SLBP

Summary

SLBP (stem-loop histone mRNA binding protein, HGNC:10904) is a protein-coding gene on chromosome 4p16.3, encoding Histone RNA hairpin-binding protein (Q14493). RNA-binding protein involved in the histone pre-mRNA processing. It is a selective cancer dependency (DepMap: 43.7% of cell lines).

This gene encodes a protein that binds to the stem-loop structure in replication-dependent histone mRNAs. Histone mRNAs do not contain introns or polyadenylation signals, and are processed by endonucleolytic cleavage. The stem-loop structure is essential for efficient processing but this structure also controls the transport, translation and stability of histone mRNAs. Expression of the protein is regulated during the cell cycle, increasing more than 10-fold during the latter part of G1.

Source: NCBI Gene 7884 — RefSeq curated summary.

At a glance

• GWAS associations: 14
• Clinical variants (ClinVar): 35 total
• Cancer dependency (DepMap): dependent in 43.7% of screened cell lines
• MANE Select transcript: NM_006527

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10904
Approved symbol	SLBP
Name	stem-loop histone mRNA binding protein
Location	4p16.3
Locus type	gene with protein product
Status	Approved
Aliases	HBP
Ensembl gene	ENSG00000163950
Ensembl biotype	protein_coding
OMIM	602422
Entrez	7884

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 12 protein_coding

ENST00000318386, ENST00000429429, ENST00000480936, ENST00000483348, ENST00000488267, ENST00000489418, ENST00000904662, ENST00000904663, ENST00000904664, ENST00000904665, ENST00000929510, ENST00000952427

RefSeq mRNA: 3 — MANE Select: NM_006527 NM_001306074, NM_001306075, NM_006527

CCDS: CCDS3350, CCDS77889, CCDS82903

Canonical transcript exons

ENST00000489418 — 8 exons

Exon	Start	End
ENSE00001079962	1700011	1700070
ENSE00001079964	1711874	1711990
ENSE00001079965	1696202	1696351
ENSE00001079968	1699564	1699701
ENSE00001079969	1694774	1694840
ENSE00001079970	1703596	1703700
ENSE00001838144	1712130	1712319
ENSE00003842723	1692731	1693713

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 98.28.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 55.0915 / max 408.6724, expressed in 1823 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
51085	42.7590	1822
51083	7.3903	1770
51084	4.9422	1715

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	98.28	gold quality
secondary oocyte	CL:0000655	96.82	gold quality
adult organism	UBERON:0007023	95.53	gold quality
right testis	UBERON:0004534	95.17	gold quality
cortical plate	UBERON:0005343	94.89	gold quality
left testis	UBERON:0004533	94.80	gold quality
bone marrow	UBERON:0002371	94.50	gold quality
parotid gland	UBERON:0001831	94.20	gold quality
testis	UBERON:0000473	94.17	gold quality
ganglionic eminence	UBERON:0004023	94.12	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	94.09	gold quality
ventricular zone	UBERON:0003053	94.09	gold quality
pigmented layer of retina	UBERON:0001782	93.84	gold quality
vermiform appendix	UBERON:0001154	93.77	gold quality
calcaneal tendon	UBERON:0003701	93.76	gold quality
embryo	UBERON:0000922	93.75	gold quality
trabecular bone tissue	UBERON:0002483	93.75	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.36	gold quality
lymph node	UBERON:0000029	93.28	gold quality
islet of Langerhans	UBERON:0000006	93.08	gold quality
monocyte	CL:0000576	92.81	gold quality
leukocyte	CL:0000738	92.81	gold quality
prefrontal cortex	UBERON:0000451	92.79	gold quality
seminal vesicle	UBERON:0000998	92.73	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	92.73	gold quality
mononuclear cell	CL:0000842	92.72	gold quality
cartilage tissue	UBERON:0002418	92.46	gold quality
skin of abdomen	UBERON:0001416	92.45	gold quality
placenta	UBERON:0001987	92.37	gold quality
bone marrow cell	CL:0002092	92.34	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-6911	no	428.50
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC, UPF1

miRNA regulators (miRDB)

52 targeting SLBP, 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-4789-3P	99.99	70.75	2484
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-1284	99.67	73.56	1353
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-4753-5P	99.54	68.51	1356
HSA-MIR-4643	99.49	67.63	1791

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 43.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 32)

• SLBP is the only cell cycle-regulated factor required for histone pre-mRNA processing (PMID:12588979)
• human HBP/SLBP is essential for the coordinate synthesis of DNA and histone proteins and is required for progression through the cell division cycle (PMID:15546920)
• SLBP is imported into the cell nucleus during the cell cycle. (PMID:15829567)
• SLBP is required for efficient DNA replication probably because a decreased ability to assemble chromatin results in a decrease in the rate of DNA replication (PMID:15916543)
• Removal of the phosphoryl group from T230 by either dephosphorylation or mutation results in a 7-fold reduction in the affinity of SLBP for the stem-loop RNA (PMID:16492733)
• replication-dependent histone mRNAs are likely to be the sole target of SLBP (PMID:16931877)
• SLBP is required for efficient histone 3’-UTR end processing. (PMID:16982637)
• Here we show that NELF interacts with the cap binding complex (CBC), a factor that plays important roles in mRNA processing steps, and the two factors together participate in the 3’ end processing of histone mRNAs, through association with the SLBP. (PMID:17499042)
• identified five conserved residues in a 15-amino-acid region in the amino-terminal portion of SLBP, each of which is required for translation. (PMID:18025107)
• Study concludes that the increase in cyclin A/Cdk1 activity at the end of S phase triggers degradation of SLBP at S/G(2). (PMID:18490441)
• These results suggest a previously undescribed role for SLBP in histone mRNA export. (PMID:19155325)
• haploinsufficiency of SLBP and/or WHSC2 (NELF-A) contributes to several novel cellular phenotypes of WHS. (PMID:22328085)
• The nuclear magnetic resonance and kinetic studies presented here provide a framework for understanding how SLBP recognizes histone mRNA and highlight possible structural roles of phosphorylation and proline isomerization in RNA binding proteins (PMID:22439849)
• This paper shows that SLBP is a substrate for the prolyl isomerase Pin1. Pin1, along with PP2A, facilitates dissociation of the SLBP-histone mRNA complex at the end of S-phase, thereby promoting histone mRNA decay and SLBP ubiquitination. (PMID:22907757)
• Using yeast two-hybrid screening, the authors identify CT initiation factor-interacting protein (CTIF) as a protein that binds directly to SLBP. SLBP preferentially associates with the CT complex of histone mRNAs consisting of CBP80/CBP20, but not with the eIF4E/eIF4G (ET) complex, as has been proposed. Rapid degradation of histone mRNA on the inhibition of DNA replication requires association of SLBP with CTIF. (PMID:23234701)
• Data suggest that oligomerization and SLBP phosphorylation regulate SLBP-SLIP1-histone-mRNA complex formation/disassociation; sequential and ordered assembly is required. (PMID:23286197)
• This paper describes the biophysical characterization of human SLBP and the SLBP-SLIP1 complex. Human SLBP is an intrinsically disordered protein that is phosphorylated at 23 Ser/Thr sites when expressed in a eukaryotic expression system such as baculovirus. Unphosphorylated human SLBP forms a high affinity heterotetramer with SLIP1 and the SLBP-SLIP1 complex is regulated by SLBP phosphorylation. (PMID:23286197)
• the crystal structure of a ternary complex of human SLBP RNA binding domain, human 3’hExo, and a 26-nucleotide stem-loop RNA is reported. (PMID:23329046)
• Alternative splicing allows the synthesis of HBP/SLBP isoforms with different properties that may be important for regulating HBP/SLBP functions during replication stress. (PMID:23941746)
• the S/G2 stable mutant form of SLBP is degraded by proteasome in G1, indicating that indicating that the SLBP degradation in G1 is independent of the previously identified SLBP degradation at S/G2 (PMID:24122909)
• C-terminal extension of Lsm4 interacts directly with the histone mRNP, contacting both SLBP and 3’hExo. (PMID:24255165)
• Although the C-terminal tail of dSLBP does not contact the RNA, phosphorylation of the tail promotes SLBP conformations competent for RNA binding and thereby appears to reduce the entropic penalty for the association. (PMID:25002523)
• arsenic, a carcinogenic metal, decreases cellular levels of SLBP by inducing its proteasomal degradation and inhibiting SLBP transcription via epigenetic mechanisms (PMID:25266719)
• CRL4(WDR23) is required for efficient histone mRNA 3’ end processing to produce mature histone mRNAs for translation. CRL4(WDR23) binds and ubiquitylates SLBP in vitro and in vivo, and this modification activates SLBP function in histone mRNA 3’ end processing without affecting its protein levels. (PMID:27203182)
• CRL4-DCAF11 mediates the degradation of SLBP at the end of S phase and this degradation is essential for the viability of cells. (PMID:27254819)
• SLBP is a potentially important cellular regulator of HIV-1, thereby establishing a link between histone metabolism, inflammation, and HIV-1 infection (PMID:27454292)
• Cyclin F-mediated degradation of SLBP limits H2A.X accumulation and apoptosis upon genotoxic stress in G2 cell cycle checkpoint. (PMID:27773672)
• FEM1 proteins are ancient regulators of Stem-Loop Binding Protein. (PMID:28118078)
• showed that inhibiting the SLBP mRNA and protein levels were rescued by epigenetic modifiers suggesting that nickel’s effects on SLBP may be mediated via epigenetic mechanisms (PMID:28306745)
• Knocking down miR-384 promotes growth and metastasis of osteosarcoma MG63 cells by targeting SLBP (PMID:31007083)
• Influenza A virus co-opts ERI1 exonuclease bound to histone mRNA to promote viral transcription. (PMID:32960265)
• DRAIC promotes growth of breast cancer by sponging miR-432-5p to upregulate SLBP. (PMID:34645975)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	slbp	ENSDARG00000100558
mus_musculus	Slbp	ENSMUSG00000004642
rattus_norvegicus	Slbp	ENSRNOG00000037162
drosophila_melanogaster	Slbp	FBGN0041186
caenorhabditis_elegans		WBGENE00000411

Protein

Protein identifiers

Histone RNA hairpin-binding protein — Q14493 (reviewed: Q14493)

Alternative names: Histone stem-loop-binding protein

All UniProt accessions (6): E7EUV9, Q14493, F8W8D3, H0YAE8, H7C4H8, Q53XR2

UniProt curated annotations — full annotation on UniProt →

Function. RNA-binding protein involved in the histone pre-mRNA processing. Binds the stem-loop structure of replication-dependent histone pre-mRNAs and contributes to efficient 3’-end processing by stabilizing the complex between histone pre-mRNA and U7 small nuclear ribonucleoprotein (snRNP), via the histone downstream element (HDE). Plays an important role in targeting mature histone mRNA from the nucleus to the cytoplasm and to the translation machinery. Stabilizes mature histone mRNA and could be involved in cell-cycle regulation of histone gene expression. Involved in the mechanism by which growing oocytes accumulate histone proteins that support early embryogenesis. Binds to the 5’ side of the stem-loop structure of histone pre-mRNAs.

Subunit / interactions. Monomer. SLBP/pre-mRNA complex interacts with ZNF473. Interacts with the Importin alpha/Importin beta receptor, LSM1, MIF4GD, TNPO3 and UPF1. Interaction with LSM1 occurs when histone mRNA is being rapidly degraded during the S phase. Found in a ternary complex with ERI1 and the stem-loop structure of the 3’ end of histone mRNA. Associates with polyribosomes. Identified in a histone pre-mRNA complex, at least composed of ERI1, LSM11, SLBP, SNRPB, SYNCRIP and YBX1. Binds in a cooperative manner with ERI1 to the mature 3’-end of histone mRNAs.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Widely expressed.

Post-translational modifications. Phosphorylated on Thr-61 and Thr-62 in the S-phase. Phosphorylation of Thr-62 by CDK1 primes phosphorylation of Thr-61 by CK2. Phosphorylation of Thr-62 is required for its degradation by the proteasome at the end of the S phase. Its degradation is not required for histone mRNA degradation at the end of the S phase. All the phosphorylated forms detected are present in the cytoplasm. Both unphosphorylated and phosphorylated forms bind the stem-loop structure of histone mRNAs. Phosphorylation at Thr-171 increases affinity for histone mRNAs. Ubiquitinated by the CRL2(FEM1A), CRL2(FEM1B) and CRL2(FEM1C) complexes, leading to its degradation.

Domain organisation. Amino acids 31-34, 96-99 and 241-244 are necessary for interaction with the Importin alpha/Importin beta receptor. The first 18 amino acids, amino acids 69-76 and 179-182 are necessary for interaction with TNPO3. Amino acids 31-34, 96-99 and 241-244 are necessary for nuclear localization.

Similarity. Belongs to the SLBP family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q14493-1	1	yes
Q14493-2	2

RefSeq proteins (3): NP_001293003, NP_001293004, NP_006518* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026502	SLBP1/SLBP2	Family
IPR029344	SLBP_RNA_bind	Domain
IPR038294	SLBP_RNA_bind_sf	Homologous_superfamily

Pfam: PF15247

UniProt features (34 total): mutagenesis site 11, modified residue 7, helix 4, region of interest 3, compositionally biased region 3, short sequence motif 2, chain 1, cross-link 1, splice variant 1, turn 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
4QOZ	X-RAY DIFFRACTION	2.3
4L8R	X-RAY DIFFRACTION	2.6
2KJM	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14493-F1	71.27	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 (8): 23, 59, 61, 62, 171, 182, 98, 20

Mutagenesis-validated functional residues (11):

Position	Phenotype
31–34	reduces interaction with the importin alpha/importin beta receptor. abolishes interaction with the importin alpha/import
59–63	does not increase its stability at the end of the s phase and through g2 and mitosis.
59	does not increase its stability at the end of the s phase and through g2 and mitosis.
61	increases its stability at the end of the s phase and through g2 and mitosis. active in histone pre-mrna processing duri
62	increases its stability at the end of the s phase and through g2 and mitosis.
63	increases its stability at the end of the s phase and through g2 and mitosis.
96–99	increases its stability at the end of the s phase and through g2 and mitosis. inhibits phosphorylation of t-62. localize
137	inhibits histone rna-binding and localization to the cytoplasm.
138	inhibits histone rna-binding and localization to the cytoplasm.
230–270	decrease in 3’-end processing efficiency.
241–244	reduces interaction with the importin alpha/importin beta receptor. abolishes interaction with the importin alpha/import

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-159230	Transport of the SLBP Dependant Mature mRNA
R-HSA-73856	RNA Polymerase II Transcription Termination
R-HSA-77588	SLBP Dependent Processing of Replication-Dependent Histone Pre-mRNAs
R-HSA-159234	Transport of Mature mRNAs Derived from Intronless Transcripts
R-HSA-72202	Transport of Mature Transcript to Cytoplasm
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

MSigDB gene sets: 279 (showing top): GSE45365_NK_CELL_VS_BCELL_UP, GOBP_CYTOPLASMIC_TRANSLATION, MORF_DNMT1, E2F_Q4_01, MORF_SMC1L1, PAL_PRMT5_TARGETS_UP, FISCHER_G1_S_CELL_CYCLE, MORF_RRM1, MORF_UBE2N, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_TRANSLATIONAL_INITIATION, GENTILE_RESPONSE_CLUSTER_D3, MORF_HDAC2, MODULE_16

GO Biological Process (4): cap-dependent translational initiation (GO:0002191), mRNA 3’-end processing by stem-loop binding and cleavage (GO:0006398), mRNA transport (GO:0051028), mRNA processing (GO:0006397)

GO Molecular Function (6): RNA binding (GO:0003723), mRNA binding (GO:0003729), identical protein binding (GO:0042802), histone pre-mRNA stem-loop binding (GO:0071207), histone pre-mRNA DCP binding (GO:0071208), protein binding (GO:0005515)

GO Cellular Component (8): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), histone mRNA stem-loop binding complex (GO:0062073), histone pre-mRNA 3’end processing complex (GO:0071204), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Metabolism of RNA	2
Transport of Mature mRNAs Derived from Intronless Transcripts	1
RNA Polymerase II Transcription	1
Processing of Capped Intronless Pre-mRNA	1
Transport of Mature Transcript to Cytoplasm	1
Processing of Capped Intron-Containing Pre-mRNA	1
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
RNA binding	2
nuclear lumen	2
cytoplasm	2
protein-containing complex	2
cytoplasmic translational initiation	1
cap-dependent translation initiation factor activity	1
histone mRNA metabolic process	1
mRNA 3’-end processing	1
RNA transport	1
RNA processing	1
mRNA metabolic process	1
nucleic acid binding	1
protein binding	1
pre-mRNA binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1

Protein interactions and networks

STRING

1870 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLBP	MIF4GD	A9UHW6	988
SLBP	ERI1	Q8IV48	971
SLBP	UPF1	Q92900	932
SLBP	NASP	P49321	911
SLBP	LSM11	P83369	868
SLBP	ZNF473	Q8WTR7	854
SLBP	LSM10	Q969L4	794
SLBP	DEDD	O75618	785
SLBP	EIF4G1	Q04637	776
SLBP	HDAC1	Q13547	759
SLBP	RBBP4	P31149	748
SLBP	H1-6	P22492	738
SLBP	SYMPK	Q92797	718
SLBP	CPSF3	Q9UKF6	704
SLBP	CPSF2	Q9P2I0	700

IntAct

55 interactions, top by confidence:

A	B	Type	Score
MIF4GD	SLBP	psi-mi:“MI:0407”(direct interaction)	0.760
MIF4GD	SLBP	psi-mi:“MI:0915”(physical association)	0.760
P4HA3	FAM171A2	psi-mi:“MI:0914”(association)	0.640
KSR2	POLR3A	psi-mi:“MI:0914”(association)	0.530
GSTM3	ECT2L	psi-mi:“MI:0914”(association)	0.530
ZFC3H1	HNRNPCL1	psi-mi:“MI:0914”(association)	0.530
GATAD1	SIN3B	psi-mi:“MI:0914”(association)	0.530
SLBP	ACAD11	psi-mi:“MI:0914”(association)	0.530
RPS3	ZNF316	psi-mi:“MI:0914”(association)	0.530
SLBP	ERI1	psi-mi:“MI:0915”(physical association)	0.520
SLBP	SLBP	psi-mi:“MI:0407”(direct interaction)	0.520

BioGRID (112): SLBP (Affinity Capture-MS), SLBP (Proximity Label-MS), SLBP (Affinity Capture-MS), FEM1A (Affinity Capture-Western), FEM1B (Affinity Capture-Western), FEM1C (Affinity Capture-Western), CUL2 (Affinity Capture-Western), NCBP1 (Affinity Capture-Western), CTIF (Affinity Capture-Western), CCNF (Affinity Capture-Western), CCNA2 (Affinity Capture-Western), UPF1 (Affinity Capture-Western), DCAF11 (Reconstituted Complex), CUL4A (Reconstituted Complex), DCAF11 (Affinity Capture-Western)

ESM2 similar proteins: A0A286YDK6, A0A286YF18, A5PKK9, A8WFF7, F5HGI9, O08664, O10331, O12165, P03407, P05856, P06499, P12479, P17473, P27114, P28925, P46695, P52511, P52512, P89457, Q00336, Q14493, Q17QW1, Q32LJ5, Q5STR5, Q66619, Q6NZY7, Q6S6U0, Q6VUC0, Q75009, Q7YR42, Q82855, Q84240, Q86YL5, Q89448, Q8BGN9, Q8BRE0, Q8C1R3, Q8N4L4, Q8N5W9, Q8QVL8

Diamond homologs: P79943, P97440, Q09599, Q14493, Q9VAN6, Q9YGP6

SIGNOR signaling

51 interactions.

A	Effect	B	Mechanism
CDK1	“down-regulates quantity by destabilization”	SLBP	phosphorylation
CyclinA2/CDK2	“down-regulates quantity by destabilization”	SLBP	phosphorylation
CSNK2A1	“down-regulates quantity by destabilization”	SLBP	phosphorylation
SLBP	“up-regulates quantity by expression”	“Histone H3”	“translation regulation”
SLBP	“up-regulates quantity by expression”	“Histone H2A”	“translation regulation”
SLBP	“up-regulates quantity by expression”	“Histone H2B”	“translation regulation”
SLBP	“up-regulates quantity by expression”	H4C1	“translation regulation”
SLBP	“up-regulates quantity by expression”	H2BC4	“translation regulation”
SLBP	“up-regulates quantity by expression”	H2BC5	“translation regulation”
SLBP	“up-regulates quantity by expression”	H2BC17	“translation regulation”
SLBP	“up-regulates quantity by expression”	H2BE1	“translation regulation”
SLBP	“up-regulates quantity by expression”	H2BC11	“translation regulation”
SLBP	“up-regulates quantity by expression”	H2BC20P	“translation regulation”
SLBP	“up-regulates quantity by expression”	H2BC12	“translation regulation”
SLBP	“up-regulates quantity by expression”	H2BS1	“translation regulation”
SLBP	“up-regulates quantity by expression”	H2BC3	“translation regulation”
SLBP	“up-regulates quantity by expression”	H2BC21	“translation regulation”
SLBP	“up-regulates quantity by expression”	H2BW1	“translation regulation”
SLBP	“up-regulates quantity by expression”	H2BU1	“translation regulation”
SLBP	“up-regulates quantity by expression”	H2BC13	“translation regulation”
SLBP	“up-regulates quantity by expression”	H2BC14	“translation regulation”
SLBP	“up-regulates quantity by expression”	H2BC9	“translation regulation”
SLBP	“up-regulates quantity by expression”	H2BC15	“translation regulation”
SLBP	“up-regulates quantity by expression”	H2BC1	“translation regulation”
SLBP	“up-regulates quantity by expression”	H2BC18	“translation regulation”
SLBP	“up-regulates quantity by expression”	H2BW2	“translation regulation”
SLBP	“up-regulates quantity by expression”	H2AC18	“translation regulation”
SLBP	“up-regulates quantity by expression”	H2AC4	“translation regulation”
SLBP	“up-regulates quantity by expression”	H2AC20	“translation regulation”
SLBP	“up-regulates quantity by expression”	H2AC7	“translation regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	24
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

910 predictions. Top by Δscore:

Variant	Effect	Δscore
4:1693710:CATC:C	acceptor_gain	1.0000
4:1693714:CTGGA:C	acceptor_loss	1.0000
4:1694770:TTA:T	donor_loss	1.0000
4:1694771:TACAA:T	donor_loss	1.0000
4:1694772:A:AC	donor_gain	1.0000
4:1694772:A:T	donor_loss	1.0000
4:1694773:C:A	donor_loss	1.0000
4:1694773:C:CG	donor_gain	1.0000
4:1694773:CA:C	donor_gain	1.0000
4:1694773:CAA:C	donor_gain	1.0000
4:1694773:CAAA:C	donor_gain	1.0000
4:1694773:CAAAG:C	donor_gain	1.0000
4:1694839:GT:G	acceptor_gain	1.0000
4:1694841:C:CC	acceptor_gain	1.0000
4:1696200:A:AC	donor_gain	1.0000
4:1696201:C:CC	donor_gain	1.0000
4:1696201:CATTT:C	donor_gain	1.0000
4:1696219:T:TA	donor_gain	1.0000
4:1699559:ACTAC:A	donor_loss	1.0000
4:1699560:CTACC:C	donor_loss	1.0000
4:1699561:TA:T	donor_loss	1.0000
4:1699562:A:T	donor_loss	1.0000
4:1699563:C:CA	donor_loss	1.0000
4:1699565:TTGGG:T	donor_gain	1.0000
4:1699566:TGGG:T	donor_gain	1.0000
4:1699573:T:TA	donor_gain	1.0000
4:1699607:T:TA	donor_gain	1.0000
4:1699608:C:A	donor_gain	1.0000
4:1699697:CAGAA:C	acceptor_gain	1.0000
4:1699698:AGAA:A	acceptor_gain	1.0000

AlphaMissense

1792 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:1696242:A:G	W197R	1.000
4:1696242:A:T	W197R	1.000
4:1696261:C:A	W190C	1.000
4:1696261:C:G	W190C	1.000
4:1696262:C:G	W190S	1.000
4:1696263:A:G	W190R	1.000
4:1696263:A:T	W190R	1.000
4:1696282:C:A	W183C	1.000
4:1696282:C:G	W183C	1.000
4:1696283:C:G	W183S	1.000
4:1696284:A:G	W183R	1.000
4:1696284:A:T	W183R	1.000
4:1696316:G:T	P172H	1.000
4:1696317:G:A	P172S	1.000
4:1696325:G:T	P169H	1.000
4:1699583:A:C	Y154D	1.000
4:1699605:C:A	K146N	1.000
4:1699605:C:G	K146N	1.000
4:1699609:C:T	G145E	1.000
4:1699629:T:A	R138S	1.000
4:1699629:T:G	R138S	1.000
4:1699630:C:G	R138T	1.000
4:1696240:C:A	W197C	0.999
4:1696240:C:G	W197C	0.999
4:1696246:A:C	H195Q	0.999
4:1696246:A:T	H195Q	0.999
4:1696248:G:C	H195D	0.999
4:1696250:A:G	L194P	0.999
4:1696250:A:T	L194Q	0.999
4:1696265:A:G	L189P	0.999

dbSNP variants (sampled 300 via entrez): RS1000154192 (4:1695038 G>A), RS1000268056 (4:1700429 G>A), RS1000379677 (4:1707680 C>A), RS1000662263 (4:1712202 G>A,C,T), RS1000868387 (4:1701764 G>A,C), RS1000899512 (4:1705568 T>C), RS1001076937 (4:1710515 CAGAA>C), RS1001275523 (4:1700208 T>C), RS1001371595 (4:1705826 AAAAT>A), RS1001389395 (4:1702080 C>G,T), RS1001392011 (4:1705308 A>G), RS1001463813 (4:1705479 C>CTT), RS1001503247 (4:1698850 G>C), RS1001503561 (4:1706780 G>A,C), RS1001660881 (4:1694854 T>G)

Disease associations

OMIM: gene MIM:602422 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST000639_2	Urinary bladder cancer	1.000000e-11
GCST003853_7	Hip minimal joint space width	1.000000e-06
GCST004067_189	Hip circumference adjusted for BMI	8.000000e-07
GCST004067_74	Hip circumference adjusted for BMI	6.000000e-10
GCST009391_766	Metabolite levels	2.000000e-06
GCST010699_17	Brain morphology (min-P)	5.000000e-10
GCST010701_28	Cortical surface area (MOSTest)	3.000000e-32
GCST010702_46	Subcortical volume (MOSTest)	5.000000e-10
GCST010703_270	Brain morphology (MOSTest)	5.000000e-13
GCST90002396_265	Mean reticulocyte volume	4.000000e-15
GCST90013407_164	Liver enzyme levels (gamma-glutamyl transferase)	1.000000e-15
GCST90020026_277	Hip index	5.000000e-09
GCST90020028_1702	Hip circumference adjusted for BMI	2.000000e-09
GCST90020028_1703	Hip circumference adjusted for BMI	2.000000e-19

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0007873	cartilage thickness measurement
EFO:0008039	BMI-adjusted hip circumference
EFO:0010392	sphingomyelin 16:1 measurement
EFO:0004346	neuroimaging measurement
EFO:0010701	mean reticulocyte volume
EFO:0004532	serum gamma-glutamyl transferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, decreases reaction, increases expression	4
Benzo(a)pyrene	increases expression, decreases expression	2
Cisplatin	decreases expression, increases expression	2
Cyclosporine	affects expression, increases expression	2
Aflatoxin B1	increases expression	2
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
manganese chloride	decreases expression, increases abundance	1
benzo(e)pyrene	decreases methylation	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
coumarin	decreases phosphorylation	1
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	decreases expression, decreases reaction	1
deguelin	increases expression	1
corosolic acid	decreases expression	1
2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole	decreases expression, decreases reaction	1
abrine	decreases expression	1
picoxystrobin	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Fulvestrant	decreases methylation	1
Troglitazone	decreases expression	1
Roscovitine	decreases expression, decreases reaction	1
Acetaminophen	increases expression	1
Adenine	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Azacitidine	decreases expression, decreases reaction	1
Azathioprine	decreases expression	1
Bungarotoxins	decreases expression, decreases reaction	1
Colchicine	decreases expression	1
Coumestrol	increases expression, affects cotreatment	1
Dichlorodiphenyl Dichloroethylene	increases expression	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A6F7	SEES3-1V human SLBP, clone1	Embryonic stem cell	Male
CVCL_A6F8	SEES3-1V human SLBP, clone2	Embryonic stem cell	Male
CVCL_A6F9	SEES3-1V human SLBP, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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