SNIP1

Summary

SNIP1 (Smad nuclear interacting protein 1, HGNC:30587) is a protein-coding gene on chromosome 1p34.3, encoding Smad nuclear-interacting protein 1 (Q8TAD8). Required for pre-mRNA splicing as component of the spliceosome. It is a selective cancer dependency (DepMap: 81.3% of cell lines).

This gene encodes a protein that contains a coiled-coil motif and C-terminal forkhead-associated (FHA) domain. The encoded protein functions as a transcriptional coactivator that increases c-Myc activity and inhibits transforming growth factor beta (TGF-beta) and nuclear factor kappa-B (NF-kB) signaling. The encoded protein also regulates the stability of cyclin D1 mRNA, and may play a role in cell proliferation and cancer progression. Mutations in this gene are a cause of psychomotor retardation, epilepsy, and craniofacial dysmorphism (PMRED).

Source: NCBI Gene 79753 — RefSeq curated summary.

At a glance

• Gene–disease (curated): psychomotor retardation, epilepsy, and craniofacial dysmorphism (Moderate, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 130 total
• GTEx eGene: eQTL in 8 tissues, sQTL in 26 (q < 0.05)
• Phenotypes (HPO): 31
• Cancer dependency (DepMap): dependent in 81.3% of screened cell lines
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.86 (unconstrained)
• MANE Select transcript: NM_024700
• Notable: 130 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30587
Approved symbol	SNIP1
Name	Smad nuclear interacting protein 1
Location	1p34.3
Locus type	gene with protein product
Status	Approved
Aliases	PML1
Ensembl gene	ENSG00000163877
Ensembl biotype	protein_coding
OMIM	608241
Entrez	79753

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 2 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

MANE Select: ENST00000296215

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 1, TSL 4: 1, TSL 5: 1

ENST00000296215, ENST00000468040, ENST00000493916, ENST00000638725, ENST00001145680

RefSeq mRNA: 1 — MANE Select: NM_024700 NM_024700

CCDS: CCDS419

Canonical transcript exons

ENST00000296215 — 4 exons

Exon	Start	End
ENSE00001079222	37540157	37540755
ENSE00001079227	37554006	37554293
ENSE00001885538	37534449	37538012
ENSE00003486891	37552645	37552747

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 88.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.6322 / max 110.6103, expressed in 1809 samples.

Highest expression (Bgee): secondary oocyte, oocyte, sural nerve, primordial germ cell in gonad, buccal mucosa cell.

Genetic regulation across tissues (GTEx eQTL / sQTL)

SNIP1 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 8 tissues and its splicing (sQTL) in 26 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 34 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Adipose Subcutaneous	sqtl	2.4e-47	+0.78	1:37548877:A:G
Skin Sun Exposed Lower leg	sqtl	1.1e-44	+0.75	1:37548877:A:G
Skin Not Sun Exposed Suprapubic	sqtl	1.7e-35	+0.73	1:37545150:C:T
Breast Mammary Tissue	sqtl	1.9e-33	+0.80	1:37548877:A:G
Cells EBV-transformed lymphocytes	sqtl	2.2e-29	+0.89	1:37548877:A:G
Artery Tibial	sqtl	3.9e-29	+0.61	1:37548877:A:G
Lung	sqtl	8.4e-28	+0.57	1:37548877:A:G
Nerve Tibial	sqtl	8.4e-26	+0.60	1:37545150:C:T
Adipose Visceral Omentum	sqtl	8.0e-25	+0.62	1:37548877:A:G
Thyroid	sqtl	5.8e-22	+0.56	1:37545150:C:T
Cells Cultured fibroblasts	sqtl	1.3e-21	+0.56	1:37548877:A:G
Testis	sqtl	2.6e-21	+0.80	1:37548877:A:G
Esophagus Mucosa	sqtl	1.1e-16	-0.57	1:37548877:A:G
Colon Transverse	sqtl	1.4e-15	+0.45	1:37548877:A:G
Cells Cultured fibroblasts	eqtl	4.5e-12	-0.18	1:37596105:G:C
Artery Aorta	sqtl	2.6e-10	+0.41	1:37545150:C:T
Pancreas	sqtl	1.0e-07	-0.62	1:37545150:C:T
Spleen	sqtl	4.2e-07	-0.67	1:37545150:C:T
Small Intestine Terminal Ileum	sqtl	7.2e-07	-0.66	1:37519036:C:A
Uterus	sqtl	3.5e-06	+0.69	1:37572787:G:A

