RABL3

Summary

RABL3 (RAB, member of RAS oncogene family like 3, HGNC:18072) is a protein-coding gene on chromosome 3q13.33, encoding Rab-like protein 3 (Q5HYI8). Small GTPase required for KRAS signaling regulation and modulation of cell proliferation.

Predicted to enable GTP binding activity; GTPase activity; and protein homodimerization activity. Involved in regulation of Ras protein signal transduction and regulation of protein lipidation. Predicted to be active in endomembrane system. Implicated in pancreatic cancer.

Source: NCBI Gene 285282 — RefSeq curated summary.

At a glance

• Gene–disease (curated): familial pancreatic carcinoma (Supportive, GenCC) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 45 total
• Phenotypes (HPO): 25
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_173825

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18072
Approved symbol	RABL3
Name	RAB, member of RAS oncogene family like 3
Location	3q13.33
Locus type	gene with protein product
Status	Approved
Aliases	MGC23920
Ensembl gene	ENSG00000144840
Ensembl biotype	protein_coding
OMIM	618542
Entrez	285282

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 6 protein_coding, 4 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined

ENST00000273375, ENST00000465022, ENST00000468192, ENST00000473654, ENST00000481015, ENST00000483733, ENST00000485161, ENST00000491398, ENST00000648525, ENST00000880049, ENST00000880050, ENST00000880051, ENST00000932419

RefSeq mRNA: 3 — MANE Select: NM_173825 NM_001363964, NM_001363965, NM_173825

CCDS: CCDS3001, CCDS87127

Canonical transcript exons

ENST00000273375 — 8 exons

Exon	Start	End
ENSE00001206486	120742462	120742516
ENSE00001315999	120684938	120689888
ENSE00003542581	120730696	120730787
ENSE00003558596	120709780	120709909
ENSE00003560174	120698423	120698573
ENSE00003616547	120706000	120706114
ENSE00003654172	120690449	120690487
ENSE00003681890	120694153	120694224

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 92.90.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.9566 / max 398.8763, expressed in 1767 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
44090	13.5044	1757
44091	1.3041	947
44089	0.1154	8
44088	0.0327	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	92.90	gold quality
islet of Langerhans	UBERON:0000006	90.96	gold quality
rectum	UBERON:0001052	89.43	gold quality
right adrenal gland	UBERON:0001233	89.17	gold quality
left adrenal gland	UBERON:0001234	89.12	gold quality
right adrenal gland cortex	UBERON:0035827	89.03	gold quality
adrenal gland	UBERON:0002369	88.78	gold quality
left adrenal gland cortex	UBERON:0035825	88.37	gold quality
adrenal cortex	UBERON:0001235	87.78	gold quality
ventricular zone	UBERON:0003053	86.83	gold quality
calcaneal tendon	UBERON:0003701	86.70	gold quality
monocyte	CL:0000576	86.54	gold quality
mononuclear cell	CL:0000842	86.41	gold quality
stromal cell of endometrium	CL:0002255	86.41	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	86.28	gold quality
leukocyte	CL:0000738	86.15	gold quality
muscle of leg	UBERON:0001383	85.98	gold quality
gastrocnemius	UBERON:0001388	85.93	gold quality
cranial nerve II	UBERON:0000941	85.87	gold quality
smooth muscle tissue	UBERON:0001135	85.83	gold quality
gall bladder	UBERON:0002110	85.55	gold quality
diaphragm	UBERON:0001103	85.54	gold quality
spinal cord	UBERON:0002240	85.25	gold quality
hindlimb stylopod muscle	UBERON:0004252	84.94	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	84.76	gold quality
skeletal muscle organ	UBERON:0014892	84.57	gold quality
muscle organ	UBERON:0001630	84.56	gold quality
ganglionic eminence	UBERON:0004023	84.56	gold quality
adipose tissue	UBERON:0001013	84.43	gold quality
biceps brachii	UBERON:0001507	84.14	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	32.29
E-ANND-3	yes	4.98

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

147 targeting RABL3, 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-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-1236-3P	99.94	68.04	1695

Literature-anchored findings (GeneRIF, showing 12)

