SNRNP70

Summary

SNRNP70 (small nuclear ribonucleoprotein U1 subunit 70, HGNC:11150) is a protein-coding gene on chromosome 19q13.33, encoding U1 small nuclear ribonucleoprotein 70 kDa (P08621). Component of the spliceosomal U1 snRNP, which is essential for recognition of the pre-mRNA 5’ splice-site and the subsequent assembly of the spliceosome. It is a common-essential gene (DepMap: required in 99.8% of cancer cell lines).

Enables U1 snRNA binding activity. Involved in mRNA splicing, via spliceosome and regulation of RNA splicing. Located in nucleoplasm. Part of U1 snRNP and spliceosomal complex. Implicated in disease of mental health and systemic lupus erythematosus. Biomarker of Alzheimer’s disease.

Source: NCBI Gene 6625 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 60 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 99.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_003089

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11150
Approved symbol	SNRNP70
Name	small nuclear ribonucleoprotein U1 subunit 70
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Aliases	U1-70K, Snp1
Ensembl gene	ENSG00000104852
Ensembl biotype	protein_coding
OMIM	180740
Entrez	6625

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 23 protein_coding, 3 nonsense_mediated_decay, 3 retained_intron

ENST00000221448, ENST00000401730, ENST00000544278, ENST00000595231, ENST00000597936, ENST00000598441, ENST00000598984, ENST00000599687, ENST00000601065, ENST00000601411, ENST00000868103, ENST00000868104, ENST00000868105, ENST00000917203, ENST00000917204, ENST00000917205, ENST00000917206, ENST00000917207, ENST00000917208, ENST00000917209, ENST00000917210, ENST00000917211, ENST00000917212, ENST00000917213, ENST00000917214, ENST00000917215, ENST00000917216, ENST00000948669, ENST00000948670

RefSeq mRNA: 2 — MANE Select: NM_003089 NM_001301069, NM_003089

CCDS: CCDS12756, CCDS74417

Canonical transcript exons

ENST00000598441 — 10 exons

Exon	Start	End
ENSE00001555728	49085451	49085636
ENSE00002503116	49101390	49101471
ENSE00003179801	49107795	49108604
ENSE00003499363	49090466	49090520
ENSE00003535913	49086405	49086561
ENSE00003552141	49098427	49098491
ENSE00003567241	49090291	49090353
ENSE00003593260	49104634	49104735
ENSE00003614741	49107625	49107712
ENSE00003683920	49098642	49098704

Expression profiles

Bgee: expression breadth ubiquitous, 297 present calls, max score 99.69.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 181.3372 / max 3038.8728, expressed in 1828 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
176927	171.0487	1828
176926	9.2593	1782
176928	0.7002	405
176931	0.2144	73
176930	0.1145	46

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	99.69	gold quality
cerebellar hemisphere	UBERON:0002245	99.63	gold quality
cerebellar cortex	UBERON:0002129	99.57	gold quality
sural nerve	UBERON:0015488	99.48	gold quality
right uterine tube	UBERON:0001302	99.47	gold quality
right lobe of thyroid gland	UBERON:0001119	99.41	gold quality
left ovary	UBERON:0002119	99.37	gold quality
body of uterus	UBERON:0009853	99.36	gold quality
right ovary	UBERON:0002118	99.35	gold quality
endocervix	UBERON:0000458	99.34	gold quality
left lobe of thyroid gland	UBERON:0001120	99.34	gold quality
body of pancreas	UBERON:0001150	99.25	gold quality
peripheral nervous system	UBERON:0000010	99.24	gold quality
nerve	UBERON:0001021	99.24	gold quality
left uterine tube	UBERON:0001303	99.24	gold quality
tibial nerve	UBERON:0001323	99.24	gold quality
adenohypophysis	UBERON:0002196	99.23	gold quality
body of stomach	UBERON:0001161	99.20	gold quality
cerebellum	UBERON:0002037	99.18	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.18	gold quality
granulocyte	CL:0000094	99.17	gold quality
metanephros cortex	UBERON:0010533	99.16	gold quality
right adrenal gland cortex	UBERON:0035827	99.16	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.16	gold quality
small intestine Peyer’s patch	UBERON:0003454	99.15	gold quality
lower esophagus	UBERON:0013473	99.14	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.14	gold quality
left adrenal gland cortex	UBERON:0035825	99.13	gold quality
right adrenal gland	UBERON:0001233	99.12	gold quality
left adrenal gland	UBERON:0001234	99.08	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	18.99
E-ANND-3	yes	7.44

