SNRPN

Summary

SNRPN (small nuclear ribonucleoprotein polypeptide N, HGNC:11164) is a protein-coding gene on chromosome 15q11.2, encoding Small nuclear ribonucleoprotein-associated protein N (P63162). May be involved in tissue-specific alternative RNA processing events.

This gene is located within the Prader-Willi Syndrome critical region on chromosome 15 and is imprinted and expressed from the paternal allele. It encodes a component of the small nuclear ribonucleoprotein complex, which functions in pre-mRNA processing and may contribute to tissue-specific alternative splicing. Alternative promoter use and alternative splicing result in a multitude of transcript variants encoding the same protein. Transcript variants that initiate at the CpG island-associated imprinting center may be bicistronic and also encode the SNRPN upstream reading frame protein (SNURF) from an upstream open reading frame. In addition, long spliced transcripts for small nucleolar RNA host gene 14 (SNHG14) may originate from the promoters at this locus and share exons with this gene. Alterations in this region are associated with parental imprint switch failure, which may cause Angelman syndrome or Prader-Willi syndrome.

Source: NCBI Gene 6638 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Prader-Willi syndrome (Definitive, GenCC)
• GWAS associations: 8
• Clinical variants (ClinVar): 6 total — 1 likely-pathogenic
• Phenotypes (HPO): 185
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_003097

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11164
Approved symbol	SNRPN
Name	small nuclear ribonucleoprotein polypeptide N
Location	15q11.2
Locus type	gene with protein product
Status	Approved
Aliases	SMN, SM-D, HCERN3, SNRNP-N, SNURF-SNRPN, RT-LI
Ensembl gene	ENSG00000128739
Ensembl biotype	protein_coding
OMIM	182279
Entrez	6638

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 12 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000346403, ENST00000390687, ENST00000400097, ENST00000400098, ENST00000400100, ENST00000553597, ENST00000554227, ENST00000577565, ENST00000579070, ENST00000584968, ENST00000642807, ENST00000645002, ENST00000912805, ENST00000969829

RefSeq mRNA: 112 — MANE Select: NM_003097 NM_001349454, NM_001349455, NM_001349456, NM_001349457, NM_001349458, NM_001349459, NM_001349460, NM_001349461, NM_001349462, NM_001349463, NM_001349464, NM_001349465, NM_001378249, NM_001378251, NM_001378252, NM_001378253, NM_001378254, NM_001378255, NM_001378256, NM_001378257, NM_001400634, NM_001400635, NM_001400636, NM_001400637, NM_001400638, NM_001400639, NM_001400640, NM_001400641, NM_001400643, NM_001400644, NM_001400646, NM_001400647, NM_001400649, NM_001400650, NM_001400652, NM_001400683, NM_001400684, NM_001400685, NM_001400686, NM_001400687, NM_001400688, NM_001400689, NM_001400690, NM_001400691, NM_001400692, NM_001400693, NM_001400694, NM_001400695, NM_001400696, NM_001400697, NM_001400698, NM_001400701, NM_001400702, NM_001400703, NM_001400704, NM_001400706, NM_001400708, NM_001400710, NM_001400712, NM_001400713, NM_001400715, NM_001400716, NM_001400717, NM_001400718, NM_001400719, NM_001400720, NM_001400721, NM_001400722, NM_001400723, NM_001400724, NM_001400725, NM_001400726, NM_001400727, NM_001400728, NM_001400729, NM_001400730, NM_001400731, NM_001400732, NM_001400733, NM_001400734, NM_001400735, NM_001400736, NM_001400737, NM_001400738, NM_001400739, NM_001400740, NM_001400741, NM_001400742, NM_001400743, NM_001400744, NM_001400745, NM_001400746, NM_001400747, NM_001400748, NM_001400753, NM_001400754, NM_001400755, NM_001400756, NM_001400757, NM_001400758, NM_001400759, NM_001400762, NM_001400763, NM_001400764, NM_001400765, NM_001400767, NM_001400768, NM_003097, NM_022805, NM_022806, NM_022807, NM_022808

CCDS: CCDS10017, CCDS91965

Canonical transcript exons

ENST00000390687 — 10 exons

Exon	Start	End
ENSE00001417721	24954987	24955062
ENSE00002477512	24978407	24978723
ENSE00003480139	24977778	24977916
ENSE00003530123	24976305	24976416
ENSE00003572932	24967932	24968082
ENSE00003639920	24975358	24975509
ENSE00003652257	24978193	24978318
ENSE00003660555	24962114	24962209
ENSE00003681087	24974311	24974456
ENSE00003688455	24976877	24977029

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.78.

FANTOM5 (CAGE): breadth broad, TPM avg 1.2710 / max 43.0608, expressed in 563 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
145497	97.1455	1611
145496	14.3124	1484
145487	4.7034	465
145484	1.4034	165
207435	1.2710	563
145502	1.0474	253
145489	0.9058	204
145485	0.4632	198
145500	0.4571	231
145486	0.3495	126

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
superior frontal gyrus	UBERON:0002661	99.78	gold quality
prefrontal cortex	UBERON:0000451	99.75	gold quality
primary visual cortex	UBERON:0002436	99.74	gold quality
frontal cortex	UBERON:0001870	99.72	gold quality
cerebellum	UBERON:0002037	99.68	gold quality
cerebellar cortex	UBERON:0002129	99.68	gold quality
cerebellar hemisphere	UBERON:0002245	99.68	gold quality
right frontal lobe	UBERON:0002810	99.68	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	99.67	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.67	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.67	gold quality
cerebral cortex	UBERON:0000956	99.62	gold quality
hypothalamus	UBERON:0001898	99.57	gold quality
brain	UBERON:0000955	99.55	gold quality
anterior cingulate cortex	UBERON:0009835	99.55	gold quality
nucleus accumbens	UBERON:0001882	99.53	gold quality
pituitary gland	UBERON:0000007	99.49	gold quality
caudate nucleus	UBERON:0001873	99.49	gold quality
Ammon’s horn	UBERON:0001954	99.49	gold quality
putamen	UBERON:0001874	99.47	gold quality
adenohypophysis	UBERON:0002196	99.47	gold quality
temporal lobe	UBERON:0001871	99.44	gold quality
amygdala	UBERON:0001876	99.44	gold quality
substantia nigra	UBERON:0002038	99.42	gold quality
right lobe of thyroid gland	UBERON:0001119	99.26	gold quality
left lobe of thyroid gland	UBERON:0001120	99.26	gold quality
thyroid gland	UBERON:0002046	99.24	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.20	gold quality
islet of Langerhans	UBERON:0000006	99.18	gold quality
heart left ventricle	UBERON:0002084	99.16	gold quality

Single-cell (SCXA)

Detected in 17 experiment(s), a significant marker in 12.

Experiment	Marker?	Max mean expression
E-MTAB-9388	yes	2272.14
E-GEOD-36552	yes	1010.45
E-HCAD-35	yes	75.58
E-HCAD-25	yes	50.91
E-CURD-114	yes	22.13
E-HCAD-10	yes	21.91
E-HCAD-5	yes	19.63
E-MTAB-7316	yes	15.24
E-HCAD-9	yes	9.49
E-GEOD-125970	yes	6.99
E-GEOD-84465	yes	6.57
E-MTAB-9154	no	1892.73
E-MTAB-10018	no	1268.76
E-MTAB-4850	no	1237.63
E-MTAB-7606	no	1074.67

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MBD1, NRF1, SP1, TFCP2, YY1

miRNA regulators (miRDB)

26 targeting SNRPN, 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-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-1276	99.36	68.18	1642
HSA-MIR-4311	99.31	70.47	3041
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-4742-5P	98.89	68.41	1542
HSA-MIR-583	98.71	67.44	1791
HSA-MIR-4709-5P	98.51	67.25	1335
HSA-MIR-9903	98.47	66.70	748
HSA-MIR-302F	98.44	69.02	1776
HSA-MIR-6870-3P	98.08	65.10	692
HSA-MIR-6865-3P	97.54	64.67	684
HSA-MIR-134-5P	97.11	66.52	976
HSA-MIR-3118	97.11	66.58	984
HSA-MIR-6857-3P	96.70	65.43	915
HSA-MIR-6834-5P	96.25	64.88	823
HSA-MIR-6855-3P	95.04	66.57	725

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 25)