• Rabl3 can be considered as a novel candidate in the control of tumorigenesis and as a new target for anticancer treatment. (PMID:20596630)
• We examine the correlation between the expression level of Rabl3 and survival of non-small cell lung cancer (NSCLC) patients in three independent cohorts containing 484 patients. We found high expression of Rabl3 might inhibit cell death in non-small cell lung cancer via repression of MAPK8/9/10-mediated autophagy (PMID:27164297)
• Our studies suggest that the Rabl3 is a valuable marker of hepatocellular carcinoma progression and that the overexpression of Rabl3 plays an important role in the development and pathogenesis of hepatocellular carcinoma. (PMID:28443498)
• Hepatocellular carcinoma patients with positive expression for both Rabl3 and Cullin7 had a remarkably shorter survival time compared with patients with negative expression for both proteins. (PMID:28739496)
• MiR-296-3p may affect the proliferation and migration of non-small cell lung cancer cells via regulating RABL3. (PMID:31298353)
• Mutations in RABL3 alter KRAS prenylation and are associated with hereditary pancreatic cancer. (PMID:31406347)
• Identification of GIMAP7 and Rabl3 as Putative Biomarkers for Oral Squamous Cell Carcinoma Through Comparative Proteomic Approach. (PMID:31748878)
• Long non-coding RNA LINC00858 promotes cells proliferation and invasion through the miR-153-3p/Rabl3 axis in hepatocellular carcinoma. (PMID:33015775)
• Low-frequency of RABL3 pathogenetic variants in hereditary and familial pancreatic cancer. (PMID:33353859)
• Knockdown of RABL3 suppresses the proliferation and invasion of oral squamous cell carcinoma through inactivating the FAK/AKT pathway. (PMID:33438143)
• Germline sequence analysis of RABL3 in a large series of pancreatic ductal adenocarcinoma patients reveals no evidence of deleterious variants. (PMID:33724601)
• circCOL1A1 Promotes the Progression of Gastric Cancer Cells through Sponging miR-145 to Enhance RABL3 Expression. (PMID:34631898)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rabl3	ENSDARG00000040959
mus_musculus	Rabl3	ENSMUSG00000022827
rattus_norvegicus	Rabl3	ENSRNOG00000026085

Protein

Protein identifiers

Rab-like protein 3 — Q5HYI8 (reviewed: Q5HYI8)

All UniProt accessions (6): Q5HYI8, C9JXM3, F8WAX9, F8WDC7, F8WF50, H7C533

UniProt curated annotations — full annotation on UniProt →

Function. Small GTPase required for KRAS signaling regulation and modulation of cell proliferation. Regulator of KRAS prenylation, and probably prenylation of other small GTPases. Required for lymphocyte development and function. Not required for myeloid cell development. Interacts with Rab11 to promote ciliary vesicle formation at the mother centriole, thereby regulating early ciliogenesis. The GTP-binding capacity of RABL3 is essential for ciliogenesis.

Subunit / interactions. Homodimer. Interacts with GPR89; the interaction stabilizes GPR89. Interacts with RAP1GDS1. Interacts (GDP-bound) with RAB11A (GTP-bound); the interaction stabilizes RABL3 and regulates ciliary vesicle formation during early ciliogenesis.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Golgi apparatus.

Disease relevance. Pancreatic cancer 5 (PNCA5) [MIM:618680] A malignant neoplasm of the pancreas. Tumors can arise from both the exocrine and endocrine portions of the pancreas, but 95% of them develop from the exocrine portion, including the ductal epithelium, acinar cells, connective tissue, and lymphatic tissue. Disease susceptibility is associated with variants affecting the gene represented in this entry. RABL3 variants have been found in families with a history of pancreatic ductal adenocarcinoma and multiple other occurrences of cancer, including melanoma, breast cancer, prostate cancer, and colon cancer.

Domain organisation. Switch I, switch II and the interswitch regions are characteristic of Rab GTPases and mediate the interactions with Rab downstream effectors. The switch regions undergo conformational changes upon nucleotide binding which drive interaction with specific sets of effector proteins, with most effectors only binding to GTP-bound Rab.

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

RefSeq proteins (3): NP_001350893, NP_001350894, NP_776186* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027417	P-loop_NTPase	Homologous_superfamily

Pfam: PF08477

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (23 total): binding site 14, region of interest 3, sequence variant 2, sequence conflict 2, chain 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5HYI8-F1	81.14	0.56

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 (14): 21; 38; 38; 66; 148; 150; 179; 180; 15; 16; 18; 19 …

Mutagenesis-validated functional residues (1):

Position	Phenotype
20	dominant-negative mutant (gdp-bound form). increased interaction with gtp-bound rab11a. increased recruitment to the cen

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 227 (showing top): TAATAAT_MIR126, GOBP_NATURAL_KILLER_CELL_DIFFERENTIATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_B_CELL_ACTIVATION, GOBP_LIPOPROTEIN_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_POSITIVE_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, GOBP_CILIUM_ORGANIZATION, GOBP_PROTEIN_STABILIZATION, GOBP_LIPOPROTEIN_BIOSYNTHETIC_PROCESS, GOBP_RAS_PROTEIN_SIGNAL_TRANSDUCTION

GO Biological Process (8): natural killer cell differentiation (GO:0001779), intracellular protein transport (GO:0006886), B cell differentiation (GO:0030183), T cell differentiation in thymus (GO:0033077), positive regulation of cilium assembly (GO:0045724), regulation of Ras protein signal transduction (GO:0046578), protein stabilization (GO:0050821), regulation of protein lipidation (GO:1903059)

GO Molecular Function (6): GTPase activity (GO:0003924), G protein activity (GO:0003925), GTP binding (GO:0005525), protein homodimerization activity (GO:0042803), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (1): endomembrane system (GO:0012505)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
lymphocyte differentiation	2
natural killer cell activation	1
intracellular protein localization	1
protein transport	1
intracellular transport	1
B cell activation	1
T cell differentiation	1
cilium assembly	1
positive regulation of plasma membrane bounded cell projection assembly	1
regulation of cilium assembly	1
positive regulation of organelle assembly	1
Ras protein signal transduction	1
regulation of small GTPase mediated signal transduction	1
regulation of protein stability	1
protein lipidation	1
regulation of macromolecule biosynthetic process	1
regulation of protein modification process	1
regulation of lipoprotein metabolic process	1
ribonucleoside triphosphate phosphatase activity	1
GTPase activity	1
molecular function regulator activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
identical protein binding	1
protein dimerization activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
vacuole	1
plasma membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

2709 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RABL3	RABL6	Q3YEC7	569
RABL3	GTF2E1	P29083	536
RABL3	RAP1GDS1	P52306	485
RABL3	RAB3IP	Q96QF0	474
RABL3	RABGGTA	Q92696	473
RABL3	RAB24	Q969Q5	458
RABL3	RABGEF1	Q9UJ41	449
RABL3	RAB3GAP1	Q15042	445
RABL3	IFT22	Q9H7X7	426
RABL3	RAB22A	Q9UL26	425
RABL3	RAB40B	Q12829	415
RABL3	SPRYD3	Q8NCJ5	415
RABL3	RAB32	Q13637	406
RABL3	SPRING1	Q9H741	396
RABL3	DMRT2	Q9Y5R5	376

