CWC22

protein-coding

CWC22 spliceosome associated protein homolog, the group of MIF4G domain containing proteins|Spliceosomal Bact complex|Spliceosomal P complex|NTC associated proteins|Spliceosomal C complex

Gene summary

Enables RNA binding activity. Involved in mRNA splicing, via spliceosome. Located in nuclear speck. Part of U2-type catalytic step 1 spliceosome; U2-type catalytic step 2 spliceosome; and U2-type precatalytic spliceosome. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_020943.3

Inheritance

—

ClinVar variants

U:128B:9

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.31

Max pathogenic AF

—

Genomic locus

chr2:179,944,876-180,007,297

External References & Databases

Ensembl (ENSG00000163510)

Transcript & Mutation Effects

hg38 • Region Span ~62.4 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 CWC22 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 126

not providedTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020943.3. 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			2 clinvar	1 clinvar	1 clinvar	4
missense			125 clinvar	6 clinvar	1 clinvar	132
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	128	7	2	137

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 27 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020943.3	RefSeq	NP_065994.1	19	MANE Select
ENST00000410053.8	Ensembl	ENSP00000387006.3	19	MANE Select
NM_001376029.1	RefSeq	NP_001362958.1	19	Standard
NM_001376030.1	RefSeq	NP_001362959.1	19	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Metabolism of RNA
mRNA Splicing - Major Pathway
mRNA Splicing
Processing of Capped Intron-Containing Pre-mRNA

Biological Process

mRNA splicing, via spliceosome
regulation of mRNA splicing, via spliceosome

Molecular Function

RNA binding
protein binding

Cellular Component

nucleoplasm
spliceosomal complex
cytosol
nuclear speck
U2-type catalytic step 1 spliceosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000410053
Coding exons: 19
Length: 62238
Individuals with no LoFs: 124581
Homozygous LoFs: 0
Heterozygous LoFs: 52
Defined: 124633
p: 0.000209

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.02	384	444	0.864	0.0000226	5985
Missense (PolyPhen)		62	94.665	0.65494		1316
Synonymous	0.898	138	152	0.907	0.00000770	1574
Loss of Function	4.50	15	48.9	0.306	0.00000301	635

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00013	rare
Latino/Admixed American	0.00015	0.00014	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.000056	0.000056	rare
Finnish	0.00060	0.00060	rare
European (Non-Finnish)	0.00026	0.00026	rare
South Asian	0	0.0	absent
Other	0.00017	0.00017	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Required for pre-mRNA splicing and for exon-junction complex (EJC) assembly. Hinders EIF4A3 from non-specifically binding RNA and escorts it to the splicing machinery to promote EJC assembly on mature mRNAs. Through its role in EJC assembly, required for nonsense-mediated mRNA decay. {ECO:0000269|PubMed:22959432, ECO:0000269|PubMed:22961380, ECO:0000269|PubMed:23236153}.;

Recessive Scores

pRec: 0.164

Intolerance Scores

LoFtool: 0.897
RVIS EVS: 0.07
RVIS percentile EVS: 59.11

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: N
Indispensability score: 0.298

Gene Damage Prediction

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