• Methylation imprints of the imprint control region of the SPRPN-gene were studied in gametes and preimplantation embryos. ametes (PMID:14500540)
• SMB and CD2BP2-GYF interact in the spliceosome (PMID:15105431)
• Identification of cis- and trans-acting regulatory elements within the endogenous SNRPN 5’ region. (PMID:16116039)
• a possibly inactivating mutation in the SNRPN minimal promoter region was identified in Prader-Willi syndrome (PMID:17262171)
• MEG3 and SNRPN genes are abnormally methylated in AML and MDS patients, and methylation of MEG3, but not SNRPN, confers worse overall prognosis. (PMID:19595458)
• Variable methylation of the imprinted gene, SNRPN, supports a relationship between intracranial germ cell tumours and neural stem cells. (PMID:20582452)
• Differences between genetic subtypes were also statistically significant in Prader Willi syndrome (PMID:21227640)
• genetic association studies using 1,000 white subjects from Midwestern United States: Three copy number variations (CNV) in PWCR are associated with body fat mass, with a higher copy number (CN) associated with an increase of in body fat mass. (PMID:21233802)
• In the skeletal muscle of neonate pigs, both NECD and SNRPN were maternally imprinted, while UBE3A was not imprinted. (PMID:22711311)
• Human amniotic fluid mesenchymal stem cells contain a unique epigenetic signature during in vitro cell culture. H19 and KCNQ1OT1 possessed a substantial degree of hypermethylation status, and variable DNA methylation patterns of SNRPN was observed. (PMID:23040914)
• The methylation patterns of the promoters of MTHFR and SNRPN are associated with changes in sperm motility and morphology, which could lead to male infertility. (PMID:24365028)
• indicate that SmN expression reduces the level of mature U2 snRNP, leading to alternative splicing (PMID:25238490)
• Knockdown of SNRPN was demonstrated to significantly inhibit medulloblastoma cell growth and induce G2/M phase arrest in vitro. (PMID:25571951)
• Data indicate that Sm nuclear antigen SmD-specific clonotypic IgGs showed extensive V- region hypermutation. (PMID:25577500)
• the cases with partial loss of methylation in KCNQ1OT1 and SNRPN present clinical features different to those associated with the corresponding imprinting syndromes (PMID:26106604)
• we have confirmed that SNRPN methylation increases with age, which raises further questions regarding the role of SNRPN expression during the aging process. (PMID:26535694)
• The first study reporting an association between variability in the SNRPN gene and the risk of being obese. (PMID:28387446)
• Methylation patterns of CpG sites within the SNRPN gene is associated with male infertility. (PMID:29708855)
• We focused on three important regulatory DNA elements which are all differentially methylated regions (DMRs), methylated on the maternal allele: the PWS imprinting center (PWS-IC), which is a germline DMR and the somatic NDN and MKRN3 DMRs, hierarchically controlled by PWS-IC (PMID:30102380)
• Imprinting methylation in SNRPN and MEST1 in adult blood predicts cognitive ability. (PMID:30707743)
• Imprinting aberrations of SNRPN, ZAC1 and INPP5F genes involved in the pathogenesis of congenital heart disease with extracardiac malformations. (PMID:32693431)
• Novel lncRNA-prader willi/angelman region RNA, SNRPN neighbour (PWARSN) aggravates tubular epithelial cell pyroptosis by regulating TXNIP via dual way in diabetic kidney disease. (PMID:36316968)
• N-Acetylglucosamine Kinase-Small Nuclear Ribonucleoprotein Polypeptide N Interaction Promotes Axodendritic Branching in Neurons via Dynein-Mediated Microtubule Transport. (PMID:37511433)
• SNRPN gene is imprinted, with monoallelic expression from the paternal allele in fetal brain and heart, and in adult brain. (PMID:7512861)
• A mouse model for Prader-Willi syndrome. Deletion of Snrpn gene and putative imprinting-centre is associated with absent expression of the imprinted genes Zfp127, Ndn and Ipw, and phenotypes similar to those found in Prader-Willi infants. (PMID:9590284)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Snrpn	ENSMUSG00000102252
rattus_norvegicus	Snrpn	ENSRNOG00000054391
rattus_norvegicus		ENSRNOG00000075074
caenorhabditis_elegans	snr-2	WBGENE00004915

Paralogs (1): SNRPB (ENSG00000125835)

Protein

Protein identifiers

Small nuclear ribonucleoprotein-associated protein N — P63162 (reviewed: P63162)

Alternative names: Sm protein D, Sm protein N, Tissue-specific-splicing protein

All UniProt accessions (4): P63162, J3KRY3, J3QLE5, X5DP00

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in tissue-specific alternative RNA processing events.

Subunit / interactions. Interacts with TDRD3.

Subcellular location. Nucleus.

Tissue specificity. Expressed in brain and lymphoblasts.

Miscellaneous. Encoded on a bicistronic transcript that code for two proteins, SNRPN and SNURF. Patients with the autoimmune disease systemic lupus erythematosus (SLE) have autoantibodies directed against some of the individual snRNP polypeptides. The most common autoantigen is called Sm. N bears Sm epitopes.

Similarity. Belongs to the snRNP SmB/SmN family.

Isoforms (2)

UniProt ID	Names	Canonical?
P63162-1	1	yes
P63162-2	2

RefSeq proteins (112): NP_001336383, NP_001336384, NP_001336385, NP_001336386, NP_001336387, NP_001336388, NP_001336389, NP_001336390, NP_001336391, NP_001336392, NP_001336393, NP_001336394, NP_001365178, NP_001365180, NP_001365181, NP_001365182, NP_001365183, NP_001365184, NP_001365185, NP_001365186, NP_001387563, NP_001387564, NP_001387565, NP_001387566, NP_001387567, NP_001387568, NP_001387569, NP_001387570, NP_001387572, NP_001387573, NP_001387575, NP_001387576, NP_001387578, NP_001387579, NP_001387581, NP_001387612, NP_001387613, NP_001387614, NP_001387615, NP_001387616, NP_001387617, NP_001387618, NP_001387619, NP_001387620, NP_001387621, NP_001387622, NP_001387623, NP_001387624, NP_001387625, NP_001387626, NP_001387627, NP_001387630, NP_001387631, NP_001387632, NP_001387633, NP_001387635, NP_001387637, NP_001387639, NP_001387641, NP_001387642, NP_001387644, NP_001387645, NP_001387646, NP_001387647, NP_001387648, NP_001387649, NP_001387650, NP_001387651, NP_001387652, NP_001387653, NP_001387654, NP_001387655, NP_001387656, NP_001387657, NP_001387658, NP_001387659, NP_001387660, NP_001387661, NP_001387662, NP_001387663, NP_001387664, NP_001387665, NP_001387666, NP_001387667, NP_001387668, NP_001387669, NP_001387670, NP_001387671, NP_001387672, NP_001387673, NP_001387674, NP_001387675, NP_001387676, NP_001387677, NP_001387682, NP_001387683, NP_001387684, NP_001387685, NP_001387686, NP_001387687, NP_001387688, NP_001387691, NP_001387692, NP_001387693, NP_001387694, NP_001387696, NP_001387697, NP_003088, NP_073716, NP_073717, NP_073718, NP_073719 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001163	Sm_dom_euk/arc	Domain
IPR010920	LSM_dom_sf	Homologous_superfamily
IPR017131	snRNP-assoc_SmB/SmN	Family
IPR047575	Sm	Domain

Pfam: PF01423

UniProt features (22 total): modified residue 8, repeat 5, compositionally biased region 2, sequence conflict 2, region of interest 2, chain 1, domain 1, splice variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
8TBP	X-RAY DIFFRACTION	3.13
5MF9	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P63162-F1	71.51	0.31

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): 108, 108, 108, 112, 112, 112, 147, 172

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-9770562	mRNA Polyadenylation
R-HSA-9918481	Dengue Virus-Host Interactions
R-HSA-9943411	CHD1 and CHD2 subfamily
R-HSA-72172	mRNA Splicing
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA
R-HSA-8953854	Metabolism of RNA

MSigDB gene sets: 495 (showing top): VALK_AML_WITH_FLT3_ITD, VERHAAK_AML_WITH_NPM1_MUTATED_DN, TGCGCANK_UNKNOWN, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, HSIAO_HOUSEKEEPING_GENES, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, YY1_Q6, BOHN_PRIMARY_IMMUNODEFICIENCY_SYNDROM_DN, chr15q11, MARTINEZ_RB1_TARGETS_UP, MUELLER_PLURINET, REACTOME_MRNA_3_END_PROCESSING, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_RNA_SPLICING, REACTOME_MRNA_SPLICING

GO Biological Process (2): mRNA splicing, via spliceosome (GO:0000398), RNA splicing (GO:0008380)

GO Molecular Function (3): RNA binding (GO:0003723), snRNP binding (GO:0070990), protein binding (GO:0005515)

