RALBP1

Summary

RALBP1 (ralA binding protein 1, HGNC:9841) is a protein-coding gene on chromosome 18p11.22, encoding RalA-binding protein 1 (Q15311). Multifunctional protein that functions as a downstream effector of RALA and RALB.

RALBP1 plays a role in receptor-mediated endocytosis and is a downstream effector of the small GTP-binding protein RAL (see RALA; MIM 179550). Small G proteins, such as RAL, have GDP-bound inactive and GTP-bound active forms, which shift from the inactive to the active state through the action of RALGDS (MIM 601619), which in turn is activated by RAS (see HRAS; MIM 190020) (summary by Feig, 2003 [PubMed 12888294]).

Source: NCBI Gene 10928 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 94 total
• MANE Select transcript: NM_006788

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9841
Approved symbol	RALBP1
Name	ralA binding protein 1
Location	18p11.22
Locus type	gene with protein product
Status	Approved
Aliases	RLIP76, RIP1, RIP
Ensembl gene	ENSG00000017797
Ensembl biotype	protein_coding
OMIM	605801
Entrez	10928

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 26 protein_coding

ENST00000019317, ENST00000383432, ENST00000458039, ENST00000577221, ENST00000585015, ENST00000609094, ENST00000893973, ENST00000922000, ENST00000922001, ENST00000922002, ENST00000922003, ENST00000922004, ENST00000922005, ENST00000922006, ENST00000922007, ENST00000922008, ENST00000922009, ENST00000922010, ENST00000922011, ENST00000922012, ENST00000922013, ENST00000943836, ENST00000943837, ENST00000943838, ENST00000943839, ENST00000943840

RefSeq mRNA: 1 — MANE Select: NM_006788 NM_006788

CCDS: CCDS11845

Canonical transcript exons

ENST00000383432 — 10 exons

Exon	Start	End
ENSE00000666007	9516845	9517303
ENSE00000666008	9522160	9522509
ENSE00000666013	9525720	9525851
ENSE00001018078	9533703	9533826
ENSE00001142648	9533335	9533456
ENSE00001187739	9530834	9530941
ENSE00001187743	9524594	9524755
ENSE00001541191	9535671	9538114
ENSE00001541207	9512991	9513289
ENSE00003849898	9475513	9475691

Expression profiles

Bgee: expression breadth ubiquitous, 298 present calls, max score 98.40.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.7032 / max 298.9872, expressed in 1816 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
169365	17.7838	1788
169361	2.2374	940
169366	2.0883	1129
169368	0.7250	371
169364	0.5829	306
169367	0.4370	190
169369	0.4262	148
169363	0.2458	105
169362	0.1767	78

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
renal medulla	UBERON:0000362	98.40	gold quality
nipple	UBERON:0002030	98.38	gold quality
dorsal root ganglion	UBERON:0000044	97.63	gold quality
buccal mucosa cell	CL:0002336	97.55	gold quality
pylorus	UBERON:0001166	97.23	gold quality
trigeminal ganglion	UBERON:0001675	97.23	gold quality
penis	UBERON:0000989	96.85	gold quality
lateral globus pallidus	UBERON:0002476	96.81	gold quality
pharyngeal mucosa	UBERON:0000355	96.78	gold quality
substantia nigra pars reticulata	UBERON:0001966	96.78	gold quality
substantia nigra pars compacta	UBERON:0001965	96.47	gold quality
saphenous vein	UBERON:0007318	96.45	gold quality
inferior vagus X ganglion	UBERON:0005363	96.41	gold quality
ventral tegmental area	UBERON:0002691	96.24	gold quality
superior surface of tongue	UBERON:0007371	96.23	gold quality
superior vestibular nucleus	UBERON:0007227	95.96	gold quality
body of tongue	UBERON:0011876	95.94	gold quality
cardia of stomach	UBERON:0001162	95.92	gold quality
secondary oocyte	CL:0000655	95.83	gold quality
endometrium epithelium	UBERON:0004811	95.83	gold quality
pericardium	UBERON:0002407	95.80	gold quality
urethra	UBERON:0000057	95.77	gold quality
lateral nuclear group of thalamus	UBERON:0002736	95.75	gold quality
tongue	UBERON:0001723	95.74	gold quality
mammary duct	UBERON:0001765	95.61	gold quality
globus pallidus	UBERON:0001875	95.48	gold quality
medulla oblongata	UBERON:0001896	95.42	gold quality
medial globus pallidus	UBERON:0002477	95.29	gold quality
frontal pole	UBERON:0002795	95.28	gold quality
calcaneal tendon	UBERON:0003701	95.25	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	34.89
E-MTAB-6678	yes	16.36
E-HCAD-10	yes	15.22
E-HCAD-13	yes	7.61
E-CURD-53	no	684.18
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYB

miRNA regulators (miRDB)

136 targeting RALBP1, 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-3613-3P	100.00	76.36	7965
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-548E-5P	99.89	72.73	4486

Literature-anchored findings (GeneRIF, showing 40)

• We have compared the transport properties of recombinant RLIP76 and human erythrocyte membrane RLIP76. (PMID:11732624)
• In this review, RLIP76-mediated transport of organic ions has physiological and toxicological relevance which may play an important role in the mechanism of drug resistance. (PMID:12433796)
• RLIP76 activity is a general determinant of 4HNE and DOX resistance. Its activity contributes to the drug-resistant phenotype of NSCLC. (PMID:12527936)
• RLIP76 has a role in Doxorubicin transport in lung cancer (PMID:12632060)
• RLIP76 has a role in triggering apoptosis in lung cancer cells and synergistically increaseing doxorubicin cytotoxicity (PMID:12632061)
• RLIP/RalBP1 is used as a platform by the mitotic cdk1 to facilitate the phosphorylation of Epsin, which makes Epsin incompetent for endocytosis during mitosis, when endocytosis is switched off. (PMID:12775724)
• These results show for the first time that POB1 can regulate the transport function of RLIP76 and are consistent with our previous studies showing that inhibition of RLIP76 induces apoptosis in cancer cells. (PMID:15707977)
• Results identify targets in RLIP76 for phosphorylation by protein kinase C alpha, which may act as substrates for differential transport of doxorubicin. (PMID:16087181)
• RLIP76 is the predominant transporter of antiepileptic drugs in the blood brain barrier and may be involved in mechanisms of drug-resistant epilepsy. (PMID:16188027)
• Augmenting cellular levels of RLIP76 using purified recombinant RLIP76 increased growth rate in all cells, and restored the sensitivity of RLIP76-/- mouse embryonic fibroblasts to both inhibition through PKCalpha-depletion and stimulation through PMA. (PMID:16890208)
• identify a role for caspase-8 in monocytes undergoing macrophagic differentiation, that is, the enzyme activated in an atypical complex down-regulates NF-kappaB activity through RIP1 cleavage. (PMID:17047155)
• phosphoprotein mapping of Ral binding protein 1 (RalBP1/Rip1/RLIP76) (PMID:17706599)
• the spatiotemporal mobilization of TICAM-1 in response to dsRNA and the formation of the TICAM-1 speckles containing RIP1 and NAP1 are important for the activation of the TLR3-TICAM-1 pathway. (PMID:17982077)
• autoantibodies to RLIP76 play a pathogenetic role in immune-mediated vascular diseases (PMID:17993611)
• common variants in RLIP76 are unlikely to contribute to epilepsy drug response. (PMID:18086001)
• Hsf-1 causes specific and saturable inhibition of the transport activity of Ralbp1 and that the combination of Hsf-1 and POB1 causes nearly complete inhibition through specific bindings with Ralbp1. (PMID:18474607)
• RLIP76 is a fundamental link between biochemical pathways and glutathione-linked metabolism of xenobiotics and stress-degense signaling pathways. (PMID:18628450)
• RLIP76 serves a key effector function for survival of prostate cancer cells; depletion of RLIP76 in mice bearing xenografts of prostate cancer cells leads to near complete regression of established subcutaneous xenografts with no apparent toxic effects. (PMID:19073149)
• the accumulation-deficient drug-resistance mediated by RLIP76 can be modulated by inhibition of RLIP76 transport activity by cdc2. (PMID:19375851)
• RLIP76 is an anticancer for kidney cancer: inhibition of RLIP76 function by antibody or its depletion by small interfering RNA or antisense DNA causes marked regression of kidney xenografts in nude mice. (PMID:19417134)
• Studies offer strong support for the hypothesis that RLIP76 is an overarching anti-apoptosis mechanism that, if inhibited, can be more broadly effective in the treatment of renal cell carcinoma. (PMID:19626587)
• a link between RLIP76 mediated GS-E transport and cell cycle signaling are presented. (PMID:20183533)
• studies suggest that the expression of RalBP1 is necessary for human cancer cell metastasis; show that the requirement for RalA expression for manifestation of this phenotype is not entirely dependent on a RalA-RalBP1 interaction (PMID:21170262)
• The impairment of RLIP76 by aaRLIP76 can play a role in the damage of vascular cells from females, contributing to the gender-associated pathogenesis of immune-mediated vascular diseases. (PMID:21671802)
• Data show that disrupting either RALA or RALBP1 leads to a loss of mitochondrial fission at mitosis, improper segregation of mitochondria during cytokinesis and a decrease in ATP levels and cell number. (PMID:21822277)
• RalB-mediated invadopodium formation was dependent on RalBP1/RLIP76; disruption of the ATPase function of RalBP1 impaired invadopodium formation. (PMID:22331470)
• RalBP1 protein is an independent predictor of poor survival and early relapse for CRC patients (PMID:22549157)
• RLIP76 may suppress apoptosis and promote the proliferation of glioma cells by direct adenosine triphosphate-dependent xenobiotic transport and by activating the Rac1-JNK signaling pathway. (PMID:23276796)
• p300 associates with the RLIP76 promoter via an overlapping cMYB and cETS binding site and regulates RLIP76 promoter activity and its expression. (PMID:23419874)
• Activation of RalBP1 during neoplastic epithelial cell transformation induces cytoplasmic accumulation of p27, this event requires p27 Ser-10 phosphorylation by protein kinase B/Akt. (PMID:23576547)
• RLIP76 is a node for Rho and Ras family signalling. [Review] (PMID:24450627)
• RLIP76 is a potential target for developing novel therapeutic strategies for leukemia (PMID:24839008)
• RLIP76 downregulation in HT29 CRC cells suppressed cell growth, enhanced cell apoptosis, induced cell cycle arrest, and inhibited cell invasion by decreasing MMP2 expression. (PMID:25213293)
• High RLIP76 expression is associated with a poor outcome of meningioma. (PMID:25993541)
• results revealed that the effect of miR-101 on prostate cancer cell apoptosis was due to RLIP76 regulation of the PI3K/Akt/Bcl-2 signaling pathway (PMID:26067553)
• report showed that RLIP76 expression was significantly increased in breast cancer samples and positively correlated with the malignant status of breast cancer patients; results indicated that high RLIP76 expression was associated with poor prognosis of breast cancer patients (PMID:26125275)
• RLIP76 expression is induced by TNF-alpha and follows the induction kinetics of inflammation markers, suggesting that inflammation can influence RLIP76 expression at the blood brain barrier. (PMID:26406496)
• In the exons and exon-intron boundaries of ABCB5 and RLIP76 genes. (PMID:26975227)
• RLIP76 knockdown increased autophagic flux and apoptosis in U251 glioma cells. (PMID:27473470)
• Phosphorylation level of Akt declined from 138.45+/-13.8 to 69.9+/-29.7% in SGC-7901, and from 115.5+/-26.6 to 49.07+/-27% in MGC-803 and phosphorylation level of mTOR also significantly decreased.While apoptosis of gastric cancer(GA) cells increased which we verified with apoptosis proteins and staining analysis. Our data showed that RLIP76 plays a significant oncogenic role in GC and it maybe a potential target in GC (PMID:27572296)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	ralbp1	ENSDARG00000078653
mus_musculus	Ralbp1	ENSMUSG00000024096
rattus_norvegicus	Ralbp1l1	ENSRNOG00000000889
rattus_norvegicus	Ralbp1	ENSRNOG00000013461
rattus_norvegicus		ENSRNOG00000078461
rattus_norvegicus		ENSRNOG00000083479
drosophila_melanogaster	Rlip	FBGN0026056
caenorhabditis_elegans	rlbp-1	WBGENE00011970

Protein

Protein identifiers

RalA-binding protein 1 — Q15311 (reviewed: Q15311)

Alternative names: 76 kDa Ral-interacting protein, Dinitrophenyl S-glutathione ATPase, Ral-interacting protein 1

All UniProt accessions (4): Q15311, A0A1W2PRI7, E7ENF8, J3QLT3

UniProt curated annotations — full annotation on UniProt →

Function. Multifunctional protein that functions as a downstream effector of RALA and RALB. As a GTPase-activating protein/GAP can inactivate CDC42 and RAC1 by stimulating their GTPase activity. As part of the Ral signaling pathway, may also regulate ligand-dependent EGF and insulin receptors-mediated endocytosis. During mitosis, may act as a scaffold protein in the phosphorylation of EPSIN/EPN1 by the mitotic kinase cyclin B-CDK1, preventing endocytosis during that phase of the cell cycle. During mitosis, also controls mitochondrial fission as an effector of RALA. Recruited to mitochondrion by RALA, acts as a scaffold to foster the mitotic kinase cyclin B-CDK1-mediated phosphorylation and activation of DNM1L. Could also function as a primary ATP-dependent active transporter for glutathione conjugates of electrophiles. May also actively catalyze the efflux of a wide range of substrates including xenobiotics like doxorubicin (DOX) contributing to cell multidrug resistance.

Subunit / interactions. Interacts with the GTP-bound form of RALA (via effector domain); during mitosis, recruits RALBP1 to the mitochondrion where it promotes DNM1L phosphorylation and mitochondrial fission. Interacts with DNM1L; mediates its mitotic kinase cyclin B-CDK1-mediated phosphorylation during mitosis to promote mitochondrial fission. Interacts with the mitotic kinase cyclin B-CDK1 during mitosis. Interacts with the GTP-bound form of RALB (via effector domain). Interacts with REPS1; the interaction is direct and does not affect RALA-binding nor GTPase activator activity of RALBP1. Interacts with REPS2; the interaction is direct and does not affect RALA-binding nor GTPase activator activity of RALBP1. Interacts with EPN1, NUMB and TFAP2A during interphase and mitosis. Interacts with AP2M1; as part of the AP2 complex. Interacts with CDC42. Interacts with RAC1.

Subcellular location. Cell membrane. Cytoplasm. Cytosol. Cytoskeleton. Spindle pole. Nucleus. Mitochondrion.

Tissue specificity. Expressed ubiquitously but at low levels. Shows a strong expression in the erythrocytes.

Post-translational modifications. Tyrosine-phosphorylated upon stimulation of cells with EGF. May undergo proteolytic cleavage to give peptides which reassemble to form a transporter complex.

Domain organisation. The Rho-GAP domain mediates the GTPase activator activity toward CDC42.

Miscellaneous. Originally designated as dinitrophenyl S-glutathione (DNP-SG) ATPase due to its ability to stimulate ATP hydrolysis in the presence of DNP-SG.

