RALB

Summary

RALB (RAS like proto-oncogene B, HGNC:9840) is a protein-coding gene on chromosome 2q14.2, encoding Ras-related protein Ral-B (P11234). Multifunctional GTPase involved in a variety of cellular processes including gene expression, cell migration, cell proliferation, oncogenic transformation and membrane trafficking.

This gene encodes a GTP-binding protein that belongs to the small GTPase superfamily and Ras family of proteins. GTP-binding proteins mediate the transmembrane signaling initiated by the occupancy of certain cell surface receptors.

Source: NCBI Gene 5899 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 30 total
• Druggable target: yes
• MANE Select transcript: NM_002881

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9840
Approved symbol	RALB
Name	RAS like proto-oncogene B
Location	2q14.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000144118
Ensembl biotype	protein_coding
OMIM	179551
Entrez	5899

Gene structure

Transcript identifiers

Ensembl transcripts: 34 — 32 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000272519, ENST00000412383, ENST00000420510, ENST00000431732, ENST00000447591, ENST00000449649, ENST00000470417, ENST00000631312, ENST00000862911, ENST00000862912, ENST00000862913, ENST00000862914, ENST00000862915, ENST00000862916, ENST00000862917, ENST00000862918, ENST00000862919, ENST00000862920, ENST00000862921, ENST00000862922, ENST00000862923, ENST00000923638, ENST00000923639, ENST00000923640, ENST00000923641, ENST00000923642, ENST00000971139, ENST00000971140, ENST00000971141, ENST00000971142, ENST00000971143, ENST00000971144, ENST00000971145, ENST00000971146

RefSeq mRNA: 2 — MANE Select: NM_002881 NM_001369400, NM_002881

CCDS: CCDS2131

Canonical transcript exons

ENST00000272519 — 5 exons

Exon	Start	End
ENSE00001895795	120252852	120252980
ENSE00001952326	120293141	120294710
ENSE00003512940	120285874	120286082
ENSE00003693677	120278618	120278778
ENSE00003789771	120289580	120289757

Expression profiles

Bgee: expression breadth ubiquitous, 298 present calls, max score 97.99.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.7664 / max 534.4872, expressed in 1809 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
22307	9.4652	1779
22306	8.4506	1746
22305	1.9603	1060
202367	0.3210	136
22304	0.2635	93
202368	0.1359	45
22308	0.1320	39
22309	0.0379	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	97.99	gold quality
mononuclear cell	CL:0000842	97.88	gold quality
leukocyte	CL:0000738	97.76	gold quality
esophagus squamous epithelium	UBERON:0006920	97.37	gold quality
blood	UBERON:0000178	96.86	gold quality
epithelium of esophagus	UBERON:0001976	96.77	gold quality
rectum	UBERON:0001052	95.67	gold quality
gall bladder	UBERON:0002110	95.15	gold quality
esophagus mucosa	UBERON:0002469	95.04	gold quality
cingulate cortex	UBERON:0003027	95.00	gold quality
oral cavity	UBERON:0000167	94.97	gold quality
anterior cingulate cortex	UBERON:0009835	94.94	gold quality
visceral pleura	UBERON:0002401	94.79	gold quality
squamous epithelium	UBERON:0006914	94.77	gold quality
smooth muscle tissue	UBERON:0001135	94.72	gold quality
granulocyte	CL:0000094	94.68	gold quality
adrenal tissue	UBERON:0018303	94.41	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.34	gold quality
adult mammalian kidney	UBERON:0000082	94.29	gold quality
colonic epithelium	UBERON:0000397	94.19	gold quality
lateral nuclear group of thalamus	UBERON:0002736	94.12	gold quality
omental fat pad	UBERON:0010414	94.09	gold quality
prefrontal cortex	UBERON:0000451	94.08	gold quality
peritoneum	UBERON:0002358	94.08	gold quality
islet of Langerhans	UBERON:0000006	94.06	gold quality
pharyngeal mucosa	UBERON:0000355	94.01	gold quality
colonic mucosa	UBERON:0000317	93.95	gold quality
vermiform appendix	UBERON:0001154	93.94	gold quality
trabecular bone tissue	UBERON:0002483	93.92	gold quality
heart right ventricle	UBERON:0002080	93.89	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-8271	yes	16.99
E-CURD-11	no	387.34
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

129 targeting RALB, 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-6867-5P	100.00	82.21	3464
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-548C-3P	99.99	74.01	7587
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-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-12133	99.92	71.82	2006

Literature-anchored findings (GeneRIF, showing 38)

• differential binding of calmodulin by RalA and RalB (PMID:12034722)
• RALA and RALB collaborate to maintain tumorigenicity through regulation of both proliferation and survival; RALB is specifically required for survival of tumour cells but not normal cells (PMID:12856001)
• These observations define the mechanistic contribution of RalGTPases to cancer cell survival and reveal the RalB/Sec5 effector complex as a component of TBK1-dependent innate immune signaling. (PMID:17018283)
• study concludes RalA function is critical to tumor initiation, while RalB is more important for tumor metastasis in the tested pancreatic carcinoma cell lines & argues for critical roles of Ral proteins during progression of Ras-driven pancreatic cancers (PMID:17174914)
• analysis of activation and differential expression of RalA and RalB in human bladder cancer (PMID:17606711)
• These data extend understanding of the functional roles of the Ral pathway and begin to identify signaling pathways relevant for organ-specific metastasis. (PMID:17709381)
• Data suggest that RalA and RalB are important, functionally distinct targets for GGTI-mediated tumor apoptosis and growth inhibition. (PMID:17875936)
• RalB was found to mediate SDF-1-induced migration (PMID:18227351)
• RalA and RalB support mitotic progression through mobilization of the exocyst for two spatially and kinetically distinct steps of cytokinesis (PMID:18756269)
• Backbone dynamics and the structure of free RalB bound to the GTP analogue GMPPNP were determined using NMR spectroscopy. (PMID:19166349)
• These results establish RalA and GRK2 as key regulators of LPA receptor signalling and demonstrate for the first time that LPA(1) activity facilitates the formation of a novel protein complex between these two proteins. (PMID:19306925)
• 1H, 13C and 15N resonance assignments for the small G protein RalB in its active conformation. Backbone amide dynamics parameters for a majority of residues have also been obtained (PMID:19636851)
• Rgl2 and RalB both localized to the leading edge, and this localization of RalB was dependent on endogenous Rgl2 expression. (PMID:20801877)
• Non-phosphorylated RalB is associated with bladder cancer cell growth and metastasis. (PMID:20940393)
• Study finds that the Ras-like small G protein, RalB, is localized to nascent autophagosomes and is activated on nutrient deprivation. (PMID:21241894)
• Our results identify a role for RalA and RalB in cell-mediated cytotoxicity (PMID:21810610)
• RalA and RalB differentially regulate development of epithelial tight junctions. (PMID:22013078)
• a novel RalB-mediated biochemical and signaling mechanism for invadopodium formation (PMID:22331470)
• phosphorylation by PKCalpha is critical for RalB-mediated vesicle trafficking and exocytosis. (PMID:22393054)
• the existence of an ubiquitination/de-ubiquitination cycle superimposed on the GDP/GTP cycle of RalA, involved in the regulation of RalA activity as well as in membrane raft trafficking. (PMID:22700969)
• The study found upregulated RalA and RalB activation in colorectal cancer tumor cell lines and tumors. (PMID:22790202)
• RalA and RalB exhibit both distinct and redundant roles in tumorigenesis (Review). (PMID:23830877)
• nutrient starvation induces RALB deubiquitylation by accumulation and relocalization of the deubiquitylase USP33 to RALB-positive vesicles (PMID:24056301)
• High RALB mRNA expression is associated with non-small-cell lung cancer growth and progression. (PMID:24389431)
• Integrin alpha(v)beta expression and the resulting KRAS-RalB-NF-kappaB pathway were both necessary and sufficient for tumour initiation, anchorage independence, self-renewal and erlotinib resistance. (PMID:24747441)
• expression of K-Ras and RalB and possibly RalA proteins is critical for maintaining low levels of p53, and down-regulation of these GTPases reactivates p53 by significantly enhancing its stability, contributing to suppression of malignant transformation (PMID:25210032)
• These findings suggest that RalB might be one of the targets for facilitating the invasive phenotype of malignant gliomas induced by GGTase-I. (PMID:25573158)
• striking isoform-specific consequences of distinct CAAX-signaled posttranslational modifications that contribute to the divergent subcellular localization and activity of RalA and RalB. (PMID:26216878)
• This study identifies a novel regulatory crosstalk between Ral and Arf6 that controls Ral function in cells. (PMID:27269287)
• Inhibition of Ral GTPases Using a Stapled Peptide Approach. (PMID:27334922)
• our work provides new insight into the specific roles of Ras effector pathways in acute myeloid leukemia and has identified RALB signaling as a key survival pathway (PMID:27556501)
• High RALB expression is associated with acute myeloid leukemia. (PMID:27991934)
• RalB expression at protein level increases in a manner consistent with progression toward metastasis. (PMID:30320548)
• RalA and RalB both relocalize to mitochondria following depolarization in a process dependent on clathrin-mediated endocytosis. Furthermore, both genetic and pharmacologic inhibition of RalA and RalB leads to an increase in the activity of the atypical IkappaB kinase TBK1 both basally and in response to mitochondrial depolarization. (PMID:30995277)
• Localization of RalB signaling at endomembrane compartments and its modulation by autophagy. (PMID:31222145)
• RALB GTPase: a critical regulator of DR5 expression and TRAIL sensitivity in KRAS mutant colorectal cancer. (PMID:33122623)
• MicroRNA-139 inhibits pancreatic-cancer carcinogenesis by suppressing RalB via the Ral/RAC/PI3K pathway. (PMID:33290747)
• Ral GTPase-activating protein regulates the malignancy of pancreatic ductal adenocarcinoma. (PMID:34009715)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ralba	ENSDARG00000040778
danio_rerio	ralbb	ENSDARG00000113643
mus_musculus	Ralb	ENSMUSG00000004451
rattus_norvegicus	Ralb	ENSRNOG00000002440

Paralogs (35): RALA (ENSG00000006451), REM1 (ENSG00000088320), RASL10A (ENSG00000100276), RASD2 (ENSG00000100302), RASL12 (ENSG00000103710), RHEB (ENSG00000106615), RASD1 (ENSG00000108551), RERGL (ENSG00000111404), RAP1A (ENSG00000116473), RASL11A (ENSG00000122035), RAP2C (ENSG00000123728), RAP2A (ENSG00000125249), RRAS (ENSG00000126458), RAP1B (ENSG00000127314), RASL11B (ENSG00000128045), KRAS (ENSG00000133703), RRAS2 (ENSG00000133818), RERG (ENSG00000134533), REM2 (ENSG00000139890), RIT1 (ENSG00000143622), RIT2 (ENSG00000152214), MRAS (ENSG00000158186), DIRAS3 (ENSG00000162595), GEM (ENSG00000164949), DIRAS2 (ENSG00000165023), RRAD (ENSG00000166592), RHEBL1 (ENSG00000167550), NKIRAS2 (ENSG00000168256), HRAS (ENSG00000174775), DIRAS1 (ENSG00000176490), RAP2B (ENSG00000181467), ERAS (ENSG00000187682), NKIRAS1 (ENSG00000197885), NRAS (ENSG00000213281), RASL10B (ENSG00000270885)

Protein

Protein identifiers

Ras-related protein Ral-B — P11234 (reviewed: P11234)

All UniProt accessions (5): P11234, C9J6B1, C9JQB3, C9JYR1, F8WEQ6

UniProt curated annotations — full annotation on UniProt →

Function. Multifunctional GTPase involved in a variety of cellular processes including gene expression, cell migration, cell proliferation, oncogenic transformation and membrane trafficking. Accomplishes its multiple functions by interacting with distinct downstream effectors. Acts as a GTP sensor for GTP-dependent exocytosis of dense core vesicles. Required both to stabilize the assembly of the exocyst complex and to localize functional exocyst complexes to the leading edge of migrating cells. Required for suppression of apoptosis. In late stages of cytokinesis, upon completion of the bridge formation between dividing cells, mediates exocyst recruitment to the midbody to drive abscission. Involved in ligand-dependent receptor mediated endocytosis of the EGF and insulin receptors.