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
11784	16.1267	1808
11783	1.5055	915

Top tissues by expression

showing 100 of 277 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	88.33	gold quality
oocyte	CL:0000023	87.21	gold quality
sural nerve	UBERON:0015488	87.16	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.95	gold quality
buccal mucosa cell	CL:0002336	85.65	gold quality
calcaneal tendon	UBERON:0003701	84.19	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.82	gold quality
islet of Langerhans	UBERON:0000006	81.09	gold quality
tendon	UBERON:0000043	80.96	gold quality
bone marrow cell	CL:0002092	80.85	gold quality
bone marrow	UBERON:0002371	80.63	gold quality
stromal cell of endometrium	CL:0002255	80.61	gold quality
leukocyte	CL:0000738	79.40	gold quality
granulocyte	CL:0000094	79.28	gold quality
blood	UBERON:0000178	79.26	gold quality
monocyte	CL:0000576	79.21	gold quality
mononuclear cell	CL:0000842	79.13	gold quality
mucosa of stomach	UBERON:0001199	78.76	gold quality
skin of abdomen	UBERON:0001416	78.11	gold quality
skin of leg	UBERON:0001511	78.01	gold quality
amniotic fluid	UBERON:0000173	77.77	gold quality
descending thoracic aorta	UBERON:0002345	77.57	gold quality
adrenal tissue	UBERON:0018303	77.40	gold quality
left uterine tube	UBERON:0001303	77.28	gold quality
hindlimb stylopod muscle	UBERON:0004252	77.25	gold quality
lower esophagus	UBERON:0013473	77.24	gold quality
lower esophagus muscularis layer	UBERON:0035833	77.23	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	77.16	gold quality
esophagus	UBERON:0001043	77.06	gold quality
pancreas	UBERON:0001264	77.05	gold quality
cortical plate	UBERON:0005343	77.04	gold quality
thoracic aorta	UBERON:0001515	77.00	gold quality
muscle of leg	UBERON:0001383	76.98	gold quality
esophagus mucosa	UBERON:0002469	76.98	gold quality
right testis	UBERON:0004534	76.97	gold quality
endothelial cell	CL:0000115	76.85	silver quality
ascending aorta	UBERON:0001496	76.85	gold quality
gastrocnemius	UBERON:0001388	76.83	gold quality
testis	UBERON:0000473	76.81	gold quality
colonic epithelium	UBERON:0000397	76.73	gold quality
zone of skin	UBERON:0000014	76.70	gold quality
lower esophagus mucosa	UBERON:0035834	76.62	gold quality
tendon of biceps brachii	UBERON:0008188	76.60	silver quality
left testis	UBERON:0004533	76.49	gold quality
muscle layer of sigmoid colon	UBERON:0035805	76.48	gold quality
body of uterus	UBERON:0009853	76.44	gold quality
left ovary	UBERON:0002119	76.31	gold quality
aorta	UBERON:0000947	76.28	gold quality
left adrenal gland	UBERON:0001234	76.23	gold quality
ovary	UBERON:0000992	76.18	gold quality
small intestine Peyer’s patch	UBERON:0003454	76.13	gold quality
mucosa of transverse colon	UBERON:0004991	76.13	gold quality
transverse colon	UBERON:0001157	76.11	gold quality
body of stomach	UBERON:0001161	76.09	gold quality
upper lobe of left lung	UBERON:0008952	76.09	gold quality
adrenal gland	UBERON:0002369	76.05	gold quality
omental fat pad	UBERON:0010414	76.05	gold quality
peritoneum	UBERON:0002358	76.02	gold quality
right ovary	UBERON:0002118	76.01	gold quality
right coronary artery	UBERON:0001625	75.99	gold quality
right lobe of liver	UBERON:0001114	75.96	gold quality
spleen	UBERON:0002106	75.93	gold quality
left adrenal gland cortex	UBERON:0035825	75.89	gold quality
popliteal artery	UBERON:0002250	75.86	gold quality
tibial artery	UBERON:0007610	75.85	gold quality
left coronary artery	UBERON:0001626	75.83	gold quality
ganglionic eminence	UBERON:0004023	75.82	gold quality
adipose tissue of abdominal region	UBERON:0007808	75.81	gold quality
right adrenal gland	UBERON:0001233	75.72	gold quality
artery	UBERON:0001637	75.72	gold quality
right adrenal gland cortex	UBERON:0035827	75.70	gold quality
ectocervix	UBERON:0012249	75.67	gold quality
ventricular zone	UBERON:0003053	75.61	gold quality
small intestine	UBERON:0002108	75.52	gold quality
upper lobe of lung	UBERON:0008948	75.46	gold quality
stomach	UBERON:0000945	75.45	gold quality
lymph node	UBERON:0000029	75.37	gold quality
vagina	UBERON:0000996	75.36	gold quality
minor salivary gland	UBERON:0001830	75.30	gold quality
coronary artery	UBERON:0001621	75.29	gold quality
adrenal cortex	UBERON:0001235	75.27	gold quality
subcutaneous adipose tissue	UBERON:0002190	75.24	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	75.24	gold quality
colon	UBERON:0001155	75.19	gold quality
smooth muscle tissue	UBERON:0001135	75.16	gold quality
body of pancreas	UBERON:0001150	75.10	gold quality
endometrium	UBERON:0001295	75.10	gold quality
gall bladder	UBERON:0002110	75.09	gold quality
intestine	UBERON:0000160	75.02	gold quality
nerve	UBERON:0001021	74.89	gold quality
rectum	UBERON:0001052	74.89	gold quality
tibial nerve	UBERON:0001323	74.89	gold quality
large intestine	UBERON:0000059	74.88	gold quality
endocervix	UBERON:0000458	74.73	gold quality
prefrontal cortex	UBERON:0000451	74.70	gold quality
apex of heart	UBERON:0002098	74.69	gold quality
liver	UBERON:0002107	74.66	gold quality
female reproductive system	UBERON:0000474	74.53	gold quality
right lung	UBERON:0002167	74.49	gold quality
prostate gland	UBERON:0002367	74.46	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.74