RefSeq proteins (1): NP_006779* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000198	RhoGAP_dom	Domain
IPR008936	Rho_GTPase_activation_prot	Homologous_superfamily
IPR039767	RALBP1	Family
IPR049041	RalBP1-like_Ral-bd	Domain

Pfam: PF00620, PF20924

Enzyme classification (BRENDA):

• EC 7.6.2.3 — ABC-type glutathione-S-conjugate transporter (BRENDA: 8 organisms, 145 substrates, 63 inhibitors, 16 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

7 substrates with measured Km, best-characterized 7. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0865–0.91	5
MONOMETHYLARSONOUS ACID DIGLUTATHIONE[SIDE 1]	0.023–0.033	4
S-(2,4-DINITROPHENYL)GLUTATHIONE[SIDE 1]	0.0141–0.032	2
S-(LEUKOTRIENE C4)GLUTATHIONE[SIDE 1]	0.0001	2
4-(GLUTATHIONE-S-YL)-QUINOLINE-1-OXIDE[SIDE 1]	0.0095	1
ARSENIC TRIGLUTATHIONE[SIDE 1]	0.0003	1
S-GLUTATHIONE[SIDE 1]	12	1

Catalyzed reactions (Rhea), 2 shown:

• an S-substituted glutathione(in) + ATP + H2O = an S-substituted glutathione(out) + ADP + phosphate + H(+) (RHEA:19121)
• leukotriene C4(in) + ATP + H2O = leukotriene C4(out) + ADP + phosphate + H(+) (RHEA:38963)

UniProt features (52 total): modified residue 12, helix 12, compositionally biased region 7, region of interest 7, turn 3, binding site 2, mutagenesis site 2, strand 2, initiator methionine 1, chain 1, site 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

5 structures.

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

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15311-F1	65.35	0.12

Functional residue map

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

Catalytic / active sites (1): 232 (arginine finger; crucial for gtp hydrolysis by stabilizing the transition state)

Ligand- & substrate-binding residues (2): 69–74; 418–425

Post-translational modifications (12): 2, 29, 30, 34, 44, 48, 62, 92, 93, 461, 463, 645

Mutagenesis-validated functional residues (2):

Position	Phenotype
74	loss of atp-binding and transport-associated atpase activity.
425	loss of atp-binding and transport-associated atpase activity.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-9013148	CDC42 GTPase cycle
R-HSA-9013149	RAC1 GTPase cycle

MSigDB gene sets: 292 (showing top): GOBP_POSITIVE_REGULATION_OF_MITOCHONDRIAL_FISSION, MORF_MBD4, TGCGCANK_UNKNOWN, GOBP_REGULATION_OF_PHOSPHORYLATION, AAGCCAT_MIR135A_MIR135B, GOBP_REGULATION_OF_GTPASE_ACTIVITY, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, GOBP_VESICLE_MEDIATED_TRANSPORT, GOMF_GTPASE_BINDING, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GGGTGGRR_PAX4_03, GOBP_ORGANIC_HYDROXY_COMPOUND_TRANSPORT, GTGCCTT_MIR506, GOBP_TAXIS

GO Biological Process (13): positive regulation of protein phosphorylation (GO:0001934), receptor-mediated endocytosis (GO:0006898), chemotaxis (GO:0006935), small GTPase-mediated signal transduction (GO:0007264), regulation of Cdc42 protein signal transduction (GO:0032489), regulation of GTPase activity (GO:0043087), positive regulation of GTPase activity (GO:0043547), regulation of small GTPase mediated signal transduction (GO:0051056), transmembrane transport (GO:0055085), positive regulation of mitochondrial fission (GO:0090141), doxorubicin transport (GO:1900753), xenobiotic detoxification by transmembrane export across the plasma membrane (GO:1990961), signal transduction (GO:0007165)

