CPSF1

cleavage and polyadenylation specific factor 1, the group of Cleavage and polyadenylation specific factor subunits|MicroRNA protein coding host genes

Basic information

Region (hg38): 8:144393228-144409335

Links

ENSG00000071894 ∙ NCBI:29894 ∙ OMIM:606027 ∙ HGNC:2324 ∙ Uniprot:Q10570 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• myopia 27 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Myopia 27, autosomal dominant	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	Ophthalmologic	30689892

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CPSF1 gene.

• Inborn genetic diseases (61 variants)
• not provided (7 variants)
• Myopia 27 (2 variants)
• CPSF1-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CPSF1 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				4		4
missense			61			61
nonsense						0
start loss						0
frameshift	2					2
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region			1			1
non coding						0
Total	2	0	62	4	0

Highest pathogenic variant AF is 0.0000328

Variants in CPSF1

This is a list of pathogenic ClinVar variants found in the CPSF1 region.

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

Position	Type	Phenotype	Significance	ClinVar
8-144393343-G-A		not specified	Uncertain significance (Dec 17, 2021)
8-144393454-T-C		not specified	Uncertain significance (Aug 11, 2023)
8-144393529-G-T		not specified	Uncertain significance (Dec 18, 2023)
8-144393547-T-G		not specified	Uncertain significance (Jan 16, 2024)
8-144393592-T-C		Myopia 27	Pathogenic (Mar 27, 2020)
8-144393595-GGC-G		CPSF1-related disorder	Likely benign (Apr 10, 2023)
8-144393689-C-T		not specified	Uncertain significance (Mar 22, 2022)
8-144393705-C-T		not specified	Uncertain significance (Jan 24, 2024)
8-144393943-C-T		not specified	Uncertain significance (Nov 04, 2023)
8-144393988-C-A		not specified	Uncertain significance (Jun 01, 2023)
8-144393988-C-T		not specified	Uncertain significance (Jan 31, 2023)
8-144394005-C-T		not specified	Uncertain significance (Jan 22, 2024)
8-144394149-C-A		Myopia 27	Pathogenic (Mar 27, 2020)
8-144394411-C-T		not specified	Uncertain significance (Jun 29, 2023)
8-144394449-G-A		not specified	Uncertain significance (Apr 25, 2022)
8-144394460-G-C		not specified	Uncertain significance (Apr 11, 2023)
8-144394471-C-T		not specified	Uncertain significance (Oct 13, 2023)
8-144394692-G-A		CPSF1-related disorder	Likely benign (May 31, 2023)
8-144394947-G-T		not specified	Uncertain significance (May 17, 2023)
8-144395154-C-G		not specified	Uncertain significance (Jun 28, 2022)
8-144395306-C-T		not specified	Uncertain significance (Sep 29, 2022)
8-144395327-G-A		not specified	Uncertain significance (Sep 22, 2023)
8-144395449-G-A		not specified	Uncertain significance (Feb 05, 2024)
8-144395469-G-A		not specified	Uncertain significance (May 25, 2022)
8-144395515-A-G		not specified	Uncertain significance (Jun 14, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CPSF1	protein_coding	protein_coding	ENST00000349769	37	16310

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.10e-10	1.00	125565	0	172	125737	0.000684

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.80	719	964	0.746	0.0000668	9325
Missense in Polyphen		173	333.37	0.51895		3253
Synonymous	-3.05	508	428	1.19	0.0000332	2919
Loss of Function	4.84	30	75.3	0.398	0.00000365	822

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00466	0.00341
Ashkenazi Jewish	0.00246	0.00159
East Asian	0.000496	0.000489
Finnish	0.0000476	0.0000462
European (Non-Finnish)	0.000808	0.000598
Middle Eastern	0.000496	0.000489
South Asian	0.000430	0.000425
Other	0.000843	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the cleavage and polyadenylation specificity factor (CPSF) complex that plays a key role in pre- mRNA 3'-end formation, recognizing the AAUAAA signal sequence and interacting with poly(A) polymerase and other factors to bring about cleavage and poly(A) addition. This subunit is involved in the RNA recognition step of the polyadenylation reaction. {ECO:0000269|PubMed:14749727}.
• Pathway: mRNA surveillance pathway - Homo sapiens (human);mRNA Processing;tRNA processing;Gene expression (Transcription);polyadenylation of mrna;RNA Polymerase II Transcription;Metabolism of RNA;Processing of Intronless Pre-mRNAs;Processing of Capped Intronless Pre-mRNA;Cleavage of Growing Transcript in the Termination Region ;RNA Polymerase II Transcription Termination;mRNA Splicing - Major Pathway;Transport of Mature mRNA Derived from an Intronless Transcript;Transport of Mature mRNAs Derived from Intronless Transcripts;tRNA processing in the nucleus;mRNA Splicing;mRNA 3,-end processing;Transport of Mature Transcript to Cytoplasm;Processing of Capped Intron-Containing Pre-mRNA (Consensus)

Recessive Scores

• pRec: 0.131

Intolerance Scores

• loftool: 0.668
• rvis_EVS: -3.4
• rvis_percentile_EVS: 0.37

Haploinsufficiency Scores

• pHI: 0.244
• hipred: Y
• hipred_score: 0.563
• ghis: 0.642

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.911

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cpsf1

Zebrafish Information Network

• Gene name: cpsf1
• Affected structure: hematopoietic stem cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: mRNA splicing, via spliceosome;termination of RNA polymerase II transcription;mRNA polyadenylation;mRNA export from nucleus;mRNA 3'-end processing;pre-mRNA cleavage required for polyadenylation
• Cellular component: nucleus;nucleoplasm;mRNA cleavage and polyadenylation specificity factor complex
• Molecular function: protein binding;enzyme binding;mRNA 3'-UTR AU-rich region binding