SSB

Summary

SSB (small RNA binding exonuclease protection factor La, HGNC:11316) is a protein-coding gene on chromosome 2q31.1, encoding Lupus La protein (P05455). Binds to the 3’ poly(U) terminus of nascent RNA polymerase III transcripts, protecting them from exonuclease digestion and facilitating their folding and maturation. It is a selective cancer dependency (DepMap: 74.8% of cell lines).

The protein encoded by this gene is involved in diverse aspects of RNA metabolism, including binding and protecting poly(U) termini of nascent RNA polymerase III transcripts from exonuclease digestion, processing 5’ and 3’ ends of pre-tRNA precursors, acting as an RNA chaperone, and binding viral RNAs associated with hepatitis C virus. Autoantibodies reacting with this protein are found in the sera of patients with Sjogren syndrome and systemic lupus erythematosus. Alternative promoter usage results in two different transcript variants which encode the same protein.

Source: NCBI Gene 6741 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 60 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 74.8% of screened cell lines
• MANE Select transcript: NM_003142

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11316
Approved symbol	SSB
Name	small RNA binding exonuclease protection factor La
Location	2q31.1
Locus type	gene with protein product
Status	Approved
Aliases	SSB/La, LARP3, La, La/SSB
Ensembl gene	ENSG00000138385
Ensembl biotype	protein_coding
OMIM	109090
Entrez	6741

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 14 protein_coding, 7 retained_intron, 1 nonsense_mediated_decay

ENST00000260956, ENST00000409333, ENST00000413002, ENST00000417292, ENST00000422006, ENST00000461708, ENST00000465871, ENST00000468600, ENST00000470621, ENST00000474273, ENST00000490914, ENST00000494051, ENST00000906406, ENST00000906407, ENST00000906408, ENST00000938524, ENST00000938525, ENST00000938526, ENST00000938527, ENST00000938528, ENST00000938529, ENST00000949512

RefSeq mRNA: 2 — MANE Select: NM_003142 NM_001294145, NM_003142

CCDS: CCDS2237

Canonical transcript exons

ENST00000260956 — 12 exons

Exon	Start	End
ENSE00000782045	169811183	169811323
ENSE00001588653	169811668	169812064
ENSE00001893329	169798871	169798976
ENSE00002471090	169805665	169805839
ENSE00002496741	169806785	169806892
ENSE00003510639	169800952	169801026
ENSE00003562426	169810858	169811044
ENSE00003578824	169810283	169810423
ENSE00003606885	169808482	169808553
ENSE00003607377	169808860	169808902
ENSE00003620133	169805474	169805577
ENSE00003787270	169806971	169807071

Expression profiles

Bgee: expression breadth ubiquitous, 300 present calls, max score 99.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 113.8853 / max 3387.4530, expressed in 1821 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
23572	104.2044	1821
23574	3.8475	1344
23573	2.1911	1141
23575	1.7421	802
23576	0.9577	513
23580	0.7895	132
23581	0.0969	40
23579	0.0356	16
23578	0.0205	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	99.33	gold quality
tendon	UBERON:0000043	98.79	gold quality
calcaneal tendon	UBERON:0003701	98.66	gold quality
ventricular zone	UBERON:0003053	98.63	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.24	gold quality
monocyte	CL:0000576	98.10	gold quality
epithelium of nasopharynx	UBERON:0001951	97.95	gold quality
nasopharynx	UBERON:0001728	97.94	gold quality
ganglionic eminence	UBERON:0004023	97.87	gold quality
cortical plate	UBERON:0005343	97.81	gold quality
mononuclear cell	CL:0000842	97.75	gold quality
peritoneum	UBERON:0002358	97.71	gold quality
omental fat pad	UBERON:0010414	97.71	gold quality
left coronary artery	UBERON:0001626	97.68	gold quality
endometrium	UBERON:0001295	97.65	gold quality
adenohypophysis	UBERON:0002196	97.65	gold quality
adipose tissue of abdominal region	UBERON:0007808	97.61	gold quality
right uterine tube	UBERON:0001302	97.58	gold quality
descending thoracic aorta	UBERON:0002345	97.58	gold quality
leukocyte	CL:0000738	97.56	gold quality
coronary artery	UBERON:0001621	97.56	gold quality
embryo	UBERON:0000922	97.54	gold quality
medial globus pallidus	UBERON:0002477	97.54	gold quality
islet of Langerhans	UBERON:0000006	97.52	gold quality
left ovary	UBERON:0002119	97.49	gold quality
right ovary	UBERON:0002118	97.48	gold quality
thoracic aorta	UBERON:0001515	97.47	gold quality
ascending aorta	UBERON:0001496	97.46	gold quality
subcutaneous adipose tissue	UBERON:0002190	97.45	gold quality
adipose tissue	UBERON:0001013	97.43	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-9067	yes	20.36
E-MTAB-7052	no	411.89
E-CURD-135	no	334.51
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
HAP1	Repression
LAMB1	Activation
XIAP	Unknown

miRNA regulators (miRDB)

40 targeting SSB, 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-4262	100.00	73.26	3931
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-548AN	99.97	70.91	2817
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-5688	99.96	73.23	4504
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-6861-3P	99.60	68.46	444
HSA-MIR-3616-5P	99.55	67.02	989
HSA-MIR-573	99.55	67.44	955
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-548AS-3P	99.12	69.12	2294
HSA-MIR-4795-5P	99.11	66.90	876
HSA-MIR-452-3P	99.01	66.25	1241

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 74.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• inhibits tRNA 3’ processing (PMID:11580243)
• nuclear trafficking by La affects the normal order of pre-tRNA processing (PMID:12049746)
• molecular characterization of the human La protein.hepatitis B virus RNA.B interaction in vitro (PMID:12121976)
• La autoantigen is required for the internal ribosome entry site-mediated translation of Coxsackievirus B3 RNA (PMID:12384597)
• binds differentially to multiple sites within the 5’ untranslated region of Coxsackievirus B3 RNA (PMID:12457960)
• in addition to full-length La protein, both N- and C-terminal halves were able to interact with hepatitis C virus internal ribosome entry site in vivo. (PMID:12540850)
• Dengue 4 virus minus strand 3’UTR RNA binds with La protein in human monocytes (PMID:12584332)
• Results suggest that La ribonucleoproteins (RNP) exist in distinct states that differ in subcellular localization, serine 366 phosphorylation, and associated RNAs. (PMID:14636586)
• La motif adopts an alpha/beta fold that comprises a winged-helix motif elaborated by the insertion of three helices (PMID:15004549)
• La protein binds to the 5’ end and with the 3’ UTR of Dengue virus RNA; interacts with the dengue virus nonstructural proteins NS5 and NS3 (PMID:15084396)
• NMR assignment and secondary structure of the La motif (PMID:15213463)
• Composition of La/hepatitis B virus ribonucleoprotein particles as well as interacting cellular factors, are critical determinants in the regulation of the stability of the HBV RNA. (PMID:15302879)
• RRM1 and La motifs bind pre-tRNA (PMID:15371415)
• CK2 is responsible for La S(366) phosphorylation in vivo (PMID:15485924)
• Nonphosphorylated SSB interacts with nucleolin at nucleolar sites involved in rRNA biogenesis. (PMID:15572691)
• This protein is s host factors responsible for the regulation of the hepatitis C virus internal ribosome entry site. (PMID:15685555)
• essential for efficient hepatitis C virus replication (PMID:15823607)
• In vitro RNA chaperone activity pf SSB was studied. (PMID:15928345)
• nuclear retention of peptidylglycine alpha-amidating monooxygenase (PAM) mRNA is lost upon expressing the La proteins that lack a conserved nuclear retention element, suggesting a direct association between PAM mRNA and La protein in vivo (PMID:16107699)
• Anti-La antibodies bound to immunodominant epitopes of La within the NH(2)-terminus and the RNA recognition motif (RRM) region of apoptotic human cells (PMID:16320341)
• Here, we show by chromatin immunoprecipitation (ChIP) that La is associated with pol III-transcribed genes in vivo (PMID:16344466)
• Results report the crystal structure of the N-terminal domain of human La, consisting of La and RRM1 motifs, bound to RNA. (PMID:16387655)
• Changes in salivary production rate are associated with aging and SSB antibodies. (PMID:16467037)
• La protein undergoes nucleocytoplasmic shuttling whereas EBER1 and EBER2 noncoding RNA’s are confined to the nucleus. (PMID:16682524)
• In mice transgenic for the mutant form of La autoantigen, mutant La mRNAs are not only repressed and translated to mutant La protein but, unexpectedly, expression of mutant La favors the development of systemic autoimmunity. (PMID:16849479)