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

12 targeting SNRNP70, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-922	99.02	67.23	1838
HSA-MIR-421	98.90	67.04	1883
HSA-MIR-4709-5P	98.51	67.25	1335
HSA-MIR-7154-3P	97.65	65.02	985
HSA-MIR-6762-5P	96.55	64.62	972
HSA-MIR-6845-5P	96.55	64.65	969
HSA-MIR-3677-5P	93.16	64.62	393

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 37)

• Apoptotic U1-70 kd is antigenically distinct from the intact form of the U1-70-kd molecule. (PMID:12115232)
• A remarkably limited and consistent pattern of T cell targeting of U1-70kDa in connective tissue disease patients is observed in T cell clones generated against U1-70kDa: all clones are specific for epitopes within the RNA binding domain of the protein. (PMID:12218166)
• Apoptotic modification and the presence of an RNA binding domain may both contribute to autoantigenicity of the lupus U1-70-kDa ribonucleoprotein. (PMID:14688384)
• Specific binding of heterogenous nuclear ribonucleoprotein E1 (hnRNP E1) and U1 small nuclear ribonucleoprotein (snRNP) in the pre-spliceosomal complex was associated with silencing of pseudoexon splicing. (PMID:17622584)
• Examine changes in phosphorylation/dephosphorylation balance and the subcellular localization of the U1-70K protein during apoptosis. (PMID:18202700)
• In a transgenic model of mixed connective tissue disease, T cell recognition of the U1 70-kDa autoantigen by HLA-DR4-transgenic mice is focused on a limited number of T cell epitopes residing primarily within the RNA-binding domain of the RNP autoantigen. (PMID:18523312)
• Our findings suggest a potential role of CMV in regulation of autoantibodies to snRNPs (PMID:19232124)
• The novel association of anti-thyroid antibodies with anti-U1RNP antibodies in juvenile onset Systemic Lupus Erythematosus seems to identify a subgroup of patients with less life-threatening organ involvement. (PMID:19419839)
• U1-70k isoforms control subunit dynamics in the human spliceosomal U1 snRNP (PMID:19784376)
• crucial association of B19-NS1 in development of autoimmunity by inducing apoptosis and specific cleavage of 70 kDa U1-snRNP (PMID:20500824)
• Recruitment of RNAPII, U1-70K and ASF/SF2 protein to transcription sites is splicing independent. (PMID:20519584)
• data identify some fungal proteins as possible triggers of anti-U1-70 kDa autoimmunity via molecular mimicry. (PMID:21348812)
• the hypo-phosphorylated RS domain of SRSF1 interacts with its own RRM, thus competing with U1-70K binding, whereas the hyper-phosphorylated RS domain permits the formation of a ternary complex containing ESE, an SR protein, and U1 snRNP (PMID:21536904)
• Serum antibodies against the 70k polypeptides of the U1 ribonucleoprotein complex are associated with psychiatric syndromes in systemic lupus erythematosus. (PMID:22454191)
• U1-snRNP activates the NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome in CD14+ human monocytes dependently of anti-U1-snRNP Abs, leading to interleukin (IL)-1beta production. (PMID:22490866)
• inhibition of U1 snRNP also leads to regulation of the usage of In3 pA, suggesting that the C/P activity in the cell can be cross-regulated by splicing, leading to coordination between these two processes. (PMID:23874216)
• High expression of U1-70K and other U1 small nuclear ribonucleoproteins spliceosome proteins in Alzheimer’s disease patients and those with mild cognitive impairment. (PMID:24023061)
• Our results demonstrate unique U1 snRNP pathology and implicate abnormal RNA splicing in Alzheimer’s disease pathogenesis. (PMID:24023061)
• [review] The presence of antibodies against U1snRNP autoantigen is considered the serological hallmark of mixed connective tissue disease (MCTD), which is characterized by overlapping features between at least two systemic autoimmune diseases. (PMID:24461387)
• These studies identify U1 snRNP pathologic changes in brain of early onset genetic forms of Alzheimer’s disease (PMID:24773620)
• U1-70K interacts with the SMN complex and is required for nuclear gem integrity. (PMID:25052091)
• Data indicate that small nuclear ribonucleoprotein U1-70K in Alzheimer disease (AD) may directly sequester normal soluble forms of U1-70K into insoluble aggregates. (PMID:25355317)
• The selection of 5’-splice site nucleotides by U1 snRNP is achieved predominantly through basepairing with U1 snRNA whilst U1-C fine-tunes relative affinities of mismatched 5’-splice sites. (PMID:25555158)
• methylation of snRNP70 by SETMAR regulates constitutive and/or alternative splicing (PMID:25795785)
• data lead to a model that FUS functions in coupling transcription to splicing via mediating an interaction between RNAP II and U1 snRNP (PMID:26124092)
• The epitopes of U1-70K autoantibodies have been mapped at single-amino acid resolution. (PMID:26333287)
• The authors propose that Gemin2 is a versatile hub for ribonucleoprotein exchange that functions broadly in RNA metabolism. (PMID:26828962)
• These results indicate that the galectin-3-U1 snRNP-pre-mRNA ternary complex is a functional E complex and that U1 snRNP is required to assemble galectin-3 onto an active spliceosome (PMID:27105840)
• Screen using siRNA revealed depletion of U1 snRNP components SNRPA, SNRNP70 or SNRPD2 caused significant cytoplasmic localization of MEG3 reporter transcripts. (PMID:31107149)
• Data show that two fragments in the low-complexity (LC) domain of small nuclear ribonucleoprotein U1 subunit 70 (U1-70K) can undergo liquid-liquid phase separation (LLPS). (PMID:31723601)
• A potential mechanism underlying U1 snRNP inhibition of the cleavage step of mRNA 3’ processing. (PMID:32828285)
• Dissection of FUS domains involved in regulation of SnRNP70 gene expression. (PMID:32915994)
• CLK1 reorganizes the splicing factor U1-70K for early spliceosomal protein assembly. (PMID:33811140)
• A specific gene-splicing alteration in the SNRNP70 gene as a hallmark of an ALS subtype. (PMID:35101583)
• Galectin-3-U1 snRNP Complexes Initiate Splicing Activity in U1-Depleted Nuclear Extracts. (PMID:35320554)
• Clinical significance of small nuclear ribonucleoprotein U1 subunit 70 in patients with hepatocellular carcinoma. (PMID:38500533)
• The U1-70K and SRSF1 interaction is modulated by phosphorylation during the early stages of spliceosome assembly. (PMID:39023093)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	snrnp70	ENSDARG00000077126
mus_musculus	Snrnp70	ENSMUSG00000063511
rattus_norvegicus	Snrnp70	ENSRNOG00000020763
drosophila_melanogaster	snRNP-U1-70K	FBGN0016978
caenorhabditis_elegans		WBGENE00004390

Paralogs (1): SNRNP35 (ENSG00000184209)

Protein

Protein identifiers

U1 small nuclear ribonucleoprotein 70 kDa — P08621 (reviewed: P08621)

All UniProt accessions (3): P08621, M0QX04, M0QYR1

UniProt curated annotations — full annotation on UniProt →

Function. Component of the spliceosomal U1 snRNP, which is essential for recognition of the pre-mRNA 5’ splice-site and the subsequent assembly of the spliceosome. SNRNP70 binds to the loop I region of U1-snRNA. Truncated isoforms that lack the RRM domain cannot bind U1-snRNA. Truncated isoforms that lack the RRM domain cannot bind U1-snRNA.

Subunit / interactions. Component of the U1 snRNP. The U1 snRNP is composed of the U1 snRNA and the 7 core Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP, and at least three U1 snRNP-specific proteins SNRNP70/U1-70K, SNRPA/U1-A and SNRPC/U1-C. Interacts with SCNM1. Found in a pre-mRNA splicing complex with SFRS4, SFRS5, SNRNP70, SNRPA1, SRRM1 and SRRM2. Found in a pre-mRNA exonic splicing enhancer (ESE) complex with SNRNP70, SNRPA1, SRRM1 and TRA2B/SFRS10. Interacts with dephosphorylated SFRS13A and SFPQ. Interacts with NUDT21/CPSF5, CPSF6, SCAF11, and ZRANB2. Interacts with GEMIN5. Interacts with FUS.

Subcellular location. Nucleus speckle. Nucleus. Nucleoplasm.

Post-translational modifications. The N-terminus is blocked. Extensively phosphorylated on serine residues in the C-terminal region.

Domain organisation. The RRM domain mediates interaction with U1 RNA.

Miscellaneous. Major ribonucleoprotein antigen recognized by the sera from patients with autoimmune diseases, such as systemic lupus erythematosus.

Isoforms (4)

UniProt ID	Names	Canonical?
P08621-1	1	yes
P08621-2	2
P08621-3	3
P08621-4	4

RefSeq proteins (2): NP_001287998, NP_003080* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR022023	U1snRNP70_N	Domain
IPR034143	snRNP70_RRM	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR051183	U1_U11-U12_snRNP_70-35kDa	Family

Pfam: PF00076, PF12220

UniProt features (41 total): helix 10, compositionally biased region 7, modified residue 7, splice variant 4, strand 4, region of interest 3, turn 2, initiator methionine 1, chain 1, domain 1, cross-link 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
4PKD	X-RAY DIFFRACTION	2.5
7VPX	ELECTRON MICROSCOPY	3
6QX9	ELECTRON MICROSCOPY	3.28
4PJO	X-RAY DIFFRACTION	3.3
9QEQ	ELECTRON MICROSCOPY	3.5
7B0Y	ELECTRON MICROSCOPY	3.6
3PGW	X-RAY DIFFRACTION	4.4
3CW1	X-RAY DIFFRACTION	5.49
8R08	ELECTRON MICROSCOPY	6.1
2L5I	SOLUTION NMR
2L5J	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P08621-F1	72.39	0.36

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 (8): 2, 118, 126, 226, 268, 320, 410, 346

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-9770562	mRNA Polyadenylation
R-HSA-72172	mRNA Splicing
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA
R-HSA-8953854	Metabolism of RNA

MSigDB gene sets: 207 (showing top): GOBP_REGULATION_OF_AUTOPHAGY, TGCGCANK_UNKNOWN, GOBP_POSITIVE_REGULATION_OF_RNA_SPLICING, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_POSITIVE_REGULATION_OF_MRNA_PROCESSING, MORF_SNRP70, MORF_UBE2I, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, HSIAO_HOUSEKEEPING_GENES, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, COUP_01, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_NEGATIVE_REGULATION_OF_AUTOPHAGY

GO Biological Process (9): mRNA splicing, via spliceosome (GO:0000398), regulation of RNA splicing (GO:0043484), positive regulation of mRNA splicing, via spliceosome (GO:0048026), negative regulation of protein refolding (GO:0061084), cellular response to retinoic acid (GO:0071300), cellular response to tumor necrosis factor (GO:0071356), cellular response to transforming growth factor beta stimulus (GO:0071560), negative regulation of chaperone-mediated autophagy (GO:1904715), mRNA processing (GO:0006397)

GO Molecular Function (6): RNA binding (GO:0003723), mRNA binding (GO:0003729), U1 snRNA binding (GO:0030619), U1 snRNP binding (GO:1990446), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (8): nucleus (GO:0005634), nucleoplasm (GO:0005654), spliceosomal complex (GO:0005681), U1 snRNP (GO:0005685), nuclear speck (GO:0016607), lysosomal lumen (GO:0043202), U2-type prespliceosome (GO:0071004), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
mRNA Splicing	1
mRNA 3’-end processing	1
Processing of Capped Intron-Containing Pre-mRNA	1
Metabolism of RNA	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
RNA splicing	1
regulation of gene expression	1
regulation of primary metabolic process	1
mRNA splicing, via spliceosome	1
positive regulation of RNA splicing	1
regulation of mRNA splicing, via spliceosome	1
positive regulation of mRNA processing	1
protein refolding	1
regulation of protein refolding	1
negative regulation of protein folding	1
response to retinoic acid	1
cellular response to lipid	1
cellular response to oxygen-containing compound	1
response to tumor necrosis factor	1
cellular response to cytokine stimulus	1
cellular response to growth factor stimulus	1
response to transforming growth factor beta	1
negative regulation of autophagy	1
negative regulation of protein catabolic process	1
chaperone-mediated autophagy	1
regulation of chaperone-mediated autophagy	1
RNA processing	1
mRNA metabolic process	1
nucleic acid binding	1
RNA binding	1
snRNA binding	1
snRNP binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1
spliceosomal snRNP complex	1
nuclear ribonucleoprotein granule	1
lysosome	1
vacuolar lumen	1
U2-type spliceosomal complex	1

Protein interactions and networks

STRING

3887 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SNRNP70	SNRPC	P09234	999
SNRNP70	SNRPA	P09012	998
SNRNP70	PAPOLA	P51003	985
SNRNP70	PAPOLG	Q9BWT3	985
SNRNP70	SRSF1	Q07955	985
SNRNP70	PAPOLB	Q9NRJ5	985
SNRNP70	SRSF2	Q01130	968
SNRNP70	RBM25	P49756	958
SNRNP70	LUC7L	Q9NQ29	924
SNRNP70	SNRPD2	P43330	923
SNRNP70	PRPF40A	O75400	918
SNRNP70	SNRPB	P14678	908
SNRNP70	SNRPE	P08578	859
SNRNP70	SNRPD3	P43331	853
SNRNP70	TRIM21	P19474	848

IntAct

274 interactions, top by confidence:

A	B	Type	Score
SMN1	GEMIN2	psi-mi:“MI:0914”(association)	0.960
IFIT1	IFIT3	psi-mi:“MI:0914”(association)	0.920
NOP10	DKC1	psi-mi:“MI:0914”(association)	0.890
SNRNP70	SMN1	psi-mi:“MI:0407”(direct interaction)	0.860
CDK8	MED19	psi-mi:“MI:0914”(association)	0.850
SNRPB	SNRNP70	psi-mi:“MI:0915”(physical association)	0.830
SNRNP70	SNRPB	psi-mi:“MI:0914”(association)	0.830
IFIT2	IFIT3	psi-mi:“MI:0914”(association)	0.780
SNRNP70	CLK2	psi-mi:“MI:0915”(physical association)	0.770
CLK2	SNRNP70	psi-mi:“MI:0915”(physical association)	0.770
XPC	CETN3	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
SNRNP70	GEMIN2	psi-mi:“MI:0914”(association)	0.640
SNRPA1	HTATSF1	psi-mi:“MI:0914”(association)	0.640
SNRNP70	SRSF1	psi-mi:“MI:0915”(physical association)	0.600
SNRNP70	SRSF1	psi-mi:“MI:2364”(proximity)	0.600
SMN1	PRMT5	psi-mi:“MI:0914”(association)	0.600
SRRM4	SNRNP70	psi-mi:“MI:0915”(physical association)	0.560
SNRNP70	GTPBP2	psi-mi:“MI:0915”(physical association)	0.560
NP	KPNA6	psi-mi:“MI:0914”(association)	0.550
DDX20	GAPDHS	psi-mi:“MI:0914”(association)	0.530
SNRPE	PRMT5	psi-mi:“MI:0914”(association)	0.530

BioGRID (1378): SNRNP70 (Two-hybrid), SNRNP70 (Affinity Capture-MS), SNRNP70 (Affinity Capture-MS), SNRNP70 (Affinity Capture-MS), SNRNP70 (Affinity Capture-MS), SNRNP70 (Affinity Capture-MS), SNRNP70 (Affinity Capture-MS), SNRNP70 (Affinity Capture-MS), ARGLU1 (Co-fractionation), LUC7L2 (Co-fractionation), PRMT1 (Co-fractionation), PRPF19 (Co-fractionation), PRPF40A (Co-fractionation), PRPF8 (Co-fractionation), RBM39 (Co-fractionation)

ESM2 similar proteins: A2RVS6, A6QR16, G3V6S8, O22315, O35326, P08621, P09406, P26686, P30352, P62995, P62996, P62997, P84104, Q01130, Q06A98, Q08170, Q09167, Q10021, Q13243, Q13247, Q13595, Q15287, Q16629, Q18409, Q1RMR2, Q23120, Q23121, Q28E41, Q3B7L6, Q3KPW1, Q3MHR5, Q3T106, Q3TWW8, Q3ZBT6, Q4R5N1, Q5NVM8, Q5R1W5, Q5XG24, Q62093, Q62376

Diamond homologs: A1C646, A1DGS2, A2R7Z2, A3GGU2, A4RHN3, A5A6M3, A5DNX9, A5E1Z4, A6SGN8, A6ZZ25, A7EWN6, A7SKE9, A7TFW4, A8NS61, A8WLV5, B0VZS1, B0XS28, B3MSP2, B3MYX2, B3NYY7, B3P935, B4G3E2, B4GUY6, B4I9X1, B4IIC7, B4K7S5, B4L710, B4LVR8, B4MA85, B4NFY1, B4NTY9, B4PP90, B4Q0Y7, B4QS37, C8V330, O74400, O75821, O89086, P08199, P08621

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
FUS	“up-regulates activity”	SNRNP70	binding
SNRNP70	“form complex”	“U1 snRNP complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 189 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
Metabolism of non-coding RNA	8	36.8×	1e-09
snRNP Assembly	15	23.0×	5e-15
SARS-CoV-2 modulates host translation machinery	13	21.1×	2e-12
Transport of Mature Transcript to Cytoplasm	7	19.3×	2e-06
RNA Polymerase II Transcription Termination	12	19.1×	7e-11
mRNA Splicing	20	15.9×	1e-16
Processing of Capped Intron-Containing Pre-mRNA	26	15.5×	3e-21
mRNA Splicing - Minor Pathway	9	14.6×	4e-07

GO biological processes:

GO term	Partners	Fold	FDR
spliceosomal snRNP assembly	15	52.2×	2e-20
spliceosomal complex assembly	11	39.6×	4e-13
regulation of mRNA splicing, via spliceosome	7	37.2×	6e-08
U2-type prespliceosome assembly	8	29.9×	3e-08
positive regulation of mRNA splicing, via spliceosome	6	19.5×	7e-05
positive regulation of viral genome replication	5	17.4×	7e-04
mRNA splicing, via spliceosome	30	16.4×	5e-25
regulation of alternative mRNA splicing, via spliceosome	11	16.1×	2e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	44
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1971 predictions. Top by Δscore:

Variant	Effect	Δscore
19:49085623:G:GT	donor_gain	1.0000
19:49085634:GCG:G	donor_gain	1.0000
19:49085635:CGGTG:C	donor_loss	1.0000
19:49085637:G:GG	donor_gain	1.0000
19:49085638:T:A	donor_loss	1.0000
19:49085639:GA:G	donor_gain	1.0000
19:49085641:G:GG	donor_gain	1.0000
19:49086403:A:AG	acceptor_gain	1.0000
19:49086404:G:GG	acceptor_gain	1.0000
19:49086558:TGAGG:T	donor_loss	1.0000
19:49086559:GAGGT:G	donor_loss	1.0000
19:49086560:AGGTG:A	donor_loss	1.0000
19:49090351:A:T	donor_gain	1.0000
19:49090354:G:GG	donor_gain	1.0000
19:49090516:AATGT:A	donor_gain	1.0000
19:49090517:ATGT:A	donor_gain	1.0000
19:49090517:ATGTG:A	donor_loss	1.0000
19:49090519:GT:G	donor_gain	1.0000
19:49090520:TG:T	donor_loss	1.0000
19:49090521:G:GG	donor_gain	1.0000
19:49090521:GT:G	donor_loss	1.0000
19:49090522:T:A	donor_loss	1.0000
19:49098423:ACAG:A	acceptor_gain	1.0000
19:49098423:ACAGG:A	acceptor_gain	1.0000
19:49098487:GAGTG:G	donor_gain	1.0000
19:49098489:GTG:G	donor_gain	1.0000
19:49098639:TA:T	acceptor_loss	1.0000
19:49098640:A:AC	acceptor_loss	1.0000
19:49098640:A:AG	acceptor_gain	1.0000
19:49098641:G:GG	acceptor_gain	1.0000

