SND1

Summary

SND1 (staphylococcal nuclease and tudor domain containing 1, HGNC:30646) is a protein-coding gene on chromosome 7q32.1, encoding Staphylococcal nuclease domain-containing protein 1 (Q7KZF4). Endonuclease that mediates miRNA decay of both protein-free and AGO2-loaded miRNAs.

This gene encodes a transcriptional co-activator that interacts with the acidic domain of Epstein-Barr virus nuclear antigen 2 (EBNA 2), a transcriptional activator that is required for B-lymphocyte transformation. Other transcription factors that interact with this protein are signal transducers and activators of transcription, STATs. This protein is also thought to be essential for normal cell growth. A similar protein in mammals and other organisms is a component of the RNA-induced silencing complex (RISC).

Source: NCBI Gene 27044 — RefSeq curated summary.

At a glance

• GWAS associations: 29
• Clinical variants (ClinVar): 190 total
• Phenotypes (HPO): 1
• Druggable target: yes
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• MANE Select transcript: NM_014390

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30646
Approved symbol	SND1
Name	staphylococcal nuclease and tudor domain containing 1
Location	7q32.1
Locus type	gene with protein product
Status	Approved
Aliases	TDRD11, p100, TSN
Ensembl gene	ENSG00000197157
Ensembl biotype	protein_coding
OMIM	602181
Entrez	27044

Gene structure

Transcript identifiers

Ensembl transcripts: 38 — 24 protein_coding, 12 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000354725, ENST00000461056, ENST00000463020, ENST00000465900, ENST00000467238, ENST00000468166, ENST00000468621, ENST00000470463, ENST00000470723, ENST00000483503, ENST00000484767, ENST00000485871, ENST00000486037, ENST00000489417, ENST00000492772, ENST00000492840, ENST00000903601, ENST00000903602, ENST00000903603, ENST00000903604, ENST00000903605, ENST00000903606, ENST00000903607, ENST00000903608, ENST00000903609, ENST00000915263, ENST00000915264, ENST00000915265, ENST00000915266, ENST00000915267, ENST00000915268, ENST00000944748, ENST00000944749, ENST00000944750, ENST00000944751, ENST00000944752, ENST00000944753, ENST00000944754

RefSeq mRNA: 1 — MANE Select: NM_014390 NM_014390

CCDS: CCDS34747

Canonical transcript exons

ENST00000354725 — 24 exons

Exon	Start	End
ENSE00000720787	127703165	127703323
ENSE00000720791	127704839	127704945
ENSE00000720793	127707557	127707647
ENSE00000977914	128084724	128084847
ENSE00000977915	128085711	128085780
ENSE00000977916	128086938	128087051
ENSE00001903029	127652194	127652451
ENSE00001925952	128091993	128092593
ENSE00003498793	128081360	128081501
ENSE00003500100	127698875	127698953
ENSE00003508949	127929188	127929329
ENSE00003509451	127844324	127844424
ENSE00003528699	127807484	127807573
ENSE00003544291	127702435	127702526
ENSE00003546948	127694828	127694948
ENSE00003547391	128074502	128074690
ENSE00003562334	127686613	127686762
ENSE00003572144	128091837	128091881
ENSE00003597953	127701163	127701323
ENSE00003645256	128089489	128089692
ENSE00003666485	127990947	127991056
ENSE00003666915	127887902	127888012
ENSE00003670397	127721287	127721400
ENSE00003685334	127904747	127904819

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 98.70.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 124.6100 / max 643.3445, expressed in 1824 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
80897	124.5260	1824
80902	0.0348	9
80898	0.0284	22
80901	0.0208	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	98.70	gold quality
stromal cell of endometrium	CL:0002255	98.61	gold quality
islet of Langerhans	UBERON:0000006	98.50	gold quality
parotid gland	UBERON:0001831	98.02	gold quality
colonic epithelium	UBERON:0000397	97.97	gold quality
pancreas	UBERON:0001264	97.79	gold quality
endocervix	UBERON:0000458	96.79	gold quality
left ovary	UBERON:0002119	96.73	gold quality
adrenal tissue	UBERON:0018303	96.73	gold quality
smooth muscle tissue	UBERON:0001135	96.63	gold quality
adenohypophysis	UBERON:0002196	96.46	gold quality
right ovary	UBERON:0002118	96.45	gold quality
pituitary gland	UBERON:0000007	96.29	gold quality
body of stomach	UBERON:0001161	96.20	gold quality
body of uterus	UBERON:0009853	96.07	gold quality
stomach	UBERON:0000945	96.00	gold quality
cartilage tissue	UBERON:0002418	95.91	gold quality
monocyte	CL:0000576	95.85	gold quality
ectocervix	UBERON:0012249	95.78	gold quality
bone marrow cell	CL:0002092	95.70	gold quality
pancreatic ductal cell	CL:0002079	95.69	silver quality
ganglionic eminence	UBERON:0004023	95.56	gold quality
left adrenal gland	UBERON:0001234	95.51	gold quality
adrenal gland	UBERON:0002369	95.48	gold quality
leukocyte	CL:0000738	95.40	gold quality
right lobe of liver	UBERON:0001114	95.38	gold quality
mononuclear cell	CL:0000842	95.36	gold quality
left adrenal gland cortex	UBERON:0035825	95.32	gold quality
saliva-secreting gland	UBERON:0001044	95.31	gold quality
corpus epididymis	UBERON:0004359	95.31	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	7.73
E-CURD-112	yes	6.83
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
AGTR1	Activation
IGFBP3	Activation

Upstream regulators (CollecTRI, top): MYB, NFKB2, NFKB, SP1, SREBF1, SREBF2

miRNA regulators (miRDB)

44 targeting SND1, 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-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-378A-5P	99.65	66.33	1311
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-1224-5P	99.48	65.59	803
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-1324	99.46	66.57	1302
HSA-MIR-4318	99.38	66.94	1505
HSA-MIR-2115-3P	99.31	69.68	2026
HSA-MIR-1273H-3P	99.29	67.55	980
HSA-MIR-29A-5P	99.08	68.59	1813
HSA-MIR-6868-5P	99.06	65.69	1284
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-6506-5P	99.04	65.66	1386
HSA-MIR-361-5P	98.95	70.16	1340
HSA-MIR-421	98.90	67.04	1883
HSA-MIR-6829-5P	98.86	65.12	1480
HSA-MIR-4520-3P	98.75	66.55	963
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-7155-5P	98.65	66.14	1290
HSA-MIR-4700-5P	98.63	67.43	1915
HSA-MIR-619-5P	98.57	64.97	1988
HSA-MIR-7114-5P	98.51	67.87	1349
HSA-MIR-326	98.25	66.44	1565

Literature-anchored findings (GeneRIF, showing 40)

• These findings identify p100 as a novel coactivator for STAT6 and suggest that p100 functions as a bridging factor between STAT6 and the basal transcription machinery. (PMID:12234934)
• p100 has an important role in the assembly of STAT6 transcriptosome, and that p100 stimulates IL-4-dependent transcription by mediating interaction between STAT6 and CBP and recruiting chromatin modifying activities to STAT6-responsive promoters (PMID:15695802)
• The p100 protein is a novel dual function regulator of gene expression that participates via distinct domains in both transcription and splicing. (PMID:17576664)
• The tudor and SN (TSN) domain of p100 interacts with U small nuclear ribonucleoprotein (snRNP) complexes, suggesting a role for p100 in the processing of precursor messenger RNA. (PMID:17632523)
• Data showed remarkable up-regulation of SND1 mRNA in human colon cancer tissues, even in early-stage lesions, and also in colon cancer cell lines. (PMID:17909068)
• Tudor-SN requires tandem repeats of SN domains for its RNA binding and cleavage activity. (PMID:18453631)
• SND! represents promising prostate cancer biomarker and therapeutic target. (PMID:19435788)
• The coacitivator p100 protein can interact with STAT6 through its SN domain both in vivo and in vitro, resulting in enhancement of STAT6-mediated gene transcriptional acitivation. (PMID:20225206)
• The kinetics of assembly of stress granules(SGs) in living cells demonstrated that Tudor-SN co-localizes with G3BP and is recruited to the same SGs in response to different stress stimuli. (PMID:20643132)
• These results provide evidence that p100 interacts with the 3’ UTR of dengue virus and is required for normal dengue virus replication. (PMID:21148275)
• SND1 as a novel MTDH-interacting protein and shown that it is a functionally and clinically significant mediator of metastasis. (PMID:21478147)
• this novel B-Raf fusion protein (SND-1 was identified as the B-Raf fusion partner) presents a novel target with potential clinical implications in the treatment of patients resistant to c-Met inhibitors. (PMID:21936566)
• SND1 promotes tumor angiogenesis in human hepatocellular carcinoma through novel pathway that involves nuclear factor kappaB and miR-221 (PMID:22396537)
• The increased expression of MTDH and/or SND1 is closely related to carcinogenesis, progression, and prognosis of colon cancer. (PMID:23065261)
• a transcriptional network associated to the key transcription factors NF-kappaB, Sp1 and NF-Y that operates in the control of the SND1 gene expression (PMID:23160072)
• SND1 silencing resolved this block in processing and induced an increase in mature miRs. Together, SND1 might be the missing link between hypoxia and the differential regulation of miRNA processing (PMID:23770094)
• High SND1 expression is associated with hepatocellular carcinoma. (PMID:23878061)
• The transcriptional co-activator SND1 is a novel regulator of alternative splicing in prostate cancer cells. (PMID:23995791)
• High Tudor-SN expression is associated with breast cancer. (PMID:24155205)
• Tudor-SN plays an important role in the assembly of AGTR1-3’UTR granules. Moreover, endogenous Tudor-SN knockdown can decrease the recovery kinetics of AGTR1-3’UTR granules. (PMID:24815690)
• MTDH supports the survival of mammary epithelial cells under oncogenic/stress conditions by interacting with and stabilizing SND1. (PMID:24981741)
• Study is the first to show a novel regulatory role of SND1, a direct target of miR-184, in glioma progression, suggesting that the miR-184/SND1 axis may be a useful diagnostic and therapeutic tool for malignant glioma. (PMID:25216670)
• we describe the crucial role of SND1 in cancer development and progression, and highlight SND1 as a potential target for therapeutic intervention. (PMID:25405367)
• Promoter activity of the cell growth- and RNA-protection associated SND1 gene is up-regulated by ER stress in human hepatoma cells (PMID:25494629)
• Tudor-SN regulates the aggregation dynamics of poly(A(+) mRNA-containing stress granules and selectively stabilizes the stress granules-associated mRNA during cellular stress. (PMID:25559396)
• SND1 promoted expression of the E3 ubiquitin ligase Smurf1, leading to RhoA ubiquitination and degradation. (PMID:25596283)
• Tudor-SN is a potential substrate of G1/S phase Cyclin-Dependent Kinases, and promotes cell cycle progression by facilitating E2F-1-mediated gene transcription. (PMID:25627688)
• Single nucleotide polymorphism in SND1 gene is associated with osteosarcoma susceptibility. (PMID:25663449)
• it could be concluded that miR-361-5p functions as a tumor-suppressive miRNA through directly binding to SND1 (PMID:25965817)
• we identified a new SND1-BRAF fusion that appeared to be present in a subpopulation of tumor cells. (PMID:25985019)
• SND1 is a determinant downstream effector of TNFalpha that contributes to support glycerophospholipid homeostasis in human hepatocellular carcinoma during inflammation. (PMID:26323317)
• This study unravels a novel mechanism of SND1 function and identifies MGLL as a unique tumor suppressor for HCC. MGLL might function as a homeostatic regulator of Akt restraining its activation. (PMID:26997225)
• These results highlight SND1 as a potential regulator of cellular cholesterol distribution and homeostasis in hepatoma cells, and support the rationale for the therapeutic use of molecules that influence cholesterol management when SND1 is overexpressed. (PMID:27238764)
• The data suggested that JNK-enhanced Tudor-SN phosphorylation promotes the interaction between Tudor-SN and G3BP and facilitates the efficient recruitment of Tudor-SN into stress granules under conditions of sodium arsenite-induced oxidative stress. (PMID:28011284)
• Findings indicate the potential values of microRNA miR-320a, staphylococcal nuclease domain-containing 1 (SND1) and beta-catenin as prognostic biomarkers and therapeutic candidates for malignant gliomas. (PMID:28160566)
• SND1 physically associated with and recruited the histone acetylase GCN5 to the promoter regions of Smad2/3/4, and consequently enhanced the gene transcriptional activation of Smad2/3/4, which are essential downstream regulators in the TGFbeta1 pathway. (PMID:28263968)
• Our work establishes an oncogenic role for SND1 in promoting tumor-initiating cell formation in hepatocellular carcinoma (PMID:28428278)
• The percentages of SND1 expression in metastatic breast cancers were significantly higher than that in primary tumors in 30 patients with advanced breast cancer (P = 0.016). Therefore, SND1 protein expression is significantly associated with breast cancer metastasis and may serve as a biomarker for prognosis of breast cancer patients. (PMID:30216461)
• our study identified SND1 as an anti-apoptotic factor in hepatocellular carcinoma cells via the modulation of lncRNA UCA1, which sheds new light on the relationship between SND1 protein and lncRNA. (PMID:30321081)
• SND1 may act as a potential biomarker of the therapeutic strategies utilizing COX2 inhibitors. (PMID:30365124)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	snd1	ENSDARG00000006766
mus_musculus	Snd1	ENSMUSG00000001424
rattus_norvegicus	Snd1	ENSRNOG00000031173
drosophila_melanogaster	Tudor-SN	FBGN0035121
caenorhabditis_elegans		WBGENE00006626

Paralogs (1): STK31 (ENSG00000196335)

Protein

Protein identifiers

Staphylococcal nuclease domain-containing protein 1 — Q7KZF4 (reviewed: Q7KZF4)

Alternative names: 100 kDa coactivator, EBNA2 coactivator p100, Tudor domain-containing protein 11, p100 co-activator

All UniProt accessions (3): A0A140VK49, Q7KZF4, H7C597

UniProt curated annotations — full annotation on UniProt →

Function. Endonuclease that mediates miRNA decay of both protein-free and AGO2-loaded miRNAs. As part of its function in miRNA decay, regulates mRNAs involved in G1-to-S phase transition. Functions as a bridging factor between STAT6 and the basal transcription factor. Plays a role in PIM1 regulation of MYB activity. Functions as a transcriptional coactivator for STAT5. (Microbial infection) Functions as a transcriptional coactivator for the Epstein-Barr virus nuclear antigen 2 (EBNA2). (Microbial infection) Promotes SARS-CoV-2 RNA synthesis by binding to negative-sense RNA and the viral protein nsp9.

Subunit / interactions. Forms a ternary complex with STAT6 and POLR2A. Associates with the RNA-induced silencing complex (RISC). Interacts with the RISC components AGO2, FMR1 and TNRC6A. Interacts with GTF2E1 and GTF2E2. Interacts with PIM1. Interacts with STAT5. Interacts with SYT11 (via C2 2 domain); the interaction with SYT11 is direct. (Microbial infection) Interacts with EAV NSP1. Binds to acidic transactivation domain of EBNA2. Interacts with SARS-CoV-2 NSP9.

Subcellular location. Cytoplasm. Nucleus. Melanosome.

Tissue specificity. Ubiquitously expressed.

Post-translational modifications. Phosphorylated by PIM1 in vitro.

RefSeq proteins (1): NP_055205* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002071	Thermonucl_AS	Active_site
IPR002999	Tudor	Domain
IPR016071	Staphylococal_nuclease_OB-fold	Domain
IPR016685	Silence_cplx_Nase-comp_TudorSN	Family
IPR035437	SNase_OB-fold_sf	Homologous_superfamily
IPR047386	Tudor_TDRD11	Domain

Pfam: PF00565, PF00567

Enzyme classification (BRENDA):

• EC 3.1.31.1 — micrococcal nuclease (BRENDA: 10 organisms, 45 substrates, 29 inhibitors, 7 Km, 1 kcat entries)

Substrate kinetics (BRENDA)

1 substrates with measured Km, best-characterized 1. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
DNA	0.0041–0.0043	2

UniProt features (111 total): strand 44, helix 33, modified residue 11, turn 11, domain 5, sequence conflict 2, short sequence motif 2, initiator methionine 1, chain 1, cross-link 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
2HQX	X-RAY DIFFRACTION	1.42
5M9O	X-RAY DIFFRACTION	1.45
3OMC	X-RAY DIFFRACTION	1.77
3OMG	X-RAY DIFFRACTION	1.85
3BDL	X-RAY DIFFRACTION	1.9
2HQE	X-RAY DIFFRACTION	2
2O4X	X-RAY DIFFRACTION	2
7KNW	X-RAY DIFFRACTION	2.65
7KNX	X-RAY DIFFRACTION	2.7
4QMG	X-RAY DIFFRACTION	2.7
2E6N	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7KZF4-F1	90.24	0.77

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 (12): 103, 193, 240, 426, 641, 645, 779, 781, 785, 909, 513, 2

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-6802952	Signaling by BRAF and RAF1 fusions
R-HSA-1643685	Disease
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers
R-HSA-6802957	Oncogenic MAPK signaling

MSigDB gene sets: 372 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, SHEPARD_BMYB_MORPHOLINO_UP, GOMF_ENDONUCLEASE_ACTIVITY, GOMF_RNA_NUCLEASE_ACTIVITY, PAX4_01, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, SWEET_KRAS_ONCOGENIC_SIGNATURE, GOMF_NUCLEASE_ACTIVITY, ENK_UV_RESPONSE_KERATINOCYTE_UP, STEARMAN_LUNG_CANCER_EARLY_VS_LATE_DN, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_OSTEOBLAST_DIFFERENTIATION

GO Biological Process (5): osteoblast differentiation (GO:0001649), mRNA catabolic process (GO:0006402), regulation of cell cycle process (GO:0010564), miRNA catabolic process (GO:0010587), regulatory ncRNA-mediated gene silencing (GO:0031047)

GO Molecular Function (11): transcription coregulator activity (GO:0003712), RNA binding (GO:0003723), nuclease activity (GO:0004518), endonuclease activity (GO:0004519), RNA endonuclease activity (GO:0004521), cadherin binding (GO:0045296), RISC complex binding (GO:1905172), 3’ overhang single-stranded DNA endonuclease activity (GO:1990599), nucleic acid binding (GO:0003676), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (8): nucleus (GO:0005634), cytosol (GO:0005829), membrane (GO:0016020), RNAi effector complex (GO:0031332), melanosome (GO:0042470), extracellular exosome (GO:0070062), dense body (GO:0097433), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Oncogenic MAPK signaling	1
Disease	1
Diseases of signal transduction by growth factor receptors and second messengers	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
RNA catabolic process	2
negative regulation of gene expression	2
binding	2
cytoplasm	2
ossification	1
cell differentiation	1
mRNA metabolic process	1
cell cycle process	1
regulation of cell cycle	1
miRNA metabolic process	1
transcription regulator activity	1
nucleic acid binding	1
catalytic activity, acting on a nucleic acid	1
nuclease activity	1
endonuclease activity	1
RNA nuclease activity	1
cell adhesion molecule binding	1
ribonucleoprotein complex binding	1
single-stranded DNA endonuclease activity	1
catalytic activity	1
intracellular membrane-bounded organelle	1
ribonucleoprotein complex	1
pigment granule	1
extracellular vesicle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2224 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SND1	MTDH	Q86UE4	991
SND1	FMR1	Q06787	962
SND1	AGO2	Q9UKV8	907
SND1	PIWIL1	Q96J94	894
SND1	STAT6	P42226	870
SND1	FXR1	P51114	801
SND1	STAT5A	P42229	798
SND1	STAT5B	P51692	796
SND1	PIWIL4	Q7Z3Z4	748
SND1	MYB	P10242	691
SND1	FXR2	P51116	657
SND1	TDRKH	Q9Y2W6	655
SND1	PPARG	P37231	627
SND1	G3BP1	Q13283	619
SND1	DROSHA	Q9NRR4	606