• Nuclear injury and the translocation of SSA/Ro and SSB/La antigens to the fetal cardiocyte plasma membrane were common downstream events of Fas and TNF receptor ligation. (PMID:16906225)
• There is a correlation between La protein and HBV mRNA and the expression of HBV protein. (PMID:17064465)
• suggest that conserved elements mediate nuclear retention, nuclear export, and RNA-binding activities of the multifunctional La protein (PMID:17308035)
• La autoantigen can interact with both the 3’ and 5’UTRs of coxsackievirus B3 independently of the poly(A) tail and may share the same binding site on the La protein. (PMID:17346312)
• Increased Ro/SSA 60 and La/SSB mRNA expression in minor salivary glands in primary Sjogren’s syndrome (pSS) suggest that these these 2 autoantigens, but not Ro/SSA 52, are involved in the tissue-specific autoimmune response in pSS. (PMID:17552056)
• Overexpression of La autoantigen is associated with neoplasms (PMID:17875783)
• Results suggest that La protein is cleaved by granzyme B and N-terminal La fragment (27 kD) translocated to the cytoplasm, thus leading to a novel autoantibody production during granzyme B-mediated cytotoxicity. (PMID:17945310)
• the autoantibodies to SSB/La may modulate neutrophils function in systemic lupus erythematosis (PMID:17985193)
• The La-mediated suppression of HAV translation and stimulation of poliovirus translation implies unexpected mechanistic differences between viral internal ribosomal entry site elements. (PMID:18282467)
• Identification of a conserved set of interactions with the last two nucleotides at the 3’ end of the RNA ligand that are key to binding by the La protein. (PMID:18547518)
• La supports the growth of nonsegmented negative-strand RNA viruses by both IFN suppression and a potentially novel IFN-independent mechanism (PMID:18550659)
• the frequency of La/SSB antibodies was higher in sporadic systemic lupus erythematosus (P = 0.048) than in those with familial SLE, although this was not significant after application of Bonferroni’s correction for the number of comparisons (PMID:19074175)
• Using electrophoretic mobility-shift and UV cross-linking assays, as well as a yeast three-hybrid system, it was shown here that La protein binds to the 3’ stem-loop (SL) structure of Japanese encephalitis virus genome. (PMID:19264640)
• The authors show that La preferentially binds pre-tRNAs over processed tRNAs or 3’ trailer products through coupled use of two sites: one on the La motif and another on the RRM1 beta-surface that binds elsewhere on tRNA. (PMID:19287396)
• Nine of the 45 consecutive CHB cases (20%) were anti-Ro/La-negative with no known cause; they were less stable and complete than the anti-Ro/La positive cases (PMID:19567621)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ssb	ENSDARG00000029252
mus_musculus	Ssb	ENSMUSG00000068882
rattus_norvegicus	Ssb	ENSRNOG00000007998
rattus_norvegicus	AABR07061825.1	ENSRNOG00000011606
drosophila_melanogaster	La	FBGN0011638
caenorhabditis_elegans	ssb-1	WBGENE00016653

Paralogs (6): LARP4B (ENSG00000107929), LARP1B (ENSG00000138709), LARP1 (ENSG00000155506), LARP4 (ENSG00000161813), LARP6 (ENSG00000166173), LARP7 (ENSG00000174720)

Protein

Protein identifiers

Lupus La protein — P05455 (reviewed: P05455)

Alternative names: La autoantigen, La ribonucleoprotein, Sjoegren syndrome type B antigen

All UniProt accessions (4): P05455, E7ERC4, E9PFL9, E9PGX9

UniProt curated annotations — full annotation on UniProt →

Function. Binds to the 3’ poly(U) terminus of nascent RNA polymerase III transcripts, protecting them from exonuclease digestion and facilitating their folding and maturation. In case of Coxsackievirus B3 infection, binds to the viral internal ribosome entry site (IRES) and stimulates the IRES-mediated translation.