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Corpus callosum	tissue	10.9
Caudate putamen	tissue	10.9
Cerebellum	tissue	10.5	medium
Spinal cord	tissue	10.0
Frontal cortex	tissue	9.9
Hypothalamus	tissue	9.6
Septum	tissue	9.6
Midbrain	tissue	9.5
Substantia nigra	tissue	9.5
Superior colliculi	tissue	9.4
Thalamus	tissue	9.3
Pons	tissue	9.2
Medulla oblongata	tissue	9.2
Hippocampal formation	tissue	9.1
Ventral forebrain	tissue	9.0
Cerebral cortex	tissue	8.9	medium
Periaqueductal gray	tissue	8.9
Somatosensory cortex	tissue	8.9
Basal ganglia	tissue	8.6	medium
Putamen	tissue	8.6
Occipital cortex	tissue	8.6
Retrosplenial and cingulate cortex	tissue	8.4
Prefrontal cortex	tissue	8.3
Retrosplenial cortex	tissue	8.1
Olfactory bulb	tissue	8.0
Temporal cortex	tissue	8.0
Entorhinal cortex	tissue	7.9
Motor cortex	tissue	7.8
Insular cortex	tissue	7.3
Amygdala	tissue	7.2
Liver	tissue	5.9	low
Choroid plexus	tissue	5.8
Postcentral gyrus	tissue	5.5
Locus coeruleus	tissue	5.4
Hippocampus	tissue	5.3	medium
Nucleus accumbens	tissue	5.2
Bone marrow	tissue	5.2	low
Breast	tissue	4.1	low
Tonsil	tissue	3.9	medium
Testis	tissue	3.8	high
Thymus	tissue	3.8
Retina	tissue	3.6
Ovary	tissue	3.6	not detected
Parathyroid gland	tissue	3.6	not detected
Adrenal gland	tissue	3.6	medium
Spleen	tissue	3.5	not detected
Prostate	tissue	3.5	not detected
Lymph node	tissue	3.4	not detected
Cervix	tissue	3.2	low
Pituitary gland	tissue	3.1
Endometrium 1	tissue	3.1	low
Epididymis	tissue	3.1	low
Adipose tissue	tissue	3.0	low
Tongue	tissue	3.0
Vagina	tissue	2.9	medium
Seminal vesicle	tissue	2.9	not detected
Urinary bladder	tissue	2.9	low
Colon	tissue	2.8	medium
Stomach 1	tissue	2.7	medium
Skeletal muscle	tissue	2.7	medium