IntAct

210 interactions, top by confidence:

A	B	Type	Score
PRKAA1	PRKAB2	psi-mi:“MI:0914”(association)	0.950
PSMC3	PSMD9	psi-mi:“MI:0914”(association)	0.940
MTDH	SND1	psi-mi:“MI:0914”(association)	0.840
MTDH	SND1	psi-mi:“MI:0915”(physical association)	0.840
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
	TOMM70	psi-mi:“MI:0914”(association)	0.690
PSMC3	PSMD12	psi-mi:“MI:0914”(association)	0.640
SND1	PIWIL1	psi-mi:“MI:0407”(direct interaction)	0.620
IGF1R	PIK3R2	psi-mi:“MI:2364”(proximity)	0.590
MMP28	TRIM68	psi-mi:“MI:0914”(association)	0.560
MAPT	KIF2A	psi-mi:“MI:0914”(association)	0.530
TFDP1	E2F3	psi-mi:“MI:0914”(association)	0.530
	XPO1	psi-mi:“MI:0914”(association)	0.530
PDPK1	PDPK1	psi-mi:“MI:0914”(association)	0.530
SPINT2	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
RPS3	ZNF316	psi-mi:“MI:0914”(association)	0.530
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
SND1		psi-mi:“MI:0407”(direct interaction)	0.440
SND1	CSNK2A1	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
SND1	PRPF8	psi-mi:“MI:0915”(physical association)	0.400
SND1	HNRNPC	psi-mi:“MI:0915”(physical association)	0.400
SND1	H2AX	psi-mi:“MI:0915”(physical association)	0.400
	GNAT3	psi-mi:“MI:0915”(physical association)	0.400
SND1	PTGER4	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (476): SND1 (Affinity Capture-MS), SND1 (Affinity Capture-MS), SND1 (Affinity Capture-RNA), SND1 (Affinity Capture-MS), SND1 (Affinity Capture-MS), SND1 (Affinity Capture-MS), SND1 (Biochemical Activity), SND1 (Reconstituted Complex), SND1 (Affinity Capture-MS), TDRD3 (Co-fractionation), TXNDC5 (Co-fractionation), SND1 (Affinity Capture-MS), SND1 (Affinity Capture-MS), SND1 (Affinity Capture-MS), SND1 (Affinity Capture-MS)

ESM2 similar proteins: A0JN39, A8WGF4, D2SW95, D2XV59, F1QGH9, O00178, O35142, O55029, O75534, O88506, O95747, P18395, P23514, P35605, P35606, P53618, Q10568, Q28943, Q28DS0, Q3US41, Q4R4I8, Q52KW8, Q5R495, Q5R664, Q5R8Q7, Q5R922, Q5RCW2, Q5REU4, Q5XGS8, Q5ZIA5, Q66X93, Q68FK8, Q6NWV3, Q6NXG1, Q6P0H6, Q6P9R2, Q78PY7, Q7KZF4, Q7ZT42, Q863B3

Diamond homologs: C4Y4X4, F4IH31, F4IZC5, P29769, Q2QUS0, Q2QYR1, Q2RBJ2, Q39635, Q57519, Q5REU4, Q7BSX4, Q7KZF4, Q942N7, Q99342, Q9X397, F1R237, Q66X93, Q78PY7, Q7ZT42, Q863B3, Q8VZG7, Q99MV1, Q9BXT4, Q9FLT0, Q9W0S7, Q9Y7U7, O60522, P61407, Q99MV7, P25823, E7FDW8, A4RMK0, A9CPT4, Q58EK5, Q99MW1, Q9BXU1, E1BPH3, Q80VL1, Q9Y2W6

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
SND1	up-regulates	Proliferation
SREBF2	“up-regulates quantity by expression”	SND1	“transcriptional regulation”
SREBF1	“down-regulates quantity by repression”	SND1	“transcriptional regulation”
SND1	“down-regulates quantity by destabilization”	MGLL	binding
SND1	“up-regulates quantity by expression”	IGFBP3	“transcriptional regulation”
SND1	“up-regulates activity”	STAT6	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 210 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
Eukaryotic Translation Initiation	6	11.7×	7e-04
Cap-dependent Translation Initiation	6	11.7×	7e-04
SARS-CoV-1 modulates host translation machinery	6	11.7×	7e-04
Eukaryotic Translation Elongation	6	10.5×	9e-04
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	6	10.3×	1e-03
SPOP-mediated proteasomal degradation of PD-L1(CD274)	7	10.1×	6e-04
SARS-CoV-2 modulates host translation machinery	7	9.9×	6e-04
Formation of the ternary complex, and subsequently, the 43S complex	7	9.5×	7e-04

GO biological processes:

GO term	Partners	Fold	FDR
U2-type prespliceosome assembly	6	19.9×	3e-04
stress granule assembly	5	16.0×	4e-03
cytoplasmic translation	9	8.9×	4e-04
negative regulation of translation	8	8.3×	2e-03
translation	10	5.5×	4e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — CESC.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	118
Likely benign	15
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

6528 predictions. Top by Δscore:

Variant	Effect	Δscore
7:127686607:AC:A	acceptor_gain	1.0000
7:127686608:C:CA	acceptor_gain	1.0000
7:127686608:C:G	acceptor_gain	1.0000
7:127686611:A:AG	acceptor_gain	1.0000
7:127686611:AG:A	acceptor_gain	1.0000
7:127686612:G:GA	acceptor_gain	1.0000
7:127686612:GG:G	acceptor_gain	1.0000
7:127686612:GGT:G	acceptor_gain	1.0000
7:127686612:GGTC:G	acceptor_gain	1.0000
7:127686612:GGTCC:G	acceptor_gain	1.0000
7:127686760:GAGG:G	donor_loss	1.0000
7:127686761:AG:A	donor_loss	1.0000
7:127686764:T:G	donor_loss	1.0000
7:127694826:A:AG	acceptor_gain	1.0000
7:127694827:G:GT	acceptor_gain	1.0000
7:127694827:GC:G	acceptor_gain	1.0000
7:127694827:GCC:G	acceptor_gain	1.0000
7:127694827:GCCC:G	acceptor_gain	1.0000
7:127694827:GCCCT:G	acceptor_gain	1.0000
7:127694948:GGTGA:G	donor_loss	1.0000
7:127698949:AATAA:A	donor_gain	1.0000
7:127698950:ATAA:A	donor_gain	1.0000
7:127698950:ATAAG:A	donor_loss	1.0000
7:127698951:TAA:T	donor_gain	1.0000
7:127698952:AA:A	donor_gain	1.0000
7:127698952:AAGTA:A	donor_loss	1.0000
7:127698953:AGTA:A	donor_loss	1.0000
7:127698954:G:GG	donor_gain	1.0000
7:127698955:TAAG:T	donor_loss	1.0000
7:127698956:AA:A	donor_loss	1.0000

AlphaMissense

5927 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:127686638:T:A	V35D	1.000
7:127694847:G:C	R83P	1.000
7:127694859:G:C	R87P	1.000
7:127702519:G:A	G225D	1.000
7:127703250:T:C	L256P	1.000
7:127703306:G:C	G275R	1.000
7:127704861:T:C	L288P	1.000
7:127704872:G:C	G292R	1.000
7:127704873:G:A	G292D	1.000
7:127704879:C:A	A294E	1.000
7:127707562:C:A	A318D	1.000
7:127721362:A:C	S372R	1.000
7:127721364:C:A	S372R	1.000
7:127721364:C:G	S372R	1.000
7:127807539:G:C	R403P	1.000
7:127807551:G:C	R407P	1.000
7:127844325:T:A	V415D	1.000
7:127844409:T:A	V443D	1.000
7:127887919:T:C	L454P	1.000
7:127887922:T:A	V455D	1.000
7:127887930:G:C	G458R	1.000
7:127887931:G:A	G458D	1.000
7:127887994:T:C	L479P	1.000
7:127887997:T:C	L480P	1.000
7:127888002:G:C	A482P	1.000
7:127904748:G:C	A486P	1.000
7:127904749:C:A	A486D	1.000
7:127904803:T:A	V504D	1.000
7:127929209:T:C	F517L	1.000
7:127929211:C:A	F517L	1.000

dbSNP variants (sampled 300 via entrez): RS1000021083 (7:127844123 G>A,T), RS1000024326 (7:127991743 G>T), RS1000034589 (7:128069574 T>C), RS1000040885 (7:127978728 G>A), RS1000049596 (7:127929550 T>G), RS1000056574 (7:128024872 G>A), RS1000058439 (7:127921993 T>C), RS1000063007 (7:127948690 T>C), RS1000064341 (7:127805018 T>C), RS1000069882 (7:127657642 C>T), RS1000073241 (7:127935725 A>G), RS1000073989 (7:127749212 A>G), RS1000084324 (7:127851021 C>G,T), RS1000085506 (7:128024707 A>G), RS1000094576 (7:127830260 G>A)

Disease associations

OMIM: gene MIM:602181 | disease phenotypes: MIM:300633

GenCC curated gene-disease

Mondo (3): hypospadias (MONDO:0005345), long QT syndrome (MONDO:0002442), teratoma (MONDO:0002601)

Orphanet (1): OBSOLETE: Familial hypospadias (Orphanet:440)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000047	Hypospadias

GWAS associations

29 associations (top):

