SART3

Summary

SART3 (spliceosome associated factor 3, U4/U6 recycling protein, HGNC:16860) is a protein-coding gene on chromosome 12q23.3, encoding Spliceosome associated factor 3, U4/U6 recycling protein (Q15020). U6 snRNP-binding protein that functions as a recycling factor of the splicing machinery. It is a common-essential gene (DepMap: required in 99.4% of cancer cell lines).

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.

Source: NCBI Gene 9733 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 157 total — 7 likely-pathogenic
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 99.4% of screened cell lines (common-essential)
• MANE Select transcript: NM_014706

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16860
Approved symbol	SART3
Name	spliceosome associated factor 3, U4/U6 recycling protein
Location	12q23.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0156, RP11-13G14, TIP110, p110
Ensembl gene	ENSG00000075856
Ensembl biotype	protein_coding
OMIM	611684
Entrez	9733

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 19 protein_coding, 6 retained_intron, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000228284, ENST00000431469, ENST00000546611, ENST00000546728, ENST00000546808, ENST00000546815, ENST00000547397, ENST00000547528, ENST00000548077, ENST00000548119, ENST00000548582, ENST00000550322, ENST00000550619, ENST00000551416, ENST00000552221, ENST00000619503, ENST00000651280, ENST00000901888, ENST00000901889, ENST00000901890, ENST00000901891, ENST00000901892, ENST00000901893, ENST00000929722, ENST00000929723, ENST00000929724, ENST00000929725, ENST00000929726, ENST00000963654

RefSeq mRNA: 2 — MANE Select: NM_014706 NM_001410983, NM_014706

CCDS: CCDS9117, CCDS91747

Canonical transcript exons

ENST00000546815 — 19 exons

Exon	Start	End
ENSE00000754639	108543028	108543152
ENSE00000754641	108544427	108544478
ENSE00000818387	108560843	108561173
ENSE00003463853	108526099	108526553
ENSE00003471965	108549088	108549214
ENSE00003502409	108530142	108530310
ENSE00003503394	108532222	108532334
ENSE00003505977	108535359	108535468
ENSE00003521917	108536708	108536785
ENSE00003567063	108524316	108524506
ENSE00003573543	108525457	108525609
ENSE00003588367	108538065	108538203
ENSE00003593339	108547887	108547991
ENSE00003603282	108538934	108539089
ENSE00003625874	108536514	108536572
ENSE00003632173	108531204	108531280
ENSE00003679860	108537488	108537595
ENSE00003784104	108545139	108545323
ENSE00003847915	108522214	108523634

Expression profiles

Bgee: expression breadth ubiquitous, 296 present calls, max score 98.41.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 41.5870 / max 650.6485, expressed in 1825 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
133119	41.5746	1825
133120	0.0087	3
133116	0.0037	1

Top tissues by expression

300 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	98.41	gold quality
secondary oocyte	CL:0000655	97.76	gold quality
tendon of biceps brachii	UBERON:0008188	97.23	gold quality
sural nerve	UBERON:0015488	96.34	gold quality
tendon	UBERON:0000043	94.68	gold quality
calcaneal tendon	UBERON:0003701	93.75	gold quality
nipple	UBERON:0002030	93.72	gold quality
oocyte	CL:0000023	93.52	gold quality
medial globus pallidus	UBERON:0002477	93.39	gold quality
cerebellar hemisphere	UBERON:0002245	92.93	gold quality
cerebellar cortex	UBERON:0002129	92.90	gold quality
cerebellar vermis	UBERON:0004720	92.84	gold quality
colonic epithelium	UBERON:0000397	92.75	gold quality
right hemisphere of cerebellum	UBERON:0014890	92.71	gold quality
cerebellum	UBERON:0002037	92.67	gold quality
corpus callosum	UBERON:0002336	92.50	gold quality
embryo	UBERON:0000922	92.36	gold quality
pericardium	UBERON:0002407	92.28	gold quality
endometrium epithelium	UBERON:0004811	92.28	gold quality
ventricular zone	UBERON:0003053	92.21	gold quality
ganglionic eminence	UBERON:0004023	92.20	gold quality
globus pallidus	UBERON:0001875	92.08	gold quality
lymph node	UBERON:0000029	91.90	gold quality
epithelial cell of pancreas	CL:0000083	91.87	gold quality
tonsil	UBERON:0002372	91.80	gold quality
left ovary	UBERON:0002119	91.79	gold quality
bone marrow cell	CL:0002092	91.75	gold quality
pylorus	UBERON:0001166	91.72	gold quality
Brodmann (1909) area 23	UBERON:0013554	91.70	gold quality
adrenal tissue	UBERON:0018303	91.68	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.52

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): KAT5, MYC, ZNF263

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.4% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 28)

• detectable in majority of colorectal carcinoma tissues studied; could be an appropriate molecule for use in specific immunotherapy for colorectal carcinoma (PMID:11920522)
• Results suggest that U4 and U6 small nuclear ribonucleoproteins (snRNPs) accumulate in Cajal bodies for the purpose of assembly into U4/U6 snRNPs by SART3/p110. (PMID:12578909)
• involvement of U6-p110 (SART3) in recycling of the U4atac/U6atac snRNP (PMID:14749385)
• Tip110 is a negative regulator of AR transcriptional activation, and may be directly involved in AR-related developmental, physiological, and pathological processes (PMID:15031286)
• Data suggest a model whereby p110 (SART3) brings together U4 and U6 snRNAs through both RNA-protein and protein-protein interactions. (PMID:15314151)
• Both purified and recombinant LSm2-8 proteins are able to recruit p110 protein to U6 snRNA via interaction with the highly conserved C-terminal region of p110. (PMID:18567812)
• Levels of anti-SART3 peptide antibody in prostate cancer patients are significantly higher than those of non-cancer subjects. (PMID:19148489)
• TIP110 is also expressed in human embryonic stem cells (hESCs) and expression was decreased with differentiation of these ESCs. (PMID:22132941)
• findings show C-MYC upregulates transcription of TIP110 through interaction with the TIP110 E-box in the TIP110 promoter, ensuring high-level Tip110 expression in proliferating embryonic stem cells (hESCs); further show TIP110 regulates OCT4 alternative splicing in hESCs (PMID:23088399)
• YB-1 potentiates the Tip110/Tat-mediated transactivation of the HIV-1 LTR promoter. (PMID:23822148)
• Results identify a novel frameshift mutation in this gene implicated in disseminated superficial actinic porokeratosis in 4 Chinese families (PMID:23834120)
• these findings have provided additional and mechanistic evidence to support Tip110 function in HIV-1 transcription. (PMID:24217245)
• SART3 recruits ubH2B, which may be evicted from DNA during transcription, for deubiquitination by Usp15 (PMID:24526689)
• miR-124 regulates Tip110 expression and differentiation of human cord blood CD34(+) cells (PMID:25928721)
• Hypoxia led to Tip110 protein degradation through the ubiquitin-proteasome system. Under hypoxia, Tip110 stabilized p53, which in return destabilized Tip110. (PMID:25939381)
• The complex structure of SART3 nuclear localization signal (NLS) and importin-alpha reveals bipartite binding, and removal of SART3 NLS prevents the entry of USP4 (and USP15) into the nucleus and abrogates the subsequent deubiquitinase activity of USP4. (PMID:27060135)
• crystal structures of SART3 in the apo-form and in complex with the DUSP-UBL domain of USP15 at 2.0 and 3.0 A, respectively. Structural analysis reveals SART3 contains 12 half-a-tetratricopeptide (HAT) repeats, organized into two subdomains, HAT-N and HAT-C. SART3 dimerizes through the concave surface of HAT-C, whereas the HAT-C convex surface binds USP15 in a novel bipartite mode. (PMID:27255711)
• We show that PRP31, a component of U4 snRNP, is modified with K63-linked ubiquitin chains by the PRP19 complex and deubiquitinated by USP15 and its substrate targeting factor SART3. USP15SART3 makes a complex with USP4 and this ternary complex serves as a platform to deubiquitinate PRP31 and PRP3 (PMID:28088760)
• Data suggest that ZIP, USP39, Prp24/p100/SART3, and Prp43 associate to form complex instrumental in spliceosome assembly; ZIP regulates pre-mRNA splicing of USP39 independent of RNA binding; stable 35S tri-snRNP particles are enriched in Cajal body. (ZIP = zinc finger and G-patch domain-containing protein; USP39 = ubiquitin specific peptidase 39; Prp43 = RNA helicase Prp43) (PMID:28878014)
• The findings demonstrate that constitutive Tip110 expression in human cord blood CD34(+) cells is regulated, at least in part, through its interaction with CstF64, recruitment of CstF64 to, and selective usage of two polyadenylation sites within its 3’UTR. (PMID:29583087)
• Study demonstrated that Tip110 contributed to the regulation of the expression of IL-8 in melanoma cells and that the expression level of Tip110 had a prognostic value for melanoma patients. (PMID:30119675)
• In vitro binding experiments revealed that the RNA-recognition motifs within the SART3 sequence are responsible for selective pre-miR-34a binding. Our results provide evidence for a significant role of SART3 in miR-34a biogenesis and cell cycle progression in non-small-cell lung cancer (NSCLC) cells. (PMID:31619517)
• LASTR promotes splicing efficiency by controlling SART3 association with the U4 and U6 small nuclear ribonucleoproteins (snRNP) during spliceosome recycling. (PMID:31956895)
• rs2072580T>A Polymorphism in the Overlapping Promoter Regions of the SART3 and ISCU Genes Associated with the Risk of Breast Cancer. (PMID:32495170)
• Genetic association study detected misalignment in previous whole exome sequence: association study of ZNF806 and SART3 in tardive dystonia. (PMID:32941384)
• Variants in SART3 cause a spliceosomopathy characterised by failure of testis development and neuronal defects. (PMID:37296101)
• USP4 regulates TUT1 ubiquitination status in concert with SART3. (PMID:38310689)
• SART3 reads methylarginine-marked glycine- and arginine-rich motifs. (PMID:38985674)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	sart3	ENSDARG00000008032
mus_musculus	Sart3	ENSMUSG00000018974
rattus_norvegicus	Sart3	ENSRNOG00000000702
drosophila_melanogaster	Rnp4F	FBGN0014024
caenorhabditis_elegans		WBGENE00007111

Protein

Protein identifiers

Spliceosome associated factor 3, U4/U6 recycling protein — Q15020 (reviewed: Q15020)

Alternative names: Squamous cell carcinoma antigen recognized by T-cells 3, Tat-interacting protein of 110 kDa, p110 nuclear RNA-binding protein

All UniProt accessions (7): Q15020, A0A494C0L2, A0A499FI31, F8VVK9, F8VZM2, F8W667, H0YHU8

UniProt curated annotations — full annotation on UniProt →

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. 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. 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. May also recruit the deubiquitinase USP15 to histone H2B and mediate histone deubiquitination, thereby regulating gene expression and/or DNA repair. May play a role in hematopoiesis probably through transcription regulation of specific genes including MYC. Regulates Tat transactivation activity through direct interaction. May be a cellular factor for HIV-1 gene expression and viral replication.

Subunit / interactions. Component of the 7SK snRNP complex at least composed of P-TEFb (composed of CDK9 and CCNT1/cyclin-T1), HEXIM1, HEXIM2, BCDIN3, SART3 proteins and 7SK and U6 snRNAs. Interacts with AGO1 and AGO2. Interacts with PRPF3 and USP4; the interaction with PRPF3 is direct and recruits USP4 to its substrate PRPF3. Interacts with USP15; the interaction is direct. Interacts with HIV-1 Tat.

Subcellular location. Nucleus. Nucleoplasm. Cajal body. Nucleus speckle. Cytoplasm.

Tissue specificity. Ubiquitously expressed.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. Inactive in U4/U6 snRNP recycling.