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — White matter (10.9), Dorsal spinal cord (10.0), Dorsal hippocampus (9.1), Ventral hippocampus (8.9), Ventral spinal cord (8.7).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets:

Target	Regulation
CCND1	Unknown
MYC	Unknown

miRNA regulators (miRDB)

Targeting SNIP1 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 166 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-128-3P	99.95	71.17	2484

Functional genomics

gnomAD constraint: pLI 4.01e-05, LOEUF 0.865, missense Z 1.52 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000296215 — one region, missense o/e 0.85. DepMap (CRISPR cell-line fitness): dependent in 81.3% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): VCaP (-1.936), KP-N-YN (-1.664), HCC1428 (-1.584), DB (-1.477), D283 Med (-1.423), KNS-60 (-1.414), NCI-H747 (-1.361), NCI-H1092 (-1.352), RT-112 (-1.312), MPP 89 (-1.303), SK-RC-52 (-1.296), SNU-5 (-1.294), BICR 31 (-1.284), Calu-1 (-1.281), C2BBe1 (-1.248).

Literature-anchored findings (GeneRIF, showing 20)

• define both a new function for SNIP1 and identify a previously unrecognized regulator of the cell cycle and cyclin D1 expression (PMID:15378006)
• Smad-binding peptide aptamers can be developed to selectively inhibit TGF-beta-induced gene expression. (PMID:15750622)
• SNIP1 functions as a regulator of c-Myc activity, binding the N c-Myc N terminus through its C terminus, and that SNIP1 enhances the transcriptional activity of c-Myc by stabilizing it against proteosomal degradation and bridging the c-Myc/p300 complex. (PMID:17157259)
• SNIP1, the human homolog of DDL, is involved in miRNA biogenesis and interacts with Drosha (PMID:18632581)
• Study shows a novel mechanism regulating Cyclin D1 expression and offers new insight into the role of SNIP1 and associated proteins as regulators of proliferation and cancer. (PMID:18794151)
• overexpression of HIF-1alpha, TWIST2 or SNIP1 correlated with poor disease-free survival in patients with tongue squamous cell carcinoma (PMID:21167768)
• SNIP1 in cells strongly activated the heat shock element signaling pathway, and SNIP1 might selectively regulate the transcription of some heat shock proteins through associating with heat shock elements (PMID:22020748)
• Study identified sequence variants in the known disease-causing genes SLC6A3 and FLVCR1, and present evidence to strongly support the pathogenicity of variants identified in TUBGCP6, BRAT1, SNIP1, CRADD, and HARS. (PMID:22279524)
• Involvement of SNIP1 in progression of lung cancer by regulating the RB/HDAC1 interaction. (PMID:23932364)
• SUMOylation of SNIP1 leads to the loss of SNIP1-mediated inhibition on expression of the TGF-beta target genes PAI-1 and MMP2 and eventually enhances TGF-beta-regulated cell migration and invasion. (PMID:27703003)
• these data demonstrated a novel mechanism whereby SNIP1 regulates intestinal inflammation through modulating intestinal epithelial barrier function (PMID:29426045)
• This study also reveals a TET2-SNIP1-c-MYC pathway in mediating DNA damage response. (PMID:30404004)
• Overexpression of miR-335 inhibits the migration and invasion of osteosarcoma by targeting SNIP1 (PMID:30954590)
• MiR-223 promotes pyroptosis of enteritis cells through activating NF-kappaB signalling pathway by targeting SNIP1 in inflammatory bowel disease. (PMID:34151668)
• Long non-coding RNA AFAP1-AS1 accelerates lung cancer cells migration and invasion by interacting with SNIP1 to upregulate c-Myc. (PMID:34168109)
• A biallelic SNIP1 Amish founder variant causes a recognizable neurodevelopmental disorder. (PMID:34570759)
• KMT5A-methylated SNIP1 promotes triple-negative breast cancer metastasis by activating YAP signaling. (PMID:35449131)
• MiR-138-5p suppresses the progression of lung cancer by targeting SNIP1. (PMID:36597175)
• MKRN1 promotes colorectal cancer metastasis by activating the TGF-beta signalling pathway through SNIP1 protein degradation. (PMID:37620897)
• SNIP1 reduces extracellular matrix degradation and inflammation via inhibiting the NF-kappaB signaling pathway in osteoarthritis. (PMID:37739115)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Snip1	ENSMUSG00000050213
rattus_norvegicus	Snip1	ENSRNOG00000024889
drosophila_melanogaster	CG17168	FBGN0039943
caenorhabditis_elegans	pmlr-1	WBGENE00016323

