CLIP2

protein-coding

CAP-Gly domain containing linker protein 2

Gene summary

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]

Previous symbols:

WBSCR4
CYLN2
WBSCR3

MANE transcript

NM_003388.5

Inheritance

—

ClinVar variants

U:146B:36

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.09

Max pathogenic AF

—

Genomic locus

chr7:74,289,407-74,405,935

External References & Databases

Ensembl (ENSG00000106665)

Transcript & Mutation Effects

hg38 • Region Span ~116.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CLIP2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 139

not providedTotal: 41

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003388.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	14 clinvar	10 clinvar	25
missense			137 clinvar	9 clinvar	3 clinvar	149
nonsense			1 clinvar			1
start loss						0
frameshift			4 clinvar			4
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	146	23	13	182

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 53 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003388.5	RefSeq	NP_003379.4	16	MANE Select
ENST00000223398.11	Ensembl	ENSP00000223398.6	16	MANE Select
NM_032421.3	RefSeq	NP_115797.2	15	Standard
ENST00000361545.10	Ensembl	ENSP00000355151.5	15	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Molecular Function

microtubule binding
microtubule plus-end binding

Cellular Component

microtubule associated complex
cytoplasmic microtubule
microtubule plus-end

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000223398
Coding exons: 16
Length: 116469
Individuals with no LoFs: 125734
Homozygous LoFs: 0
Heterozygous LoFs: 14
Defined: 125748
p: 0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.36	493	664	0.743	0.0000464	6629
Missense (PolyPhen)		116	223.76	0.51842		2271
Synonymous	-0.701	338	322	1.05	0.0000244	2161
Loss of Function	5.79	4	46.7	0.0857	0.00000235	535

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.000056	0.000054	rare
Finnish	0.00010	0.000092	rare
European (Non-Finnish)	0.000054	0.000053	rare
South Asian	0.000098	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Seems to link microtubules to dendritic lamellar body (DLB), a membranous organelle predominantly present in bulbous dendritic appendages of neurons linked by dendrodendritic gap junctions. May operate in the control of brain-specific organelle translocations (By similarity). {ECO:0000250}.;
Disease: DISEASE: Note=CLIP2 is located in the Williams-Beuren syndrome (WBS) critical region (PubMed:9799601). WBS results from a hemizygous deletion of several genes on chromosome 7q11.23, thought to arise as a consequence of unequal crossing over between highly homologous low-copy repeat sequences flanking the deleted region. Haploinsufficiency of CLIP2 may be the cause of certain cardiovascular and musculo-skeletal abnormalities observed in the disease. However, it has been demonstrated that haploinsufficiency of this gene alone is not sufficient to cause any of the cognitive or facial features of WBS (PubMed:22608712). {ECO:0000305|PubMed:22608712, ECO:0000305|PubMed:9799601}.;

Intolerance Scores

LoFtool: 0.127
RVIS EVS: -1.19
RVIS percentile EVS: 5.9

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.838

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium