CPSF7

protein-coding

cleavage and polyadenylation specific factor 7, the group of RNA binding motif containing|Cleavage factor Im complex subunits

Gene summary

Cleavage factor Im (CFIm) is one of six factors necessary for correct cleavage and polyadenylation of pre-mRNAs. CFIm is composed of three different subunits of 25, 59, and 68 kDa, and it functions as a heterotetramer, with a dimer of the 25 kDa subunit binding to two of the 59 or 68 kDa subunits. The protein encoded by this gene represents the 59 kDa subunit, which can interact with the splicing factor U2 snRNP Auxiliary Factor (U2AF) 65 to link the splicing and polyadenylation complexes. [provided by RefSeq, Oct 2016]

MANE transcript

NM_001142565.3

Inheritance

—

ClinVar variants

U:49

Top phenotype

Prostate cancer

gnomAD constraint

pLI —, LoF o/e 0.04

Max pathogenic AF

—

Genomic locus

chr11:61,402,641-61,430,031

External References & Databases

Ensembl (ENSG00000149532)

Transcript & Mutation Effects

hg38 • Region Span ~27.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CPSF7 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 51

Prostate cancerTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001142565.3. 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			1
missense			46 clinvar			46
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	49	0	0	49

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 63 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001142565.3	RefSeq	NP_001136037.1	8	MANE Select
ENST00000439958.8	Ensembl	ENSP00000397203.3	8	MANE Select
NM_001136040.4	RefSeq	NP_001129512.1	8	Standard
NM_024811.4	RefSeq	NP_079087.3	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

mRNA surveillance pathway - Homo sapiens (human)
Gene expression (Transcription)
RNA Polymerase II Transcription
Metabolism of RNA
Processing of Intronless Pre-mRNAs

Biological Process

mRNA splicing, via spliceosome
termination of RNA polymerase II transcription
mRNA 3'-end processing
protein tetramerization
protein heterotetramerization

Molecular Function

RNA binding
protein binding

Cellular Component

nucleus
nucleoplasm
cytoplasm
mRNA cleavage and polyadenylation specificity factor complex
mRNA cleavage factor complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000340437
Coding exons: 9
Length: 27383
Individuals with no LoFs: 125733
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 125735
p: 0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.59	187	317	0.591	0.0000189	3309
Missense (PolyPhen)		66	135.84	0.48586		1360
Synonymous	1.46	94	114	0.826	0.00000595	1115
Loss of Function	4.33	1	23.8	0.0420	0.00000157	240

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000088	0.0000088	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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:8626397, PubMed:17024186, 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:8626397, PubMed:17024186). 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). CPSF7 activates directly the mRNA 3'-processing machinery (PubMed:29276085). Binds to pA signals in RNA substrates (PubMed:8626397, PubMed:17024186). {ECO:0000269|PubMed:17024186, ECO:0000269|PubMed:20695905, ECO:0000269|PubMed:23187700, ECO:0000269|PubMed:29276085, ECO:0000269|PubMed:8626397}.;

Intolerance Scores

LoFtool: 0.0256
RVIS EVS: -0.63
RVIS percentile EVS: 17.03

Essentials

Essential (CRISPR): E
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.910

Gene Damage Prediction

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