Isoforms (4)

UniProt ID	Names	Canonical?
Q15020-1	1	yes
Q15020-2	2
Q15020-3	3
Q15020-4	4

RefSeq proteins (2): NP_001397912, NP_055521* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR003107	HAT	Repeat
IPR008669	LSM_interact	Domain
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR034217	SART3_RRM1	Domain
IPR034218	SART3_RRM2	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR059164	HAT_PRP39_C	Repeat

Pfam: PF00076, PF05391, PF16605, PF23240, PF23241

UniProt features (103 total): helix 33, strand 13, modified residue 10, region of interest 9, compositionally biased region 9, repeat 8, splice variant 5, turn 5, coiled-coil region 3, sequence variant 3, domain 2, initiator methionine 1, chain 1, short sequence motif 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
5CTT	X-RAY DIFFRACTION	1.7
5JJX	X-RAY DIFFRACTION	2
5CTQ	X-RAY DIFFRACTION	2.6
5JJW	X-RAY DIFFRACTION	3.01
5CTR	X-RAY DIFFRACTION	3.01
5JPZ	X-RAY DIFFRACTION	3.04
2DO4	SOLUTION NMR
7XX8	SOLUTION NMR
7XX9	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15020-F1	78.57	0.54

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (10): 2, 10, 16, 215, 650, 657, 769, 795, 852, 906

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 207 (showing top): MORF_MTA1, PAX4_01, TGACCTY_ERR1_Q2, MORF_HDAC2, GOBP_STEM_CELL_PROLIFERATION, PUJANA_CHEK2_PCC_NETWORK, GOBP_SPLICEOSOMAL_TRI_SNRNP_COMPLEX_ASSEMBLY, YY1_02, MORF_RAB6A, GOBP_HEMATOPOIETIC_STEM_CELL_PROLIFERATION, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION, GOBP_RNA_SPLICING, GOBP_MULTICELLULAR_ORGANISMAL_LEVEL_HOMEOSTASIS, GNF2_ELAC2, MORF_AATF

GO Biological Process (13): spliceosomal tri-snRNP complex assembly (GO:0000244), spliceosomal snRNP assembly (GO:0000387), mRNA splicing, via spliceosome (GO:0000398), cell morphogenesis (GO:0000902), nucleosome assembly (GO:0006334), regulation of gene expression (GO:0010468), homeostasis of number of cells (GO:0048872), regulation of RNA metabolic process (GO:0051252), hematopoietic stem cell proliferation (GO:0071425), transcription elongation-coupled chromatin remodeling (GO:0140673), RNA processing (GO:0006396), mRNA processing (GO:0006397), RNA splicing (GO:0008380)

GO Molecular Function (9): RNA binding (GO:0003723), U6 snRNA binding (GO:0017070), U4 snRNA binding (GO:0030621), U6atac snRNA binding (GO:0030624), protein-macromolecule adaptor activity (GO:0030674), histone binding (GO:0042393), ubiquitin-specific protease binding (GO:1990381), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (8): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), Cajal body (GO:0015030), nuclear speck (GO:0016607), ASAP complex (GO:0061574), U6atac snRNP (GO:0005691), U4/U6 snRNP (GO:0071001)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
snRNA binding	3
gene expression	2
RNA processing	2
protein binding	2
binding	2
cellular anatomical structure	2
nuclear ribonucleoprotein granule	2
spliceosomal snRNP complex	2
spliceosomal snRNP assembly	1
mRNA splicing, via spliceosome	1
protein-RNA complex assembly	1
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
anatomical structure morphogenesis	1
chromatin organization	1
nucleosome organization	1
protein-DNA complex assembly	1
regulation of macromolecule biosynthetic process	1
multicellular organismal-level homeostasis	1
RNA metabolic process	1
regulation of nucleobase-containing compound metabolic process	1
regulation of macromolecule metabolic process	1
hemopoiesis	1
stem cell proliferation	1
chromatin remodeling	1
transcription elongation by RNA polymerase II	1
RNA biosynthetic process	1
primary metabolic process	1
mRNA metabolic process	1
nucleic acid binding	1
molecular adaptor activity	1
protease binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
protein-containing complex	1
U4 snRNP	1
U6 snRNP	1

Protein interactions and networks

STRING

2364 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SART3	USP15	Q9Y4E8	940
SART3	USP4	Q13107	935
SART3	MEPCE	Q7L2J0	875
SART3	LARP7	Q4G0J3	819
SART3	PRPF3	O43395	802
SART3	LSM2	Q9Y333	788
SART3	HEXIM1	O94992	787
SART3	COIL	P38432	761
SART3	PRPF31	Q8WWY3	711
SART3	SNRNP200	O75643	709
SART3	CDK9	P50750	692
SART3	LSM7	Q9UK45	671
SART3	CCNT1	O60563	633
SART3	SART1	O43290	627
SART3	LSM8	O95777	617

IntAct

187 interactions, top by confidence:

A	B	Type	Score
LSM3	LSM1	psi-mi:“MI:0914”(association)	0.950
PRPF4	PPIH	psi-mi:“MI:0914”(association)	0.910
LARP7	CCNT1	psi-mi:“MI:0914”(association)	0.850
LSM6	LSM1	psi-mi:“MI:0914”(association)	0.840
SART3	PRPF3	psi-mi:“MI:0914”(association)	0.790
SNRPE	GEMIN2	psi-mi:“MI:0914”(association)	0.770
SART3	PRPF4	psi-mi:“MI:0914”(association)	0.730
PRPF3	PRPF4	psi-mi:“MI:0914”(association)	0.730
MEPCE	SART3	psi-mi:“MI:0914”(association)	0.730
SNRPD2	GEMIN2	psi-mi:“MI:0914”(association)	0.710
SNRPG	GEMIN2	psi-mi:“MI:0914”(association)	0.710
SNRPB	PRMT5	psi-mi:“MI:0914”(association)	0.670
RPL10A	RRP8	psi-mi:“MI:0914”(association)	0.640
NOL12	RRP8	psi-mi:“MI:0914”(association)	0.640
LSM5	LSM1	psi-mi:“MI:0914”(association)	0.640
PRPF31	PRPF4	psi-mi:“MI:0914”(association)	0.640
SNRPB	SART1	psi-mi:“MI:0914”(association)	0.640
USP4	PRPF3	psi-mi:“MI:0914”(association)	0.640
RNPS1	SART3	psi-mi:“MI:0915”(physical association)	0.610
SART3	RNPS1	psi-mi:“MI:0915”(physical association)	0.610
SART3	ZNF620	psi-mi:“MI:0915”(physical association)	0.560
SART3	ZNF71	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (767): SART3 (Affinity Capture-Western), SART3 (Affinity Capture-MS), SART3 (Affinity Capture-MS), SART3 (Affinity Capture-MS), SART3 (Affinity Capture-MS), SART3 (Affinity Capture-MS), DNAJC9 (Co-fractionation), GTF2E2 (Co-fractionation), UBR4 (Co-fractionation), SART3 (Affinity Capture-MS), SART3 (Affinity Capture-RNA), SART3 (Affinity Capture-MS), SART3 (Affinity Capture-MS), SART3 (Affinity Capture-MS), SART3 (Affinity Capture-MS)

ESM2 similar proteins: A1A5S1, A1Z9G2, B3DJT0, B3MIF1, O01422, O74970, O94906, P0CO10, P0CO11, P17886, P25991, P63154, P63155, P87312, Q12309, Q12381, Q15020, Q2KJJ0, Q4KLU2, Q4PB37, Q4WT84, Q4WVF4, Q527H0, Q52DF3, Q54XP4, Q54Z08, Q5B3U7, Q5BDX1, Q5BH69, Q5K654, Q5RCC2, Q5REG1, Q6BSP7, Q6C186, Q6CAR6, Q750X3, Q7SAK5, Q7SGD2, Q7SI58, Q86UA1

