SNRPA

Summary

SNRPA (small nuclear ribonucleoprotein polypeptide A, HGNC:11151) is a protein-coding gene on chromosome 19q13.2, encoding U1 small nuclear ribonucleoprotein A (P09012). Component of the spliceosomal U1 snRNP, which is essential for recognition of the pre-mRNA 5’ splice-site and the subsequent assembly of the spliceosome. It is a selective cancer dependency (DepMap: 27.2% of cell lines).

The protein encoded by this gene associates with stem loop II of the U1 small nuclear ribonucleoprotein, which binds the 5’ splice site of precursor mRNAs and is required for splicing. The encoded protein autoregulates itself by polyadenylation inhibition of its own pre-mRNA via dimerization and has been implicated in the coupling of splicing and polyadenylation.

Source: NCBI Gene 6626 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Limited, GenCC)
• GWAS associations: 23
• Clinical variants (ClinVar): 47 total — 2 likely-pathogenic
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 27.2% of screened cell lines
• MANE Select transcript: NM_004596

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11151
Approved symbol	SNRPA
Name	small nuclear ribonucleoprotein polypeptide A
Location	19q13.2
Locus type	gene with protein product
Status	Approved
Aliases	U1A, U1-A, Mud1
Ensembl gene	ENSG00000077312
Ensembl biotype	protein_coding
OMIM	182285
Entrez	6626

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 18 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000243563, ENST00000596860, ENST00000597353, ENST00000598452, ENST00000598923, ENST00000599362, ENST00000599570, ENST00000600456, ENST00000601253, ENST00000601393, ENST00000601545, ENST00000861887, ENST00000861888, ENST00000925553, ENST00000925554, ENST00000925555, ENST00000925556, ENST00000925557, ENST00000925558, ENST00000925559, ENST00000925560, ENST00000925561, ENST00000925562

RefSeq mRNA: 1 — MANE Select: NM_004596 NM_004596

CCDS: CCDS12565

Canonical transcript exons

ENST00000243563 — 6 exons

Exon	Start	End
ENSE00000707961	40762901	40763074
ENSE00000842333	40763587	40763675
ENSE00000842334	40765008	40765389
ENSE00001052136	40751203	40751481
ENSE00003584254	40757332	40757504
ENSE00003785400	40759431	40759610

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 97.66.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 160.2469 / max 1015.9595, expressed in 1824 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
175890	100.8426	1820
175891	16.6577	1788
175889	14.7544	1765
175893	12.5539	1706
175894	10.9033	1683
175892	1.6499	871
175888	1.2689	717
175895	1.2548	651
175896	0.3613	190

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	97.66	gold quality
embryo	UBERON:0000922	97.50	gold quality
endometrium epithelium	UBERON:0004811	97.22	gold quality
mucosa of transverse colon	UBERON:0004991	96.84	gold quality
left ovary	UBERON:0002119	96.67	gold quality
ventricular zone	UBERON:0003053	96.58	gold quality
endocervix	UBERON:0000458	96.55	gold quality
right ovary	UBERON:0002118	96.43	gold quality
body of uterus	UBERON:0009853	96.28	gold quality
right lobe of thyroid gland	UBERON:0001119	96.25	gold quality
popliteal artery	UBERON:0002250	96.23	gold quality
tibial artery	UBERON:0007610	96.22	gold quality
ectocervix	UBERON:0012249	96.20	gold quality
left lobe of thyroid gland	UBERON:0001120	96.05	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.81	gold quality
spleen	UBERON:0002106	95.78	gold quality
mucosa of stomach	UBERON:0001199	95.74	gold quality
adenohypophysis	UBERON:0002196	95.73	gold quality
aorta	UBERON:0000947	95.72	gold quality
transverse colon	UBERON:0001157	95.71	gold quality
left coronary artery	UBERON:0001626	95.65	gold quality
coronary artery	UBERON:0001621	95.56	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.56	gold quality
lymph node	UBERON:0000029	95.46	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.46	gold quality
left uterine tube	UBERON:0001303	95.45	gold quality
right coronary artery	UBERON:0001625	95.45	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.36	gold quality
descending thoracic aorta	UBERON:0002345	95.30	gold quality
right uterine tube	UBERON:0001302	95.29	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.81

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

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

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-4716-3P	99.69	66.73	1022
HSA-MIR-625-5P	99.02	68.64	2031
HSA-MIR-9898	99.00	67.89	500
HSA-MIR-3611	98.76	68.76	1290
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-6776-5P	98.54	67.43	1304
HSA-MIR-326	98.25	66.44	1565
HSA-MIR-4724-3P	97.57	67.31	785
HSA-MIR-514A-5P	96.94	65.49	801
HSA-MIR-874-5P	96.93	63.92	1014
HSA-MIR-1225-5P	96.76	66.85	417
HSA-MIR-6861-5P	96.23	67.19	800
HSA-MIR-764	94.16	64.85	656

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 27.2% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 13)

• 13)C NMR relaxation studies of base and ribose dynamics for the RNA internal loop target of human U1A protein located within the 3’-untranslated region (3’-UTR) of the mRNA coding for U1A itself (PMID:15890361)
• Identification of PSF, p54(nrb), PTB, and U1A as proteins specifically bound to the COX-2 polyadenylation signal upstream sequence elements . (PMID:17507659)
• Functional U1A site in a cellular gene and of a single gene containing two dissimilar elements that inhibit nuclear polyadenylation. (PMID:17942741)
• study shows that the yellow fever virus (YFV) NS5 protein is able to interact with U1A, a protein involved in splicing and polyadenylation; a region between amino acids 368 and 448 was identified as the site of interaction of the NS5 protein with U1A (PMID:21298455)
• structural analysis of U1A protein-stem loop 2 RNA recognition (PMID:21384338)
• An analysis of the kinetic data suggests three phases of U1A-SL2 RNA complex dissociation with time scales of approximately 100 mus, approximately 50 ms, and approximately 2 s. We propose that the first step of dissociation is a fast rearrangement of the complex to form a loosely bound complex. (PMID:21419778)
• a new mechanism for regulating SMN levels and provides new insight into the roles of U1A in 3’ processing of mRNAs. (PMID:24362020)
• p65 activation triggered by TCR signaling could promote SNRPA transcription and 3’ UTR shortening of STAT5B. Thus we propose that the alternative polyadenylation switching of STAT5B induced by TCR activation is mediated by SNRPA. (PMID:28954886)
• the previously unreported concurrence of intellectual disability, short stature, poor speech, and minor craniofacial and hand anomalies in 2 female siblings with 3 homozygous missense variants in SNRPA, is reported. (PMID:29437235)
• SNRPA may contribute to GC progression via NGF and could be a prognostic biomarker for GC. (PMID:30039889)
• Screen using siRNA revealed depletion of U1 snRNP components SNRPA, SNRNP70 or SNRPD2 caused significant cytoplasmic localization of MEG3 reporter transcripts. (PMID:31107149)
• The Small Nuclear Ribonucleoprotein Polypeptide A (SNRPA) binds to the G-quadruplex of the BAG-1 5’UTR. (PMID:32629040)
• Circ_0009910 Serves as miR-361-3p Sponge to Promote the Proliferation, Metastasis, and Glycolysis of Gastric Cancer via Regulating SNRPA. (PMID:35098410)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	snrpa	ENSDARG00000018890
mus_musculus	Snrpa	ENSMUSG00000061479
rattus_norvegicus	Snrpa	ENSRNOG00000001501
drosophila_melanogaster	snf	FBGN0003449
caenorhabditis_elegans		WBGENE00004385
caenorhabditis_elegans		WBGENE00004386

Paralogs (1): SNRPB2 (ENSG00000125870)

Protein

Protein identifiers

U1 small nuclear ribonucleoprotein A — P09012 (reviewed: P09012)

All UniProt accessions (7): P09012, M0QXK2, M0QZG7, M0R0G9, M0R221, M0R268, M0R2B8

UniProt curated annotations — full annotation on UniProt →

Function. Component of the spliceosomal U1 snRNP, which is essential for recognition of the pre-mRNA 5’ splice-site and the subsequent assembly of the spliceosome. U1 snRNP is the first snRNP to interact with pre-mRNA. This interaction is required for the subsequent binding of U2 snRNP and the U4/U6/U5 tri-snRNP. SNRPA binds stem loop II of U1 snRNA. In a snRNP-free form (SF-A) may be involved in coupled pre-mRNA splicing and polyadenylation process. May bind preferentially to the 5’-UGCAC-3’ motif on RNAs.

Subunit / interactions. U1 snRNP is composed of the 7 core Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP, and at least three U1 snRNP-specific proteins SNRNP70/U1-70K, SNRPA/U1-A and SNRPC/U1-C. Interacts with SFPQ; component of a snRNP-free complex with SFPQ. Interacts with IVNS1ABP (via BACK domain); the interaction is indirect.

Subcellular location. Nucleus.

Similarity. Belongs to the RRM U1 A/B’’ family.

RefSeq proteins (1): NP_004587* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR034407	U1A_RRM1	Domain
IPR034409	U1A_RRM2	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily

Pfam: PF00076

UniProt features (36 total): strand 11, helix 9, mutagenesis site 5, modified residue 4, domain 2, turn 2, initiator methionine 1, chain 1, region of interest 1

Structure

Experimental structures (PDB)

95 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
6XH2	X-RAY DIFFRACTION	1.71
1NU4	X-RAY DIFFRACTION	1.8
6SQT	X-RAY DIFFRACTION	1.84
6SR7	X-RAY DIFFRACTION	1.86
1URN	X-RAY DIFFRACTION	1.92
6SQN	X-RAY DIFFRACTION	2.05
4YB1	X-RAY DIFFRACTION	2.08
8GXB	X-RAY DIFFRACTION	2.15
7QR3	X-RAY DIFFRACTION	2.18
1M5O	X-RAY DIFFRACTION	2.2
1SJ3	X-RAY DIFFRACTION	2.2
3EGZ	X-RAY DIFFRACTION	2.2
7LHX	X-RAY DIFFRACTION	2.2
1DRZ	X-RAY DIFFRACTION	2.3
3MXH	X-RAY DIFFRACTION	2.3
4PR6	X-RAY DIFFRACTION	2.3
5DDP	X-RAY DIFFRACTION	2.3
6XH3	X-RAY DIFFRACTION	2.35
6SQQ	X-RAY DIFFRACTION	2.37
4PRF	X-RAY DIFFRACTION	2.4
1M5K	X-RAY DIFFRACTION	2.4
1M5V	X-RAY DIFFRACTION	2.4
1OIA	X-RAY DIFFRACTION	2.4
2OIH	X-RAY DIFFRACTION	2.4
5DDQ	X-RAY DIFFRACTION	2.4
6SQV	X-RAY DIFFRACTION	2.45
2NZ4	X-RAY DIFFRACTION	2.5
1VC0	X-RAY DIFFRACTION	2.5
8GXC	X-RAY DIFFRACTION	2.5
1M5P	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P09012-F1	80.42	0.49

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 (4): 2, 60, 131, 152

Mutagenesis-validated functional residues (5):

Position	Phenotype
13	substantially reduces rna binding.
15	abolishes rna binding.
16	substantially reduces rna binding.
52	abolishes rna binding.
11	abolishes rna binding.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

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

MSigDB gene sets: 225 (showing top): MORF_MTA1, MORF_DNMT1, HORIUCHI_WTAP_TARGETS_DN, MORF_ESPL1, PAL_PRMT5_TARGETS_UP, MORF_RRM1, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, MORF_HDAC1, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, MORF_CDK2, MITSIADES_RESPONSE_TO_APLIDIN_DN, MORF_HDAC2, PUJANA_CHEK2_PCC_NETWORK, MODULE_388, MUELLER_PLURINET

GO Biological Process (3): mRNA splicing, via spliceosome (GO:0000398), mRNA processing (GO:0006397), RNA splicing (GO:0008380)

GO Molecular Function (7): DNA binding (GO:0003677), RNA binding (GO:0003723), U1 snRNA binding (GO:0030619), identical protein binding (GO:0042802), U1 snRNP binding (GO:1990446), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), spliceosomal complex (GO:0005681), U1 snRNP (GO:0005685), U4/U6 x U5 tri-snRNP complex (GO:0046540), spliceosomal snRNP complex (GO:0097525), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-4 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA processing	2
nucleic acid binding	2
binding	2
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
mRNA metabolic process	1
snRNA binding	1
protein binding	1
snRNP binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1
spliceosomal snRNP complex	1
U5 snRNP	1
U4/U6 snRNP	1
spliceosomal tri-snRNP complex	1
small nuclear ribonucleoprotein complex	1
protein-containing complex	1

