CCNF

cyclin F, the group of Cyclins|MicroRNA protein coding host genes|F-boxes other

Basic information

Region (hg38): 16:2429394-2458854

Links

ENSG00000162063 ∙ NCBI:899 ∙ OMIM:600227 ∙ HGNC:1591 ∙ Uniprot:P41002 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• amyotrophic lateral sclerosis (Supportive), mode of inheritance: AD
• amyotrophic lateral sclerosis (Limited), mode of inheritance: AD
• frontotemporal dementia and/or amyotrophic lateral sclerosis 5 (Strong), mode of inheritance: AD
• frontotemporal dementia and/or amyotrophic lateral sclerosis 5 (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Frontotemporal dementia and/or amyotrophic lateral sclerosis 5	AD	General	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	Neurologic	27080313

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CCNF gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CCNF gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				12	3	15
missense		1	60	8	4	73
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				4	1	5
non coding				2	36	38
Total	0	1	61	22	43

Variants in CCNF

This is a list of pathogenic ClinVar variants found in the CCNF region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
16-2429481-G-C			Benign (May 05, 2021)
16-2429488-A-G			Uncertain significance (Jan 08, 2024)
16-2429711-A-C			Benign (May 10, 2021)
16-2430947-A-G			Benign (May 10, 2021)
16-2431103-C-G			Benign (May 21, 2021)
16-2431175-G-A		Frontotemporal dementia and/or amyotrophic lateral sclerosis 5	Uncertain significance (-)
16-2431184-G-A			Uncertain significance (Jun 08, 2020)
16-2431198-A-C		not specified	Uncertain significance (Aug 30, 2022)
16-2431224-A-G			Benign/Likely benign (Dec 01, 2022)
16-2431276-G-A		not specified	Uncertain significance (May 24, 2023)
16-2432966-C-T			Likely benign (Jul 29, 2018)
16-2432968-C-A		not specified	Uncertain significance (Oct 08, 2024)
16-2432994-C-T		Frontotemporal dementia and/or amyotrophic lateral sclerosis 5	Uncertain significance (Feb 22, 2023)
16-2433004-T-C		not specified	Uncertain significance (May 02, 2024)
16-2433009-G-A		CCNF-related disorder	Benign (Jul 02, 2019)
16-2433037-C-T			Uncertain significance (Nov 05, 2023)
16-2433046-G-A		not specified	Conflicting classifications of pathogenicity (Nov 06, 2023)
16-2433051-C-G			Uncertain significance (Mar 10, 2023)
16-2433074-C-G			Likely benign (Jun 01, 2018)
16-2433179-T-C			Benign (May 24, 2021)
16-2435596-GAT-G			Benign (May 10, 2021)
16-2435600-T-G			Benign (May 10, 2021)
16-2435619-ACACACACACATATATATG-A			Benign (May 10, 2021)
16-2435655-G-GCA			Benign (Jun 03, 2021)
16-2435662-CACACATATATATAT-C			Benign (Jun 03, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CCNF	protein_coding	protein_coding	ENST00000397066	17	29461

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.127	0.873	125729	0	19	125748	0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.741	424	469	0.904	0.0000286	5084
Missense in Polyphen		101	144.6	0.69847		1540
Synonymous	0.433	203	211	0.962	0.0000142	1572
Loss of Function	4.44	10	40.5	0.247	0.00000222	427

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000119	0.000119
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.0000892	0.0000879
Middle Eastern	0.000163	0.000163
South Asian	0.0000993	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Substrate recognition component of a SCF (SKP1-CUL1-F- box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of CP110 during G2 phase, thereby acting as an inhibitor of centrosome reduplication. {ECO:0000269|PubMed:20596027}.
• Pathway: Post-translational protein modification;Metabolism of proteins;Immune System;Adaptive Immune System;Antigen processing: Ubiquitination & Proteasome degradation;Class I MHC mediated antigen processing & presentation;Neddylation (Consensus)

Recessive Scores

• pRec: 0.131

Intolerance Scores

• loftool: 0.488
• rvis_EVS: -1.22
• rvis_percentile_EVS: 5.67

Haploinsufficiency Scores

• pHI: 0.572
• hipred: Y
• hipred_score: 0.712
• ghis: 0.673

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.869

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ccnf
• Phenotype: cellular phenotype; growth/size/body region phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; embryo phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan)

Gene ontology

• Biological process: regulation of cyclin-dependent protein serine/threonine kinase activity;protein polyubiquitination;mitotic cell cycle;re-entry into mitotic cell cycle;placenta development;protein phosphorylation;regulation of mitotic nuclear division;positive regulation of cell population proliferation;negative regulation of centrosome duplication;protein ubiquitination;SCF-dependent proteasomal ubiquitin-dependent protein catabolic process;post-translational protein modification;positive regulation of cell cycle;cell division
• Cellular component: cyclin-dependent protein kinase holoenzyme complex;nucleus;cytoplasm;centrosome;centriole;cytosol;SCF ubiquitin ligase complex;cell junction
• Molecular function: protein kinase activity;ubiquitin-protein transferase activity;protein binding;cyclin-dependent protein serine/threonine kinase regulator activity;protein kinase binding