Diamond homologs: A0A8M1NHK4, A0AV96, A0JM51, A1D4K4, A2Q848, A4FV72, O01671, O04425, O43040, O43390, O60506, P25299, P33240, P49314, P86049, Q08937, Q08BH5, Q08E07, Q0P4R6, Q0V9L3, Q10B98, Q15020, Q28IQ9, Q2UK72, Q4R2Z0, Q4R535, Q4WK03, Q54PB2, Q5NVC8, Q5R5P4, Q5R723, Q5R9H4, Q5RDA3, Q5REG1, Q5SZQ8, Q5YD48, Q66H68, Q6CEW9, Q6DCB7, Q6DGV1

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 176 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
mRNA decay by 5’ to 3’ exoribonuclease	7	42.6×	1e-08
Metabolism of non-coding RNA	6	30.4×	2e-06
mRNA Splicing	21	18.4×	8e-19
Processing of Capped Intron-Containing Pre-mRNA	23	15.1×	8e-19
Pre-NOTCH Expression and Processing	5	14.7×	3e-04
mRNA Splicing - Major Pathway	31	13.6×	4e-24
SARS-CoV-2 modulates host translation machinery	7	12.5×	6e-05
snRNP Assembly	7	11.8×	9e-05

GO biological processes:

GO term	Partners	Fold	FDR
spliceosomal snRNP assembly	10	37.5×	3e-11
RNA splicing, via transesterification reactions	7	28.2×	6e-07
U2-type prespliceosome assembly	7	28.2×	6e-07
NLS-bearing protein import into nucleus	5	25.9×	1e-04
spliceosomal complex assembly	5	19.4×	5e-04
mRNA splicing, via spliceosome	29	17.1×	9e-25
cytoplasmic translation	9	10.8×	2e-05
RNA splicing	18	10.2×	5e-11

Disease & clinical

Clinical variants and AI predictions

ClinVar

157 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	7
Uncertain significance	113
Likely benign	4
Benign	5

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
2444506	NM_014706.4(SART3):c.631G>A (p.Glu211Lys)	Likely pathogenic
2444507	NM_014706.4(SART3):c.2299C>T (p.Arg767Trp)	Likely pathogenic
2444508	NM_014706.4(SART3):c.757C>T (p.Arg253Ter)	Likely pathogenic
2444509	NM_014706.4(SART3):c.1477C>T (p.Arg493Trp)	Likely pathogenic
2444510	NM_014706.4(SART3):c.646T>C (p.Ser216Pro)	Likely pathogenic
2444511	NM_014706.4(SART3):c.2153C>T (p.Pro718Leu)	Likely pathogenic
2444512	NM_014706.4(SART3):c.1555A>G (p.Arg519Gly)	Likely pathogenic

SpliceAI

2721 predictions. Top by Δscore:

Variant	Effect	Δscore
12:108524314:A:AC	donor_gain	1.0000
12:108524314:ACG:A	donor_gain	1.0000
12:108524314:ACGCT:A	donor_gain	1.0000
12:108524315:C:CC	donor_gain	1.0000
12:108524315:CG:C	donor_gain	1.0000
12:108524315:CGC:C	donor_gain	1.0000
12:108524315:CGCT:C	donor_gain	1.0000
12:108524315:CGCTC:C	donor_gain	1.0000
12:108524359:T:TA	donor_gain	1.0000
12:108524386:T:A	donor_gain	1.0000
12:108524502:AGGCC:A	acceptor_gain	1.0000
12:108524503:GGCC:G	acceptor_gain	1.0000
12:108524504:GCC:G	acceptor_gain	1.0000
12:108524505:CC:C	acceptor_gain	1.0000
12:108524505:CCC:C	acceptor_gain	1.0000
12:108524506:CC:C	acceptor_gain	1.0000
12:108524507:C:CC	acceptor_gain	1.0000
12:108524507:C:CG	acceptor_loss	1.0000
12:108524507:C:T	acceptor_gain	1.0000
12:108524508:T:A	acceptor_loss	1.0000
12:108525452:CTGA:C	donor_loss	1.0000
12:108525453:TGAC:T	donor_loss	1.0000
12:108525456:C:CT	donor_loss	1.0000
12:108525607:CAC:C	acceptor_gain	1.0000
12:108525608:AC:A	acceptor_gain	1.0000
12:108525609:CC:C	acceptor_gain	1.0000
12:108525610:C:CC	acceptor_gain	1.0000
12:108526094:CCTA:C	donor_loss	1.0000
12:108526096:TACCT:T	donor_loss	1.0000
12:108526153:C:A	donor_gain	1.0000