Protein interactions and networks

STRING

3466 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SNRPA	SNRPC	P09234	999
SNRPA	SNRNP70	P08621	998
SNRPA	U2AF2	P26368	933
SNRPA	MMP10	P09238	892
SNRPA	SNRPA1	P09661	871
SNRPA	RBM25	P49756	852
SNRPA	SNRPD2	P43330	842
SNRPA	SNRPN	P14648	818
SNRPA	RBM39	Q14498	817
SNRPA	PAPOLA	P51003	790
SNRPA	PAPOLB	Q9NRJ5	790
SNRPA	PAPOLG	Q9BWT3	789
SNRPA	SNRPD1	P13641	789
SNRPA	SNRPE	P08578	778
SNRPA	PRPF40A	O75400	773

IntAct

344 interactions, top by confidence:

A	B	Type	Score
SNRPA1	SNRPA	psi-mi:“MI:0915”(physical association)	0.830
SNRPA	RBM3	psi-mi:“MI:0915”(physical association)	0.830
SNRPA	SNRPA1	psi-mi:“MI:0915”(physical association)	0.830
RBM3	SNRPA	psi-mi:“MI:0915”(physical association)	0.830
PTBP1	SNRPA	psi-mi:“MI:0915”(physical association)	0.800
SNRPA	SNRPA	psi-mi:“MI:0915”(physical association)	0.800
SNRPA	PTBP1	psi-mi:“MI:0915”(physical association)	0.800
SNRPA	LENG8	psi-mi:“MI:0915”(physical association)	0.780
SNRPA	PCBP1	psi-mi:“MI:0915”(physical association)	0.780
LENG8	SNRPA	psi-mi:“MI:0915”(physical association)	0.780
PCBP1	SNRPA	psi-mi:“MI:0915”(physical association)	0.780
SNRPA	HNRNPK	psi-mi:“MI:0915”(physical association)	0.740
SNRPA	TRIR	psi-mi:“MI:0915”(physical association)	0.740

BioGRID (708): PTBP1 (Reconstituted Complex), SFPQ (Affinity Capture-Western), SNRPA (Two-hybrid), SNRPA (Two-hybrid), SNRPA (Two-hybrid), SNRPA (Two-hybrid), SNRPA (Two-hybrid), SNRPA (Two-hybrid), SNRPA (Two-hybrid), SNRPA (Two-hybrid), SNRPA (Two-hybrid), SNRPA1 (Two-hybrid), QKI (Two-hybrid), ENOX2 (Two-hybrid), U2AF2 (Two-hybrid)

ESM2 similar proteins: A2Y0J7, B5DF91, B8AM21, O22922, O95758, P09012, P17225, P26368, P26369, P26599, P43332, P45429, P70372, Q00438, Q06AA4, Q08E07, Q0DKM4, Q10MR0, Q12926, Q14576, Q15717, Q24562, Q28FX0, Q29099, Q2KIR1, Q39244, Q54J05, Q5R9Z6, Q5SZQ8, Q60899, Q60900, Q62189, Q66H20, Q6GLB5, Q8BHD7, Q8BHN5, Q8CFD1, Q8CH84, Q8CIN6, Q8H1S6

Diamond homologs: A2Y0J7, A5A6M3, A6NDE4, A6NEQ0, B8AM21, O22922, O74968, O75494, P08579, P09012, P0C7P1, P0DJD3, P0DJD4, P38159, P40567, P43332, P45429, P59708, Q06AA4, Q0DKM4, Q10MR0, Q15415, Q2KIR1, Q39244, Q4R7F0, Q4V898, Q54J05, Q62189, Q6IRQ4, Q7LL14, Q7ZWA3, Q8H1S6, Q8ITY4, Q8WXF0, Q91VM5, Q9CQI7, Q9FMP4, Q9R0U0, Q9WV02, Q9Y3B4

SIGNOR signaling

2 interactions.

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

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 101 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
Processing of Capped Intron-Containing Pre-mRNA	15	20.2×	7e-14
mRNA Polyadenylation	13	18.7×	1e-11
snRNP Assembly	5	17.3×	3e-04
mRNA Splicing	9	16.2×	2e-07
mRNA Splicing - Major Pathway	17	15.2×	7e-14
CHD1 and CHD2 subfamily	6	10.7×	6e-04
Dengue Virus-Host Interactions	14	10.5×	3e-09
Metabolism of RNA	11	7.5×	1e-05

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of mRNA splicing, via spliceosome	6	51.1×	1e-07
positive regulation of mRNA splicing, via spliceosome	8	48.3×	6e-10
spliceosomal complex assembly	6	40.1×	6e-07
spliceosomal snRNP assembly	5	32.3×	2e-05
regulation of alternative mRNA splicing, via spliceosome	10	27.1×	6e-10
intrinsic apoptotic signaling pathway	6	23.9×	1e-05
RNA splicing	14	13.7×	6e-10
G1/S transition of mitotic cell cycle	6	13.4×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	2
Uncertain significance	30
Likely benign	5
Benign	2

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
446205	NM_004596.5(SNRPA):c.100T>A (p.Phe34Ile)	Likely pathogenic
446220	NM_004596.5(SNRPA):c.98T>C (p.Ile33Thr)	Likely pathogenic

SpliceAI

918 predictions. Top by Δscore:

Variant	Effect	Δscore
19:40757329:CAG:C	acceptor_gain	1.0000
19:40757330:A:AG	acceptor_gain	1.0000
19:40757330:AGA:A	acceptor_gain	1.0000
19:40757331:G:A	acceptor_loss	1.0000
19:40757331:G:GG	acceptor_gain	1.0000
19:40757331:GA:G	acceptor_gain	1.0000
19:40757331:GAG:G	acceptor_gain	1.0000
19:40757331:GAGCT:G	acceptor_gain	1.0000
19:40757439:G:GT	donor_gain	1.0000
19:40757504:GGTG:G	donor_loss	1.0000
19:40757507:GAGCA:G	donor_loss	1.0000
19:40759421:T:A	acceptor_gain	1.0000
19:40759425:T:TA	acceptor_gain	1.0000
19:40759429:A:AG	acceptor_gain	1.0000
19:40759429:AGC:A	acceptor_gain	1.0000
19:40759430:G:GC	acceptor_gain	1.0000
19:40759430:GC:G	acceptor_gain	1.0000
19:40759430:GCG:G	acceptor_gain	1.0000
19:40759430:GCGT:G	acceptor_gain	1.0000
19:40759430:GCGTA:G	acceptor_gain	1.0000
19:40759517:G:GT	donor_gain	1.0000
19:40759550:G:GT	donor_gain	1.0000
19:40759554:G:GT	donor_gain	1.0000
19:40759607:CCCGG:C	donor_loss	1.0000
19:40759608:CCGG:C	donor_loss	1.0000
19:40759609:CGGTA:C	donor_loss	1.0000
19:40759610:GGTAA:G	donor_loss	1.0000
19:40759611:G:GC	donor_loss	1.0000
19:40759611:G:GG	donor_gain	1.0000
19:40762897:ACAG:A	acceptor_gain	1.0000

AlphaMissense

1880 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:40751443:T:A	I12N	1.000
19:40751445:T:C	Y13H	1.000
19:40751445:T:G	Y13D	1.000
19:40751449:T:A	I14N	1.000
19:40751449:T:G	I14S	1.000
19:40751456:C:A	N16K	1.000
19:40751456:C:G	N16K	1.000
19:40751458:T:A	L17H	1.000
19:40751458:T:C	L17P	1.000
19:40751458:T:G	L17R	1.000
19:40751462:T:A	N18K	1.000
19:40751462:T:G	N18K	1.000
19:40751463:G:A	E19K	1.000
19:40751464:A:T	E19V	1.000
19:40757335:T:C	L26P	1.000
19:40757339:A:C	K27N	1.000
19:40757339:A:T	K27N	1.000
19:40757343:T:C	S29P	1.000
19:40757344:C:T	S29F	1.000
19:40757347:T:A	L30Q	1.000
19:40757347:T:C	L30P	1.000
19:40757347:T:G	L30R	1.000
19:40757352:G:C	A32P	1.000
19:40757353:C:A	A32D	1.000
19:40757356:T:A	I33N	1.000
19:40757356:T:G	I33S	1.000
19:40757358:T:A	F34I	1.000
19:40757358:T:C	F34L	1.000
19:40757359:T:C	F34S	1.000
19:40757360:C:A	F34L	1.000

dbSNP variants (sampled 300 via entrez): RS1000077433 (19:40754194 C>G), RS1000302033 (19:40760104 A>C,G), RS1000377746 (19:40749653 G>C,T), RS1000434082 (19:40765592 G>A), RS1000571615 (19:40764434 G>A,T), RS1000771966 (19:40753992 G>A,C), RS1000835956 (19:40752888 T>A,C,G), RS1001145503 (19:40754100 G>A,T), RS1001166185 (19:40753699 CAT>C), RS1001239679 (19:40753394 T>G), RS1002041287 (19:40750171 C>G,T), RS1002404623 (19:40761626 C>T), RS1002414981 (19:40755448 C>G,T), RS1002854707 (19:40752598 A>G), RS1003034076 (19:40757950 T>A)

Disease associations

OMIM: gene MIM:182285 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Limited	Autosomal recessive

Mondo (1): complex neurodevelopmental disorder (MONDO:0100038)

Orphanet (0):

HPO phenotypes

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

GWAS associations

23 associations (top):

Study	Trait	p-value
GCST003262_1055	Post bronchodilator FEV1	1.000000e-06
GCST003847_2	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) level)	6.000000e-08
GCST003849_1	Caffeine metabolism (plasma 3,7-dimethylxanthine (theobromine) level)	4.000000e-06
GCST003851_10	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	5.000000e-12
GCST003851_11	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	8.000000e-09
GCST003851_12	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	2.000000e-10
GCST003851_13	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	9.000000e-22
GCST003851_14	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	9.000000e-10
GCST003851_15	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	9.000000e-11
GCST003851_16	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	3.000000e-09
GCST003851_17	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	2.000000e-11
GCST003851_18	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	1.000000e-08
GCST003851_19	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	3.000000e-11
GCST003851_20	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	3.000000e-09
GCST003851_21	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	1.000000e-09
GCST003851_22	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	2.000000e-08
GCST003851_23	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	3.000000e-08
GCST003851_26	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	5.000000e-12
GCST003851_27	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	1.000000e-08
GCST003851_9	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	6.000000e-09
GCST004604_39	Hematocrit	4.000000e-09
GCST009573_2	melanoma-derived growth regulatory protein levels	7.000000e-17
GCST009921_7	Carotid intima media thickness (mean)	1.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004314	forced expiratory volume
EFO:0007872	caffeine metabolite measurement
EFO:0004348	hematocrit

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725098 (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
7.45	Kd	35.61	nM	CHEMBL5653589
7.45	ED50	35.61	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	2149454: Binding affinity to human SNRPA incubated for 45 mins by Kinobead based pull down assay	kd	0.0356	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases methylation	3
Air Pollutants	decreases expression, increases abundance, increases expression	2
Benzo(a)pyrene	decreases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
FR900359	increases phosphorylation	1
bisphenol A	decreases expression	1
pyrogallol 1,3-dimethyl ether	increases expression, affects cotreatment, affects localization	1
arsenite	decreases reaction, increases reaction, affects binding	1
sodium arsenite	decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation	1
beta-methylcholine	affects expression	1
2,3-dimethoxy-1,4-naphthoquinone	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
bisphenol S	decreases expression	1
incobotulinumtoxinA	decreases expression	1
(+)-JQ1 compound	decreases expression	1
bisphenol AF	increases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	decreases expression	1
Troglitazone	decreases expression	1
Acrolein	affects cotreatment, increases oxidation	1
Antimony	increases expression	1
Antimony Potassium Tartrate	increases expression	1
Benztropine	increases expression	1
Cadmium	decreases expression, increases abundance	1
Carbamazepine	affects 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
CHEMBL5652496	Binding	Binding affinity to human SNRPA 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
NCT06310681	Not specified	COMPLETED	Pilot Testing of a Co-adapted Group Programme for Parents/Carers of Children With Complex Neurodisability
NCT07303049	Not specified	NOT_YET_RECRUITING	Cognitive Benefit of Intensive Rehabilitation Using Rhythmic Music Training in Children With Complex Neurodevelopmental Disorder