Paralogs (2): PPP1R8 (ENSG00000117751), SLC4A1AP (ENSG00000163798)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2156003) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 5 distinct phenotype terms.

Mouse phenotype (MP)	Records
neuron degeneration	1
abnormal behavior	1
decreased circulating total protein level	1
abnormal placement of pupils	1
prenatal lethality, complete penetrance	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Xenopus tropicalis	A0JM08	84.3%	Diamond
Xenopus laevis	Q498L0	84.2%	Diamond
Arabidopsis thaliana	Q8W4D8	65.8%	Diamond
Saccharomyces cerevisiae S288C	Q07930	30.7%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
RSPO1	protein-coding	284654
GNL2	protein-coding	29889
DNALI1	protein-coding	7802
MIR6732	ncRNA	102465438
MEAF6	protein-coding	64769
LITATS1	ncRNA	728431
ZC3H12A	protein-coding	80149
MIR5581	ncRNA	100847010
AIRIM	protein-coding	54955

Protein

Protein identifiers

Smad nuclear-interacting protein 1 — Q8TAD8 (reviewed: Q8TAD8)

Alternative names: FHA domain-containing protein SNIP1

All UniProt accessions (3): Q8TAD8, A0A1W2PRA0, B1AK66

UniProt curated annotations — full annotation on UniProt →

Function. Required for pre-mRNA splicing as component of the spliceosome. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs. Down-regulates NF-kappa-B signaling by competing with RELA for CREBBP/EP300 binding. Involved in the microRNA (miRNA) biogenesis. May be involved in cyclin-D1/CCND1 mRNA stability through the SNARP complex which associates with both the 3’end of the CCND1 gene and its mRNA.

Subunit / interactions. Component of activated spliceosome complexes. Component of the minor spliceosome, which splices U12-type introns. Binds SMAD4 and CREBBP/EP300. Binds the SMAD1/OAZ1/PSMB4 complex. Interacts with DROSHA and SMARCA4. Component of the SNARP complex which consists at least of SNIP1, SNW1, THRAP3, BCLAF1 and PNN.

Subcellular location. Nucleus.

Tissue specificity. Ubiquitous, with highest expression in heart and skeletal muscle.

Post-translational modifications. Degraded by the proteasome upon binding to the SMAD1/OAZ1/PSMB4 complex.

Disease relevance. Neurodevelopmental disorder with hypotonia, craniofacial abnormalities, and seizures (NEDHCS) [MIM:614501] An autosomal recessive disease characterized by severe psychomotor retardation, intractable seizures, dysmorphic features, and a lumpy skull surface. Patients are hypotonic and have poor feeding in the neonatal period. The disease is caused by variants affecting the gene represented in this entry.