Subunit / interactions. Interacts with DDX15. May interact with RUFY1.

Subcellular location. Nucleus.

Post-translational modifications. Phosphorylated. The phosphorylation sites are at the C-terminal part of the protein. The N-terminus is blocked.

Miscellaneous. Sera from patients with systemic lupus erythematosus (SLE) often contain antibodies that react with the normal cellular La protein as if this antigen was foreign.

RefSeq proteins (2): NP_001281074, NP_003133* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR002344	Lupus_La	Family
IPR006630	La_HTH	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR014886	La_xRRM	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR045180	La_dom_prot	Family

Pfam: PF00076, PF05383, PF08777

UniProt features (49 total): helix 13, strand 13, modified residue 11, turn 4, domain 3, compositionally biased region 2, chain 1, sequence conflict 1, region of interest 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
2VOO	X-RAY DIFFRACTION	1.8
1ZH5	X-RAY DIFFRACTION	1.85
2VOD	X-RAY DIFFRACTION	2.1
2VON	X-RAY DIFFRACTION	2.1
1YTY	X-RAY DIFFRACTION	2.29
9NFA	ELECTRON MICROSCOPY	2.7
2VOP	X-RAY DIFFRACTION	2.8
9NF8	ELECTRON MICROSCOPY	3.1
1OWX	SOLUTION NMR
1S79	SOLUTION NMR
1S7A	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P05455-F1	75.19	0.37

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 (11): 120, 128, 225, 328, 341, 360, 362, 366, 92, 94, 116

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-73980	RNA Polymerase III Transcription Termination
R-HSA-749476	RNA Polymerase III Abortive And Retractive Initiation
R-HSA-74158	RNA Polymerase III Transcription
R-HSA-74160	Gene expression (Transcription)

MSigDB gene sets: 261 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, RNGTGGGC_UNKNOWN, SHEPARD_BMYB_MORPHOLINO_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, REACTOME_RNA_POLYMERASE_III_TRANSCRIPTION_TERMINATION, BERENJENO_ROCK_SIGNALING_NOT_VIA_RHOA_DN, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_10, GOBP_TRNA_METABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, MORF_CDK2, HSIAO_HOUSEKEEPING_GENES, MORF_HDAC2, PUJANA_CHEK2_PCC_NETWORK, GOBP_TRANSLATION, GOBP_NUCLEAR_TRANSPORT

GO Biological Process (11): tRNA 5’-leader removal (GO:0001682), tRNA modification (GO:0006400), tRNA export from nucleus (GO:0006409), tRNA processing (GO:0008033), histone mRNA metabolic process (GO:0008334), tRNA 3’-end processing (GO:0042780), positive regulation of translation (GO:0045727), nuclear histone mRNA catabolic process (GO:0071045), IRES-dependent viral translational initiation (GO:0075522), protein localization to cytoplasmic stress granule (GO:1903608), RNA processing (GO:0006396)

GO Molecular Function (7): tRNA binding (GO:0000049), RNA binding (GO:0003723), mRNA binding (GO:0003729), poly(U) RNA binding (GO:0008266), sequence-specific mRNA binding (GO:1990825), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (6): chromosome, telomeric region (GO:0000781), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), cytoplasmic stress granule (GO:0010494), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
RNA Polymerase III Transcription	2
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
tRNA processing	2
RNA binding	2
binding	2
cellular anatomical structure	2
tRNA 5’-end processing	1
RNA modification	1
RNA export from nucleus	1
tRNA transport	1
RNA processing	1
tRNA metabolic process	1
mRNA metabolic process	1
RNA 3’-end processing	1
translation	1
regulation of translation	1
positive regulation of gene expression	1
positive regulation of protein metabolic process	1
histone mRNA catabolic process	1
viral process	1
viral translation	1
protein localization to organelle	1
gene expression	1
RNA biosynthetic process	1
primary metabolic process	1
nucleic acid binding	1
poly-pyrimidine tract binding	1
mRNA binding	1
chromosomal region	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
cytoplasmic ribonucleoprotein granule	1
protein-containing complex	1