Study	Trait	p-value
GCST000824_2	Erectile dysfunction and prostate cancer treatment	1.000000e-06
GCST001919_1	Type 2 diabetes	2.000000e-10
GCST002518_2	Food antigen IgG levels	8.000000e-07
GCST002936_22	Cadmium levels	8.000000e-07
GCST003944_36	Hepcidin/ferritin ratio	8.000000e-06
GCST005352_4	Paclitaxel disposition in epithelial ovarian cancer	3.000000e-06
GCST005359_8	Disease progression in age-related macular degeneration	9.000000e-06
GCST006001_22	Hemoglobin A1c levels	1.000000e-09
GCST006269_396	General cognitive ability	2.000000e-10
GCST006269_803	General cognitive ability	7.000000e-09
GCST007094_18	Diastolic blood pressure	1.000000e-08
GCST007098_15	Diastolic blood pressure	6.000000e-06
GCST007325_143	General risk tolerance (MTAG)	2.000000e-12
GCST007325_290	General risk tolerance (MTAG)	7.000000e-17
GCST007326_26	Number of sexual partners	6.000000e-11
GCST007327_79	Smoking status (ever vs never smokers)	4.000000e-08
GCST008058_294	Estimated glomerular filtration rate	2.000000e-11
GCST008059_241	Estimated glomerular filtration rate	6.000000e-10
GCST008362_174	Birth weight	1.000000e-11
GCST008363_63	Offspring birth weight	2.000000e-09
GCST008526_74	Coffee consumption	7.000000e-06
GCST010118_156	Type 2 diabetes	5.000000e-105
GCST010136_49	Fruit consumption	9.000000e-10
GCST010702_42	Subcortical volume (MOSTest)	2.000000e-10
GCST010703_208	Brain morphology (MOSTest)	2.000000e-11
GCST012052_8	Waist circumference	5.000000e-07
GCST012298_16	Schizophrenia, bipolar disorder or major depressive disorder x sex interaction	8.000000e-06
GCST012305_8	Major depressive disorder x sex interaction	4.000000e-06
GCST90014033_84	Haemorrhoidal disease	4.000000e-11

EFO canonical traits (14, from GWAS)

EFO ID	Trait name
EFO:0005844	response to dietary antigen
EFO:0007901	hepcidin:ferritin ratio
EFO:0008336	disease progression measurement
EFO:0004541	HbA1c measurement
EFO:0004337	intelligence
EFO:0006336	diastolic blood pressure
EFO:0008579	risk-taking behaviour
EFO:0004318	smoking behavior
EFO:0004344	birth weight
EFO:0005939	parental genotype effect measurement
EFO:0006781	coffee consumption measurement
EFO:0008111	diet measurement
EFO:0004346	neuroimaging measurement
EFO:0008343	sex interaction measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D007021	Hypospadias	C12.050.351.875.466; C12.100.500.494.400; C12.200.294.494.400; C12.200.706.516; C12.800.516; C16.131.939.516
D008133	Long QT Syndrome	C14.280.067.565; C14.280.123.625; C16.131.240.400.715; C23.550.073.547
D013724	Teratoma	C04.557.465.910

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3879865 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.24	Kd	569.8	nM	CHEMBL5653589
6.24	ED50	569.8	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 8 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149452: Binding affinity to human SND1 incubated for 45 mins by Kinobead based pull down assay	kd	0.5698	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	4
Cisplatin	increases cleavage, increases reaction, increases response to substance, increases activity, decreases expression	3
Cyclosporine	increases expression	3
sodium arsenite	decreases activity, decreases expression, increases expression, affects binding, decreases reaction	2
Tunicamycin	increases expression	2
Valproic Acid	affects expression, increases expression	2
Aflatoxin B1	increases methylation, decreases expression	2
Thapsigargin	increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
methylselenic acid	decreases expression	1
titanium dioxide	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
arsenite	affects localization	1
sodium bichromate	decreases expression	1
benzo(e)pyrene	increases methylation	1
coumarin	decreases phosphorylation	1
cupric oxide	increases expression	1
leptomycin B	affects localization	1
cyclic 3’,5’-uridine monophosphate	affects binding	1
chloropicrin	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
bisphenol B	increases expression	1
bromovanin	increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Sorafenib	decreases response to substance	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3859088	Binding	Binding affinity to SND1 (unknown origin) at 200 uM by DSF assay	Discovery of a Potent, Selective, and Cell-Active Dual Inhibitor of Protein Arginine Methyltransferase 4 and Protein Arginine Methyltransferase 6. — J Med Chem

