SNRNP35

Summary

SNRNP35 (small nuclear ribonucleoprotein U11/U12 subunit 35, HGNC:30852) is a protein-coding gene on chromosome 12q24.31, encoding U11/U12 small nuclear ribonucleoprotein 35 kDa protein (Q16560). It is a common-essential gene (DepMap: required in 99.8% of cancer cell lines).

The protein encoded by this gene is a homolog of the U1-snRNP binding protein. The N-terminal half contains a RNA recognition motif and the C-terminal half is rich in Arg/Asp and Arg/Glu dipeptides, which is a characteristic of a variety of splicing factors. This protein is a component of the U11/U12 small nuclear ribonucleoproteins (snRNP) that form part of the U12-type spliceosome. Alternative splicing results in multiple transcript variants encoding two distinct isoforms and representing a non-protein coding variant.

Source: NCBI Gene 11066 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 44 total
• Cancer dependency (DepMap): dependent in 99.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_022717

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30852
Approved symbol	SNRNP35
Name	small nuclear ribonucleoprotein U11/U12 subunit 35
Location	12q24.31
Locus type	gene with protein product
Status	Approved
Aliases	U1SNRNPBP
Ensembl gene	ENSG00000184209
Ensembl biotype	protein_coding
OMIM	619631
Entrez	11066

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 15 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000350887, ENST00000412157, ENST00000526639, ENST00000527158, ENST00000529201, ENST00000529904, ENST00000906442, ENST00000906443, ENST00000906444, ENST00000906445, ENST00000906446, ENST00000906447, ENST00000906448, ENST00000906449, ENST00000932193, ENST00000932194, ENST00000932195, ENST00000953482

RefSeq mRNA: 2 — MANE Select: NM_022717 NM_022717, NM_180699

CCDS: CCDS45005, CCDS9249

Canonical transcript exons

ENST00000526639 — 2 exons

Exon	Start	End
ENSE00002141244	123465538	123466936
ENSE00002155237	123458139	123458216

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 97.38.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.4901 / max 139.8894, expressed in 1818 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
128580	18.4901	1818

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	97.38	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.71	gold quality
gastrocnemius	UBERON:0001388	94.16	gold quality
apex of heart	UBERON:0002098	94.04	gold quality
muscle of leg	UBERON:0001383	93.81	gold quality
muscle organ	UBERON:0001630	92.49	gold quality
mucosa of transverse colon	UBERON:0004991	92.49	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.34	gold quality
heart left ventricle	UBERON:0002084	91.82	gold quality
parotid gland	UBERON:0001831	91.64	silver quality
descending thoracic aorta	UBERON:0002345	91.61	gold quality
cardiac ventricle	UBERON:0002082	91.60	gold quality
gluteal muscle	UBERON:0002000	91.56	gold quality
right atrium auricular region	UBERON:0006631	91.43	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.42	gold quality
thoracic aorta	UBERON:0001515	91.18	gold quality
right lobe of thyroid gland	UBERON:0001119	91.16	gold quality
lower esophagus mucosa	UBERON:0035834	91.16	gold quality
ascending aorta	UBERON:0001496	91.15	gold quality
left coronary artery	UBERON:0001626	91.09	gold quality
spinal cord	UBERON:0002240	91.02	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	90.99	gold quality
triceps brachii	UBERON:0001509	90.82	gold quality
coronary artery	UBERON:0001621	90.79	gold quality
adenohypophysis	UBERON:0002196	90.78	gold quality
aorta	UBERON:0000947	90.69	gold quality
medial globus pallidus	UBERON:0002477	90.66	gold quality
body of tongue	UBERON:0011876	90.48	gold quality
heart	UBERON:0000948	90.44	gold quality
popliteal artery	UBERON:0002250	90.40	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.69

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 3)

• Anti-U11/U12 RNP antibodies are present in the sera of approximately 3% of patients with systemic sclerosis and are a marker for lung fibrosis, which is often severe. (PMID:19565553)
• An Fc-fusion protein of 35kDa with a modified human immunoglobulin IgG1 Fc domain is capable of inhibiting CC chemokine-induced calcium flux, chemotaxis, and beta-arrestin recruitment in primary macrophages and transfected cells. (PMID:21586597)
• Analysis of Genetically Regulated Gene Expression Identifies a Prefrontal PTSD Gene, SNRNP35, Specific to Military Cohorts. (PMID:32492425)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	snrnp35	ENSDARG00000099913
mus_musculus	Snrnp35	ENSMUSG00000029402
rattus_norvegicus	Snrnp35	ENSRNOG00000001060

Paralogs (1): SNRNP70 (ENSG00000104852)

Protein

Protein identifiers

U11/U12 small nuclear ribonucleoprotein 35 kDa protein — Q16560 (reviewed: Q16560)

Alternative names: Protein HM-1, U1 snRNP-binding protein homolog

All UniProt accessions (1): Q16560

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Component of the U11/U12 snRNPs that are part of the U12-type spliceosome.