GO Cellular Component (13): nucleoplasm (GO:0005654), spliceosomal complex (GO:0005681), U5 snRNP (GO:0005682), U1 snRNP (GO:0005685), U2 snRNP (GO:0005686), U4 snRNP (GO:0005687), cytoplasm (GO:0005737), small nuclear ribonucleoprotein complex (GO:0030532), U4/U6 x U5 tri-snRNP complex (GO:0046540), U2-type prespliceosome (GO:0071004), catalytic step 2 spliceosome (GO:0071013), nucleus (GO:0005634), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
mRNA Splicing	1
mRNA 3’-end processing	1
Dengue Virus Infection	1
CHD chromatin remodelers	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
spliceosomal snRNP complex	4
cellular anatomical structure	2
nuclear protein-containing complex	2
ribonucleoprotein complex	2
U5 snRNP	2
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
RNA processing	1
nucleic acid binding	1
ribonucleoprotein complex binding	1
binding	1
nuclear lumen	1
intracellular anatomical structure	1
Sm-like protein family complex	1
U4/U6 snRNP	1
spliceosomal tri-snRNP complex	1
U2-type spliceosomal complex	1
U1 snRNP	1
U2 snRNP	1
prespliceosome	1
Prp19 complex	1
spliceosomal complex	1
catalytic complex	1
intracellular membrane-bounded organelle	1
protein-containing complex	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

70 interactions, top by confidence:

A	B	Type	Score
MAPK14	RPS6KA4	psi-mi:“MI:0914”(association)	0.870
SNRPE	GEMIN2	psi-mi:“MI:0914”(association)	0.770
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
SNRPG	GEMIN2	psi-mi:“MI:0914”(association)	0.710
CD2BP2	SNRPN	psi-mi:“MI:0407”(direct interaction)	0.690
SNRPN	CD2BP2	psi-mi:“MI:0407”(direct interaction)	0.690
SNRPB	PRMT5	psi-mi:“MI:0914”(association)	0.670
SNRPA1	U2SURP	psi-mi:“MI:0914”(association)	0.640
SNRPA1	HTATSF1	psi-mi:“MI:0914”(association)	0.640
YES1	HSP90AB1	psi-mi:“MI:0914”(association)	0.560
SNRPE	PRMT5	psi-mi:“MI:0914”(association)	0.530
SNRPN	PRMT5	psi-mi:“MI:0914”(association)	0.530
SNRPE	SNRPGP15	psi-mi:“MI:0914”(association)	0.530
SNRPF	SNRPGP15	psi-mi:“MI:0914”(association)	0.530
SNRPN	CFTR	psi-mi:“MI:0915”(physical association)	0.520
CFTR	SNRPN	psi-mi:“MI:0915”(physical association)	0.520
SNRPN	Dlg4	psi-mi:“MI:0407”(direct interaction)	0.440
Sf3a1	U2SURP	psi-mi:“MI:0915”(physical association)	0.400
Snu13		psi-mi:“MI:0915”(physical association)	0.400
SNRPN	CLK2	psi-mi:“MI:0915”(physical association)	0.400
SNRPN	RBFOX1	psi-mi:“MI:0915”(physical association)	0.370
SNRPN	CTBP1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (303): SNRPN (Affinity Capture-MS), SNRPN (Affinity Capture-MS), SNRPN (Affinity Capture-MS), SNRPN (Affinity Capture-MS), SNRPN (Affinity Capture-MS), SNRPN (Affinity Capture-MS), SNRPN (Synthetic Lethality), SNRPN (Affinity Capture-MS), SNRPN (Affinity Capture-MS), SNRPN (Affinity Capture-MS), SNRPN (Affinity Capture-MS), SNRPN (Affinity Capture-MS), SNRPA1 (Affinity Capture-MS), SART3 (Affinity Capture-MS), SNRPN (Affinity Capture-MS)

ESM2 similar proteins: D4A055, O00305, O14639, O70133, P14678, P17136, P17427, P18484, P27048, P30626, P48444, P62314, P62315, P62318, P62320, P62323, P63162, P63163, P63164, Q08211, Q13330, Q16514, Q17QN3, Q28141, Q2HJH9, Q3T174, Q3ZC10, Q4R5F6, Q58DW4, Q5R4U9, Q5R6I0, Q5R874, Q5RA77, Q5XIT1, Q5XJY5, Q60HD3, Q62599, Q66H80, Q6P069, Q6PER3

Diamond homologs: A1CE19, A1DM27, A4FUI2, A4RQ29, A5DRQ6, A6R363, A6S5C9, A7F5M4, A7UXE4, A8MWD9, A8NHT8, B0DWN3, B6YUU5, C5A1H1, C6A1T2, O22823, O26745, O29386, O42978, O59734, O74016, O74499, O74966, P0CR24, P0CR25, P14678, P17136, P27048, P34659, P40089, P40204, P54999, P57670, P57743, P62306, P62307, P62308, P62309, P62310, P62311