Protein interactions and networks

STRING

2556 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SSB	TRIM21	P19474	997
SSB	RO60	P10155	903
SSB	SNRNP70	P08621	824
SSB	HNRNPA1	P09651	670
SSB	ELAVL1	Q15717	569
SSB	PABPC1	P11940	544
SSB	FTL	P02792	543
SSB	SNRPN	P14648	527
SSB	ILF3	Q12906	523
SSB	MEPCE	Q7L2J0	509
SSB	RBM8A	Q9Y5S9	509
SSB	APOH	P02749	507
SSB	NUCLEOLIN	P19338	497
SSB	PCBP2	Q15366	479
SSB	SPTAN1	Q13813	479

IntAct

246 interactions, top by confidence:

A	B	Type	Score
FBL	NOP56	psi-mi:“MI:0914”(association)	0.800
TRIM33	TRIM24	psi-mi:“MI:0914”(association)	0.790
YBX1	SSB	psi-mi:“MI:0914”(association)	0.710
SNRPD2	GEMIN2	psi-mi:“MI:0914”(association)	0.710
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
HSPA2	SSB	psi-mi:“MI:0915”(physical association)	0.560
NDUFB10	SSB	psi-mi:“MI:0915”(physical association)	0.560
RAPGEF4	SSB	psi-mi:“MI:0915”(physical association)	0.560
	SSB	psi-mi:“MI:0915”(physical association)	0.560
SSB	HTT	psi-mi:“MI:0915”(physical association)	0.560
RPS6	IPO7	psi-mi:“MI:0914”(association)	0.530
H1-4	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
N	RBM47	psi-mi:“MI:0914”(association)	0.530
CBX6	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
SURF2	HEXIM1	psi-mi:“MI:0914”(association)	0.530
SART3	NSA2	psi-mi:“MI:0914”(association)	0.530
RO60	SSB	psi-mi:“MI:0914”(association)	0.530
RPS2	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
PRPF31	SSB	psi-mi:“MI:0914”(association)	0.510
steC	SCD	psi-mi:“MI:0914”(association)	0.460

BioGRID (616): SSB (Affinity Capture-MS), SSB (Affinity Capture-MS), SSB (Affinity Capture-MS), SSB (Affinity Capture-MS), SSB (Affinity Capture-MS), SSB (Affinity Capture-MS), ANKMY2 (Co-fractionation), EEF1A1 (Co-fractionation), LARP7 (Co-fractionation), NAT10 (Co-fractionation), NIFK (Co-fractionation), POLE (Co-fractionation), POLR1C (Co-fractionation), RBM34 (Co-fractionation), SMC3 (Co-fractionation)

ESM2 similar proteins: A1DAY1, A3LSY0, A3LXL0, A5DGV3, A6ZPY2, B3DJT0, O42929, P04147, P05455, P09874, P10881, P11103, P18493, P20232, P26446, P27008, P27124, P28048, P28049, P31669, P32067, P33399, P37838, P38656, P40796, P47089, P87058, Q02790, Q09464, Q15020, Q16VC0, Q26457, Q4WBL6, Q5AI15, Q5AJS6, Q5REG1, Q5RHR0, Q6BH22, Q6BI95, Q6CDH3

