CCNQ
protein-codingcyclin Q, the group of Cyclins
Gene summary
Mutations in this gene have been shown to cause an X-linked dominant STAR syndrome that typically manifests syndactyly, telecanthus and anogenital and renal malformations. The protein encoded by this gene contains a cyclin-box-fold domain which suggests it may have a role in controlling nuclear cell division cycles. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Oct 2008]
- FAM58A
MANE transcript
Inheritance
ClinVar variants
Top phenotype
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~12.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: XL
Disease ID:MONDO:0010408
Submitter: Orphanet
Inheritance Pattern: XL
Disease ID:MONDO:0010408
Submitter: G2P
Inheritance Pattern: XL
Disease ID:MONDO:0010408
Submitter: ClinGen
The *CCNQ* gene is located on chromosome X at Xq28 and encodes the ubiquitously expressed cyclin Q, the activating cyclin for the cyclin-associated kinase CDK10. *CCNQ* was first reported in relation to X-linked Toe Syndactyly, Telecanthus, Anogenital and Renal malformations (STAR) syndrome in 2008 (Unger et al., 2008, PMID:18297069). Only female probands are reported as affected with this developmental disorder which is characterized by a broad spectrum of variable phenotypes that include dysmorphic facial features, cardiovascular and skeletal abnormalities as well as the toe syndactyly, telecanthus, anogenital and renal malformations described by the disorder’s acronym. Severity of disease is also highly variable and dependent upon the level of X-inactivation. Genetic evidence supporting the relationship between *CCNQ* and STAR syndrome includes six unique variants (one gross deletion, two splice site, two stop gain and one frameshift) which have been reported in six probands from three publications (PMID: 18297069, Boczek et al., 2016, PMID: 28322501; Che et al., 2023, PMID:36284407) and are included in this curation. Loss of function is implicated as the mechanism of disease.This gene-disease relationship is also supported by biochemical pathway and protein-protein interaction studies (PMID: 18297069; Guen et al.,(2016), PMID: 27104747). In summary, there is moderate evidence supporting the relationship between *CCNQ* and X-linked STAR syndrome. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged. This classification was approved by the ClinGen Syndromic Disorders GCEP on July 19th, 2024 (SOP Version 10). Of note, an additional six probands have been reported in the literature with deletions encompassing additional genetic material and were not included in the curation (PMID:18297069; Boone et al.,(2010) PMID: 20848651; Zarate et al.,( 2015); PMID: 25845904; Orge et al.,(2016), PMID:26882209; Bedeschi et al.,2017, PMID: 29088509; Lefroy et al. , 2017, PMID: 28225384). One additional proband reported to have STAR syndrome was not included in this curation due to insufficient phenotype information (Gabriel et al., 2021, PMID: 34958143).
Inheritance Pattern: XL
Disease ID:MONDO:0010408
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: XL
Disease ID:MONDO:0010408
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Renal
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
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CCNQ variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_152274.5. 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 | 3 | 15 | 5 | 23 | ||
| missense | 35 | 7 | 1 | 43 | ||
| nonsense | 1 | 2 | 3 | 6 | ||
| start loss | 0 | |||||
| frameshift | 1 | 1 | 1 | 3 | 6 | |
| splice donor/acceptor (+/-2bp) | 3 | 10 | 13 | |||
| Total | 5 | 3 | 52 | 22 | 9 | 91 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_689487.2 | 5 | MANE Select | |
| Ensembl | ENSP00000461135.1 | 5 | MANE Select | |
| RefSeq | NP_001124469.1 | 5 | Standard | |
| Ensembl | ENSP00000412865.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- regulation of cyclin-dependent protein serine/threonine kinase activity
- regulation of transcription by RNA polymerase II
Molecular Function
- protein binding
- cyclin-dependent protein serine/threonine kinase regulator activity
Cellular Component
- nucleus
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Activating cyclin for the cyclin-associated kinase CDK10. {ECO:0000269|PubMed:18297069, ECO:0000269|PubMed:24218572}.;
- Disease
- DISEASE: Toe syndactyly, telecanthus, and anogenital and renal malformations (STAR) [MIM:300707]: A syndrome characterized by anal, genital and renal tract anomalies, facial dysmorphism and syndactyly. Features include anal stenosis, a rectovaginal fistula, clitoral hypertrophy, a pelvic right kidney, toe syndactyly, and telecanthus. {ECO:0000269|PubMed:18297069}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.0970