GO Molecular Function (10): GTPase activator activity (GO:0005096), ATP binding (GO:0005524), ABC-type xenobiotic transporter activity (GO:0008559), ABC-type glutathione S-conjugate transporter activity (GO:0015431), transmembrane transporter activity (GO:0022857), small GTPase binding (GO:0031267), ATPase-coupled transmembrane transporter activity (GO:0042626), xenobiotic transmembrane transporter activity (GO:0042910), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (10): spindle pole (GO:0000922), nucleoplasm (GO:0005654), mitochondrion (GO:0005739), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), nuclear body (GO:0016604), nucleus (GO:0005634), cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
RHO GTPase cycle	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
GTPase activity	3
cellular process	2
ABC-type transporter activity	2
cytoplasm	2
intracellular membrane-bounded organelle	2
intracellular membraneless organelle	2
regulation of protein phosphorylation	1
protein phosphorylation	1
positive regulation of protein modification process	1
positive regulation of phosphorylation	1
endocytosis	1
response to chemical	1
taxis	1
intracellular signaling cassette	1
Cdc42 protein signal transduction	1
regulation of Rho protein signal transduction	1
regulation of hydrolase activity	1
regulation of GTPase activity	1
positive regulation of hydrolase activity	1
small GTPase-mediated signal transduction	1
regulation of intracellular signal transduction	1
transport	1
mitochondrial fission	1
positive regulation of organelle organization	1
positive regulation of developmental process	1
regulation of mitochondrial fission	1
organic hydroxy compound transport	1
nitrogen compound transport	1
glycoside transport	1
xenobiotic export from cell	1
detoxification	1
export across plasma membrane	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
enzyme activator activity	1
GTPase regulator activity	1
adenyl ribonucleotide binding	1

Protein interactions and networks

STRING

674 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RALBP1	RALA	P11233	998
RALBP1	RALB	P11234	970
RALBP1	REPS2	Q8NFH8	943
RALBP1	REPS1	Q96D71	834
RALBP1	RALGDS	Q12967	784
RALBP1	EXOC8	Q8IYI6	759
RALBP1	RASA1	P20936	741
RALBP1	RRAS	P10301	691
RALBP1	EXOC2	Q96KP1	690
RALBP1	EPN1	Q9Y6I3	682
RALBP1	EPN3	Q9H201	626
RALBP1	EPN2	O95208	617
RALBP1	CDK1	P06493	610
RALBP1	CDC42	P21181	573
RALBP1	EPS15	P42566	566

IntAct

485 interactions, top by confidence:

A	B	Type	Score
RALBP1	GPS2	psi-mi:“MI:0915”(physical association)	0.900
GPS2	RALBP1	psi-mi:“MI:0915”(physical association)	0.900
RALBP1	CCDC6	psi-mi:“MI:0915”(physical association)	0.840
RALBP1	SAPCD2	psi-mi:“MI:0915”(physical association)	0.800
RALBP1	DLG1	psi-mi:“MI:0915”(physical association)	0.790
DLG1	RALBP1	psi-mi:“MI:0407”(direct interaction)	0.790
SCRIB	RALBP1	psi-mi:“MI:0915”(physical association)	0.780
SCRIB	RALBP1	psi-mi:“MI:0407”(direct interaction)	0.780
DLG4	RALBP1	psi-mi:“MI:0407”(direct interaction)	0.780
RALBP1	DLG4	psi-mi:“MI:0915”(physical association)	0.780
RALBP1	CREBZF	psi-mi:“MI:0915”(physical association)	0.740
RALBP1	MSANTD4	psi-mi:“MI:0915”(physical association)	0.740
PSMC5	PSMD11	psi-mi:“MI:0914”(association)	0.730
STAMBP	PIK3C2A	psi-mi:“MI:0914”(association)	0.730
RALBP1	C1orf216	psi-mi:“MI:0915”(physical association)	0.720
SMARCE1	RALBP1	psi-mi:“MI:0915”(physical association)	0.720
ZNF707	RALBP1	psi-mi:“MI:0915”(physical association)	0.720
C1orf216	RALBP1	psi-mi:“MI:0915”(physical association)	0.720
RALBP1	ZNF707	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (306): RALBP1 (Two-hybrid), RALBP1 (Two-hybrid), RALBP1 (Two-hybrid), RALBP1 (Two-hybrid), RALBP1 (Two-hybrid), GSE1 (Two-hybrid), TFPT (Two-hybrid), AMOTL2 (Two-hybrid), TBRG1 (Two-hybrid), C1orf216 (Two-hybrid), ZBTB38 (Two-hybrid), ZNF707 (Two-hybrid), EPN1 (Affinity Capture-Western), EPN2 (Affinity Capture-Western), EPN3 (Affinity Capture-Western)