RefSeq proteins (1): NP_078976* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000253	FHA_dom	Domain
IPR008984	SMAD_FHA_dom_sf	Homologous_superfamily
IPR050923	Cell_Proc_Reg/RNA_Proc	Family

Pfam: PF00498

UniProt features (43 total): modified residue 10, strand 10, compositionally biased region 6, cross-link 5, region of interest 2, sequence conflict 2, turn 2, chain 1, domain 1, sequence variant 1, mutagenesis site 1, helix 1, coiled-coil region 1

Structure

Experimental structures (PDB)

10 structures by resolution:

PDB	Title	Method	Resolution (Å)
7DVQ	Cryo-EM Structure of the Activated Human Minor Spliceosome (minor Bact Complex)	ELECTRON MICROSCOPY	2.89
8I0R	The cryo-EM structure of human Bact-I complex	ELECTRON MICROSCOPY	3
8I0P	The cryo-EM structure of human pre-Bact complex	ELECTRON MICROSCOPY	3.4
6FF7	human Bact spliceosome core structure	ELECTRON MICROSCOPY	4.5
7ABH	Human pre-Bact-2 spliceosome (SF3b/U2 snRNP portion)	ELECTRON MICROSCOPY	4.5
5Z58	Cryo-EM structure of a human activated spliceosome (early Bact) at 4.9 angstrom.	ELECTRON MICROSCOPY	4.9
5Z56	cryo-EM structure of a human activated spliceosome (mature Bact) at 5.1 angstrom.	ELECTRON MICROSCOPY	5.1
5Z57	Cryo-EM structure of the human activated spliceosome (late Bact) at 6.5 angstrom	ELECTRON MICROSCOPY	6.5
7ABG	Human pre-Bact-1 spliceosome	ELECTRON MICROSCOPY	7.8
7ABI	Human pre-Bact-2 spliceosome	ELECTRON MICROSCOPY	8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TAD8-F1	66.66	0.31

Human Protein Atlas

Protein class: Predicted intracellular proteins, Disease related genes, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; cytosol

Antibody reliability (HPA): IH approved · IF supported

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 (15)

Type	Positions
Phosphoserine	35, 49, 52, 54, 58, 99, 153, 202, 394
Phosphothreonine	57
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo)	30
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo1)	30
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo2)	30, 108, 223

Mutagenesis-validated functional residues (1)

Position	Phenotype
30	abolishes sumoylation.

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 4; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

4 pathways:

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

MSigDB gene sets: 281 (showing top): GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, TGCACTT_MIR519C_MIR519B_MIR519A, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GGAANCGGAANY_UNKNOWN, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, chr1p34, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION, GOBP_RNA_SPLICING, REACTOME_MRNA_SPLICING, GOBP_NEGATIVE_REGULATION_OF_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN

GO Biological Process (9): mRNA splicing, via spliceosome (GO:0000398), miRNA processing (GO:0035196), negative regulation of canonical NF-kappaB signal transduction (GO:0043124), mRNA stabilization (GO:0048255), U2-type prespliceosome assembly (GO:1903241), mRNA processing (GO:0006397), RNA splicing (GO:0008380), regulation of gene expression (GO:0010468), regulatory ncRNA-mediated gene silencing (GO:0031047)

GO Molecular Function (4): RNA binding (GO:0003723), mRNA binding (GO:0003729), transcription regulator inhibitor activity (GO:0140416), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), U2-type precatalytic spliceosome (GO:0071005), spliceosomal complex (GO:0005681)

Reactome top-level categories

3 top-level categories:

Category	Pathways
mRNA Splicing	1
Processing of Capped Intron-Containing Pre-mRNA	1
Metabolism of RNA	1

GO top-level categories

31 GO namespaces:

Category	Terms
RNA processing	2
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
regulatory ncRNA processing	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
negative regulation of intracellular signal transduction	1
regulation of mRNA stability	1
RNA stabilization	1
negative regulation of mRNA catabolic process	1
spliceosomal complex assembly	1
mRNA metabolic process	1
gene expression	1
regulation of macromolecule biosynthetic process	1
negative regulation of gene expression	1
nucleic acid binding	1
RNA binding	1
regulation of gene expression	1
transcription regulator activity	1
molecular function inhibitor activity	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
U2-type spliceosomal complex	1
U1 snRNP	1
U2 snRNP	1
U4/U6 x U5 tri-snRNP complex	1
precatalytic spliceosome	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 6 of 17 annotations. The rest are phylogenetic / computational / electronic (IEA).

