SNRPE

Summary

SNRPE (small nuclear ribonucleoprotein polypeptide E, HGNC:11161) is a protein-coding gene on chromosome 1q32.1, encoding Small nuclear ribonucleoprotein E (P62304). Plays a role in pre-mRNA splicing as a core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome. It is a common-essential gene (DepMap: required in 100.0% of cancer cell lines).

The protein encoded by this gene is a core component of U small nuclear ribonucleoproteins, which are key components of the pre-mRNA processing spliceosome. The encoded protein plays a role in the 3’ end processing of histone transcripts. This protein is one of the targets in the autoimmune disease systemic lupus erythematosus, and mutations in this gene have been associated with hypotrichosis. Several pseudogenes of this gene have been identified.

Source: NCBI Gene 6635 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hypotrichosis 11 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 25 total — 2 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 11
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• MANE Select transcript: NM_003094

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11161
Approved symbol	SNRPE
Name	small nuclear ribonucleoprotein polypeptide E
Location	1q32.1
Locus type	gene with protein product
Status	Approved
Aliases	Sm-E
Ensembl gene	ENSG00000182004
Ensembl biotype	protein_coding
OMIM	128260
Entrez	6635

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000367208, ENST00000414487, ENST00000469451, ENST00000470492, ENST00000475035, ENST00000483099, ENST00000867899, ENST00000917032, ENST00000917033

RefSeq mRNA: 4 — MANE Select: NM_003094 NM_001304464, NM_001328637, NM_001328638, NM_003094

CCDS: CCDS30979

Canonical transcript exons

ENST00000414487 — 5 exons

Exon	Start	End
ENSE00001220488	203861599	203861713
ENSE00001443815	203862196	203862222
ENSE00001794044	203869877	203871152
ENSE00003567113	203863663	203863725
ENSE00003616226	203865041	203865119

Expression profiles

Bgee: expression breadth ubiquitous, 175 present calls, max score 99.24.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 71.0923 / max 1675.4200, expressed in 1813 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
7946	63.4438	1813
7947	3.8710	1368
7948	3.7774	957

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	99.24	gold quality
ventricular zone	UBERON:0003053	98.82	gold quality
cortical plate	UBERON:0005343	98.72	gold quality
left ovary	UBERON:0002119	98.08	gold quality
adrenal tissue	UBERON:0018303	97.81	gold quality
right ovary	UBERON:0002118	97.75	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.61	gold quality
body of pancreas	UBERON:0001150	97.59	gold quality
endocervix	UBERON:0000458	97.57	gold quality
ectocervix	UBERON:0012249	97.45	gold quality
body of uterus	UBERON:0009853	97.44	gold quality
mucosa of transverse colon	UBERON:0004991	97.42	gold quality
right adrenal gland	UBERON:0001233	97.38	gold quality
islet of Langerhans	UBERON:0000006	97.29	gold quality
right adrenal gland cortex	UBERON:0035827	97.24	gold quality
vermiform appendix	UBERON:0001154	97.23	gold quality
left adrenal gland	UBERON:0001234	97.23	gold quality
left adrenal gland cortex	UBERON:0035825	97.23	gold quality
left uterine tube	UBERON:0001303	97.22	gold quality
metanephros cortex	UBERON:0010533	97.09	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	96.99	gold quality
granulocyte	CL:0000094	96.90	gold quality
calcaneal tendon	UBERON:0003701	96.90	gold quality
body of stomach	UBERON:0001161	96.89	gold quality
stromal cell of endometrium	CL:0002255	96.87	gold quality
left coronary artery	UBERON:0001626	96.66	gold quality
minor salivary gland	UBERON:0001830	96.61	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.59	gold quality
tibial nerve	UBERON:0001323	96.56	gold quality
transverse colon	UBERON:0001157	96.53	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	138.42
E-HCAD-13	yes	20.06
E-CURD-112	yes	19.06
E-CURD-122	yes	17.74
E-MTAB-10042	yes	14.25
E-HCAD-1	yes	12.10
E-MTAB-9801	yes	6.22
E-MTAB-9388	no	1526.25
E-CURD-79	no	866.62
E-MTAB-8271	no	10.55
E-GEOD-93593	no	6.37
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

40 targeting SNRPE, 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-4692	100.00	67.32	2066
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-4671-3P	99.88	72.46	1045
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-802	99.61	67.70	1254
HSA-MIR-892A	99.54	68.16	1141
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-1324	99.46	66.57	1302
HSA-MIR-4762-3P	99.43	69.72	2363
HSA-MIR-6507-5P	99.36	70.46	2524
HSA-MIR-1276	99.36	68.18	1642
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-4520-2-3P	99.14	69.28	1009
HSA-MIR-5001-3P	98.91	67.28	1394
HSA-MIR-320A-5P	98.88	66.75	1248
HSA-MIR-3192-3P	98.62	65.80	970

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 100.0% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 5)

• In the SME intron, the position of the branchpoint A residue within the region base paired with U12 differs from that in P120 and XTF. (PMID:12022225)
• Mutations in SNRPE, which encodes a core protein of the spliceosome, cause autosomal-dominant hypotrichosis simplex (PMID:23246290)
• Overexpression of SNRPE is associated with highly aggressive breast cancers. (PMID:23358685)
• Study reports de novo heterozygous missense mutation within the SNRPE gene disturbing appropriate spatiotemporal gene expression in the brain through aberrant mRNA splicing, and likely to cause the microcephaly phenotype. (PMID:31671093)
• Oncofetal SNRPE promotes HCC tumorigenesis by regulating the FGFR4 expression through alternative splicing. (PMID:38796598)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	snrpe	ENSDARG00000033175
mus_musculus	Snrpe	ENSMUSG00000090553
rattus_norvegicus		ENSRNOG00000063412
drosophila_melanogaster	SmE	FBGN0261790
caenorhabditis_elegans		WBGENE00004919

Protein

Protein identifiers

Small nuclear ribonucleoprotein E — P62304 (reviewed: P62304)

Alternative names: Sm protein E

All UniProt accessions (2): A6NHK2, P62304

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in pre-mRNA splicing as a core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome. Component of both the pre-catalytic spliceosome B complex and activated spliceosome C complexes. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs. As part of the U7 snRNP it is involved in histone 3’-end processing.

Subunit / interactions. Core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome. Most spliceosomal snRNPs contain a common set of Sm proteins, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP. Component of the U1 snRNP. The U1 snRNP is composed of the U1 snRNA and the 7 core Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG, and at least three U1 snRNP-specific proteins SNRNP70/U1-70K, SNRPA/U1-A and SNRPC/U1-C. Component of the U4/U6-U5 tri-snRNP complex composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF, SNRPG, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39, plus LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8. Component of the U7 snRNP complex, or U7 Sm protein core complex, that is composed of the U7 snRNA and at least LSM10, LSM11, SNRPB, SNRPD3, SNRPE, SNRPF and SNRPG; the complex does not contain SNRPD1 and SNRPD2. Component of the minor spliceosome, which splices U12-type introns. Part of the SMN-Sm complex that contains SMN1, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8, STRAP/UNRIP and the Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG; catalyzes core snRNPs assembly. Forms a 6S pICln-Sm complex composed of CLNS1A/pICln, SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG; ring-like structure where CLNS1A/pICln mimics additional Sm proteins and which is unable to assemble into the core snRNP. Interacts with SMN1; the interaction is direct. Interacts with GEMIN2 (via N-terminus); the interaction is direct. Interacts with SNRPF; the interaction is direct. Interacts with SNRPG; the interaction is direct.

Subcellular location. Cytoplasm. Cytosol. Nucleus.

Tissue specificity. Widely expressed. In scalp skin, it is present in the hair follicle, the epidermis, and the dermis.

Disease relevance. Hypotrichosis 11 (HYPT11) [MIM:615059] A form of hypotrichosis, a condition characterized by the presence of less than the normal amount of hair and abnormal hair follicles and shafts, which are thin and atrophic. The extent of scalp and body hair involvement can be very variable, within as well as between families. HYPT11 is an autosomal dominant form characterized by scanty or absent eyebrows and a highly variable degree of alopecia since birth, ranging from slight thinning of scalp and axillary hair to complete loss of scalp and body hair. Pubic hair remains mainly unaffected. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. Patients with systemic lupus erythematosus produce antibodies which interact with snRNP proteins.

Similarity. Belongs to the snRNP Sm proteins family.

RefSeq proteins (4): NP_001291393, NP_001315566, NP_001315567, NP_003085* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001163	Sm_dom_euk/arc	Domain
IPR010920	LSM_dom_sf	Homologous_superfamily
IPR027078	snRNP-E	Family
IPR047575	Sm	Domain

Pfam: PF01423

UniProt features (10 total): strand 5, helix 2, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

84 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
4F7U	X-RAY DIFFRACTION	1.9
5XJL	X-RAY DIFFRACTION	2.5
7EVO	ELECTRON MICROSCOPY	2.5
5XJU	X-RAY DIFFRACTION	2.58
8H6L	ELECTRON MICROSCOPY	2.6
8H6K	ELECTRON MICROSCOPY	2.7
8HK1	ELECTRON MICROSCOPY	2.7
8C6J	ELECTRON MICROSCOPY	2.8
9NH5	ELECTRON MICROSCOPY	2.82
9NH6	ELECTRON MICROSCOPY	2.82
6ID1	ELECTRON MICROSCOPY	2.86
7DVQ	ELECTRON MICROSCOPY	2.89
6ID0	ELECTRON MICROSCOPY	2.9
5XJT	X-RAY DIFFRACTION	2.92
6QW6	ELECTRON MICROSCOPY	2.92
6ICZ	ELECTRON MICROSCOPY	3
7VPX	ELECTRON MICROSCOPY	3
8I0R	ELECTRON MICROSCOPY	3
8I0T	ELECTRON MICROSCOPY	3
8I0V	ELECTRON MICROSCOPY	3
9GCL	ELECTRON MICROSCOPY	3
4V98	X-RAY DIFFRACTION	3.1
7QTT	ELECTRON MICROSCOPY	3.1
8Q91	ELECTRON MICROSCOPY	3.1
5XJR	X-RAY DIFFRACTION	3.12
9N96	ELECTRON MICROSCOPY	3.18
6V4X	ELECTRON MICROSCOPY	3.2
8H6E	ELECTRON MICROSCOPY	3.2
8Q7Q	ELECTRON MICROSCOPY	3.2
8RC0	ELECTRON MICROSCOPY	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P62304-F1	90.98	0.83

Function

Pathways and Gene Ontology

Reactome pathways

23 pathways

ID	Pathway
R-HSA-111367	SLBP independent Processing of Histone Pre-mRNAs
R-HSA-191859	snRNP Assembly
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-72165	mRNA Splicing - Minor Pathway
R-HSA-73856	RNA Polymerase II Transcription Termination
R-HSA-77588	SLBP Dependent Processing of Replication-Dependent Histone Pre-mRNAs
R-HSA-9754678	SARS-CoV-2 modulates host translation machinery
R-HSA-9770562	mRNA Polyadenylation
R-HSA-9918481	Dengue Virus-Host Interactions
R-HSA-9943411	CHD1 and CHD2 subfamily
R-HSA-1643685	Disease
R-HSA-194441	Metabolism of non-coding RNA
R-HSA-5663205	Infectious disease
R-HSA-72172	mRNA Splicing
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-75067	Processing of Capped Intronless Pre-mRNA
R-HSA-8953854	Metabolism of RNA
R-HSA-9679506	SARS-CoV Infections
R-HSA-9694516	SARS-CoV-2 Infection
R-HSA-9705683	SARS-CoV-2-host interactions
R-HSA-9824446	Viral Infection Pathways

MSigDB gene sets: 299 (showing top): MODULE_151, GCM_NPM1, MORF_UBE2I, GOBP_NEGATIVE_REGULATION_OF_RNA_SPLICING, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, MORF_HDAC1, MORF_UBE2N, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, MORF_RAD21, MORF_HDAC2, RIZKI_TUMOR_INVASIVENESS_3D_DN, GOBP_RNA_METHYLATION, PATIL_LIVER_CANCER, PUJANA_CHEK2_PCC_NETWORK, MODULE_388

GO Biological Process (7): spliceosomal complex assembly (GO:0000245), spliceosomal snRNP assembly (GO:0000387), mRNA splicing, via spliceosome (GO:0000398), 7-methylguanosine cap hypermethylation (GO:0036261), U2-type prespliceosome assembly (GO:1903241), mRNA processing (GO:0006397), RNA splicing (GO:0008380)

GO Molecular Function (2): RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (23): nucleus (GO:0005634), nucleoplasm (GO:0005654), spliceosomal complex (GO:0005681), U5 snRNP (GO:0005682), U7 snRNP (GO:0005683), U2-type spliceosomal complex (GO:0005684), U1 snRNP (GO:0005685), U2 snRNP (GO:0005686), U4 snRNP (GO:0005687), U12-type spliceosomal complex (GO:0005689), telomerase holoenzyme complex (GO:0005697), cytosol (GO:0005829), small nuclear ribonucleoprotein complex (GO:0030532), methylosome (GO:0034709), pICln-Sm protein complex (GO:0034715), SMN-Sm protein complex (GO:0034719), U4/U6 x U5 tri-snRNP complex (GO:0046540), U2-type precatalytic spliceosome (GO:0071005), U2-type catalytic step 2 spliceosome (GO:0071007), precatalytic spliceosome (GO:0071011), catalytic step 2 spliceosome (GO:0071013), cytoplasm (GO:0005737), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
Metabolism of RNA	3
Processing of Capped Intronless Pre-mRNA	2
mRNA Splicing	2
Metabolism of non-coding RNA	1
RNA Polymerase II Transcription	1
SARS-CoV-2-host interactions	1
mRNA 3’-end processing	1
Dengue Virus Infection	1
CHD chromatin remodelers	1
Disease	1
Processing of Capped Intron-Containing Pre-mRNA	1
Gene expression (Transcription)	1
Viral Infection Pathways	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
spliceosomal snRNP complex	4
cytoplasm	4
nuclear protein-containing complex	3
ribonucleoprotein complex	3
spliceosomal complex	3
Sm-like protein family complex	3
mRNA splicing, via spliceosome	2
protein-RNA complex assembly	2
RNA processing	2
cellular anatomical structure	2
U2-type spliceosomal complex	2
U2 snRNP	2
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
RNA methylation	1
RNA capping	1
spliceosomal complex assembly	1
mRNA metabolic process	1
nucleic acid binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
small nuclear ribonucleoprotein complex	1
catalytic complex	1
methyltransferase complex	1
SMN complex	1
U5 snRNP	1
U4/U6 snRNP	1
spliceosomal tri-snRNP complex	1
U1 snRNP	1
U4/U6 x U5 tri-snRNP complex	1
precatalytic spliceosome	1
U6 snRNP	1
catalytic step 2 spliceosome	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

173 interactions, top by confidence:

A	B	Type	Score
SMN1	GEMIN2	psi-mi:“MI:0914”(association)	0.960
SNRPE	SNRPF	psi-mi:“MI:0915”(physical association)	0.940
IFIT1	IFIT3	psi-mi:“MI:0914”(association)	0.920
SNRPG	SNRPE	psi-mi:“MI:0915”(physical association)	0.870
SNRPE	SNRPG	psi-mi:“MI:0915”(physical association)	0.870
SNRPB	SNRNP70	psi-mi:“MI:0915”(physical association)	0.830
CLNS1A	PRMT5	psi-mi:“MI:0914”(association)	0.830
IFIT2	IFIT3	psi-mi:“MI:0914”(association)	0.780
CLNS1A	SNRPE	psi-mi:“MI:0914”(association)	0.770
CLNS1A	SNRPE	psi-mi:“MI:0915”(physical association)	0.770
GEMIN2	SNRPE	psi-mi:“MI:0914”(association)	0.770
GEMIN2	SNRPE	psi-mi:“MI:0915”(physical association)	0.770
GEMIN5	SNRPE	psi-mi:“MI:0915”(physical association)	0.770
SNRPE	GEMIN2	psi-mi:“MI:0914”(association)	0.770
GEMIN6	SNRPE	psi-mi:“MI:0407”(direct interaction)	0.760
LSM5	SNRPE	psi-mi:“MI:0915”(physical association)	0.740

BioGRID (546): SNRPE (Affinity Capture-MS), SNRPE (Affinity Capture-MS), SNRPE (Affinity Capture-MS), SNRPE (Affinity Capture-RNA), SNRPE (Co-fractionation), SNRPE (Co-fractionation), SNRPE (Co-fractionation), SNRPE (Co-fractionation), SNRPE (Co-fractionation), SNRPE (Co-fractionation), SNRPE (Co-fractionation), SNRPE (Co-fractionation), SNRPE (Co-fractionation), SNRPE (Co-fractionation), SNRPE (Proximity Label-MS)

ESM2 similar proteins: A0A324, A1XQR9, A4FUI2, A5JSS2, A6MZM2, G1SHQ2, O09167, O14602, O35900, O60739, P20280, P25800, P41567, P46778, P47813, P48024, P49666, P51971, P61220, P62303, P62304, P62305, P62308, P62309, Q09028, Q0D5W6, Q0P5B3, Q2KIA3, Q3B8H4, Q3ZBL0, Q4R4X9, Q503U0, Q5E938, Q5RA42, Q5RBW7, Q5RFF4, Q60872, Q60972, Q6GVM3, Q6QN05

Diamond homologs: A1XQR9, A4FUI2, A8MWD9, A8XDT0, C6A1T2, O26745, P40089, P62303, P62304, P62305, P62322, Q0W8R9, Q12330, Q12U30, Q2HJH0, Q54RX0, Q5R628, Q7ZUG0, Q9FKB0, Q9N4G9, Q9USZ3, Q9VLV5, Q9VXE0, Q9XTU6, Q9Y4Y9, Q9YEQ5, O29386, O74966, O82221, P24715, P40204, P47017, P53905, P62308, P62309, P62312, P62313, Q0UWI9, Q3ZBL0, Q465S1

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
SNRPE	“form complex”	“U4/U6.U5 snRNP complex”	binding
SNRPE	“form complex”	“U2 snRNP complex”	binding
SNRPE	“form complex”	“U1 snRNP complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 165 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Metabolism of non-coding RNA	8	38.7×	7e-10
mRNA decay by 5’ to 3’ exoribonuclease	6	34.9×	4e-07
mRNA Splicing	30	25.1×	2e-32
Processing of Capped Intron-Containing Pre-mRNA	33	20.7×	1e-32
snRNP Assembly	12	19.4×	7e-11
mRNA Splicing - Major Pathway	41	17.1×	3e-37
mRNA Splicing - Minor Pathway	10	17.1×	1e-08
SARS-CoV-2 modulates host translation machinery	10	17.1×	1e-08

GO biological processes:

GO term	Partners	Fold	FDR
spliceosomal snRNP assembly	17	66.8×	1e-25
U2-type prespliceosome assembly	12	50.6×	7e-16
spliceosomal tri-snRNP complex assembly	5	38.0×	2e-05
spliceosomal complex assembly	9	36.6×	3e-10
mRNA cis splicing, via spliceosome	5	33.5×	3e-05
mRNA splicing, via spliceosome	44	27.2×	7e-49
RNA splicing, via transesterification reactions	5	21.1×	3e-04
intrinsic apoptotic signaling pathway	6	14.5×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	6
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
3066048	NM_003094.4(SNRPE):c.221T>C (p.Leu74Pro)	Pathogenic
39506	NM_003094.4(SNRPE):c.133G>A (p.Gly45Ser)	Pathogenic
4278382	NM_003094.4(SNRPE):c.277_278insTTGT (p.Ter93PheextTer?)	Likely pathogenic

SpliceAI

670 predictions. Top by Δscore:

Variant	Effect	Δscore
1:203869871:TTGCA:T	acceptor_loss	1.0000
1:203869872:TGCAG:T	acceptor_loss	1.0000
1:203869873:GCAGG:G	acceptor_loss	1.0000
1:203869874:CAG:C	acceptor_loss	1.0000
1:203869875:A:AG	acceptor_gain	1.0000
1:203869875:A:T	acceptor_loss	1.0000
1:203869876:G:GG	acceptor_gain	1.0000
1:203861727:G:GT	donor_gain	0.9900
1:203861735:GAC:G	donor_gain	0.9900
1:203861846:G:GT	donor_gain	0.9900
1:203861850:A:T	donor_gain	0.9900
1:203863657:TTTCA:T	acceptor_loss	0.9900
1:203863658:TTCA:T	acceptor_loss	0.9900
1:203863659:TCA:T	acceptor_loss	0.9900
1:203863660:CAGA:C	acceptor_loss	0.9900
1:203863661:A:AG	acceptor_gain	0.9900
1:203863662:G:GG	acceptor_gain	0.9900
1:203863662:G:GT	acceptor_loss	0.9900
1:203863662:GA:G	acceptor_gain	0.9900
1:203863722:CATTG:C	donor_loss	0.9900
1:203863723:ATTG:A	donor_loss	0.9900
1:203863724:TT:T	donor_gain	0.9900
1:203863725:TG:T	donor_loss	0.9900
1:203863726:G:GA	donor_loss	0.9900
1:203863726:G:GG	donor_gain	0.9900
1:203863727:TG:T	donor_loss	0.9900
1:203863728:G:GT	donor_loss	0.9900
1:203863729:AGT:A	donor_loss	0.9900
1:203865035:TTCTA:T	acceptor_loss	0.9900
1:203865036:TCTA:T	acceptor_loss	0.9900

AlphaMissense

604 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:203861708:C:T	P17S	1.000
1:203861709:C:A	P17H	1.000
1:203861709:C:T	P17L	1.000
1:203861712:T:A	I18N	1.000
1:203862200:T:C	L20P	1.000
1:203862205:T:A	F22I	1.000
1:203862205:T:C	F22L	1.000
1:203862205:T:G	F22V	1.000
1:203862206:T:C	F22S	1.000
1:203862206:T:G	F22C	1.000
1:203862207:C:A	F22L	1.000
1:203862207:C:G	F22L	1.000
1:203862209:G:C	R23T	1.000
1:203862209:G:T	R23I	1.000
1:203862215:T:C	L25S	1.000
1:203863681:T:A	W34R	1.000
1:203863681:T:C	W34R	1.000
1:203863714:G:A	G45S	1.000
1:203863714:G:C	G45R	1.000
1:203863714:G:T	G45C	1.000
1:203863715:G:A	G45D	1.000
1:203863715:G:T	G45V	1.000
1:203863721:T:A	I47N	1.000
1:203865041:G:C	G49R	1.000
1:203865042:G:A	G49D	1.000
1:203865042:G:T	G49V	1.000
1:203865044:T:A	F50I	1.000
1:203865044:T:C	F50L	1.000
1:203865044:T:G	F50V	1.000
1:203865045:T:C	F50S	1.000

dbSNP variants (sampled 300 via entrez): RS1000040101 (1:203864432 C>A), RS1000066757 (1:203868587 G>T), RS1000672610 (1:203869726 A>C), RS1001212262 (1:203870141 G>A,C), RS1002093683 (1:203868949 G>A), RS1002263568 (1:203862851 T>C), RS1002269985 (1:203870506 C>G), RS1002378211 (1:203863195 G>A), RS1002544641 (1:203864496 A>G), RS1002654292 (1:203869232 C>G), RS1002766192 (1:203866098 A>C), RS1002820837 (1:203859728 C>T), RS1002915827 (1:203860045 T>C), RS1002980508 (1:203860208 G>A), RS1003054240 (1:203860417 A>G)

Disease associations

OMIM: gene MIM:128260 | disease phenotypes: MIM:615059, MIM:192500

GenCC curated gene-disease

Disease	Classification	Inheritance
hypotrichosis 11	Strong	Autosomal dominant
hypotrichosis simplex	Supportive	Autosomal dominant

Mondo (3): hypotrichosis 11 (MONDO:0014027), long QT syndrome 1 (MONDO:0100316), hypotrichosis simplex (MONDO:0018914)

Orphanet (3): Hypotrichosis simplex (Orphanet:55654), Romano-Ward syndrome (Orphanet:101016), Congenital long QT syndrome (Orphanet:768)

HPO phenotypes

11 total (11 of 11 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000653	Sparse eyelashes
HP:0001596	Alopecia
HP:0002209	Sparse scalp hair
HP:0002221	Absent axillary hair
HP:0002231	Sparse body hair
HP:0002289	Alopecia universalis
HP:0008070	Sparse hair
HP:0045075	Sparse eyebrow
HP:0100840	Aplasia/Hypoplasia of the eyebrow
HP:0200102	Sparse or absent eyelashes

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006661_122	Male-pattern baldness	1.000000e-15
GCST008359_1	Response to cognitive-behavioural therapy in anxiety disorder	7.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007820	cognitive behavioural therapy

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C537160	Hypotrichosis simplex (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725028 (SINGLE PROTEIN)

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
5.10	Kd	7916	nM	CHEMBL5653589
5.10	ED50	7916	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	2149461: Binding affinity to human SNRPE incubated for 45 mins by Kinobead based pull down assay	kd	7.9155	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, decreases expression, affects cotreatment	5
bisphenol A	affects expression, decreases expression, increases expression, decreases reaction, increases abundance	4
bisphenol F	increases expression, affects cotreatment	2
Arsenic Trioxide	increases expression, increases response to substance	2
Valproic Acid	decreases expression	2
aristolochic acid I	decreases expression	1
ginger extract	decreases reaction, increases abundance, increases expression	1
dicrotophos	decreases expression	1
testosterone enanthate	affects expression	1
methylmercuric chloride	decreases expression	1
trichostatin A	decreases expression	1
tetrahydropalmatine	decreases expression	1
arsenite	affects binding, increases reaction	1
methylparaben	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
gossypol acetic acid	increases expression	1
yessotoxin	decreases expression	1
bisphenol B	increases expression	1
bisphenol S	affects cotreatment, increases expression	1
MT19c compound	increases expression	1
PP242	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects cotreatment, increases abundance, increases expression, decreases expression	1
Cadmium	increases abundance, increases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	affects expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Indomethacin	affects cotreatment, increases expression	1
Ivermectin	decreases expression	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
CHEMBL5652503	Binding	Binding affinity to human SNRPE incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03492866	PHASE2	UNKNOWN	Efficacy of Topical Gentamycin for Hereditary Hypotrichosis Simplex Caused by Nonsense Mutations in CDSN
NCT01745666	Not specified	UNKNOWN	Comparison Between Epinephrine and Exercise Test in QT Long Syndrome Patients