ESM2 similar proteins: A5PMU4, B2RQE8, D3ZFJ3, F1LQX4, F1LXF1, G9CGD6, O00499, O08539, O08839, P55194, P59672, Q13191, Q13905, Q15311, Q15678, Q17R89, Q3TTA7, Q3UIA2, Q5SSM3, Q62172, Q62415, Q62739, Q62796, Q68EM7, Q6P9K8, Q6PAJ1, Q6PCS4, Q6ZM86, Q6ZT62, Q7Z628, Q80YS6, Q86XZ4, Q8BL80, Q8BMI3, Q8K0Q5, Q8K4S7, Q8N392, Q8N556, Q8VH46, Q8VHK2

Diamond homologs: A0A0G2JTR4, A1A4S6, A2AB59, A2RUV4, A4IF90, A4II46, A6QNS3, A6X8Z5, A7KAX9, A7YY57, A8WRJ2, D3ZFJ3, E7EZG2, E7F3F0, F1LXF1, O14559, O94466, P11274, P15882, P30337, P34288, P38339, P46941, P52757, P55194, P81128, P97393, Q03070, Q08DP6, Q10164, Q12979, Q13017, Q15311, Q17QN0, Q20498, Q2M1Z3, Q3TBD2, Q3UIA2, Q52LW3, Q53QZ3

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
RALBP1	“down-regulates activity”	RAC1	“gtpase-activating protein”
PRKCA	“up-regulates activity”	RALBP1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 100 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
Nef-mediates down modulation of cell surface receptors by recruiting them to clathrin adapters	6	54.4×	9e-08
The role of Nef in HIV-1 replication and disease pathogenesis	6	54.4×	9e-08
WNT5A-dependent internalization of FZD4	5	54.4×	1e-06
VLDLR internalisation and degradation	5	51.0×	1e-06
Trafficking of GluR2-containing AMPA receptors	5	48.0×	2e-06
LDL clearance	6	46.6×	2e-07
Plasma lipoprotein clearance	6	40.8×	3e-07
Host Interactions of HIV factors	6	28.8×	2e-06

GO biological processes:

GO term	Partners	Fold	FDR
clathrin coat assembly	7	71.4×	3e-09
clathrin-dependent endocytosis	7	46.8×	4e-08
synaptic vesicle endocytosis	7	34.8×	2e-07
endocytosis	10	10.9×	4e-06
vesicle-mediated transport	7	7.8×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	75
Likely benign	7
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1968 predictions. Top by Δscore:

Variant	Effect	Δscore
18:9501035:G:GT	donor_gain	1.0000
18:9513252:G:T	donor_gain	1.0000
18:9513285:GAGGA:G	donor_gain	1.0000
18:9513286:AGGA:A	donor_gain	1.0000
18:9513287:GGA:G	donor_gain	1.0000
18:9513287:GGAG:G	donor_gain	1.0000
18:9513287:GGAGT:G	donor_loss	1.0000
18:9513288:GA:G	donor_gain	1.0000
18:9513288:GAG:G	donor_gain	1.0000
18:9513289:AGTAA:A	donor_loss	1.0000
18:9513290:G:GG	donor_gain	1.0000
18:9513290:GTA:G	donor_loss	1.0000
18:9513291:TAAGT:T	donor_loss	1.0000
18:9516839:T:TA	acceptor_gain	1.0000
18:9516843:A:AG	acceptor_gain	1.0000
18:9516844:G:GG	acceptor_gain	1.0000
18:9524590:TTA:T	acceptor_loss	1.0000
18:9524591:TA:T	acceptor_loss	1.0000
18:9524592:A:AG	acceptor_gain	1.0000
18:9524593:G:GA	acceptor_gain	1.0000
18:9524593:GA:G	acceptor_gain	1.0000
18:9524593:GAT:G	acceptor_gain	1.0000
18:9524593:GATC:G	acceptor_gain	1.0000
18:9524593:GATCA:G	acceptor_gain	1.0000
18:9524629:T:G	acceptor_gain	1.0000
18:9524751:GACAG:G	donor_gain	1.0000
18:9524754:AGG:A	donor_loss	1.0000
18:9524756:G:GG	donor_gain	1.0000
18:9524756:GT:G	donor_loss	1.0000
18:9524757:T:A	donor_loss	1.0000

