GeneBe

CPSF6

protein-coding

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

Gene summary

The protein encoded by this gene is one subunit of a cleavage factor required for 3' RNA cleavage and polyadenylation processing. The interaction of the protein with the RNA is one of the earliest steps in the assembly of the 3' end processing complex and facilitates the recruitment of other processing factors. The cleavage factor complex is composed of four polypeptides. This gene encodes the 68kD subunit. It has a domain organization reminiscent of spliceosomal proteins. [provided by RefSeq, Jul 2008]

MANE transcript

NM_007007.3

Inheritance

AD

ClinVar variants

U:42

Top phenotype

Neurodevelopmental disorder

gnomAD constraint

pLI —, LoF o/e 0.03

Max pathogenic AF

—

Genomic locus

chr12:69,239,569-69,274,358

External References & Databases

Ensembl (ENSG00000111605)NCBI Gene (11052)OMIM (604979)HGNC:13871GenCCUniProt (Q16630)AlphaFoldClinVar (CPSF6)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~34.8 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorderLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: Broad Center for Mendelian Genomics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CPSF6 variants in ClinVar

3 Conditions Cataloged
not specifiedTotal: 33
not providedTotal: 2
Neurodevelopmental disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_007007.3. 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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
 1
missense
36
clinvar
 36
nonsense
0
start loss
0
frameshift
2
clinvar
 2
splice donor/acceptor (+/-2bp)
3
clinvar
 3
Total00420042
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 92 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_007007.3RefSeqNP_008938.29MANE Select
ENST00000435070.7EnsemblENSP00000391774.29MANE Select
NM_001300947.2RefSeqNP_001287876.110Standard
ENST00000266679.8EnsemblENSP00000266679.810Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • mRNA surveillance pathway - Homo sapiens (human)
  • Disease
  • Signaling by FGFR in disease
  • Signaling by cytosolic FGFR1 fusion mutants
  • FGFR1 mutant receptor activation

Biological Process

  • mRNA processing
  • positive regulation of RNA export from nucleus
  • protein tetramerization
  • protein heterotetramerization
  • pre-mRNA cleavage required for polyadenylation

Molecular Function

  • RNA binding
  • mRNA binding
  • protein binding
  • ribosomal large subunit binding
  • exon-exon junction complex binding

Cellular Component

  • nucleus
  • nucleoplasm
  • perichromatin fibrils
  • cytoplasm
  • mRNA cleavage and polyadenylation specificity factor complex

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000435070
Coding exons
9
Length
34822
Individuals with no LoFs
122335
Homozygous LoFs
0
Heterozygous LoFs
1
Defined
122336
p
0.00000409
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense3.941323350.3940.00001943518
Missense (PolyPhen)1040.4940.24695483
Synonymous-0.5771181101.070.000005661200
Loss of Function4.83129.10.03440.00000217276

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)0.00000890.0000089rare
South Asian00.0absent
Other00.0absent

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: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}.;

Recessive Scores

pRec
0.142

Intolerance Scores

LoFtool
0.0971
RVIS EVS
-0.36
RVIS percentile EVS
28.63

Essentials

Essential (CRISPR)
E
Essential (CRISPR2)
E
Essential (gene trap)
E
Indispensability pred.
E
Indispensability score
0.942

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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