SART3

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

Basic information

Region (hg38): 12:108522213-108561400

Links

ENSG00000075856 ∙ NCBI:9733 ∙ OMIM:611684 ∙ HGNC:16860 ∙ Uniprot:Q15020 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• disseminated superficial actinic porokeratosis (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Porokeratosis, disseminated superficial actinic, 1	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	Dermatologic	15840095

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SART3 gene.

• Inborn genetic diseases (26 variants)
• not provided (5 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SART3 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	3
missense			24	2		26
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding					1	1
Total	0	0	24	2	4

Variants in SART3

This is a list of pathogenic ClinVar variants found in the SART3 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-108523525-C-T		not specified	Likely benign (Jan 16, 2024)
12-108523531-C-G		not specified	Uncertain significance (Aug 14, 2023)
12-108523553-G-A			Benign (Dec 31, 2019)
12-108523563-T-C		not specified	Uncertain significance (Jul 09, 2021)
12-108523632-C-T		not specified	Uncertain significance (Feb 05, 2024)
12-108524323-A-G		not specified	Uncertain significance (Jun 05, 2023)
12-108524481-T-C		not specified	Uncertain significance (Dec 28, 2023)
12-108525473-C-T		Intellectual disability, Neurodevelopmental defects and Developmental delay with 46,XY gonadal dysgenesis	Likely pathogenic (Mar 06, 2023)
12-108525476-T-C		not specified	Uncertain significance (Feb 28, 2024)
12-108525545-C-T		not specified	Uncertain significance (Jun 10, 2022)
12-108525604-G-C		not specified	Uncertain significance (Jun 27, 2022)
12-108526170-G-A		Intellectual disability, Neurodevelopmental defects and Developmental delay with 46,XY gonadal dysgenesis	Likely pathogenic (Mar 06, 2023)
12-108526187-T-C		not specified	Uncertain significance (Oct 16, 2023)
12-108526257-T-C		not specified	Uncertain significance (Oct 26, 2022)
12-108526316-G-A		Intellectual disability, Neurodevelopmental defects and Developmental delay with 46,XY gonadal dysgenesis	Likely pathogenic (Mar 06, 2023)
12-108526396-G-A			Benign (Dec 31, 2019)
12-108526433-G-A		not specified	Uncertain significance (Oct 06, 2022)
12-108526491-C-G		not specified	Likely benign (Aug 11, 2022)
12-108526551-G-T		not specified	Uncertain significance (Sep 26, 2022)
12-108530286-C-T		Porokeratosis 3, disseminated superficial actinic type	Uncertain significance (Aug 01, 2007)
12-108532252-C-T		not specified	Uncertain significance (Dec 21, 2022)
12-108532330-G-A		not specified	Uncertain significance (Jun 03, 2022)
12-108535360-T-C		Intellectual disability, Neurodevelopmental defects and Developmental delay with 46,XY gonadal dysgenesis	Likely pathogenic (Mar 06, 2023)
12-108535438-G-A		Intellectual disability, Neurodevelopmental defects and Developmental delay with 46,XY gonadal dysgenesis	Likely pathogenic (Mar 06, 2023)
12-108536558-C-T		not specified	Uncertain significance (Dec 03, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SART3	protein_coding	protein_coding	ENST00000228284	19	38820

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.997	0.00339	125720	0	28	125748	0.000111

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.806	498	551	0.903	0.0000335	6335
Missense in Polyphen		132	194.36	0.67915		2148
Synonymous	0.208	208	212	0.982	0.0000136	1788
Loss of Function	5.85	9	56.4	0.159	0.00000324	635

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000271	0.000271
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000141	0.000141
Middle Eastern	0.00	0.00
South Asian	0.0000653	0.0000653
Other	0.000164	0.000163

dbNSFP

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

Haploinsufficiency Scores

• pHI: 0.0816
• hipred: Y
• hipred_score: 0.704
• ghis: 0.666

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.992

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sart3
• Phenotype: hematopoietic system phenotype

Zebrafish Information Network

• Gene name: sart3
• Affected structure: pharyngeal arch
• Phenotype tag: abnormal
• Phenotype quality: malformed

Gene ontology

• Biological process: spliceosomal tri-snRNP complex assembly;regulation of alternative mRNA splicing, via spliceosome;spliceosomal snRNP assembly;mRNA splicing, via spliceosome;cell morphogenesis;nucleosome assembly;RNA splicing;regulation of gene expression;homeostasis of number of cells;hematopoietic stem cell proliferation;positive regulation of histone deubiquitination
• Cellular component: nucleus;nucleoplasm;U6atac snRNP;cytoplasm;Cajal body;nuclear speck;U4/U6 x U5 tri-snRNP complex;ASAP complex;U4/U6 snRNP;U4atac/U6atac snRNP
• Molecular function: RNA binding;protein binding;U6 snRNA binding;U4 snRNA binding;U6atac snRNA binding;histone binding;ubiquitin-specific protease binding