CWF19L1

protein-coding

CWF19 like cell cycle control factor 1, the group of Small nucleolar RNA protein coding host genes

Gene summary

This gene encodes a member of the CWF19 protein family. Mutations in this gene have been associated with autosomal recessive spinocerebellar ataxia-17 and mild cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

MANE transcript

NM_018294.6

Inheritance

ClinVar variants

P:35U:90B:24

Top phenotype

Spinocerebellar ataxia, autosomal recessive 17

gnomAD constraint

pLI —, LoF o/e 0.83

Max pathogenic AF

—

Genomic locus

chr10:100,232,298-100,267,680

External References & Databases

Ensembl (ENSG00000095485)

Transcript & Mutation Effects

hg38 • Region Span ~35.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

autosomal recessive cerebellar ataxiaDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0015244

Submitter: ClinGen

*CWF19L1* was first reported in relation to autosomal recessive spinocerebellar ataxia in 2014 (Burns R, et al., PMID: 25361784). The *CWF19L1* gene is thought to play a role in cell cycle control, endosomal trafficking and mRNA processing (PMID: 36357319). Autosomal recessive cerebellar ataxia due to variants in *CWF19L1* is characterized by gait, limb, and truncal ataxia, developmental delay, hypotonia, intellectual disability, and cerebellar atrophy or hypoplasia on brain imaging. Other features may be present as well and patients typically, but not always, have an early age of onset (PMID: 36453471). Fourteen variants (4 canonical splice-site, 5 missense, 2 frameshift, 2 nonsense, 1 in-frame deletion) that have been reported in 12 probands in 9 publications (PMIDs: 25361784, 26197978, 27016154, 38681507, 36357319, 36530930, 36453471, 37752213, 33012273) are included in this curation. More evidence is available in the literature, but the maximum score for genetic evidence has been reached. The mechanism of pathogenicity is loss of function. This gene-disease relationship is also supported by a morpholino-mediated knockdown of *CWF19L1* in zebrafish that led to cerebellar and movement abnormalities (PMID: 25361784). In summary, there is definitive evidence supporting the relationship between *CWF19L1* and autosomal recessive spinocerebellar ataxia. This has been repeatedly demonstrated in both the research and clinical diagnostic settings and has been upheld over time. This classification was approved by the ClinGen Ataxia GCEP on the meeting date May 14, 2025 (SOP Version 11).

autosomal recessive spinocerebellar ataxia 17STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014503

Submitter: Labcorp Genetics (formerly Invitae)

autosomal recessive spinocerebellar ataxia 17SUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014503

Submitter: Orphanet

autosomal recessive spinocerebellar ataxia 17STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014503

Submitter: G2P

autosomal recessive spinocerebellar ataxia 17MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0014503

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Spinocerebellar ataxia, autosomal recessive 17AR

Manifestation: Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 15981765; 25361784

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CWF19L1 variants in ClinVar

6 Conditions Cataloged

Inborn genetic diseasesTotal: 65

not providedTotal: 54

Autosomal recessive spinocerebellar ataxia 17Total: 32

CWF19L1-related disorderTotal: 14

not specifiedTotal: 11

Intellectual disabilityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018294.6. 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		15
missense	1 clinvar	4 clinvar	85 clinvar	9 clinvar	1 clinvar	100
nonsense	5 clinvar	7 clinvar	1 clinvar			13
start loss						0
frameshift	2 clinvar	7 clinvar				9
splice donor/acceptor (+/-2bp)	4 clinvar	5 clinvar	3 clinvar			12
Total	12	23	90	23	1	149

Highest pathogenic variant AF is 0.00008208261

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 38 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_018294.6	RefSeq	NP_060764.3	14	MANE Select
ENST00000354105.10	Ensembl	ENSP00000326411.6	14	MANE Select
NM_001303404.2	RefSeq	NP_001290333.1	13	Standard
NM_001303405.2	RefSeq	NP_001290334.1	10	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
cwf19l1	Danio rerio	Structure: cerebellum Quality: morphology abnormal

Gene / Model

Organism

Observed Phenotype

cwf19l1

Danio rerio

Structure: cerebellum

Quality: morphology

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

biological_process

Molecular Function

molecular_function

Cellular Component

cellular_component

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000354105
Coding exons: 14
Length: 35383
Individuals with no LoFs: 125610
Homozygous LoFs: 0
Heterozygous LoFs: 137
Defined: 125747
p: 0.000545

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.10	232	284	0.817	0.0000140	3529
Missense (PolyPhen)		64	79.96	0.8004		961
Synonymous	1.01	88	101	0.872	0.00000490	998
Loss of Function	0.887	26	31.4	0.829	0.00000156	382

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00080	0.00080	rare
Latino/Admixed American	0.00036	0.00035	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0014	0.0014	notable
Finnish	0.0014	0.0014	notable
European (Non-Finnish)	0.00043	0.00043	rare
South Asian	0.00013	0.00013	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.0825

Intolerance Scores

LoFtool: 0.901
RVIS EVS: 0.46
RVIS percentile EVS: 78.69

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Indispensability pred.: N
Indispensability score: 0.00112

Gene Damage Prediction

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