SFPQ

splicing factor proline and glutamine rich, the group of RNA binding motif containing|Protein phosphatase 1 regulatory subunits

Basic information

Region (hg38): 1:35176377-35193446

Links

ENSG00000116560 ∙ NCBI:6421 ∙ OMIM:605199 ∙ HGNC:10774 ∙ Uniprot:P23246 ∙ 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 SFPQ gene.

• Inborn genetic diseases (17 variants)
• not provided (5 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SFPQ 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				3	2	5
missense			17			17
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	17	3	2

Variants in SFPQ

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

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

Position	Type	Phenotype	Significance	ClinVar
1-35187032-G-C		not specified	Uncertain significance (Feb 15, 2023)
1-35189008-T-C			Benign (Apr 18, 2018)
1-35189272-T-G		not specified	Uncertain significance (Dec 16, 2023)
1-35189370-G-A			Likely benign (Nov 01, 2023)
1-35190591-G-A		not specified	Uncertain significance (Jan 20, 2023)
1-35190780-T-C			Benign (Sep 05, 2018)
1-35190949-G-A		not specified	Uncertain significance (Jan 24, 2024)
1-35191394-C-T		not specified	Uncertain significance (Aug 10, 2021)
1-35192251-G-C		not specified	Uncertain significance (Apr 05, 2023)
1-35192282-G-A			Likely benign (Dec 01, 2022)
1-35192302-G-A		not specified	Uncertain significance (Jul 19, 2023)
1-35192307-T-G		not specified	Uncertain significance (Jul 16, 2021)
1-35192311-G-A		not specified	Uncertain significance (Apr 27, 2022)
1-35192421-C-G		not specified	Uncertain significance (Apr 13, 2023)
1-35192526-G-A		not specified	Uncertain significance (Oct 12, 2021)
1-35192598-G-C		not specified	Uncertain significance (Dec 19, 2023)
1-35192629-C-A		not specified	Uncertain significance (Aug 04, 2023)
1-35192640-G-T		not specified	Uncertain significance (Nov 30, 2021)
1-35192745-G-C		not specified	Uncertain significance (Dec 20, 2022)
1-35192756-C-G		not specified	Uncertain significance (Jan 27, 2022)
1-35192821-G-A		not specified	Uncertain significance (Aug 14, 2023)
1-35192843-C-G			Uncertain significance (Aug 16, 2021)
1-35192865-G-A		not specified	Uncertain significance (Sep 16, 2021)
1-35192884-G-A		not specified	Uncertain significance (Nov 27, 2023)
1-35192967-A-G		not specified	Uncertain significance (Aug 12, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SFPQ	protein_coding	protein_coding	ENST00000357214	10	16771

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000764	125733	0	1	125734	0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.98	187	342	0.547	0.0000188	4538
Missense in Polyphen		29	84.025	0.34514		1006
Synonymous	-4.60	172	110	1.56	0.00000563	1443
Loss of Function	5.02	1	31.3	0.0319	0.00000197	344

