FIP1L1

factor interacting with PAPOLA and CPSF1, the group of Cleavage and polyadenylation specific factor subunits

Basic information

Region (hg38): 4:53377568-53464382

Links

ENSG00000145216 ∙ NCBI:81608 ∙ OMIM:607686 ∙ HGNC:19124 ∙ Uniprot:Q6UN15 ∙ 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 FIP1L1 gene.

• Inborn genetic diseases (15 variants)
• not specified (4 variants)
• not provided (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FIP1L1 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				1		1
missense			11			11
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				3		3
non coding			3		1	4
Total	0	0	14	1	1

Variants in FIP1L1

This is a list of pathogenic ClinVar variants found in the FIP1L1 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-53377893-G-A		not specified	Uncertain significance (May 11, 2022)
4-53379088-A-G		not specified	not provided (Sep 19, 2013)
4-53383804-G-A		not specified	Uncertain significance (May 25, 2022)
4-53390521-G-T		not specified	Uncertain significance (Jan 23, 2024)
4-53390575-C-T		not specified	Uncertain significance (Jun 01, 2023)
4-53391053-A-G		not specified	Uncertain significance (Jan 06, 2023)
4-53391054-C-A		not specified	Uncertain significance (Dec 19, 2022)
4-53391078-A-T		not specified	Uncertain significance (May 06, 2022)
4-53391104-G-A		not specified	Uncertain significance (Dec 28, 2023)
4-53391110-C-G		not specified	Uncertain significance (Nov 21, 2023)
4-53391488-A-G		not specified	not provided (Sep 19, 2013)
4-53399808-T-C		not specified	Uncertain significance (Oct 20, 2023)
4-53399809-C-G		not specified	Uncertain significance (Nov 18, 2022)
4-53399834-G-A			Likely benign (Mar 01, 2023)
4-53414665-A-G		not specified	Uncertain significance (Feb 27, 2023)
4-53414706-G-A		not specified	Uncertain significance (Dec 18, 2023)
4-53444114-T-G		not specified	Benign (Feb 21, 2013)
4-53453014-C-A		not specified	Uncertain significance (Sep 16, 2021)
4-53458645-A-C			Likely benign (Mar 01, 2023)
4-53458653-C-T		not specified	Likely benign (May 24, 2023)
4-53459298-C-T			Likely benign (Feb 25, 2018)
4-53459394-C-T		not specified	Uncertain significance (Jul 25, 2023)
4-53459425-C-G		not specified	Uncertain significance (Jan 16, 2024)
4-53460936-T-A		not specified	Uncertain significance (Nov 10, 2022)
4-53460945-T-A		not specified	Uncertain significance (Dec 13, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FIP1L1	protein_coding	protein_coding	ENST00000337488	18	917630

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.789	0.211	125730	0	18	125748	0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.07	178	336	0.530	0.0000182	3885
Missense in Polyphen		68	155.5	0.4373		1751
Synonymous	-1.01	123	110	1.12	0.00000591	1124
Loss of Function	4.72	8	40.4	0.198	0.00000266	418

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000931	0.0000905
Ashkenazi Jewish	0.000299	0.000298
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000621	0.0000615
Middle Eastern	0.0000544	0.0000544
South Asian	0.000164	0.000163
Other	0.00	0.00

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. FIP1L1 contributes to poly(A) site recognition and stimulates poly(A) addition. Binds to U-rich RNA sequence elements surrounding the poly(A) site. May act to tether poly(A) polymerase to the CPSF complex. {ECO:0000269|PubMed:14749727}.
• Disease: DISEASE: Note=A chromosomal aberration involving FIP1L1 is found in some cases of hypereosinophilic syndrome. Interstitial chromosomal deletion del(4)(q12q12) causes the fusion of FIP1L1 and PDGFRA (FIP1L1-PDGFRA). {ECO:0000269|PubMed:12660384, ECO:0000269|PubMed:12808148}.
• Pathway: mRNA surveillance pathway - Homo sapiens (human);Gene expression (Transcription);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;mRNA Splicing;mRNA 3,-end processing;Transport of Mature Transcript to Cytoplasm;Processing of Capped Intron-Containing Pre-mRNA (Consensus)

Recessive Scores

• pRec: 0.141

Intolerance Scores

• loftool: 0.235
• rvis_EVS: -0.58
• rvis_percentile_EVS: 18.44

Haploinsufficiency Scores

• pHI: 0.654
• hipred: Y
• hipred_score: 0.716
• ghis: 0.689

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.988

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Fip1l1

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: nucleoplasm;mRNA cleavage and polyadenylation specificity factor complex
• Molecular function: RNA binding;protein binding