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
PPM1G	“up-regulates quantity by stabilization”	SNRPN	dephosphorylation
MIB1	“down-regulates quantity by destabilization”	SNRPN	ubiquitination
TDRD3	unknown	SNRPN	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 56 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	5	77.4×	1e-07
snRNP Assembly	7	36.1×	3e-08
mRNA Splicing - Minor Pathway	6	32.8×	6e-07
SARS-CoV-2 modulates host translation machinery	6	32.8×	6e-07
mRNA Splicing	11	29.5×	2e-11
CHD1 and CHD2 subfamily	9	23.9×	5e-09
mRNA Polyadenylation	11	23.6×	6e-11
Processing of Capped Intron-Containing Pre-mRNA	11	22.0×	1e-10

GO biological processes:

GO term	Partners	Fold	FDR
U2-type prespliceosome assembly	9	112.3×	2e-14
spliceosomal snRNP assembly	9	104.6×	2e-14
mRNA splicing, via spliceosome	12	22.0×	3e-11
RNA splicing	10	17.6×	2e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	4
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
442188	GRCh37/hg19 15q11.2(chr15:25196959-25200389)x1	Likely pathogenic

SpliceAI

4371 predictions. Top by Δscore:

Variant	Effect	Δscore
15:24886513:CAGAT:C	acceptor_loss	1.0000
15:24886514:A:AG	acceptor_gain	1.0000
15:24886514:AGA:A	acceptor_loss	1.0000
15:24886515:G:C	acceptor_loss	1.0000
15:24886515:G:GA	acceptor_gain	1.0000
15:24886515:GAT:G	acceptor_gain	1.0000
15:24886515:GATA:G	acceptor_gain	1.0000
15:24886515:GATAC:G	acceptor_gain	1.0000
15:24886586:CCAGG:C	donor_loss	1.0000
15:24886587:CAGG:C	donor_loss	1.0000
15:24886589:GGTA:G	donor_loss	1.0000
15:24886590:GTAA:G	donor_loss	1.0000
15:24919996:A:AG	acceptor_gain	1.0000
15:24919997:A:G	acceptor_gain	1.0000
15:24962106:T:A	acceptor_gain	1.0000
15:24962106:T:TA	acceptor_gain	1.0000
15:24962110:TCA:T	acceptor_loss	1.0000
15:24962112:A:AG	acceptor_gain	1.0000
15:24962112:A:AT	acceptor_loss	1.0000
15:24962112:A:C	acceptor_loss	1.0000
15:24962112:AG:A	acceptor_gain	1.0000
15:24962112:AGG:A	acceptor_gain	1.0000
15:24962113:G:A	acceptor_gain	1.0000
15:24962113:G:C	acceptor_loss	1.0000
15:24962113:G:GA	acceptor_gain	1.0000
15:24962113:GGG:G	acceptor_gain	1.0000
15:24962113:GGGA:G	acceptor_gain	1.0000
15:24962113:GGGAT:G	acceptor_gain	1.0000
15:24962205:CAAGA:C	donor_gain	1.0000
15:24962206:AAGA:A	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000004065 (15:24878940 T>C), RS1000009692 (15:24845265 C>A), RS1000016488 (15:24978204 C>T), RS1000023170 (15:24860250 C>T), RS1000032737 (15:24822504 G>T), RS1000033610 (15:24878771 A>G), RS1000038652 (15:24939089 A>G), RS1000039655 (15:24971956 A>G), RS1000046969 (15:24883385 T>C), RS1000060693 (15:24900909 A>G), RS1000073488 (15:24839678 C>T), RS1000107776 (15:24912660 G>A,C), RS1000110964 (15:24876700 A>C), RS1000113433 (15:24835837 AT>A,ATT), RS1000121589 (15:24895385 G>A)

Disease associations

OMIM: gene MIM:182279 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
Prader-Willi syndrome	Definitive	Autosomal dominant

Mondo (1): Prader-Willi syndrome (MONDO:0008300)

Orphanet (0):

HPO phenotypes

185 total (30 of 185 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000044	Hypogonadotropic hypogonadism
HP:0000046	Small scrotum
HP:0000060	Clitoral hypoplasia
HP:0000064	Hypoplastic labia minora
HP:0000077	Abnormality of the kidney
HP:0000154	Wide mouth
HP:0000158	Macroglossia
HP:0000175	Cleft palate
HP:0000193	Bifid uvula
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000232	Everted lower lip vermilion
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000278	Retrognathia
HP:0000303	Mandibular prognathia
HP:0000316	Hypertelorism
HP:0000327	Hypoplasia of the maxilla
HP:0000341	Narrow forehead
HP:0000347	Micrognathia
HP:0000384	Preauricular skin tag
HP:0000446	Narrow nasal bridge
HP:0000448	Prominent nose
HP:0000455	Broad nasal tip
HP:0000463	Anteverted nares
HP:0000470	Short neck
HP:0000486	Strabismus
HP:0000490	Deeply set eye

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST000106_2	Pulmonary function	1.000000e-06
GCST001762_231	Obesity-related traits	2.000000e-06
GCST002129_7	Periodontitis (DPAL)	6.000000e-06
GCST004162_35	Carotid plaque burden	5.000000e-06
GCST007130_5	Cerebrospinal fluid t-tau:AB1-42 ratio	5.000000e-09
GCST008174_5	Aspartate aminotransferase levels	3.000000e-06
GCST008442_2	Periodontal disease related phenotype (PCT5)	4.000000e-08
GCST009525_4	Panic disorder	3.000000e-06

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0003892	pulmonary function measurement
EFO:0004730	hormone measurement
EFO:0006501	carotid plaque build
EFO:0007708	t-tau:beta-amyloid 1-42 ratio measurement
EFO:0004736	aspartate aminotransferase measurement
EFO:0007780	periodontal measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D011218	Prader-Willi Syndrome	C10.597.606.360.690; C16.131.077.730; C16.131.260.700; C16.320.180.700; C16.320.447.500; C18.654.726.750.500.740

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, affects expression, decreases methylation, affects cotreatment	3
trichostatin A	affects cotreatment, increases expression	3
methylmercuric chloride	decreases expression, affects cotreatment	2
sodium arsenite	decreases expression	2
entinostat	affects expression, affects cotreatment	2
Benzo(a)pyrene	affects methylation, decreases methylation, increases methylation	2
Tobacco Smoke Pollution	decreases expression, increases methylation	2
Valproic Acid	decreases expression	2
bisphenol F	increases expression, affects cotreatment	1
testosterone enanthate	affects expression	1
propionaldehyde	increases expression	1
domiphen	affects response to substance	1
testosterone undecanoate	affects cotreatment, decreases expression	1
terbufos	increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	decreases expression	1
aflatoxin B2	increases methylation	1
monomethylpropion	increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, affects expression, decreases expression, increases expression	1
dorsomorphin	affects cotreatment, affects expression, decreases expression, increases expression	1
bisphenol S	increases methylation	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Vorinostat	decreases expression	1
Atenolol	increases expression	1
Chromium	decreases expression	1
Demecolcine	decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1