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D9SG	Ubigene HEK293 SND1 KO	Transformed cell line	Female
CVCL_E2KF	HAP1 SND1 (-)	Cancer cell line	Male
CVCL_VS67	GTL16R1	Cancer cell line	Female
CVCL_VS68	GTL16R3	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02848157	PHASE4	COMPLETED	Effects of Dexmedetomidine as Adjunct to Pudendal Block for Pediatric Penile Surgery
NCT02861950	PHASE4	COMPLETED	Does Caudal Block Increase the Incidence of Urethrocutaneous Fistula Formation Following Hypospadias Repair in Infants?
NCT03902249	PHASE4	COMPLETED	Effect of Intravenous Dexamethasone With Pudendal Nerve Block on Postoperative Pain in Pediatric Hypospadias Repair
NCT05708989	PHASE4	WITHDRAWN	Caudal vs. Pudendal Block in Peds GU
NCT05837000	PHASE4	UNKNOWN	Dexmedetomidine, Ketamine and Magnesium Sulphate in Caudal Block for Hypospadias Repair
NCT05922605	PHASE4	UNKNOWN	Analgesic Effects of Caudal S-ketamine for Supplementation of Ropivacaine Caudal Analgesia in Children With Hypospadias
NCT07121764	PHASE4	COMPLETED	Postoperative Pain Relief in Children: Comparing Caudal Bupivacaine Alone Versus Bupivacaine With Dexmedetomidine for Infra-Umbilical Surgeries Under General Anesthesia
NCT07240649	PHASE4	NOT_YET_RECRUITING	Outcomes From Hyperbaric Oxygen (HBO2) Treatment for Emerging Indications
NCT02513940	PHASE4	COMPLETED	Influence of Testosterone Administration on Drug-Induced QT Interval Prolongation and Torsades de Pointes
NCT03834883	PHASE4	COMPLETED	Reducing the Risk of Drug-Induced QT Interval Lengthening in Women
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04675788	PHASE4	COMPLETED	Novel Approaches for Minimizing Drug-Induced QT Interval Lengthening
NCT01370798	PHASE3	COMPLETED	Local Oestrogen Versus Placebo as Preoperative Treatment in Patients With Severe Hypospadias: Effects on Post-operative Complications
NCT04423107	PHASE3	UNKNOWN	Assessment of Postop Hypospadias Pain
NCT04826484	PHASE3	TERMINATED	Opioid Reduction Initiative During Outpatient Pediatric Urologic Procedures Using Exparel
NCT07197203	PHASE3	NOT_YET_RECRUITING	Comparison of Caudal Block and Sacral Erector Spinae Plane Block With Dexmedetomidine in Pediatric Penile Hypospadias Repair
NCT00104676	PHASE3	COMPLETED	Combination Chemotherapy in Treating Patients With Stage II or Stage III Germ Cell Tumors
NCT02375204	PHASE3	ACTIVE_NOT_RECRUITING	Standard-Dose Combination Chemotherapy or High-Dose Combination Chemotherapy and Stem Cell Transplant in Treating Patients with Relapsed or Refractory Germ Cell Tumors
NCT05253456	PHASE2	COMPLETED	Modified Second Layer Repair for Distal Penile Hypospadias
NCT01648205	PHASE2	COMPLETED	Long-term Efficacy Study of Sodium Channel Blocker in LQT3 Patients
NCT02412709	PHASE2	UNKNOWN	Long QT Syndrome Screening in Newborns
NCT04581408	PHASE2	COMPLETED	Mutation-specific Therapy for the Long QT Syndrome
NCT00002931	PHASE2	COMPLETED	Combination Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Relapsed Germ Cell Cancer
NCT00301782	PHASE2	COMPLETED	Combination Chemotherapy in Treating Male Patients With Germ Cell Tumors
NCT00432094	PHASE2	COMPLETED	Autologous Peripheral Blood Stem Cell Transplant for Germ Cell Tumors
NCT00453232	PHASE2	COMPLETED	Combination Chemotherapy and Pegfilgrastim in Treating Men With Metastatic Germ Cell Tumors
NCT00453310	PHASE2	COMPLETED	Sunitinib in Treating Patients With Metastatic Germ Cell Tumors That Have Relapsed or Not Responded to Treatment
NCT00470366	PHASE2	COMPLETED	Combination Chemotherapy and Pegfilgrastim in Treating Patients With Previously Untreated Germ Cell Tumors
NCT02300987	PHASE2	COMPLETED	A Randomized, Blinded, Placebo-controlled, Phase II Trial of LEE011 in Patients With Relapsed, Refractory, Incurable Teratoma With Recent Progression
NCT04479371	PHASE1	WITHDRAWN	Liposomal Bupivacaine vs Standard Penile Block for Hypospadias Repair
NCT00316459	PHASE1	COMPLETED	Study Evaluating the Effects of Multiple Oral Doses of ERB-041 on Cardiac Repolarization in Healthy Subjects
NCT01849003	PHASE1	COMPLETED	Study of the Effect of GS-6615 in Subjects With LQT-3
NCT02365532	PHASE1	COMPLETED	Effect of Oral GS-6615 on Dofetilide-Induced QT Prolongation, Safety, and Tolerability in Healthy Adults
NCT02412098	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Hepatic Function
NCT02441829	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Renal Function
NCT05759962	PHASE1	COMPLETED	Phase 1 Study of LQT-1213 in Healthy Adults
NCT02752308	PHASE2/PHASE3	COMPLETED	Effectiveness of Caudal Epidural Block on Intraoperative Blood Loss During Hypospadias Repair
NCT04876976	PHASE2/PHASE3	COMPLETED	Isoamyl 2-Cyanoacrylate in the Urethro-cutaneous Fistula Repair
NCT05093166	PHASE1/PHASE2	TERMINATED	Clinical Trial to Assess the Safety and Efficacy of Investigational Product in Patients Due to Hypospadias Treatment Failure
NCT04196400	EARLY_PHASE1	UNKNOWN	The Role of Local Long Acting Corticosteroid Injection in Hypospadias Surgery.