
493 obs / 663.8 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.09 (0.04–0.20)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.74 (0.69–0.80)
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.1.05
0≤1.21.6
LoF obs/exp: 4 / 46.7Missense obs/exp: 493 / 663.8Syn Z: -0.70

ClinVar Variant Classifications

343 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic157
Likely Pathogenic7
VUS142
Likely Benign24
Benign13
157
Pathogenic
7
Likely Pathogenic
142
VUS
24
Likely Benign
13
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
157
0
157
Likely Pathogenic
0
0
7
0
7
VUS
1
131
10
0
142
Likely Benign
0
9
3
12
24
Benign
0
3
0
10
13
Total114317722343

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

View 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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Neuropsychological Genotype-Phenotype in Patients with Williams Syndrome with Atypical Deletions: A Systematic Review.
Serrano-Juárez CA et al.·Neuropsychol Rev
2023Review
Clinical, pathologic, and genomic characteristics of two pediatric glioneuronal tumors with a CLIP2::MET fusion.
Chapman N et al.·Acta Neuropathol Commun
2024Case report
CLIP2 as radiation biomarker in papillary thyroid carcinoma.
Selmansberger M et al.·Oncogene
2015
Animal models of Williams syndrome.
Osborne LR·Am J Med Genet C Semin Med Genet
2010Review
Genome-wide CRISPR/Cas9 screen identifies AraC-daunorubicin-etoposide response modulators associated with outcomes in pediatric AML.
Nguyen NHK et al.·Blood Adv
2025
The contribution of CLIP2 haploinsufficiency to the clinical manifestations of the Williams-Beuren syndrome.
Vandeweyer G et al.·Am J Hum Genet
2012
Molecular Diversity of Embryonic-Type Neuroectodermal Tumors Arising From Testicular Germ Cell Tumors.
Zong Y et al.·Mod Pathol
2025
[Clinicopathological features of inflammatory myofibroblastic tumor].
Zhu Y et al.·Zhonghua Bing Li Xue Za Zhi
2021
BRAF fusion Spitz neoplasms; clinical morphological, and genomic findings in six cases.
Kim D et al.·J Cutan Pathol
2020Cohort
Insights Into the Antigenic Repertoire of Unclassified Synaptic Antibodies.
Gilligan M et al.·Ann Clin Transl Neurol
2026
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