Cellosaurus cell lines

2 cell lines: 1 transformed cell line, 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_C7L4	GM27891	Transformed cell line	Female
CVCL_F0Z9	GM29378	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01298180	PHASE4	COMPLETED	Is There a Sensibility Increased in the Growth Hormone at Child With Prader-Willi Syndrome?
NCT01542242	PHASE4	TERMINATED	Liraglutide Use in Prader-Willi Syndrome
NCT03031626	PHASE4	COMPLETED	Oxygen Versus Medical Air for Treatment of CSA in Prader Will Syndrome
NCT03616509	PHASE4	COMPLETED	GH in Adults With PWS, Effect on Hypotonia Evaluated by Functional MRI, Relationship With Strength and Body Composition
NCT04066088	PHASE4	WITHDRAWN	Dose Clinical Trial of Guanfacine Extended Release for the Reduction of Aggression and Self-injuries Behavior Associated With Prader-Willi Syndrome
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT06901245	PHASE4	RECRUITING	Tirzepatide in PWS, HO and GNSO
NCT00175305	PHASE3	TERMINATED	Prader-Willi Syndrome and Appetite
NCT00444964	PHASE3	COMPLETED	Growth Hormone Use in Adults With Prader-Willi Syndrome
NCT00603109	PHASE3	TERMINATED	Effect of Rimonabant on Weight Gain and Body Composition in Adults With Prader Willi Syndrome
NCT02179151	PHASE3	TERMINATED	Double-Blind, Placebo Controlled, Phase 3 Trial of ZGN-440 (Beloranib) in Obese Subjects With Prader-Willi Syndrome
NCT02204163	PHASE3	COMPLETED	Study to Assess the Efficacy and Safety of Eutropin in Prader-Willi Syndrome
NCT02810483	PHASE3	TERMINATED	Study of the Efficacy of Topiramate in Patients With Prader Willi Syndrome Over 8 Weeks
NCT03440814	PHASE3	COMPLETED	A Study of Diazoxide Choline in Patients With Prader-Willi Syndrome
NCT03554031	PHASE3	UNKNOWN	A Study to Evaluate the Efficacy and Safety of Recombinant Human Growth Hormone Injection in Patients With Prader-Willi Syndrome
NCT03649477	PHASE3	COMPLETED	Phase 3 Study of Intranasal Carbetocin (LV-101) in Patients With Prader-Willi Syndrome
NCT03714373	PHASE3	COMPLETED	Open-Label Extension Study of DCCR in PWS Followed by Double-Blind, Placebo-Controlled, Randomized Withdrawal Period
NCT04086810	PHASE3	WITHDRAWN	An Open-Label Study of DCCR Tablet in Patients With PWS
NCT04283578	PHASE3	COMPLETED	Oxytocin Treatment in Neonates and Infants With Prader-Willi Syndrome
NCT04697381	PHASE3	COMPLETED	Study of the Efficacy and Safety of Somatropin in Japanese Participants With PWS
NCT05032326	PHASE3	UNKNOWN	Long-term Interventional Follow-up Study of Children With Prader-Willi Syndrome Included in the OTBB3 Clinical Trial
NCT05387798	PHASE3	WITHDRAWN	A Phase 3 Extension Study of RAD011 (Cannabidiol Oral Solution) in Patients With Prader-Willi Syndrome
NCT05701774	PHASE3	ACTIVE_NOT_RECRUITING	Open-Label Extension Study of DCCR in Patients With Prader-Willi Syndrome
NCT06144645	PHASE3	ACTIVE_NOT_RECRUITING	A Clinical Evaluation of Non-Invasive Vagus Nerve Stimulation for Temper Outbursts in People With PWS
NCT06366464	PHASE3	RECRUITING	A Study of Pitolisant in Patients With Prader-Willi Syndrome
NCT06828861	PHASE3	SUSPENDED	ARD-101 for Treatment of PWS: The Hunger Elimination or Reduction Objective Trial
NCT07197034	PHASE3	SUSPENDED	The Hunger Elimination or Reduction Objective (HERO ) Open -Label Extension (OLE) Trial
NCT07219485	PHASE3	ENROLLING_BY_INVITATION	A Study of Pitolisant in Participants With Prader-Willi Syndrome
NCT01038570	PHASE2	COMPLETED	Comparative Study Between Prader-Willi Patients Who Take Oxytocin Versus Placebo
NCT01818921	PHASE2	COMPLETED	An Efficacy, Safety, and Pharmacokinetics Study of Beloranib in Obese Subjects With Prader-Willi Syndrome
NCT02311673	PHASE2	COMPLETED	Phase 2 Trial to Evaluate Safety and Efficacy of Setmelanotide (RM-493) in Obese Participants With Prader-Willi Syndrome
NCT02629991	PHASE2	COMPLETED	Oxytocin vs. Placebo for the Treatment Hyperphagia in Children and Adolescents With Prader-Willi Syndrome
NCT02844933	PHASE2	TERMINATED	Cannabidiol Oral Solution for the Treatment of Patients With Prader-Willi Syndrome
NCT02893618	PHASE2	UNKNOWN	A 5 Treatment Period Pharmacokinetic Study Evaluating Dose Proportionality and Food Effects of Diazoxide Choline Controlled-Release Tablet (DCCR)
NCT03197662	PHASE2	COMPLETED	Intranasal Oxytocin vs. Placebo for the Treatment of Hyperphagia in Prader-Willi Syndrome
NCT03274856	PHASE2	COMPLETED	A Study of GLWL-01 in Patients With Prader-Willi Syndrome
NCT03458416	PHASE2	TERMINATED	A Study to Assess the Long-Term Safety of Pharmaceutical Grade Synthetic Cannabidiol Oral Solution in Participants With Prader-Willi Syndrome
NCT03831425	PHASE2	WITHDRAWN	Mitochondrial Complex I Dysfunction in PWS
NCT03848481	PHASE2	TERMINATED	CBDV vs Placebo in Children and Adults up to Age 30 With Prader-Willi Syndrome (PWS)
NCT04257929	PHASE2	COMPLETED	A Phase 2 Study to Evaluate the Safety and Efficacy of Pitolisant in Patients With Prader-Willi Syndrome, Followed by an Open Label Extension