6 experimentally-supported GO terms:

GO term	NS	Evidence
mRNA splicing, via spliceosome	BP	direct assay
miRNA processing	BP	mutant phenotype
U2-type precatalytic spliceosome	CC	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
RNA binding	MF	high-throughput assay

Protein interactions and networks

STRING

showing 15 of 1,368 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SNIP1	RBMX2	Q9Y388	784
SNIP1	BUD13	Q9BRD0	741
SNIP1	CWC25	Q9NXE8	578
SNIP1	PPP1R10	Q96QC0	573
SNIP1	SMAD4	Q13485	556
SNIP1	GALC	P54803	551
SNIP1	EP300	Q09472	497
SNIP1	SMAD2	Q15796	489
SNIP1	ITPR1	Q14643	486
SNIP1	SMAD6	O43541	484
SNIP1	SF3A3	Q12874	459
SNIP1	CWC22	Q9HCG8	459
SNIP1	YJU2	Q9BW85	452
SNIP1	SF3B1	O75533	442
SNIP1	ZFYVE9	O95405	438

IntAct

Human interaction partners of SNIP1 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 58 partners by confidence:

Partner	Interaction type	MIscore	Records
CLK2	physical association	0.870	7
SNW1	association	0.770	7
CLK3	physical association	0.740	3
THRAP3	association	0.740	2
MFAP1	physical association	0.670	4
SRPK2	physical association	0.670	4
TNIP1	physical association	0.670	4
RNPS1	association	0.670	2
SF3B1	physical association	0.670	2
NCBP3	physical association	0.660	1
SRRM2	physical association	0.660	1
WSB2	association	0.640	1
MYC	physical association	0.630	9
SRRM4	physical association	0.560	6
ZBTB9	physical association	0.560	6
DVL3	physical association	0.560	3
ESRRG	physical association	0.560	3
GYS1	physical association	0.560	3
KRTAP10-6	physical association	0.560	3
PHF19	physical association	0.560	3
POU2F1	physical association	0.560	3
SPANXN2	physical association	0.560	3
STK3	physical association	0.560	3
TSPYL2	physical association	0.560	3
SUMO1	physical association	0.560	1
DVL2	physical association	0.550	2
SP100	physical association	0.550	1
CASC3	association	0.530	2
SMARCA4	colocalization	0.510	3
IK	physical association	0.510	2

BioGRID (578 interactions; top human partners by supporting records): CLK2 (Two-hybrid; 7 records), DPF3 (Affinity Capture-Western; 6 records), MYC (Affinity Capture-MS; 6 records), SNW1 (Affinity Capture-MS; 6 records), SRRM2 (Affinity Capture-MS; 6 records), TET2 (Two-hybrid; 6 records), C17orf85 (Affinity Capture-MS; 5 records), MFAP1 (Two-hybrid; 5 records), RNPS1 (Affinity Capture-MS; 5 records), ACIN1 (Affinity Capture-MS; 4 records), AQR (Affinity Capture-MS; 4 records), BCLAF1 (Affinity Capture-MS; 4 records), CCDC12 (Affinity Capture-MS; 4 records), CDC40 (Affinity Capture-MS; 4 records), CLK3 (Affinity Capture-MS; 4 records)

SIGNOR signaling

3 signaling interactions:

A	Effect	B	Mechanism
SNIP1	down-regulates	CBP/p300	binding
SNIP1	“form complex”	“U2 snRNP complex”	binding
SNIP1	down-regulates	SMAD4	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 58 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
SUMOylation of transcription cofactors	5	27.6×	4e-05
SUMOylation of DNA damage response and repair proteins	6	20.0×	4e-05
mRNA Splicing	6	15.0×	1e-04
mRNA Splicing - Major Pathway	10	12.4×	1e-06
Processing of Capped Intron-Containing Pre-mRNA	6	11.2×	4e-04
Epigenetic regulation of gene expression	5	8.1×	5e-03
Dengue Virus-Host Interactions	7	7.3×	9e-04
Metabolism of RNA	6	5.7×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
protein sumoylation	7	42.0×	1e-07
mRNA splicing, via spliceosome	9	15.3×	1e-06
RNA splicing	7	11.4×	2e-04

Disease & clinical

Genetic variants

Variant evidence for SNIP1: 130 ClinVar records (0 pathogenic / likely pathogenic); 2 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	77
Likely benign	43
Benign	2