Diamond homologs: D5MCN2, J9VT60, O80567, P05455, P10881, P25567, P28048, P28049, P32067, P33399, P38656, P40796, Q05CL8, Q12034, Q26457, Q28G87, Q4G0J3, Q4R627, Q5XI01, Q659C4, Q6PKG0, Q6ZQ58, Q71RC2, Q7ZWE3, Q8BN59, Q8BWW4, Q8RWR2, Q94A38, Q94K80, Q9BRS8, Q9I7T7, Q9LHL3, Q9P6K0, Q9VAW5, Q940X9, P87058, Q04504, Q0V7U7, Q6A0A2, Q92615

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CSNK2A1	up-regulates	SSB	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 204 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
SARS-CoV-2 modulates host translation machinery	10	16.2×	1e-07
Eukaryotic Translation Initiation	7	15.7×	9e-06
Cap-dependent Translation Initiation	7	15.7×	9e-06
SARS-CoV-1 modulates host translation machinery	7	15.7×	9e-06
Eukaryotic Translation Elongation	7	14.1×	1e-05
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	7	13.8×	2e-05
Influenza Viral RNA Transcription and Replication	8	12.5×	9e-06
Nonsense-Mediated Decay (NMD)	7	11.8×	4e-05

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of cytoplasmic translation	5	28.2×	1e-04
ribosomal small subunit biogenesis	9	11.7×	2e-05
cytoplasmic translation	11	11.6×	2e-06
rRNA processing	12	9.7×	2e-06
translation	14	8.2×	2e-06
negative regulation of translation	7	7.8×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

60 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	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1587 predictions. Top by Δscore:

Variant	Effect	Δscore
2:169798975:AG:A	donor_gain	1.0000
2:169798976:GG:G	donor_gain	1.0000
2:169798977:G:GG	donor_gain	1.0000
2:169801023:TGAG:T	donor_loss	1.0000
2:169801025:AGGTA:A	donor_loss	1.0000
2:169801027:GTAT:G	donor_loss	1.0000
2:169801028:T:A	donor_loss	1.0000
2:169805468:TCACA:T	acceptor_loss	1.0000
2:169805470:ACAGT:A	acceptor_loss	1.0000
2:169805471:CAGTA:C	acceptor_loss	1.0000
2:169805472:A:AG	acceptor_gain	1.0000
2:169805472:AGTA:A	acceptor_loss	1.0000
2:169805473:G:GT	acceptor_gain	1.0000
2:169805473:GT:G	acceptor_gain	1.0000
2:169805473:GTA:G	acceptor_gain	1.0000
2:169805473:GTAT:G	acceptor_gain	1.0000
2:169805473:GTATT:G	acceptor_gain	1.0000
2:169805573:AACAG:A	donor_loss	1.0000
2:169805574:ACAGG:A	donor_loss	1.0000
2:169805575:CAGG:C	donor_loss	1.0000
2:169805576:AG:A	donor_loss	1.0000
2:169805577:GGTAA:G	donor_loss	1.0000
2:169805578:G:C	donor_loss	1.0000
2:169805579:T:A	donor_loss	1.0000
2:169805659:CTTCA:C	acceptor_loss	1.0000
2:169805660:TTCA:T	acceptor_loss	1.0000
2:169805662:CAG:C	acceptor_loss	1.0000
2:169805663:A:AG	acceptor_gain	1.0000
2:169805663:A:AT	acceptor_loss	1.0000
2:169805664:G:GG	acceptor_gain	1.0000

AlphaMissense

2741 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:169805477:T:C	Y24H	1.000
2:169805496:T:C	L30S	1.000
2:169805504:G:C	D33H	1.000
2:169805505:A:C	D33A	1.000
2:169805505:A:G	D33G	1.000
2:169805505:A:T	D33V	1.000
2:169805506:C:A	D33E	1.000
2:169805506:C:G	D33E	1.000
2:169805510:T:C	F35L	1.000
2:169805511:T:C	F35S	1.000
2:169805511:T:G	F35C	1.000
2:169805512:T:A	F35L	1.000
2:169805512:T:G	F35L	1.000
2:169805514:T:C	L36P	1.000
2:169805543:T:A	W46R	1.000
2:169805543:T:C	W46R	1.000
2:169805570:T:A	F55I	1.000
2:169805570:T:C	F55L	1.000
2:169805570:T:G	F55V	1.000
2:169805571:T:C	F55S	1.000
2:169805572:C:A	F55L	1.000
2:169805572:C:G	F55L	1.000
2:169805577:G:C	R57T	1.000
2:169805577:G:T	R57M	1.000
2:169805665:G:C	R57S	1.000
2:169805665:G:T	R57S	1.000
2:169805667:T:C	L58S	1.000
2:169805763:G:C	R90T	1.000
2:169805766:G:C	R91T	1.000
2:169805766:G:T	R91M	1.000

dbSNP variants (sampled 300 via entrez): RS1000062870 (2:169812221 T>C), RS1000367676 (2:169805228 A>G), RS1000399055 (2:169812515 C>T), RS1000745872 (2:169809125 A>C,G), RS1000749513 (2:169801955 G>A), RS1000803233 (2:169802269 A>C,T), RS1001125468 (2:169798965 G>A,C), RS1001306882 (2:169811411 G>A,T), RS1001432478 (2:169805062 G>A), RS1001586899 (2:169799000 G>A), RS1001921129 (2:169805285 T>C), RS1002100014 (2:169800580 A>G), RS1002266736 (2:169809786 G>A), RS1002683764 (2:169807286 TTTTC>T), RS1002770878 (2:169803796 G>A,C)

Disease associations

OMIM: gene MIM:109090 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST005184_8	Common carotid intima-media thickness in HIV infection	5.000000e-06
GCST005891_7	Glomerular filtration rate in diabetes	1.000000e-06
GCST008504_9	Fasting glucose change (long-term)	4.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2040701 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
8.00	IC50	10	nM	MOLIBRESIB
7.55	Kd	27.85	nM	CHEMBL5653589
7.55	ED50	27.85	nM	CHEMBL5653589
5.71	Kd	1940	nM	CHEMBL3752910
5.71	ED50	1940	nM	CHEMBL3752910

PubChem BioAssay actives

3 with measured affinity, of 24 total; 3 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
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178552: Inhibition of SSB (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.0100	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149496: Binding affinity to human SSB incubated for 45 mins by Kinobead based pull down assay	kd	0.0278	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149496: Binding affinity to human SSB incubated for 45 mins by Kinobead based pull down assay	kd	1.9399	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol F	increases expression, affects cotreatment	2
bisphenol A	decreases expression	2
sodium arsenite	decreases expression, increases abundance, increases expression	2
perfluorooctane sulfonic acid	decreases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
dicrotophos	decreases expression	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
coumarin	increases phosphorylation	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
SB 203580	decreases reaction, increases secretion	1
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	decreases reaction, increases secretion	1
deguelin	increases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	increases expression	1
bisphenol B	increases expression	1
2-amino-14,16-dimethyloctadecan-3-ol	decreases expression	1
pyrachlostrobin	increases expression	1
jinfukang	decreases expression	1
bisphenol AF	increases expression	1
Resveratrol	increases expression, affects cotreatment	1
Arsenic Trioxide	decreases expression	1
Acetaminophen	decreases expression	1
Aminoglutethimide	decreases expression	1
Ammonium Chloride	decreases reaction, increases expression, increases secretion	1
Arsenic	increases abundance, increases expression	1
Caffeine	affects phosphorylation	1
Chloroquine	decreases reaction, increases expression, increases secretion	1
Dichlorodiphenyl Dichloroethylene	increases expression	1

ChEMBL screening assays

10 unique, capped per target: 9 binding, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2046250	ADMET	Binding affinity to human La antigen by NMR based ALARM assay	A novel class of highly potent irreversible hepatitis C virus NS5B polymerase inhibitors. — J Med Chem
CHEMBL3419563	Binding	Induction of thiol reactivity with La protein (unknown origin) using 13C labeled compound assessed as protein reactivity by ALARM NMR	PAINS in the assay: chemical mechanisms of assay interference and promiscuous enzymatic inhibition observed during a sulfhydryl-scavenging HTS. — J Med Chem

Clinical trials (associated diseases)

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