SRSF1

serine and arginine rich splicing factor 1, the group of RNA binding motif containing|Serine and arginine rich splicing factors

Basic information

Region (hg38): 17:58000918-58007346

Previous symbols: [ "SFRS1" ]

Links

ENSG00000136450 ∙ NCBI:6426 ∙ OMIM:600812 ∙ HGNC:10780 ∙ Uniprot:Q07955 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with dysmorphic facies and behavioral abnormalities	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	Craniofacial; Musculoskeletal; Neurologic	37071997

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SRSF1 gene.

• Neurodevelopmental delay;Intellectual disability (10 variants)
• Neurodevelopmental disorder with dysmorphic facies and behavioral abnormalities (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SRSF1 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						0
missense	4		5			9
nonsense	3		2			5
start loss						0
frameshift	3					3
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	10	0	7	0	0

Variants in SRSF1

This is a list of pathogenic ClinVar variants found in the SRSF1 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-58005420-G-A		Inborn genetic diseases	Uncertain significance (Feb 28, 2023)
17-58005551-CT-C		Neurodevelopmental delay;Intellectual disability	Pathogenic (Feb 15, 2023)
17-58005573-C-CT		Neurodevelopmental delay;Intellectual disability • Neurodevelopmental disorder with dysmorphic facies and behavioral abnormalities	Pathogenic (Feb 15, 2023)
17-58005805-T-C		Neurodevelopmental delay;Intellectual disability	Uncertain significance (Feb 15, 2023)
17-58005875-C-T		Neurodevelopmental delay;Intellectual disability • Neurodevelopmental disorder with dysmorphic facies and behavioral abnormalities	Pathogenic (Feb 15, 2023)
17-58005893-G-A		Inborn genetic diseases	Uncertain significance (Mar 12, 2024)
17-58006343-CAG-C		Neurodevelopmental delay;Intellectual disability	Pathogenic (Feb 15, 2023)
17-58006433-G-A			Uncertain significance (Oct 21, 2016)
17-58006471-A-C		Neurodevelopmental delay;Intellectual disability • Neurodevelopmental disorder with dysmorphic facies and behavioral abnormalities	Pathogenic (Feb 15, 2023)
17-58006491-A-C		Neurodevelopmental delay;Intellectual disability	Pathogenic (Feb 15, 2023)
17-58006513-G-A		Inborn genetic diseases	Uncertain significance (Mar 11, 2024)
17-58006514-C-T		Neurodevelopmental delay;Intellectual disability	Pathogenic (Feb 15, 2023)
17-58007008-C-T		Neurodevelopmental delay;Intellectual disability	Uncertain significance (Feb 16, 2023)
17-58007019-C-A		Neurodevelopmental delay;Intellectual disability • Neurodevelopmental disorder with dysmorphic facies and behavioral abnormalities	Pathogenic (Feb 15, 2023)
17-58007041-C-A		Neurodevelopmental delay;Intellectual disability	Pathogenic (Feb 15, 2023)
17-58007056-G-A		Neurodevelopmental delay;Intellectual disability	Pathogenic (Feb 15, 2023)
17-58007067-G-A		Neurodevelopmental disorder with dysmorphic facies and behavioral abnormalities • Intellectual disability;Neurodevelopmental delay	Conflicting classifications of pathogenicity (Feb 15, 2023)
17-58007068-G-A		Autism spectrum disorder	Uncertain significance (Aug 16, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SRSF1	protein_coding	protein_coding	ENST00000258962	4	3987

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.983	0.0173	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.96	22	165	0.133	0.00000878	1585
Missense in Polyphen		1	43.296	0.023097		478
Synonymous	-0.254	59	56.6	1.04	0.00000260	527
Loss of Function	3.26	0	12.4	0.00	6.87e-7	124

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
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: Plays a role in preventing exon skipping, ensuring the accuracy of splicing and regulating alternative splicing. Interacts with other spliceosomal components, via the RS domains, to form a bridge between the 5'- and 3'-splice site binding components, U1 snRNP and U2AF. Can stimulate binding of U1 snRNP to a 5'-splice site-containing pre-mRNA. Binds to purine-rich RNA sequences, either the octamer, 5'-RGAAGAAC-3' (r=A or G) or the decamers, AGGACAGAGC/AGGACGAAGC. Binds preferentially to the 5'- CGAGGCG-3' motif in vitro. Three copies of the octamer constitute a powerful splicing enhancer in vitro, the ASF/SF2 splicing enhancer (ASE) which can specifically activate ASE-dependent splicing. Isoform ASF-2 and isoform ASF-3 act as splicing repressors. May function as export adapter involved in mRNA nuclear export through the TAP/NXF1 pathway. {ECO:0000269|PubMed:8139654}.
• Pathway: IL-17 signaling pathway - Homo sapiens (human);Spliceosome - Homo sapiens (human);Herpes simplex infection - Homo sapiens (human);mRNA Processing;Gene expression (Transcription);RNA Polymerase II Transcription;Metabolism of RNA;Cleavage of Growing Transcript in the Termination Region ;RNA Polymerase II Transcription Termination;mRNA Splicing - Major Pathway;Transport of Mature mRNA derived from an Intron-Containing Transcript;mRNA Splicing - Minor Pathway;mRNA Splicing;mRNA 3,-end processing;Transport of Mature Transcript to Cytoplasm;Processing of Capped Intron-Containing Pre-mRNA (Consensus)

Recessive Scores

• pRec: 0.0447

Intolerance Scores

• rvis_EVS: -0.01
• rvis_percentile_EVS: 52.85

Haploinsufficiency Scores

• pHI: 0.851
• hipred: Y
• hipred_score: 0.748
• ghis: 0.660

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.539

Mouse Genome Informatics

• Gene name: Srsf1
• Phenotype: cellular phenotype; muscle phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system 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)

Gene ontology

• Biological process: alternative mRNA splicing, via spliceosome;regulation of alternative mRNA splicing, via spliceosome;mRNA 5'-splice site recognition;mRNA splicing, via spliceosome;in utero embryonic development;mRNA splice site selection;mRNA processing;RNA export from nucleus;mRNA export from nucleus;mRNA 3'-end processing;positive regulation of RNA splicing;mRNA cis splicing, via spliceosome;oligodendrocyte differentiation;cardiac muscle contraction;liver regeneration
• Cellular component: nucleus;nucleoplasm;cytoplasm;nuclear speck;exon-exon junction complex;catalytic step 2 spliceosome
• Molecular function: RNA binding;mRNA binding;protein binding;protein kinase B binding;DNA topoisomerase binding;RS domain binding