Subcellular location. Nucleus.

Tissue specificity. Expressed in heart, liver, skeletal muscle and pancreas.

Isoforms (2)

UniProt ID	Names	Canonical?
Q16560-1	1	yes
Q16560-2	2

RefSeq proteins (2): NP_073208, NP_851030 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR034146	snRNP35_RRM	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR051183	U1_U11-U12_snRNP_70-35kDa	Family

Pfam: PF00076

UniProt features (23 total): strand 7, helix 7, turn 3, chain 1, domain 1, region of interest 1, compositionally biased region 1, cross-link 1, splice variant 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
9GCM	ELECTRON MICROSCOPY	3.1
8Y6O	ELECTRON MICROSCOPY	3.38
8R7N	ELECTRON MICROSCOPY	3.4
9GBZ	ELECTRON MICROSCOPY	3.4
9GBW	ELECTRON MICROSCOPY	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16560-F1	75.07	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 (1): 172

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-72165	mRNA Splicing - Minor Pathway

MSigDB gene sets: 119 (showing top): TGCGCANK_UNKNOWN, YANG_BREAST_CANCER_ESR1_LASER_UP, ONKEN_UVEAL_MELANOMA_UP, YY1_02, BLALOCK_ALZHEIMERS_DISEASE_UP, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION, GOBP_RNA_SPLICING, GENTILE_UV_HIGH_DOSE_DN, REACTOME_MRNA_SPLICING, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS, REACTOME_METABOLISM_OF_RNA, GCCATNTTG_YY1_Q6, GOCC_PRECATALYTIC_SPLICEOSOME, MARSON_BOUND_BY_FOXP3_STIMULATED

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

GO Molecular Function (5): mRNA binding (GO:0003729), snRNA binding (GO:0017069), nucleic acid binding (GO:0003676), RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), U12-type spliceosomal complex (GO:0005689), nucleolus (GO:0005730), spliceosomal complex (GO:0005681), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
mRNA Splicing	1

GO top-level categories

Rollup of top GO terms by namespace:

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

Protein interactions and networks

STRING

1774 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SNRNP35	SNRNP48	Q6IEG0	784
SNRNP35	SNRNP25	Q9BV90	756
SNRNP35	PDCD7	Q8N8D1	711
SNRNP35	ZMAT5	Q9UDW3	664
SNRNP35	RNPC3	Q96LT9	633
SNRNP35	ZCRB1	Q8TBF4	595
SNRNP35	SNRNP40	Q96DI7	533
SNRNP35	LSM10	Q969L4	522
SNRNP35	SNU13	P55769	517
SNRNP35	ZNF140	P52738	507
SNRNP35	TRUB2	O95900	472
SNRNP35	TRMT61A	Q96FX7	470
SNRNP35	SNRPC	P09234	455
SNRNP35	PHF5A	Q7RTV0	454
SNRNP35	SNRPD2	P43330	453

IntAct

29 interactions, top by confidence:

A	B	Type	Score
SNRPE	GEMIN2	psi-mi:“MI:0914”(association)	0.770
SNRPD2	GEMIN2	psi-mi:“MI:0914”(association)	0.710
SNRPG	GEMIN2	psi-mi:“MI:0914”(association)	0.710
SF3B1	SAP18	psi-mi:“MI:0914”(association)	0.640
ZCRB1	SF3B1	psi-mi:“MI:0914”(association)	0.640
SNRPE	SNRPGP15	psi-mi:“MI:0914”(association)	0.530
SNRPF	SNRPGP15	psi-mi:“MI:0914”(association)	0.530
SNRPN	PRMT5	psi-mi:“MI:0914”(association)	0.530
ZMAT5	DENND4B	psi-mi:“MI:0914”(association)	0.530
SNRPE	PRMT5	psi-mi:“MI:0914”(association)	0.530
SRPK2	SNRNP35	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
SNRNP35	ILK	psi-mi:“MI:0915”(physical association)	0.370
SNRNP35	TAB1	psi-mi:“MI:0915”(physical association)	0.370
MAP4K2	SNRNP35	psi-mi:“MI:0915”(physical association)	0.370
TNFSF11	SNRNP35	psi-mi:“MI:0915”(physical association)	0.370
SNRPB	DDX39A	psi-mi:“MI:0914”(association)	0.350
SNRPF	SUPT5H	psi-mi:“MI:0914”(association)	0.350
SNRPD3	PRMT5	psi-mi:“MI:0914”(association)	0.350
PHF5A	VPS26C	psi-mi:“MI:0914”(association)	0.350
ZCRB1	U2SURP	psi-mi:“MI:0914”(association)	0.350
JMJD6	U2SURP	psi-mi:“MI:0914”(association)	0.350
ZRSR2	U2SURP	psi-mi:“MI:0914”(association)	0.350
SNRNP35	SNRNP48	psi-mi:“MI:0914”(association)	0.350
SF3B1	RBM10	psi-mi:“MI:0914”(association)	0.350
SF3B1	FAM83G	psi-mi:“MI:0914”(association)	0.350
PTBP3		psi-mi:“MI:0914”(association)	0.350

BioGRID (54): SNRNP35 (Affinity Capture-MS), SNRNP35 (Affinity Capture-MS), SNRNP35 (Affinity Capture-MS), SNRNP35 (Affinity Capture-MS), SNRNP35 (Affinity Capture-MS), SNRNP35 (Affinity Capture-MS), SNRNP35 (Affinity Capture-MS), SNRNP35 (Affinity Capture-MS), PDCD7 (Affinity Capture-MS), RNPC3 (Affinity Capture-MS), SNRNP48 (Affinity Capture-MS), SNRNP35 (Affinity Capture-MS), SNRNP35 (Affinity Capture-MS), SNRNP35 (Two-hybrid), SNRNP35 (Two-hybrid)

ESM2 similar proteins: A2SW84, A6PVI3, A8Y1R8, B0W939, B1WC40, B3LYP1, B3P0D7, B4GLK8, B4IBA4, B4JUT1, B4KCD5, B4LZ88, B4M205, B4NB54, B4PL68, B4QV17, B5G279, B7P877, C0H859, C1BY64, P34541, P40565, P52298, P52299, Q05AT9, Q08920, Q16560, Q177H0, Q1HE01, Q1LZH0, Q293V6, Q3ZBJ1, Q4QQV1, Q4R5S7, Q54KR9, Q5ZKR5, Q6DES0, Q754W7, Q7QCB6, Q84L14

Diamond homologs: A0A0F6MY85, O02008, P19018, P33240, Q05AT9, Q16560, Q1LZH0, Q4KMD3, Q5RDA3, Q5U1W5, Q8BIQ5, Q8C7E9, Q8HXM1, Q8LPQ9, Q9D384, Q9H0L4, Q9SHZ6, A0A0D1C8Z4, A2SW84, A6PVI3, A8Y1R8, B0W939, B1WC40, B3LYP1, B3P0D7, B4GLK8, B4IBA4, B4JUT1, B4KCD5, B4LZ88, B4M205, B4NB54, B4PL68, B4QV17, B5DGI7, B5G279, B7P877, C0H859, C0HFE5, C1BY64

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 31 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	7	170.8×	1e-13
mRNA Splicing - Minor Pathway	11	94.7×	4e-18
snRNP Assembly	8	65.1×	3e-12
SARS-CoV-2 modulates host translation machinery	7	60.3×	2e-10
mRNA Splicing	11	46.5×	6e-15
RNA Polymerase II Transcription Termination	5	42.2×	6e-07
CHD1 and CHD2 subfamily	10	41.8×	2e-13
Processing of Capped Intron-Containing Pre-mRNA	12	37.9×	3e-15

GO biological processes:

GO term	Partners	Fold	FDR
U2-type prespliceosome assembly	8	172.2×	3e-15
spliceosomal snRNP assembly	8	160.3×	4e-15
spliceosomal complex assembly	7	145.3×	6e-13
RNA splicing	16	48.7×	4e-22
mRNA splicing, via spliceosome	13	41.1×	1e-16
mRNA processing	7	19.0×	1e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	42
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

482 predictions. Top by Δscore:

Variant	Effect	Δscore
12:123465536:A:AG	acceptor_gain	1.0000
12:123465537:G:GG	acceptor_gain	1.0000
12:123458214:GAG:G	donor_gain	0.9900
12:123458216:GGT:G	donor_loss	0.9900
12:123458217:G:GC	donor_loss	0.9900
12:123458218:T:G	donor_loss	0.9900
12:123465532:TCATA:T	acceptor_loss	0.9900
12:123465533:CATAG:C	acceptor_loss	0.9900
12:123465534:ATAG:A	acceptor_loss	0.9900
12:123465535:TA:T	acceptor_loss	0.9900
12:123465536:AG:A	acceptor_loss	0.9900
12:123465537:G:T	acceptor_loss	0.9900
12:123465537:GA:G	acceptor_gain	0.9900
12:123465537:GAA:G	acceptor_gain	0.9900
12:123465537:GAAC:G	acceptor_gain	0.9900
12:123465537:GAACA:G	acceptor_gain	0.9900
12:123472682:CC:C	acceptor_loss	0.9900
12:123472682:CCTT:C	acceptor_gain	0.9900
12:123472685:T:C	acceptor_gain	0.9900
12:123472685:T:TC	acceptor_gain	0.9900
12:123458270:G:GT	donor_gain	0.9800
12:123465535:T:G	acceptor_gain	0.9800
12:123458217:G:GG	donor_gain	0.9700
12:123458219:GAGTG:G	donor_loss	0.9700
12:123459033:TC:T	donor_gain	0.9700
12:123465530:A:AG	acceptor_gain	0.9700
12:123472679:AAACC:A	acceptor_gain	0.9700
12:123472681:ACCTT:A	acceptor_gain	0.9700
12:123472682:CCTTT:C	acceptor_gain	0.9700
12:123472683:C:CC	acceptor_gain	0.9700

AlphaMissense

1598 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:123465943:T:A	W135R	1.000
12:123465943:T:C	W135R	1.000
12:123466003:T:C	F155L	1.000
12:123466005:T:A	F155L	1.000
12:123466005:T:G	F155L	1.000
12:123465571:T:C	Y11H	0.999
12:123465589:G:C	G17R	0.999
12:123465590:G:A	G17D	0.999
12:123465592:A:C	S18R	0.999
12:123465594:C:A	S18R	0.999
12:123465594:C:G	S18R	0.999
12:123465600:T:A	D20E	0.999
12:123465600:T:G	D20E	0.999
12:123465623:A:C	D28A	0.999
12:123465623:A:T	D28V	0.999
12:123465632:T:A	V31D	0.999
12:123465704:T:A	V55E	0.999
12:123465710:G:T	R57I	0.999
12:123465740:T:C	L67S	0.999
12:123465788:T:A	V83D	0.999
12:123465823:G:C	A95P	0.999
12:123465824:C:A	A95D	0.999
12:123465826:T:C	F96L	0.999
12:123465827:T:C	F96S	0.999
12:123465828:C:A	F96L	0.999
12:123465828:C:G	F96L	0.999
12:123465830:T:A	I97N	0.999
12:123465945:G:C	W135C	0.999
12:123465945:G:T	W135C	0.999
12:123465962:G:A	G141E	0.999

dbSNP variants (sampled 300 via entrez): RS1000119773 (12:123458720 C>G,T), RS1000151850 (12:123470012 A>G,T), RS1000266928 (12:123456536 ACCACTGCTGTACTTT>A), RS1000297231 (12:123464966 A>G), RS1000298129 (12:123471448 G>C), RS1000328868 (12:123471728 C>T), RS1000461567 (12:123460237 T>C), RS1000629632 (12:123465316 T>C), RS1000758558 (12:123469845 C>G,T), RS1000823016 (12:123473011 G>T), RS1001034928 (12:123463650 T>G), RS1001672997 (12:123457865 T>A,C), RS1001790649 (12:123457486 G>A), RS1001973492 (12:123457002 T>C), RS1002191877 (12:123467151 T>C,G)

Disease associations

OMIM: gene MIM:619631 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002598_15	Educational attainment	7.000000e-08
GCST005956_10	Waist-to-hip ratio adjusted for BMI	6.000000e-08
GCST005958_11	Waist-to-hip ratio adjusted for BMI (age >50)	4.000000e-07
GCST005962_22	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	1.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004784	self reported educational attainment
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression	2
aristolochic acid I	decreases expression	1
TAK-243	increases sumoylation	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
trichostatin A	affects expression	1
sodium arsenite	decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
perfluoro-n-nonanoic acid	decreases expression	1
Scutellaria barbata extract	decreases expression	1
(+)-JQ1 compound	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Sunitinib	increases expression	1
Leflunomide	decreases expression	1
Amiodarone	increases expression	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Cadmium	decreases expression	1
Doxorubicin	decreases expression	1
Phenobarbital	affects expression	1
Selenium	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	affects expression	1
Vitamin E	increases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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