AlphaMissense

4364 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:9513157:T:C	F38L	1.000
18:9513158:T:C	F38S	1.000
18:9513158:T:G	F38C	1.000
18:9513159:T:A	F38L	1.000
18:9513159:T:G	F38L	1.000
18:9522260:G:C	K268N	1.000
18:9522260:G:T	K268N	1.000
18:9525792:T:A	W430R	1.000
18:9525792:T:C	W430R	1.000
18:9525793:G:C	W430S	1.000
18:9525794:G:C	W430C	1.000
18:9525794:G:T	W430C	1.000
18:9525803:A:C	Q433H	1.000
18:9525803:A:T	Q433H	1.000
18:9525806:A:C	R434S	1.000
18:9525806:A:T	R434S	1.000
18:9525823:A:T	K440I	1.000
18:9525826:G:C	R441T	1.000
18:9525827:A:C	R441S	1.000
18:9525827:A:T	R441S	1.000
18:9533429:T:C	L517P	1.000
18:9513157:T:G	F38V	0.999
18:9513164:G:A	G40E	0.999
18:9513167:T:C	L41S	0.999
18:9516853:T:C	Y85H	0.999
18:9516863:T:C	F88S	0.999
18:9516863:T:G	F88C	0.999
18:9517295:G:C	R232T	0.999
18:9517296:A:C	R232S	0.999
18:9517296:A:T	R232S	0.999

dbSNP variants (sampled 300 via entrez): RS1000089842 (18:9512804 G>A,C,T), RS1000091799 (18:9498484 C>G,T), RS1000115058 (18:9487584 A>C,G), RS1000146629 (18:9529070 A>C,G), RS1000229096 (18:9509604 C>A,T), RS1000255989 (18:9503523 A>G), RS1000261616 (18:9504656 A>G,T), RS1000318275 (18:9492197 C>G), RS1000354958 (18:9475300 G>A,C,T), RS1000391843 (18:9515347 C>G,T), RS1000391936 (18:9479188 T>C), RS1000439046 (18:9486449 C>A,T), RS1000506942 (18:9497933 G>T), RS1000608568 (18:9493985 C>G,T), RS1000608966 (18:9534008 C>G)

Disease associations

OMIM: gene MIM:605801 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006612_96	LDL cholesterol	3.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs329007	RALBP1		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Doxorubicin	affects export, decreases response to substance, affects cotreatment, increases phosphorylation, increases transport (+3 more)	5
Adenosine Triphosphate	affects transport, increases reaction, affects cotreatment, increases phosphorylation, increases transport	2
Tobacco Smoke Pollution	decreases methylation, increases expression	2
Valproic Acid	increases methylation, affects expression	2
FR900359	affects phosphorylation	1
bisphenol F	increases expression, affects cotreatment	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression, affects cotreatment	1
3,4-dichloroaniline	increases expression	1
sodium arsenite	decreases expression	1
4-hydroxy-2-nonenal	decreases response to substance	1
coumarin	affects phosphorylation	1
bisindolylmaleimide	decreases phosphorylation	1
CGP 52608	affects binding, increases reaction	1
4-(3-(1-adamantyl)-4-hydroxyphenyl)-3-chlorocinnamic acid	increases expression	1
abrine	decreases expression	1
bisphenol S	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1
Fulvestrant	increases methylation	1
Atrazine	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Caffeine	affects phosphorylation	1
Cisplatin	affects cotreatment, increases expression	1
Colchicine	affects transport, decreases reaction	1
Dexamethasone	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Quercetin	decreases phosphorylation	1
Selenium	decreases expression, affects cotreatment	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2DB	Abcam HeLa RALBP1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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