Subunit / interactions. Interacts with EXOC2/Sec5 and EXOC8/Exo84. Interacts (via effector domain) with RALBP1.

Subcellular location. Cell membrane. Midbody.

Post-translational modifications. Prenylation is essential for membrane localization. The geranylgeranylated form and the farnesylated mutant does not undergo alternative prenylation in response to geranylgeranyltransferase I inhibitors (GGTIs) and farnesyltransferase I inhibitors (FTIs). The farnesylated form confers resistance to the proapoptotic and anti-anchorage-dependent growth effects of geranylgeranyltransferase I inhibitors, including GGTI-2417.

Activity regulation. Alternates between an inactive form bound to GDP and an active form bound to GTP. Activated by a guanine nucleotide-exchange factor (GEF) and inactivated by a GTPase-activating protein (GAP).

Similarity. Belongs to the small GTPase superfamily. Ras family.

Isoforms (3)

UniProt ID	Names	Canonical?
P11234-1	1	yes
P11234-2	2
P11234-3	3

RefSeq proteins (2): NP_001356329, NP_002872* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001806	Small_GTPase	Family
IPR005225	Small_GTP-bd	Domain
IPR020849	Small_GTPase_Ras-type	Family
IPR027417	P-loop_NTPase	Homologous_superfamily

Pfam: PF00071

Catalyzed reactions (Rhea), 1 shown:

• GTP + H2O = GDP + phosphate + H(+) (RHEA:19669)

UniProt features (39 total): mutagenesis site 11, strand 6, helix 6, binding site 4, turn 3, splice variant 2, chain 1, propeptide 1, lipid moiety-binding region 1, region of interest 1, short sequence motif 1, compositionally biased region 1, modified residue 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
6ZRN	X-RAY DIFFRACTION	1.48
6ZQT	X-RAY DIFFRACTION	1.51
2KE5	SOLUTION NMR
2KWI	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P11234-F1	88.04	0.74

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (4): 21–29; 68–72; 128–131; 158–160

Post-translational modifications (2): 203, 203

Mutagenesis-validated functional residues (11):

Position	Phenotype
1–11	no effect on cytokinesis. impaired cytokinesis, as shown by increased number of binucleate cells; when associated with v
23	impaired cytokinesis, as shown by increased number of binucleate cells. impaired cytokinesis; when associated with 1-m–
38	no effect on cytokinesis. no effect on cytokinesis; when associated with v-23. decreased interaction with exoc2 and exoc
46	reduces the binding affinity to exoc2 effector.
48	impaired abscission, the last step of cytokinesis, as shown by the accumulation of bridged cells. no effect on cytokines
49	impaired abscission, the last step of cytokinesis. no effect on cytokinesis; when associated with v-23.
49	no effect on cytokinesis. impaired cytokinesis, as shown by increased number of binucleate cells; when associated with v
72	loss of gtpase activity.
203	loss of geranylgeranylation and membrane localization.
206	converts geranyl-geranylation to farnesylation. no effect on membrane localization. confers resistance to ggti-induced p

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-171007	p38MAPK events

MSigDB gene sets: 303 (showing top): GOBP_REGULATION_OF_AUTOPHAGY, GOBP_REGULATION_OF_ERBB_SIGNALING_PATHWAY, GOBP_VACUOLE_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_VACUOLE_ORGANIZATION, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_REGULATION_OF_VACUOLE_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GGGTGGRR_PAX4_03, GOBP_MACROAUTOPHAGY, GOBP_MEMBRANE_DOCKING, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, REACTOME_SIGNALLING_TO_RAS, GOBP_EXOCYTOSIS, GOBP_REGULATION_OF_IMMUNE_RESPONSE

GO Biological Process (10): regulation of exocyst assembly (GO:0001928), apoptotic process (GO:0006915), signal transduction (GO:0007165), Ras protein signal transduction (GO:0007265), receptor internalization (GO:0031623), positive regulation of innate immune response (GO:0045089), positive regulation of epidermal growth factor receptor signaling pathway (GO:0045742), cell division (GO:0051301), regulation of exocyst localization (GO:0060178), positive regulation of autophagosome assembly (GO:2000786)

GO Molecular Function (9): GTPase activity (GO:0003924), G protein activity (GO:0003925), GTP binding (GO:0005525), GDP binding (GO:0019003), ubiquitin protein ligase binding (GO:0031625), ATPase binding (GO:0051117), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (5): plasma membrane (GO:0005886), midbody (GO:0030496), extracellular exosome (GO:0070062), endomembrane system (GO:0012505), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Signalling to RAS	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cellular process	2
guanyl ribonucleotide binding	2
exocyst assembly	1
regulation of protein-containing complex assembly	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
small GTPase-mediated signal transduction	1
receptor-mediated endocytosis	1
positive regulation of response to biotic stimulus	1
positive regulation of defense response	1
positive regulation of response to external stimulus	1
innate immune response	1
regulation of innate immune response	1
positive regulation of immune response	1
epidermal growth factor receptor signaling pathway	1
regulation of epidermal growth factor receptor signaling pathway	1
positive regulation of ERBB signaling pathway	1
regulation of localization	1
exocyst localization	1
autophagosome assembly	1
positive regulation of macroautophagy	1
positive regulation of vacuole organization	1
positive regulation of organelle assembly	1
regulation of autophagosome assembly	1
ribonucleoside triphosphate phosphatase activity	1
GTPase activity	1
molecular function regulator activity	1
purine ribonucleoside triphosphate binding	1
anion binding	1
ubiquitin-like protein ligase binding	1
enzyme binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1

Protein interactions and networks

STRING

2599 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RALB	EXOC2	Q96KP1	999
RALB	EXOC8	Q8IYI6	996
RALB	RALBP1	Q15311	970
RALB	RALGDS	Q12967	953
RALB	TBK1	Q9UHD2	907
RALB	YBX3	P16989	723
RALB	PLD1	Q13393	647
RALB	RGL2	O15211	631
RALB	FLNA	P21333	617
RALB	FLNB	O75369	611
RALB	FLNC	Q14315	611
RALB	REPS1	Q96D71	611
RALB	RGL3	Q3MIN7	605
RALB	AZI2	Q9H6S1	596
RALB	EXOC1	Q9NV70	589

IntAct

58 interactions, top by confidence:

A	B	Type	Score
EXOC2	EXOC3	psi-mi:“MI:0914”(association)	0.790
EXOC8	EXOC5	psi-mi:“MI:0914”(association)	0.730
TGIF2LY	PGP	psi-mi:“MI:0914”(association)	0.640
RALBP1	JUN	psi-mi:“MI:0914”(association)	0.640
Exoc2	RALA	psi-mi:“MI:0914”(association)	0.590
CALM1	RALB	psi-mi:“MI:0407”(direct interaction)	0.590
CALM1	RALB	psi-mi:“MI:0915”(physical association)	0.590
RALB	INCA1	psi-mi:“MI:0915”(physical association)	0.560
RALB	RALBP1	psi-mi:“MI:0915”(physical association)	0.550
RALB	DBT	psi-mi:“MI:0914”(association)	0.530
RALB	EI24	psi-mi:“MI:0914”(association)	0.510
	AP3D1	psi-mi:“MI:0914”(association)	0.460
Ccnd1	RALB	psi-mi:“MI:0915”(physical association)	0.400
Ralbp1	RALB	psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
Flnb	RPL22	psi-mi:“MI:0914”(association)	0.350
Coro1c	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
RALB	XPO1	psi-mi:“MI:0914”(association)	0.350
CSK	LCK	psi-mi:“MI:0914”(association)	0.350
RALB	IPO8	psi-mi:“MI:0914”(association)	0.350
RALB	ATG12	psi-mi:“MI:0914”(association)	0.350
	AGPS	psi-mi:“MI:0914”(association)	0.350
ATP6V1A		psi-mi:“MI:0914”(association)	0.350
	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
	HLA-C	psi-mi:“MI:0914”(association)	0.350
HCN1	USP27X	psi-mi:“MI:0914”(association)	0.350

BioGRID (122): RALBP1 (Two-hybrid), RALB (Affinity Capture-MS), RALB (Affinity Capture-MS), TPP2 (Affinity Capture-MS), RALB (Affinity Capture-MS), MAPK14 (Affinity Capture-MS), PAM (Affinity Capture-MS), ALDH18A1 (Affinity Capture-MS), ANKRD13A (Affinity Capture-MS), DBT (Affinity Capture-MS), RALB (Affinity Capture-MS), XPO5 (Affinity Capture-MS), EXOC2 (Affinity Capture-MS), HAUS4 (Affinity Capture-MS), OCIAD1 (Affinity Capture-MS)

ESM2 similar proteins: E9Q9D5, E9R5S0, O42277, O94363, O95057, P01122, P11234, P22123, P22124, P24406, P36860, P48148, P48555, P49139, P61585, P61586, P61589, P62833, P62834, P62835, P62836, P79800, P87027, Q07983, Q08DE8, Q22038, Q4R379, Q5PR73, Q5R4B8, Q5R573, Q5R6S2, Q5REY6, Q5ZJW6, Q640R7, Q6DGL2, Q6IP71, Q6NUX8, Q7ZXH7, Q8VEA8, Q91Z61

Diamond homologs: A1DZY4, A6QP66, A8NU18, C4YKT4, O08989, O14807, O35929, O88667, O93856, O94363, P01119, P03967, P08645, P08647, P0CY32, P10114, P10536, P11233, P11234, P15064, P17609, P22124, P22126, P22278, P22279, P22280, P28775, P32254, P36860, P36863, P48555, P59279, P61105, P61225, P61226, P61227, P62070, P62071, P63320, P63321

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PRKCA	unknown	RALB	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 58 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
VxPx cargo-targeting to cilium	6	79.9×	2e-08
Insulin processing	6	70.3×	2e-08
Translocation of SLC2A4 (GLUT4) to the plasma membrane	9	35.6×	9e-10

GO biological processes:

GO term	Partners	Fold	FDR
obsolete vesicle docking involved in exocytosis	6	82.5×	1e-08
membrane fission	7	58.7×	6e-09
Golgi to plasma membrane transport	5	57.3×	3e-06
mitotic cytokinesis	6	31.8×	3e-06
regulation of macroautophagy	5	30.2×	4e-05
exocytosis	7	21.7×	3e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	21
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1332 predictions. Top by Δscore:

Variant	Effect	Δscore
2:120278775:CGAGG:C	donor_loss	1.0000
2:120278776:GAG:G	donor_gain	1.0000
2:120278778:GGTA:G	donor_loss	1.0000
2:120278779:G:A	donor_loss	1.0000
2:120278780:T:G	donor_loss	1.0000
2:120285870:TCA:T	acceptor_loss	1.0000
2:120285872:A:AG	acceptor_gain	1.0000
2:120285873:G:GA	acceptor_gain	1.0000
2:120285873:GT:G	acceptor_gain	1.0000
2:120285873:GTTT:G	acceptor_gain	1.0000
2:120286079:TCAGG:T	donor_loss	1.0000
2:120286081:AGGT:A	donor_loss	1.0000
2:120286082:GGT:G	donor_loss	1.0000
2:120286084:T:G	donor_loss	1.0000
2:120289754:CAAGG:C	donor_loss	1.0000
2:120289755:AAGG:A	donor_loss	1.0000
2:120289756:AGG:A	donor_loss	1.0000
2:120289758:G:GA	donor_loss	1.0000
2:120289758:G:GG	donor_gain	1.0000
2:120289759:T:G	donor_loss	1.0000
2:120293133:A:AG	acceptor_gain	1.0000
2:120293140:GGT:G	acceptor_gain	1.0000
2:120268978:C:G	acceptor_gain	0.9900
2:120269133:G:A	acceptor_gain	0.9900
2:120278612:CAGCA:C	acceptor_gain	0.9900
2:120278613:A:AG	acceptor_gain	0.9900
2:120278613:AGCAG:A	acceptor_gain	0.9900
2:120278614:G:GG	acceptor_gain	0.9900
2:120278614:GCA:G	acceptor_gain	0.9900
2:120278616:A:AG	acceptor_gain	0.9900

AlphaMissense

1369 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:120278725:G:C	G21R	1.000
2:120278740:G:C	G26R	1.000
2:120278741:G:A	G26D	1.000
2:120278741:G:T	G26V	1.000
2:120278743:A:C	K27Q	1.000
2:120278745:G:C	K27N	1.000
2:120278745:G:T	K27N	1.000
2:120278747:C:T	S28L	1.000
2:120278759:T:C	L32P	1.000
2:120285874:T:C	F39L	1.000
2:120285875:T:C	F39S	1.000
2:120285875:T:G	F39C	1.000
2:120285876:T:A	F39L	1.000
2:120285876:T:G	F39L	1.000
2:120285959:T:C	L67P	1.000
2:120285961:G:A	D68N	1.000
2:120285961:G:C	D68H	1.000
2:120285962:A:C	D68A	1.000
2:120285962:A:G	D68G	1.000
2:120285962:A:T	D68V	1.000
2:120285963:C:A	D68E	1.000
2:120285963:C:G	D68E	1.000
2:120285968:C:A	A70D	1.000
2:120285970:G:A	G71R	1.000
2:120285970:G:C	G71R	1.000
2:120285970:G:T	G71W	1.000
2:120285971:G:A	G71E	1.000
2:120289641:A:G	K129E	1.000
2:120289643:G:C	K129N	1.000
2:120289643:G:T	K129N	1.000

dbSNP variants (sampled 300 via entrez): RS1000110488 (2:120280944 T>C), RS1000113281 (2:120242794 G>A), RS1000178048 (2:120282133 C>A,T), RS1000181983 (2:120238556 AGGCCTGGGTGAGGG>A), RS1000182575 (2:120293610 C>A,T), RS1000240714 (2:120277965 ATGTG>A,ATG,ATGTGTG), RS1000272343 (2:120248336 T>A), RS1000410744 (2:120254602 G>T), RS1000446197 (2:120260998 A>C), RS1000572792 (2:120246876 A>G,T), RS1000614226 (2:120285365 A>T), RS1000623985 (2:120285520 G>A), RS1000631349 (2:120239749 C>A,T), RS1000642861 (2:120248025 A>T), RS1000741824 (2:120253161 G>A,C,T)

Disease associations

OMIM: gene MIM:179551 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST003985_2	Breast size	6.000000e-18
GCST004599_281	Mean platelet volume	1.000000e-25
GCST004603_212	Platelet count	2.000000e-18
GCST005580_158	Intraocular pressure	8.000000e-09
GCST005580_291	Intraocular pressure	2.000000e-09
GCST009391_156	Metabolite levels	7.000000e-06
GCST90002395_340	Mean platelet volume	7.000000e-71
GCST90002400_328	Plateletcrit	2.000000e-13
GCST90002401_385	Platelet distribution width	4.000000e-11
GCST90002402_249	Platelet count	4.000000e-50

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0004695	intraocular pressure measurement
EFO:0010486	glucuronate measurement
EFO:0007985	platelet crit
EFO:0007984	platelet component distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3879851 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation, increases expression	2
Cisplatin	affects expression, decreases response to substance	2
Tetrachlorodibenzodioxin	increases expression	2
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases expression	1
decabromobiphenyl ether	decreases expression	1
trichostatin A	affects cotreatment, decreases expression	1
tetrabromobisphenol A	decreases expression	1
ochratoxin A	affects binding	1
nickel sulfate	decreases expression, increases expression	1
di-n-butylphosphoric acid	affects expression	1
chloropicrin	increases expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	affects cotreatment, increases methylation	1
(+)-JQ1 compound	decreases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Decitabine	affects expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Vorinostat	affects cotreatment, decreases expression	1
Norethindrone Acetate	affects cotreatment, increases expression	1
Glyphosate	increases expression	1
Aspirin	decreases expression	1
Doxorubicin	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3870850	Binding	Inhibition of RalB activity in human H2122 spheroids after 4 hrs by RalBP1 pull down assay	Synthesis of novel Ral inhibitors: An in vitro and in vivo study. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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