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: DNA- and RNA binding protein, involved in several nuclear processes. Essential pre-mRNA splicing factor required early in spliceosome formation and for splicing catalytic step II, probably as a heteromer with NONO. Binds to pre-mRNA in spliceosome C complex, and specifically binds to intronic polypyrimidine tracts. Involved in regulation of signal-induced alternative splicing. During splicing of PTPRC/CD45, a phosphorylated form is sequestered by THRAP3 from the pre-mRNA in resting T-cells; T-cell activation and subsequent reduced phosphorylation is proposed to lead to release from THRAP3 allowing binding to pre-mRNA splicing regulatotry elements which represses exon inclusion. Interacts with U5 snRNA, probably by binding to a purine-rich sequence located on the 3' side of U5 snRNA stem 1b. May be involved in a pre-mRNA coupled splicing and polyadenylation process as component of a snRNP-free complex with SNRPA/U1A. The SFPQ-NONO heteromer associated with MATR3 may play a role in nuclear retention of defective RNAs. SFPQ may be involved in homologous DNA pairing; in vitro, promotes the invasion of ssDNA between a duplex DNA and produces a D-loop formation. The SFPQ-NONO heteromer may be involved in DNA unwinding by modulating the function of topoisomerase I/TOP1; in vitro, stimulates dissociation of TOP1 from DNA after cleavage and enhances its jumping between separate DNA helices. The SFPQ-NONO heteromer binds DNA (PubMed:25765647). The SFPQ-NONO heteromer may be involved in DNA non-homologous end joining (NHEJ) required for double-strand break repair and V(D)J recombination and may stabilize paired DNA ends; in vitro, the complex strongly stimulates DNA end joining, binds directly to the DNA substrates and cooperates with the Ku70/G22P1-Ku80/XRCC5 (Ku) dimer to establish a functional preligation complex. SFPQ is involved in transcriptional regulation. Functions as transcriptional activator (PubMed:25765647). Transcriptional repression is mediated by an interaction of SFPQ with SIN3A and subsequent recruitment of histone deacetylases (HDACs). The SFPQ-NONO-NR5A1 complex binds to the CYP17 promoter and regulates basal and cAMP-dependent transcriptional activity. SFPQ isoform Long binds to the DNA binding domains (DBD) of nuclear hormone receptors, like RXRA and probably THRA, and acts as transcriptional corepressor in absence of hormone ligands. Binds the DNA sequence 5'-CTGAGTC-3' in the insulin-like growth factor response element (IGFRE) and inhibits IGF-I-stimulated transcriptional activity. Regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-ARNTL/BMAL1 heterodimer. Required for the transcriptional repression of circadian target genes, such as PER1, mediated by the large PER complex through histone deacetylation (By similarity). Required for the assembly of nuclear speckles (PubMed:25765647). Plays a role in the regulation of DNA virus- mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728). {ECO:0000250|UniProtKB:Q8VIJ6, ECO:0000269|PubMed:10847580, ECO:0000269|PubMed:10858305, ECO:0000269|PubMed:10931916, ECO:0000269|PubMed:11259580, ECO:0000269|PubMed:11525732, ECO:0000269|PubMed:11897684, ECO:0000269|PubMed:15590677, ECO:0000269|PubMed:20932480, ECO:0000269|PubMed:25765647, ECO:0000269|PubMed:28712728, ECO:0000269|PubMed:8045264, ECO:0000269|PubMed:8449401}.
• Disease: DISEASE: Note=A chromosomal aberration involving SFPQ may be a cause of papillary renal cell carcinoma (PRCC). Translocation t(X;1)(p11.2;p34) with TFE3.
• Pathway: mRNA Processing;Type 2 papillary renal cell carcinoma;Signaling by PTK6;Signal Transduction;antisense pathway;PTK6 Regulates Proteins Involved in RNA Processing;EGFR1;Signaling by Non-Receptor Tyrosine Kinases (Consensus)

Recessive Scores

• pRec: 0.113

Haploinsufficiency Scores

• pHI: 0.922
• hipred: Y
• hipred_score: 0.739
• ghis: 0.660

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.973

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sfpq
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Zebrafish Information Network

• Gene name: sfpq
• Affected structure: pigment cell
• Phenotype tag: abnormal
• Phenotype quality: quality

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;alternative mRNA splicing, via spliceosome;double-strand break repair via homologous recombination;activation of innate immune response;mRNA processing;RNA splicing;regulation of circadian rhythm;negative regulation of circadian rhythm;innate immune response;positive regulation of sister chromatid cohesion;negative regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;rhythmic process;histone H3 deacetylation;dendritic transport of messenger ribonucleoprotein complex;positive regulation of oxidative stress-induced intrinsic apoptotic signaling pathway
• Cellular component: chromatin;nucleus;nucleoplasm;nuclear matrix;nuclear speck;dendrite cytoplasm;paraspeckles;RNA polymerase II transcription factor complex
• Molecular function: transcription regulatory region sequence-specific DNA binding;RNA polymerase II distal enhancer sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;chromatin binding;RNA binding;protein binding;protein homodimerization activity;histone deacetylase binding;transcription regulatory region DNA binding;E-box binding