SRSF3

protein-coding

serine and arginine rich splicing factor 3, the group of RNA binding motif containing|Serine and arginine rich splicing factors

Gene summary

The protein encoded by this gene is a member of the serine/arginine (SR)-rich family of pre-mRNA splicing factors, which constitute part of the spliceosome. Each of these factors contains an RNA recognition motif (RRM) for binding RNA and an RS domain for binding other proteins. The RS domain is rich in serine and arginine residues and facilitates interaction between different SR splicing factors. In addition to being critical for mRNA splicing, the SR proteins have also been shown to be involved in mRNA export from the nucleus and in translation. Two transcript variants, one protein-coding and the other non-coding, have been found for this gene. [provided by RefSeq, Sep 2010]

Previous symbols:

SFRS3

MANE transcript

NM_003017.5

Inheritance

—

ClinVar variants

U:10

Top phenotype

SRSF3-related condition

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr6:36,594,353-36,605,911

External References & Databases

Ensembl (ENSG00000112081)

Transcript & Mutation Effects

hg38 • Region Span ~11.6 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 SRSF3 variants in ClinVar

3 Conditions Cataloged

not providedTotal: 3

not specifiedTotal: 2

SRSF3-related conditionTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003017.5. 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						0
missense			7 clinvar			7
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	10	0	0	10

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 48 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003017.5	RefSeq	NP_003008.1	5	MANE Select
ENST00000373715.11	Ensembl	ENSP00000362820.5	5	MANE Select
ENST00000477442.6	Ensembl	ENSP00000436036.1	3	Standard
ENST00000613941.4	Ensembl	ENSP00000484891.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Spliceosome - Homo sapiens (human)
Herpes simplex infection - Homo sapiens (human)
mRNA Processing
Gene expression (Transcription)
RNA Polymerase II Transcription

Biological Process

regulation of alternative mRNA splicing, via spliceosome
mRNA splicing, via spliceosome
RNA export from nucleus
mRNA export from nucleus
mRNA 3'-end processing

Molecular Function

RNA binding
protein binding
sequence-specific mRNA binding

Cellular Component

nucleoplasm
cytoplasm
nuclear speck

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000373715
Coding exons: 5
Length: 11233
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.07	18	108	0.167	0.00000685	1046
Missense (PolyPhen)		0	25.834	0		300
Synonymous	-1.00	42	34.5	1.22	0.00000174	342
Loss of Function	2.97	0	10.3	0.00	7.47e-7	92

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
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	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Splicing factor that specifically promotes exon- inclusion during alternative splicing (PubMed:26876937). Interaction with YTHDC1, a RNA-binding protein that recognizes and binds N6-methyladenosine (m6A)-containing RNAs, promotes recruitment of SRSF3 to its mRNA-binding elements adjacent to m6A sites, leading to exon-inclusion during alternative splicing (PubMed:26876937). Also functions as export adapter involved in mRNA nuclear export (PubMed:11336712, PubMed:18364396, PubMed:28984244). Binds mRNA which is thought to be transferred to the NXF1-NXT1 heterodimer for export (TAP/NXF1 pathway); enhances NXF1-NXT1 RNA-binding activity (PubMed:11336712, PubMed:18364396). Involved in nuclear export of m6A-containing mRNAs via interaction with YTHDC1: interaction with YTHDC1 facilitates m6A-containing mRNA-binding to both SRSF3 and NXF1, promoting mRNA nuclear export (PubMed:28984244). RNA-binding is semi-sequence specific (PubMed:17036044). {ECO:0000269|PubMed:11336712, ECO:0000269|PubMed:17036044, ECO:0000269|PubMed:18364396, ECO:0000269|PubMed:26876937, ECO:0000269|PubMed:28984244}.;

Recessive Scores

pRec: 0.136

Intolerance Scores

RVIS EVS: 0.04
RVIS percentile EVS: 56.25

Essentials

Essential (CRISPR): E
Essential (CRISPR2): S
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.539