AlphaMissense

6355 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:108526139:A:T	V777D	1.000
12:108526346:A:T	V708D	1.000
12:108532293:C:G	R533P	1.000
12:108535384:A:G	W511R	1.000
12:108535384:A:T	W511R	1.000
12:108535429:A:G	W496R	1.000
12:108535429:A:T	W496R	1.000
12:108549123:C:G	R135P	1.000
12:108524402:G:C	S876R	0.999
12:108524402:G:T	S876R	0.999
12:108524404:T:G	S876R	0.999
12:108524461:C:G	A857P	0.999
12:108524499:G:T	A844D	0.999
12:108525457:C:A	K841N	0.999
12:108525457:C:G	K841N	0.999
12:108525482:A:T	V833D	0.999
12:108525568:G:C	F804L	0.999
12:108525568:G:T	F804L	0.999
12:108525570:A:G	F804L	0.999
12:108526229:C:T	G747D	0.999
12:108526348:A:C	F707L	0.999
12:108526348:A:T	F707L	0.999
12:108526350:A:G	F707L	0.999
12:108526352:A:T	V706D	0.999
12:108532287:A:T	V535D	0.999
12:108532290:G:T	A534D	0.999
12:108532291:C:G	A534P	0.999
12:108532299:A:G	L531P	0.999
12:108532308:C:G	R528P	0.999
12:108535365:A:G	L517P	0.999

dbSNP variants (sampled 300 via entrez): RS1000037162 (12:108559938 C>T), RS1000081552 (12:108557380 T>C), RS1000118301 (12:108555731 C>A), RS1000124046 (12:108547297 G>A), RS1000131363 (12:108534462 T>C), RS1000145232 (12:108557824 T>C), RS1000165363 (12:108542402 C>A,T), RS1000196961 (12:108542039 G>A,C,T), RS1000201270 (12:108560334 T>C), RS1000316305 (12:108560637 G>A,T), RS1000386872 (12:108554710 A>C,T), RS1000474512 (12:108541227 C>T), RS1000485143 (12:108536050 G>A,C), RS1000496169 (12:108536235 C>A,T), RS1000514653 (12:108544058 A>G)

Disease associations

OMIM: gene MIM:611684 | disease phenotypes: MIM:175900

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Strong	Autosomal recessive
disseminated superficial actinic porokeratosis	Moderate	Autosomal dominant
complex neurodevelopmental disorder	Moderate	Autosomal recessive

Mondo (4): porokeratosis 3, disseminated superficial actinic type (MONDO:0008293), disseminated superficial actinic porokeratosis (MONDO:0019212), neurodevelopmental disorder (MONDO:0700092), complex neurodevelopmental disorder (MONDO:0100038)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002481_2	Acne (severe)	5.000000e-06

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625
C536339	Porokeratosis, disseminated superficial actinic 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066463 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

46 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
methylmercuric chloride	increases expression, affects cotreatment	3
sodium arsenite	increases expression, affects binding, increases reaction, increases abundance	3
bisphenol A	decreases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	2
Arsenic	affects methylation, increases abundance, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cyclosporine	increases expression	2
Cadmium Chloride	increases expression, decreases expression	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
2,4,6-tribromophenol	decreases expression	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, decreases reaction, increases reaction	1
cobaltous chloride	increases expression	1
tetrabromobisphenol A	decreases expression	1
ochratoxin A	increases expression	1
aflatoxin B2	decreases methylation	1
di-n-butylphosphoric acid	affects expression	1
torcetrapib	increases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
LDN 193189	increases expression, affects cotreatment	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652386	Binding	Binding affinity to human SART3 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_AV04	Chor-IN-1	Cancer cell line	Male

Clinical trials (associated diseases)

204 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice