RBM38

Summary

RBM38 (RNA binding motif protein 38, HGNC:15818) is a protein-coding gene on chromosome 20q13.31, encoding RNA-binding protein 38 (Q9H0Z9). RNA-binding protein that specifically bind the 3’-UTR of CDKN1A transcripts, leading to maintain the stability of CDKN1A transcripts, thereby acting as a mediator of the p53/TP53 family to regulate CDKN1A.

Enables mRNA 3’-UTR binding activity. Involved in several processes, including DNA damage response, signal transduction by p53 class mediator; negative regulation of cell population proliferation; and regulation of gene expression. Located in cytosol and nucleus.

Source: NCBI Gene 55544 — RefSeq curated summary.

At a glance

• GWAS associations: 29
• Clinical variants (ClinVar): 36 total
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
• MANE Select transcript: NM_017495

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15818
Approved symbol	RBM38
Name	RNA binding motif protein 38
Location	20q13.31
Locus type	gene with protein product
Status	Approved
Aliases	HSRNASEB, SEB4D, seb4B, dJ800J21.2
Ensembl gene	ENSG00000132819
Ensembl biotype	protein_coding
OMIM	612428
Entrez	55544

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 nonsense_mediated_decay

ENST00000342690, ENST00000344785, ENST00000356208, ENST00000371219, ENST00000440234

RefSeq mRNA: 3 — MANE Select: NM_017495 NM_001291780, NM_017495, NM_183425

CCDS: CCDS46617, CCDS46618

Canonical transcript exons

ENST00000356208 — 4 exons

Exon	Start	End
ENSE00001429750	57391396	57391818
ENSE00003512619	57393279	57393333
ENSE00003586035	57392654	57392777
ENSE00003677560	57407543	57409333

Expression profiles

Bgee: expression breadth ubiquitous, 274 present calls, max score 98.14.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 73.5607 / max 5877.1316, expressed in 1805 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
185472	73.4173	1805
185473	0.1434	78

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	98.14	gold quality
gastrocnemius	UBERON:0001388	97.30	gold quality
blood	UBERON:0000178	96.66	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.34	gold quality
muscle of leg	UBERON:0001383	96.13	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.94	gold quality
lower esophagus	UBERON:0013473	95.91	gold quality
gluteal muscle	UBERON:0002000	95.85	gold quality
right atrium auricular region	UBERON:0006631	95.70	gold quality
triceps brachii	UBERON:0001509	95.68	gold quality
mucosa of stomach	UBERON:0001199	95.54	gold quality
granulocyte	CL:0000094	95.45	gold quality
muscle organ	UBERON:0001630	95.30	gold quality
cardiac atrium	UBERON:0002081	95.27	gold quality
monocyte	CL:0000576	95.26	gold quality
mononuclear cell	CL:0000842	95.21	gold quality
leukocyte	CL:0000738	95.18	gold quality
bone marrow	UBERON:0002371	95.11	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.03	gold quality
bone marrow cell	CL:0002092	94.89	gold quality
apex of heart	UBERON:0002098	94.76	gold quality
skeletal muscle tissue	UBERON:0001134	94.56	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	94.21	gold quality
spleen	UBERON:0002106	93.64	gold quality
oocyte	CL:0000023	93.35	gold quality
trabecular bone tissue	UBERON:0002483	93.15	gold quality
heart left ventricle	UBERON:0002084	93.02	gold quality
muscle tissue	UBERON:0002385	92.91	gold quality
cardiac ventricle	UBERON:0002082	92.66	gold quality
sigmoid colon	UBERON:0001159	92.52	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-9221	yes	20.79
E-CURD-122	yes	6.19
E-HCAD-9	yes	6.18
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1, MYOD1, TP53, TP73

miRNA regulators (miRDB)

61 targeting RBM38, 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-4534	99.99	66.58	1907
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4500	99.99	72.72	2367
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-4320	99.75	65.80	793
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-5004-3P	99.54	68.27	1371

Literature-anchored findings (GeneRIF, showing 40)

• RNPC1a is required to maintain the stability of p21 transcript induced by p53. (PMID:17050675)
• it was found that this protein Rbm38 regulates myogenic differentiation via the p21 signal pathway. (PMID:19817877)
• found that RNPC1, a RNA-binding protein and a target of the p53 family, regulates p63 mRNA stability and consequently p63 activity. (PMID:20457941)
• identified RNPC1, a p53 target and a RNA-binding protein, as a critical regulator of p53 translation (PMID:21764855)
• identify RBM38 in a genetic screen for RBPs whose expression controls miRNA access to target mRNAs (PMID:22027593)
• RNPC1 contributes to tumor resistance to radiotherapy, which likely occurs through a p21-mediated G/G accumulation mechanism (PMID:22214381)
• a novel mechanism by which HuR is regulated by RNPC1 via mRNA stability and HuR is a mediator of RNPC1-induced growth suppression. (PMID:22371495)
• knockdown of p73 or p21, another target of RNPC1, attenuates the inhibitory effect of RNPC1 on cell proliferation and premature senescence, whereas combined knockdown of p73 and p21 completely abolishes it (PMID:22508983)
• Novel regulation of MDM2 gene expression by the RNA binding protein RNPC1 via mRNA stability. (PMID:22710720)
• RBM38 as novel transcriptional target of E2F1 restricts E2F1-induced proliferation. Furthermore, this negative feedback loop seems to restrict tumor aggressiveness, thereby promoting survival of patients with cancer. (PMID:22798430)
• knockdown of MIC-1 can decrease RNPC1-induced cell growth suppression. (PMID:23836903)
• Data suggest that RNPC1 is a critical regulator of Mdm2. (PMID:23912475)
• GSK3 promotes p53 mRNA translation through phosphorylation of RNPC1 (PMID:24142875)
• A role for RBM38 in regulating alternative splicing during erythroid differentiation. (PMID:24250749)
• Data indicate that long non-coding RNA HOTAIR is functionally related to RNA binding motif protein 38 (RBM38). (PMID:24663081)
• Suggest that RNPC1 had a potential function to play a tumor-suppressor role which may be a potential marker in the therapeutic and prognostic of breast cancer. (PMID:24884756)
• our data suggest that RBM38 is a novel translational regulator of HIF1alpha under a hypoxic condition. (PMID:25622105)
• RNPC1 was found to be expressed in bladder, blood, brain, breast, colorectal, eye, head and neck, lung, ovarian, skin and soft tissue cancer. In 14 of the 94 tests, an association between RNPC1 gene expression and cancer prognosis was observed. (PMID:26046131)
• RBM38 and DND1 are repressed in primary acute myeloid leukemia, neutrophil differentiation is dependent on increased expression of both proteins, and they have a role in regulating p21(CIP1) expression during acute promyelocytic leukemia differentiation (PMID:26740055)
• Overexpression of RNA-binding region-containing protein 1 (RNPC1) increased, whereas knockdown of RNPC1 decreased, the level of progesterone receptor (PR) protein and transcripts. (PMID:27634883)
• Results report that RBM38 mediates direct inhibition of c-Myc expression, which in turn suppresses RBM38 expression. Thus, it can be concluded that RBM38 and c-Myc form a unique mutually antagonistic RBM38-c-Myc loop in breast cancer. (PMID:28399911)
• aplan-Meier analysis showed that renal cell carcinoma patients with lower expression of RBM38 had a significantly shorter survival time than those with higher expression of RBM38 ( p = 0.028). All these suggested that RBM38 acts as a tumor suppressor in renal cell carcinoma, which has the potential value for the prediction of renal cell carcinoma prognosis. (PMID:28459215)
• Here we uncovered a novel mechanism that RBM38 is a positive posttranscriptional regulator of ZO-1 in breast cancer. (PMID:28683467)
• Results showed that the expressions of RBM38 and PTEN was positively correlated in human breast cancer tissues. RBM38 upregulated PTEN expression and activity in breast cancer cells through its direct binding to PTEN mRNA 3’UTR enhancing its stability. These data implied that RBM38 acted as a tumor suppressor partly by enhancing PTEN expression. (PMID:29052531)
• Investigated RNA-binding region-containing protein 1 (RNPC1) action on signal pathways and disease progression in lung cancer samples and cells. Found RNPC1 acts to downregulate the miR-181a mediated inhibition of cancer susceptibility 2 (CASC2) expression in lung cancer. Results show RNPC1 inhibits NSCLC progression in a miR-181a/CASC2 axis-dependent manner. (PMID:29288351)
• Taken together, these results suggest that the 11-kDa protein facilitates B19V DNA replication and that RBM38 is an essential host factor for B19V pre-mRNA splicing and for the expression of the 11-kDa protein. (PMID:29437973)
• Study investigates the biological significance of the Rbm38-p63 loop and finds that Rbm38 and p63 function as intergenic suppressors in aging and tumorigenesis. (PMID:29520104)
• Study disclosed that RNPC1 expression was positively correlated with breast cancer patients’ relapse-free and overall survival and that RNPC1 suppressed breast cancer cell metastasis. Mechanistically, RNPC1 promotes competing endogenous RNA (ceRNA) network crosstalk among STARD13, CDH5, HOXD10, and HOXD1 (STARD13-correlated ceRNA network) thus facilitating the expression of these four genes in breast cancer cells. (PMID:29733656)
• Our findings suggested that RBM38 may be a core contributor in stabilizing the p53-mdm2 loop function to prevent hepatocellular carcinoma (HCC) and a potential novel target to provide a therapeutic strategy for HCC by inhibiting mdm2 and rescuing p53 from inactivation (PMID:30176896)
• results reveal a critical mechanism by which Ser-195 phosphorylation in Rbm38 increases p63 expression by attenuating the association of Rbm38 with the Ago2-miR203 complex. (PMID:30567739)
• Cumulatively, these results reveal a novel mechanism of RBM38-mediated regulation of the HIF1A/miR-34a/SIRT1/p53 axis under hypoxia in non-small cell lung cancer cells. (PMID:31760527)
• The authors report the crystal structure of the RNA-recognition motif domain of human RBM38 in complex with a single-stranded RNA, reveal the RNA-recognition mechanism of human RBM38 and provide structural information for understanding the RNA-binding property of RBM38. (PMID:31860021)
• RNA Binding Protein RNPC1 Suppresses the Stemness of Human Endometrial Cancer Cells via Stabilizing MST1/2 mRNA. (PMID:32088727)
• Rbm38 Reduces the Transcription Elongation Defect of the SMEK2 Gene Caused by Splicing Deficiency. (PMID:33233740)
• Survivin Expression Is Differentially Regulated by a Selective Cross-talk between RBM38 and miRNAs let-7b or miR-203a. (PMID:33472892)
• RNA-binding protein RNPC1 acts as an oncogene in gastric cancer by stabilizing aurora kinase B mRNA. (PMID:34302858)
• RNA-binding protein RBM38 inhibits colorectal cancer progression by partly and competitively binding to PTEN 3’UTR with miR-92a-3p. (PMID:34453780)
• RNA binding Motif protein-38 regulates myocardial hypertrophy in LXR-alpha-dependent lipogenesis pathway. (PMID:34854353)
• [RBM38 Mediates the Proliferation of Acute Myeloid Leukemia Cells HL-60 by Regulating FZD1 mRNA Stability]. (PMID:34893109)
• LncRNA CALML3-AS1 suppresses papillary thyroid cancer progression via sponging miR-20a-5p/RBM38 axis. (PMID:35351042)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	rbm38	ENSDARG00000058818
mus_musculus	Rbm38	ENSMUSG00000027510
rattus_norvegicus	Rbm38	ENSRNOG00000006420
caenorhabditis_elegans		WBGENE00006321

Paralogs (24): ELAVL1 (ENSG00000066044), PABPC1 (ENSG00000070756), RBMS2 (ENSG00000076067), PABPC4 (ENSG00000090621), PABPC1L (ENSG00000101104), ELAVL2 (ENSG00000107105), RBM24 (ENSG00000112183), TARDBP (ENSG00000120948), HNRNPR (ENSG00000125944), SYNCRIP (ENSG00000135316), SF3B4 (ENSG00000143368), RBMS3 (ENSG00000144642), PABPC3 (ENSG00000151846), RBMS1 (ENSG00000153250), RBM45 (ENSG00000155636), ELAVL4 (ENSG00000162374), PABPC5 (ENSG00000174740), PUF60 (ENSG00000179950), PABPC1L2B (ENSG00000184388), PABPC1L2A (ENSG00000186288), RBM34 (ENSG00000188739), ELAVL3 (ENSG00000196361), RBM14 (ENSG00000239306), PABPC4L (ENSG00000254535)

Protein

Protein identifiers

RNA-binding protein 38 — Q9H0Z9 (reviewed: Q9H0Z9)

Alternative names: CLL-associated antigen KW-5, HSRNASEB, RNA-binding motif protein 38, RNA-binding region-containing protein 1, ssDNA-binding protein SEB4

All UniProt accessions (4): Q9H0Z9, A6NG75, E9PSF1, F6VZ39

UniProt curated annotations — full annotation on UniProt →

Function. RNA-binding protein that specifically bind the 3’-UTR of CDKN1A transcripts, leading to maintain the stability of CDKN1A transcripts, thereby acting as a mediator of the p53/TP53 family to regulate CDKN1A. CDKN1A is a cyclin-dependent kinase inhibitor transcriptionally regulated by the p53/TP53 family to induce cell cycle arrest. Isoform 1, but not isoform 2, has the ability to induce cell cycle arrest in G1 and maintain the stability of CDKN1A transcripts induced by p53/TP53. Also acts as a mRNA splicing factor. Specifically regulates the expression of FGFR2-IIIb, an epithelial cell-specific isoform of FGFR2. Plays a role in myogenic differentiation. (Microbial infection) Essential factor for the splicing of the pre-mRNAs of human parvovirus B19 (B19V) and for the expression of B19V 11-kDa protein, which enhances viral replication.

Subcellular location. Cytoplasm. Cytosol. Nucleus.

Induction. By p53/TP53 family. Directly induced by p53/TP53, TP63/p63 and TP73/p73.

Similarity. Belongs to the RBM38 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H0Z9-1	1, RNPC1a	yes
Q9H0Z9-2	2, RNPC1b

RefSeq proteins (3): NP_001278709, NP_059965, NP_906270 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR050886	RNA-binding_reg	Family

Pfam: PF00076

UniProt features (23 total): sequence conflict 5, strand 5, helix 4, sequence variant 4, turn 2, chain 1, domain 1, splice variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
6JVY	X-RAY DIFFRACTION	2
6JVX	X-RAY DIFFRACTION	2.3
2CQD	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H0Z9-F1	67.43	0.33

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 240 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, BROWNE_HCMV_INFECTION_8HR_UP, PEREZ_TP63_TARGETS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_3_UTR_MEDIATED_MRNA_STABILIZATION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, GOBP_REGULATION_OF_STRIATED_MUSCLE_CELL_DIFFERENTIATION, ATGCAGT_MIR217, BROWNE_HCMV_INFECTION_12HR_UP, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, MISSIAGLIA_REGULATED_BY_METHYLATION_UP

GO Biological Process (9): mRNA processing (GO:0006397), negative regulation of cell population proliferation (GO:0008285), RNA splicing (GO:0008380), regulation of myotube differentiation (GO:0010830), cell differentiation (GO:0030154), DNA damage response, signal transduction by p53 class mediator (GO:0030330), regulation of RNA splicing (GO:0043484), regulation of cell cycle (GO:0051726), 3’-UTR-mediated mRNA stabilization (GO:0070935)

GO Molecular Function (5): RNA binding (GO:0003723), mRNA binding (GO:0003729), mRNA 3’-UTR binding (GO:0003730), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), cytosol (GO:0005829), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA processing	2
binding	2
cellular anatomical structure	2
mRNA metabolic process	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
myotube differentiation	1
regulation of striated muscle cell differentiation	1
cellular developmental process	1
signal transduction in response to DNA damage	1
signal transduction by p53 class mediator	1
RNA splicing	1
regulation of gene expression	1
regulation of primary metabolic process	1
cell cycle	1
regulation of cellular process	1
mRNA stabilization	1
nucleic acid binding	1
RNA binding	1
mRNA binding	1
intracellular membrane-bounded organelle	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

950 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RBM38	EIF4E	P06730	733
RBM38	TP73	O15350	669
RBM38	ELAVL1	Q15717	634
RBM38	CDKN1A	P38936	603
RBM38	CELF1	Q92879	600
RBM38	MDM2	Q00987	596
RBM38	TP63	Q9H3D4	579
RBM38	TP53	P04637	577
RBM38	PTBP1	P26599	544
RBM38	EIF4G1	Q04637	544
RBM38	PCBP4	P57723	461
RBM38	ESRP2	Q9H6T0	460
RBM38	HIF1A	Q16665	458
RBM38	RCHY1	Q96PM5	451
RBM38	SRPK2	P78362	436

IntAct

31 interactions, top by confidence:

A	B	Type	Score
ARHGEF6	PAK1	psi-mi:“MI:0914”(association)	0.800
HNRNPH1	RBM38	psi-mi:“MI:0915”(physical association)	0.560
ZC3H10	RBM38	psi-mi:“MI:0915”(physical association)	0.560
RBM24	PPL	psi-mi:“MI:0914”(association)	0.530
CD53	FAM171A2	psi-mi:“MI:0914”(association)	0.530
RCHY1	RBM38	psi-mi:“MI:0915”(physical association)	0.370
RBFOX2	PRMT5	psi-mi:“MI:0914”(association)	0.350
CLASRP	GAK	psi-mi:“MI:0914”(association)	0.350
TMEM184A	NRDC	psi-mi:“MI:0914”(association)	0.350
PTCD3	RBM38	psi-mi:“MI:0914”(association)	0.350
RBM38	RAF1	psi-mi:“MI:0914”(association)	0.350
TRIM68	BTN3A3	psi-mi:“MI:0914”(association)	0.350
TMEM18	GALT	psi-mi:“MI:0914”(association)	0.350
ZCCHC9	S100A10	psi-mi:“MI:0914”(association)	0.350
ECD	POLR3G	psi-mi:“MI:0914”(association)	0.350
PICALM	DDX3Y	psi-mi:“MI:0914”(association)	0.350
TRIM68	NRP2	psi-mi:“MI:0914”(association)	0.350
LARS2	CREB1	psi-mi:“MI:0914”(association)	0.350
ZC3H10	RBM38	psi-mi:“MI:0915”(physical association)	0.000
HNRNPH1	RBM38	psi-mi:“MI:0915”(physical association)	0.000
RBM38	dppB	psi-mi:“MI:0915”(physical association)	0.000
RBM38		psi-mi:“MI:0915”(physical association)	0.000
mtr	RBM38	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (30): RBM38 (Affinity Capture-MS), RBM38 (Affinity Capture-MS), RBM38 (Affinity Capture-MS), RBM38 (Affinity Capture-MS), RBM38 (Affinity Capture-MS), RBM38 (Affinity Capture-MS), RBM38 (Affinity Capture-MS), HIF1A (Affinity Capture-Western), RBM38 (Affinity Capture-RNA), RBM38 (Affinity Capture-MS), ZC3H10 (Two-hybrid), HNRNPH1 (Two-hybrid), RBM38 (Affinity Capture-MS), RBM38 (Affinity Capture-RNA), RBM38 (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IEW8, A0JM51, A4QNI8, O09032, O57406, P26378, P29558, Q08E07, Q0V9L3, Q14576, Q15434, Q1RMJ7, Q28GD4, Q3ZBP3, Q3ZC34, Q4R535, Q5NVC8, Q5PQP1, Q5R995, Q5RBD3, Q5SZQ8, Q60899, Q60900, Q61701, Q62176, Q6DGV1, Q6DIV4, Q6XE24, Q6YZW2, Q7SZT7, Q7T3I7, Q7TN33, Q7TSY6, Q7ZWM3, Q8BWL5, Q8CH84, Q8CIN6, Q8N6W0, Q8VC70, Q8VXZ9

Diamond homologs: A0A0A0LLY1, A0A0D1C8Z4, A5A6M3, C0HFE5, D3Z4I3, D4AE41, M0R7T6, O22703, O35698, O75526, O89086, O93235, P04147, P0C8Z4, P10979, P19682, P19683, P19684, P28644, P38159, P39697, P48809, P49310, P49311, P49313, P49314, P60824, P60825, P60826, P84586, P98179, Q03250, Q03251, Q03878, Q04836, Q05966, Q08473, Q08935, Q08937, Q14011

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
GSK3B	down-regulates	RBM38	phosphorylation
RBM38	“up-regulates quantity by stabilization”	CDKN1A	“post transcriptional regulation”
PPM1D	“up-regulates activity”	RBM38	dephosphorylation

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — DLBCLNOS.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	32
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

817 predictions. Top by Δscore:

Variant	Effect	Δscore
20:57391814:GCTTC:G	donor_gain	1.0000
20:57391815:CTTC:C	donor_gain	1.0000
20:57391816:TTC:T	donor_gain	1.0000
20:57391817:TC:T	donor_gain	1.0000
20:57391817:TCG:T	donor_loss	1.0000
20:57391819:G:GC	donor_loss	1.0000
20:57391819:G:GG	donor_gain	1.0000
20:57391820:T:TC	donor_loss	1.0000
20:57392649:A:AG	acceptor_gain	1.0000
20:57392649:ACCAG:A	acceptor_gain	1.0000
20:57392651:CA:C	acceptor_loss	1.0000
20:57392652:A:AG	acceptor_gain	1.0000
20:57392652:AG:A	acceptor_gain	1.0000
20:57392652:AGGT:A	acceptor_gain	1.0000
20:57392653:G:GT	acceptor_gain	1.0000
20:57392653:GG:G	acceptor_gain	1.0000
20:57392653:GGT:G	acceptor_gain	1.0000
20:57392653:GGTG:G	acceptor_gain	1.0000
20:57392653:GGTGA:G	acceptor_gain	1.0000
20:57392773:GACGG:G	donor_gain	1.0000
20:57392774:ACGG:A	donor_gain	1.0000
20:57392775:CGG:C	donor_gain	1.0000
20:57392776:GG:G	donor_gain	1.0000
20:57392776:GGG:G	donor_gain	1.0000
20:57392776:GGGTG:G	donor_loss	1.0000
20:57392777:GG:G	donor_gain	1.0000
20:57392778:G:A	donor_loss	1.0000
20:57392778:G:GG	donor_gain	1.0000
20:57392779:T:A	donor_loss	1.0000
20:57393331:CGGG:C	donor_loss	1.0000

AlphaMissense

1522 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:57391669:G:C	D30H	1.000
20:57391682:C:T	T34I	1.000
20:57391684:A:C	K35Q	1.000
20:57391684:A:G	K35E	1.000
20:57391685:A:T	K35M	1.000
20:57391686:G:C	K35N	1.000
20:57391686:G:T	K35N	1.000
20:57391688:T:A	I36N	1.000
20:57391688:T:C	I36T	1.000
20:57391688:T:G	I36S	1.000
20:57391690:T:A	F37I	1.000
20:57391690:T:C	F37L	1.000
20:57391690:T:G	F37V	1.000
20:57391691:T:C	F37S	1.000
20:57391691:T:G	F37C	1.000
20:57391692:C:A	F37L	1.000
20:57391692:C:G	F37L	1.000
20:57391693:G:A	V38M	1.000
20:57391694:T:A	V38E	1.000
20:57391696:G:A	G39S	1.000
20:57391696:G:C	G39R	1.000
20:57391696:G:T	G39C	1.000
20:57391697:G:A	G39D	1.000
20:57391697:G:T	G39V	1.000
20:57391699:G:C	G40R	1.000
20:57391699:G:T	G40C	1.000
20:57391700:G:A	G40D	1.000
20:57391700:G:T	G40V	1.000
20:57391703:T:A	L41Q	1.000
20:57391703:T:C	L41P	1.000

dbSNP variants (sampled 300 via entrez): RS1000052603 (20:57398703 C>T), RS1000142457 (20:57402942 T>G), RS1000260400 (20:57404707 G>A,C), RS1000313099 (20:57404887 G>A,C), RS1000416911 (20:57398881 T>C), RS1000423184 (20:57400906 C>T), RS1000485573 (20:57402064 C>T), RS1000516151 (20:57401912 A>G), RS1000538228 (20:57401665 C>A,T), RS1000606728 (20:57400744 A>G), RS1000799961 (20:57409641 G>T), RS1000907721 (20:57393912 C>G,T), RS1001026791 (20:57406136 G>A), RS1001160160 (20:57401938 G>A,T), RS1001186693 (20:57403712 T>C)

Disease associations

OMIM: gene MIM:612428 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

29 associations (top):

Study	Trait	p-value
GCST000585_3	Mean corpuscular volume	1.000000e-08
GCST000635_28	Response to statin therapy	4.000000e-06
GCST001765_26	Red blood cell traits	4.000000e-13
GCST001809_13	Type 2 diabetes	2.000000e-06
GCST004004_23	Mean corpuscular volume	2.000000e-07
GCST004004_51	Mean corpuscular volume	2.000000e-19
GCST004006_15	Mean corpuscular hemoglobin	3.000000e-08
GCST004006_38	Mean corpuscular hemoglobin	1.000000e-08
GCST004335_8	Mean corpuscular volume	8.000000e-06
GCST004599_213	Mean platelet volume	2.000000e-11
GCST004611_165	High light scatter reticulocyte count	1.000000e-20
GCST004612_185	High light scatter reticulocyte percentage of red cells	1.000000e-24
GCST004619_104	Reticulocyte fraction of red cells	1.000000e-18
GCST004622_90	Reticulocyte count	9.000000e-13
GCST005993_22	Mean corpuscular hemoglobin	2.000000e-25
GCST006011_60	Mean corpuscular volume	1.000000e-39
GCST010796_929	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-12
GCST010796_931	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-12
GCST010796_932	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-09
GCST90002385_541	High light scatter reticulocyte count	3.000000e-39
GCST90002386_521	High light scatter reticulocyte percentage of red cells	1.000000e-38
GCST90002387_169	Immature fraction of reticulocytes	7.000000e-28
GCST90002395_603	Mean platelet volume	2.000000e-09
GCST90002396_65	Mean reticulocyte volume	9.000000e-28
GCST90002396_66	Mean reticulocyte volume	1.000000e-09
GCST90002398_60	Neutrophil count	4.000000e-09
GCST90002405_454	Reticulocyte count	6.000000e-50
GCST90002406_557	Reticulocyte fraction of red cells	2.000000e-55
GCST90014033_74	Haemorrhoidal disease	4.000000e-12

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004527	mean corpuscular hemoglobin
EFO:0007986	reticulocyte count
EFO:0004327	electrocardiography
EFO:0010701	mean reticulocyte volume
EFO:0004833	neutrophil count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, affects methylation, decreases expression	4
Valproic Acid	increases methylation, affects expression, increases expression	3
arsenite	affects binding, increases reaction, increases methylation	2
Acetaminophen	increases expression	2
Cisplatin	affects cotreatment, increases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
Tretinoin	affects cotreatment, increases expression	2
aristolochic acid I	increases expression	1
GSK-J4	increases expression	1
bisphenol A	decreases expression	1
kojic acid	decreases expression	1
quercitrin	increases expression	1
mono-(2-ethylhexyl)phthalate	increases abundance, increases methylation	1
sodium arsenite	increases expression	1
aflatoxin B2	increases methylation	1
beta-methylcholine	affects expression	1
nutlin 3	affects cotreatment, increases expression	1
abrine	decreases expression	1
licochalcone B	increases expression	1
bisphenol S	increases expression	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	affects cotreatment, increases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects methylation	1
Dactinomycin	affects cotreatment, increases expression	1
Diazinon	increases methylation	1
Diethylhexyl Phthalate	increases abundance, increases methylation	1

Clinical trials (associated diseases)

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