CLIP2

Chr 7

CAP-Gly domain containing linker protein 2

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

NCBI Gene: 7461 ENSG00000106665 UniProt: Q9UDT6 OMIM: 603432

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.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.20

Clinical Summary— CLIP2

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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.

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ClinVar Variants

135 VUS of 186 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

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?

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?

LoF OE?0.09 (0.04–0.20)

0≤0.351.4

Missense OE?0.74 (0.69–0.80)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 4 / 46.7Missense obs/exp: 493 / 663.8Syn Z: -0.70

This gene — mechanism propensity

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

186 submitted variants in ClinVar

ClinVar

Classification Summary

VUS135

Likely Benign24

Benign13

135

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	1	134	0	0	135
Likely Benign	0	9	2	13	24
Benign	0	3	0	10	13
Total	1	146	2	23	172

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

View in ClinVar →

167 pathogenic / likely-pathogenic (of 177) ClinVar copy-number / structural variants overlap CLIP2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →