GeneBe

SART3

protein-coding

spliceosome associated factor 3, U4/U6 recycling protein, the group of RNA binding motif containing

Gene summary

The protein encoded by this gene is an RNA-binding nuclear protein that is a tumor-rejection antigen. This antigen possesses tumor epitopes capable of inducing HLA-A24-restricted and tumor-specific cytotoxic T lymphocytes in cancer patients and may be useful for specific immunotherapy. This gene product is found to be an important cellular factor for HIV-1 gene expression and viral replication. It also associates transiently with U6 and U4/U6 snRNPs during the recycling phase of the spliceosome cycle. This encoded protein is thought to be involved in the regulation of mRNA splicing. [provided by RefSeq, Jul 2008]

MANE transcript

NM_014706.4

Inheritance

AR, AD

ClinVar variants

P:8U:131B:12

Top phenotype

Porokeratosis, disseminated superficial actinic, 1

gnomAD constraint

pLI —, LoF o/e 0.16

Max pathogenic AF

—

Genomic locus

chr12:108,522,214-108,561,400

External References & Databases

Ensembl (ENSG00000075856)NCBI Gene (9733)OMIM (611684)HGNC:16860GenCCUniProt (Q15020)AlphaFoldClinVar (SART3)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~39.2 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

complex neurodevelopmental disorderMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0100038

Submitter: G2P

neurodevelopmental disorderSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0700092

Submitter: PanelApp Australia

disseminated superficial actinic porokeratosisMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0019212

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Porokeratosis, disseminated superficial actinic, 1AD

Manifestation: Dermatologic

Intervention: General

Rationale: 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

Refs: 15840095Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SART3 variants in ClinVar

4 Conditions Cataloged
not specifiedTotal: 131
Intellectual disability, Neurodevelopmental defects and Developmental delay with 46,XY gonadal dysgenesisTotal: 8
not providedTotal: 7
Porokeratosis 3, disseminated superficial actinic typeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014706.4. 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
5
clinvar
3
clinvar
 9
missense
7
clinvar
121
clinvar
4
clinvar
 132
nonsense
1
clinvar
4
clinvar
 5
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
5
clinvar
 5
Total0813193151

Highest pathogenic variant AF is 0.0000092929895

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 45 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_014706.4RefSeqNP_055521.119MANE Select
ENST00000546815.6EnsemblENSP00000449386.219MANE Select
NM_001410983.1RefSeqNP_001397912.119Standard
ENST00000228284.8EnsemblENSP00000228284.419Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
sart3Danio rerio

Structure: pharyngeal arch

Quality: malformed

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

  • spliceosomal tri-snRNP complex assembly
  • regulation of alternative mRNA splicing, via spliceosome
  • spliceosomal snRNP assembly
  • mRNA splicing, via spliceosome
  • cell morphogenesis

Molecular Function

  • RNA binding
  • protein binding
  • U6 snRNA binding
  • U4 snRNA binding
  • U6atac snRNA binding

Cellular Component

  • nucleus
  • nucleoplasm
  • U6atac snRNP
  • cytoplasm
  • Cajal body

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000228284
Coding exons
19
Length
38820
Individuals with no LoFs
125720
Homozygous LoFs
0
Heterozygous LoFs
28
Defined
125748
p
0.000111
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.8064985510.9030.00003356335
Missense (PolyPhen)132194.360.679152148
Synonymous0.2082082120.9820.00001361788
Loss of Function5.85956.40.1590.00000324635

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000180.00018rare
Latino/Admixed American0.0000870.000087rare
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish0.000140.00014rare
European (Non-Finnish)0.000140.00014rare
South Asian0.0000650.000065rare
Other0.000160.00016rare

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: U6 snRNP-binding protein that functions as a recycling factor of the splicing machinery. Promotes the initial reassembly of U4 and U6 snRNPs following their ejection from the spliceosome during its maturation (PubMed:12032085). Also binds U6atac snRNPs and may function as a recycling factor for U4atac/U6atac spliceosomal snRNP, an initial step in the assembly of U12-type spliceosomal complex. The U12-type spliceosomal complex plays a role in the splicing of introns with non-canonical splice sites (PubMed:14749385). May also function as a substrate-targeting factor for deubiquitinases like USP4 and USP15. Recruits USP4 to ubiquitinated PRPF3 within the U4/U5/U6 tri-snRNP complex, promoting PRPF3 deubiquitination and thereby regulating the spliceosome U4/U5/U6 tri-snRNP spliceosomal complex disassembly (PubMed:20595234). May also recruit the deubiquitinase USP15 to histone H2B and mediate histone deubiquitination, thereby regulating gene expression and/or DNA repair (PubMed:24526689). May play a role in hematopoiesis probably through transcription regulation of specific genes including MYC (By similarity). {ECO:0000250|UniProtKB:Q9JLI8, ECO:0000269|PubMed:12032085, ECO:0000269|PubMed:14749385, ECO:0000269|PubMed:20595234, ECO:0000269|PubMed:24526689}.;

Recessive Scores

pRec
0.151

Intolerance Scores

LoFtool
0.607
RVIS EVS
-1.04
RVIS percentile EVS
7.84

Essentials

Essential (CRISPR)
E
Essential (CRISPR2)
E
Essential (gene trap)
E
Indispensability pred.
E
Indispensability score
0.992

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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