CPSF6

cleavage and polyadenylation specific factor 6, the group of Cleavage factor Im complex subunits|RNA binding motif containing

Basic information

Region (hg38): 12:69239568-69274358

Links

ENSG00000111605 ∙ NCBI:11052 ∙ OMIM:604979 ∙ HGNC:13871 ∙ Uniprot:Q16630 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CPSF6 gene.

• Inborn genetic diseases (12 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CPSF6 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						0
missense			12			12
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	12	0	0

Variants in CPSF6

This is a list of pathogenic ClinVar variants found in the CPSF6 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-69251179-A-G		not specified	Uncertain significance (Feb 07, 2023)
12-69253081-G-A		not specified	Uncertain significance (Feb 17, 2022)
12-69253132-C-T		not specified	Uncertain significance (Dec 17, 2021)
12-69256788-G-A		not specified	Uncertain significance (Feb 28, 2024)
12-69257828-G-A		not specified	Uncertain significance (Apr 08, 2022)
12-69257848-G-A		not specified	Uncertain significance (Jan 09, 2024)
12-69257890-C-G		not specified	Uncertain significance (Jun 29, 2022)
12-69257896-C-T		not specified	Uncertain significance (Dec 11, 2023)
12-69258709-C-T		not specified	Uncertain significance (Jun 05, 2023)
12-69258757-C-T		not specified	Uncertain significance (Dec 17, 2023)
12-69258811-C-G		not specified	Uncertain significance (Jul 07, 2022)
12-69258860-C-T		not specified	Uncertain significance (Jan 31, 2022)
12-69258872-G-A		not specified	Uncertain significance (Aug 12, 2021)
12-69258881-G-C		not specified	Uncertain significance (Jan 30, 2024)
12-69259042-C-G		not specified	Uncertain significance (Dec 05, 2022)
12-69259091-G-A		not specified	Uncertain significance (Dec 20, 2023)
12-69260136-A-G		not specified	Uncertain significance (Jan 10, 2022)
12-69262457-C-A		not specified	Uncertain significance (Dec 27, 2022)
12-69262526-G-C		not specified	Uncertain significance (Nov 12, 2021)
12-69262539-C-T		not specified	Uncertain significance (Feb 12, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CPSF6	protein_coding	protein_coding	ENST00000435070	9	34822

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000176	122335	0	1	122336	0.00000409

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.94	132	335	0.394	0.0000194	3518
Missense in Polyphen		10	40.494	0.24695		483
Synonymous	-0.577	118	110	1.07	0.00000566	1200
Loss of Function	4.83	1	29.1	0.0344	0.00000217	276

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000892	0.00000892
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the cleavage factor Im (CFIm) complex that functions as an activator of the pre-mRNA 3'-end cleavage and polyadenylation processing required for the maturation of pre-mRNA into functional mRNAs (PubMed:9659921, PubMed:8626397, PubMed:14690600, PubMed:29276085). CFIm contributes to the recruitment of multiprotein complexes on specific sequences on the pre-mRNA 3'-end, so called cleavage and polyadenylation signals (pA signals) (PubMed:9659921, PubMed:8626397, PubMed:14690600). Most pre-mRNAs contain multiple pA signals, resulting in alternative cleavage and polyadenylation (APA) producing mRNAs with variable 3'-end formation (PubMed:23187700, PubMed:29276085). The CFIm complex acts as a key regulator of cleavage and polyadenylation site choice during APA through its binding to 5'- UGUA-3' elements localized in the 3'-untranslated region (UTR) for a huge number of pre-mRNAs (PubMed:20695905, PubMed:29276085). CPSF6 enhances NUDT21/CPSF5 binding to 5'-UGUA-3' elements localized upstream of pA signals and promotes RNA looping, and hence activates directly the mRNA 3'-processing machinery (PubMed:15169763, PubMed:29276085, PubMed:21295486). Plays a role in mRNA export (PubMed:19864460). {ECO:0000269|PubMed:14690600, ECO:0000269|PubMed:15169763, ECO:0000269|PubMed:19864460, ECO:0000269|PubMed:20695905, ECO:0000269|PubMed:21295486, ECO:0000269|PubMed:23187700, ECO:0000269|PubMed:29276085, ECO:0000269|PubMed:8626397, ECO:0000269|PubMed:9659921}.
• Pathway: mRNA surveillance pathway - Homo sapiens (human);Disease;Signaling by FGFR in disease;Signaling by cytosolic FGFR1 fusion mutants;FGFR1 mutant receptor activation;Signaling by FGFR1 in disease;Diseases of signal transduction (Consensus)

Recessive Scores

• pRec: 0.142

Intolerance Scores

• loftool: 0.0971
• rvis_EVS: -0.36
• rvis_percentile_EVS: 28.63

Haploinsufficiency Scores

• pHI: 0.463
• hipred: Y
• hipred_score: 0.696
• ghis: 0.707

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.942

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cpsf6

Gene ontology

• Biological process: mRNA processing;positive regulation of RNA export from nucleus;protein tetramerization;protein heterotetramerization;pre-mRNA cleavage required for polyadenylation;mRNA alternative polyadenylation;messenger ribonucleoprotein complex assembly
• Cellular component: nucleus;nucleoplasm;perichromatin fibrils;cytoplasm;mRNA cleavage and polyadenylation specificity factor complex;mRNA cleavage factor complex;membrane;nuclear speck;interchromatin granule;paraspeckles;ribonucleoprotein complex
• Molecular function: RNA binding;mRNA binding;protein binding;ribosomal large subunit binding;exon-exon junction complex binding