AlphaMissense

2820 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:49086424:T:C	F4L	1.000
19:49086426:C:A	F4L	1.000
19:49086426:C:G	F4L	1.000
19:49086428:T:A	L5Q	1.000
19:49086428:T:C	L5P	1.000
19:49086428:T:G	L5R	1.000
19:49086431:C:A	P6Q	1.000
19:49086431:C:G	P6R	1.000
19:49086438:C:A	N8K	1.000
19:49086438:C:G	N8K	1.000
19:49086440:T:A	L9H	1.000
19:49086440:T:C	L9P	1.000
19:49086440:T:G	L9R	1.000
19:49086443:T:C	L10P	1.000
19:49086446:C:A	A11D	1.000
19:49086449:T:A	L12H	1.000
19:49086449:T:C	L12P	1.000
19:49086449:T:G	L12R	1.000
19:49086451:T:A	F13I	1.000
19:49086451:T:C	F13L	1.000
19:49086451:T:G	F13V	1.000
19:49086452:T:C	F13S	1.000
19:49086452:T:G	F13C	1.000
19:49086453:T:A	F13L	1.000
19:49086453:T:G	F13L	1.000
19:49086455:C:A	A14D	1.000
19:49086460:C:A	R16S	1.000
19:49086532:G:C	G40R	1.000
19:49086533:G:A	G40D	1.000
19:49086556:T:C	F48L	1.000

dbSNP variants (sampled 300 via entrez): RS1000085813 (19:49104040 A>C,T), RS1000089452 (19:49108974 G>A), RS1000163515 (19:49085315 C>CG), RS1000199406 (19:49090912 G>A), RS1000295039 (19:49094348 A>G), RS1000325966 (19:49099581 A>T), RS1000573989 (19:49103812 T>C,G), RS1000588875 (19:49089317 G>A), RS1000615775 (19:49097978 G>A), RS1000667904 (19:49098152 G>A), RS1000776656 (19:49092895 C>T), RS1000806272 (19:49089471 C>G,T), RS1000854311 (19:49099970 G>A), RS1000885639 (19:49103649 G>A,T), RS1000935982 (19:49103489 G>A,T)

Disease associations

OMIM: gene MIM:180740 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST006628_13	Systolic blood pressure	7.000000e-17
GCST010796_2226	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-20
GCST010796_2227	Electrocardiogram morphology (amplitude at temporal datapoints)	7.000000e-17
GCST010796_2228	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-08
GCST011359_14	Venous thromboembolism	1.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0004327	electrocardiography

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725032 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression	2
sodium arsenite	increases expression	2
Air Pollutants	affects expression, increases abundance, increases expression	2
Valproic Acid	affects cotreatment, increases expression, affects expression	2
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation, increases expression	2
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
lead acetate	increases expression	1
decabromobiphenyl ether	increases expression	1
arsenite	decreases reaction, affects binding	1
methylparaben	increases expression	1
tetrabromobisphenol A	increases expression	1
pyrrolidine dithiocarbamic acid	affects cotreatment, increases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
bathocuproine sulfonate	affects cotreatment, increases expression	1
cupric chloride	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
perfluoro-n-nonanoic acid	decreases expression	1
benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone	decreases degradation	1
benzyloxycarbonyl-isoleucyl-glutamyl-threonyl-aspartic acid fluoromethyl ketone	decreases degradation	1
ICG 001	decreases expression	1
abrine	increases expression	1
bromovanin	decreases expression	1
pentabrominated diphenyl ether 100	increases expression	1
bisphenol AF	increases expression	1
Resveratrol	increases expression, affects cotreatment	1
Decitabine	increases expression	1
Atrazine	increases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697425	Binding	Inhibition of SNRNP70 (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Clinical trials (associated diseases)

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