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 22 predictions of 271):

Position(s)	Effect	Δscore	Sites
1:37537743	donor_gain	1.0000
1:37538013–37538014	acceptor_loss	1.0000	6
1:37540155–37540156	donor_loss	1.0000	4
1:37537795	donor_gain	0.9900
1:37538018	acceptor_gain	0.9900
1:37540156	donor_loss	0.9900
1:37540756–37540757	acceptor_loss	0.9900	5
1:37548832	donor_gain	0.9900
1:37537751	donor_gain	0.9800
1:37540756	acceptor_loss	0.9800

AlphaMissense

978 missense substitutions predicted likely pathogenic (of 2,580 scored), across 179 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D356	8	1.000	1.000
D291	8	0.999	1.000
H296	8	0.999	1.000
H303	8	0.999	1.000
D330	8	0.999	1.000
S363	8	0.999	1.000
N335	8	0.998	1.000
F360	8	0.998	1.000
F264	8	0.997	1.000
H276	8	0.996	0.999
D295	8	0.996	1.000
N340	8	0.993	1.000
N237	8	0.970	0.995
D235	8	0.969	0.992
F226	8	0.966	0.997
S279	8	0.963	0.999
F362	8	0.954	1.000
H371	8	0.948	0.979
F306	8	0.928	0.999
D375	8	0.870	0.952

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	3.66e-05
Kidney Renal Clear Cell Carcinoma (validation)	favorable	0.000234
Prostate Adenocarcinoma (TCGA)	unfavorable	0.000597

Disease associations

OMIM: gene MIM:608241 | disease phenotypes:

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
psychomotor retardation, epilepsy, and craniofacial dysmorphism	Moderate	Autosomal recessive	4

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (6 panels, 6 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

6 panels:

Panel	Rating
Early onset or syndromic epilepsy	green
Hypotonic infant	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Paediatric disorders	green
Unexplained death in infancy and sudden unexplained death in childhood	green

Mondo (1): psychomotor retardation, epilepsy, and craniofacial dysmorphism (MONDO:0013787)

HPO phenotypes

31 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000154	Wide mouth
HP:0000158	Macroglossia
HP:0000218	High palate
HP:0000347	Micrognathia
HP:0000414	Bulbous nose
HP:0000486	Strabismus
HP:0000666	Horizontal nystagmus
HP:0001182	Tapered finger
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001265	Hyporeflexia
HP:0001518	Small for gestational age
HP:0001537	Umbilical hernia
HP:0001601	Laryngomalacia
HP:0001607	Subglottic stenosis
HP:0001647	Bicuspid aortic valve
HP:0001650	Aortic valve stenosis
HP:0001762	Talipes equinovarus
HP:0001943	Hypoglycemia
HP:0002079	Hypoplasia of the corpus callosum
HP:0002119	Ventriculomegaly
HP:0002263	Exaggerated cupid’s bow
HP:0002353	EEG abnormality
HP:0002500	Abnormal cerebral white matter morphology
HP:0003429	CNS hypomyelination
HP:0004279	Short palm
HP:0011304	Broad thumb
HP:0011344	Severe global developmental delay
HP:0011968	Feeding difficulties
HP:0012802	Broad jaw

GWAS associations

2 associations:

Study	Trait	p-value
GCST002115_4	Axial length	4e-13
GCST003476_9	Eyebrow thickness	7e-6

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0005318	axial length measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, affects expression, affects cotreatment	3
Arsenic	affects methylation, affects cotreatment, increases abundance, increases expression	2
Tobacco Smoke Pollution	increases expression	2
aristolochic acid I	increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	affects cotreatment, increases expression	1
pyrimidin-2-one beta-ribofuranoside	decreases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
cobaltous chloride	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
coumarin	decreases phosphorylation	1
cupric oxide	increases expression	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
epigallocatechin gallate	affects cotreatment, increases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
abrine	decreases expression, increases expression	1
neodymium oxide	increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
PCI 5002	affects cotreatment, increases expression	1
Air Pollutants	affects expression, increases abundance	1
Arbutin	decreases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Caffeine	decreases phosphorylation	1
Copper	affects binding, decreases expression	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.