IntAct

152 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
INSR	PIK3R2	psi-mi:“MI:2364”(proximity)	0.570
	XPO1	psi-mi:“MI:0914”(association)	0.530
VAMP4	SNAP29	psi-mi:“MI:0914”(association)	0.530
EDA	AP3B1	psi-mi:“MI:0914”(association)	0.530
TMEM184A	SLC33A1	psi-mi:“MI:0914”(association)	0.530
SCAMP2	SCAMP3	psi-mi:“MI:0914”(association)	0.530
SIGMAR1	NPC1	psi-mi:“MI:0914”(association)	0.530
LHFPL4	ATP5F1B	psi-mi:“MI:0914”(association)	0.530
AGPAT3	ENDOD1	psi-mi:“MI:0914”(association)	0.530
C5AR1	PTPN1	psi-mi:“MI:0914”(association)	0.530
CERS6	ATP5F1B	psi-mi:“MI:0914”(association)	0.530
SLC30A2	ESYT2	psi-mi:“MI:0914”(association)	0.530
SLC7A1	STXBP3	psi-mi:“MI:0914”(association)	0.530
SLC6A8	ILVBL	psi-mi:“MI:0914”(association)	0.530
STOM	EI24	psi-mi:“MI:0914”(association)	0.510
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
CEP43	CCHCR1	psi-mi:“MI:0914”(association)	0.350
Bmpr1a	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Rmdn3	DERL1	psi-mi:“MI:0914”(association)	0.350
ATP6AP2	TMUB1	psi-mi:“MI:0914”(association)	0.350
Atp2a2	ESYT2	psi-mi:“MI:0914”(association)	0.350
PKN2	TMUB1	psi-mi:“MI:0914”(association)	0.350
ATL3	SNX14	psi-mi:“MI:0914”(association)	0.350
Ktn1	ESYT2	psi-mi:“MI:0914”(association)	0.350
Tmed2		psi-mi:“MI:0914”(association)	0.350
Uso1	SLC30A6	psi-mi:“MI:0914”(association)	0.350
YIPF5	SSR3	psi-mi:“MI:0914”(association)	0.350

BioGRID (266): RABL3 (Proximity Label-MS), RABL3 (Proximity Label-MS), RABL3 (Proximity Label-MS), RABL3 (Proximity Label-MS), RABL3 (Proximity Label-MS), RABL3 (Affinity Capture-MS), RABL3 (Affinity Capture-MS), RABL3 (Affinity Capture-MS), RABL3 (Affinity Capture-MS), RABL3 (Affinity Capture-MS), RABL3 (Affinity Capture-MS), RABL3 (Affinity Capture-MS), RABL3 (Affinity Capture-MS), RABL3 (Affinity Capture-MS), RABL3 (Affinity Capture-MS)

ESM2 similar proteins: A2AGL3, A4FUD6, A4IHM6, B0LPN4, E9PZQ0, O35626, O94844, P16960, P51157, P51158, Q12829, Q15413, Q32LJ6, Q32NS2, Q3SWY9, Q3SX43, Q4R4K5, Q5E9J4, Q5F361, Q5FVD6, Q5FVJ7, Q5HYI8, Q5M8K8, Q5R8I6, Q5RCC1, Q5RFI2, Q5XGS8, Q5ZKR4, Q63486, Q66JN8, Q6GPS4, Q6NRC7, Q6TNS7, Q7L523, Q7SXV1, Q7ZUV0, Q80X95, Q8BHL5, Q8K0F1, Q91V93

Diamond homologs: A4IHM6, F1PTE3, F4KFD8, O13876, O23657, O49841, P35286, P51153, P51157, P51158, P51159, Q14964, Q17QU4, Q18969, Q32LJ6, Q3SWY9, Q58DS5, Q5HYI8, Q5KTJ6, Q5RFI2, Q5UQ27, Q5ZKR4, Q6GPS4, Q6TNS7, Q7T3A4, Q7Z6P3, Q8BHC1, Q8BHD0, Q8N4Z0, Q948K8, Q96DA2, Q99KL7, Q9C5J9, Q9D4V7, Q9DD03, Q9SJ11, P22127, P36862, Q05976, Q15286

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 182 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
FCERI mediated MAPK activation	5	14.5×	1e-03
R-HSA-425366	5	7.6×	7e-03
RHOQ GTPase cycle	5	7.6×	7e-03
Signaling by BRAF and RAF1 fusions	5	7.2×	9e-03
COPI-dependent Golgi-to-ER retrograde traffic	6	5.6×	9e-03
SLC-mediated transmembrane transport	10	5.0×	1e-03
Neutrophil degranulation	14	2.7×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
amino acid transport	8	16.3×	3e-05
protein transport	16	4.6×	3e-04

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	17
Likely benign	9
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1196 predictions. Top by Δscore:

Variant	Effect	Δscore
3:120698417:ACAT:A	donor_loss	1.0000
3:120698418:CAT:C	donor_loss	1.0000
3:120698419:AT:A	donor_loss	1.0000
3:120698420:TACC:T	donor_loss	1.0000
3:120698421:A:AC	donor_gain	1.0000
3:120698421:A:C	donor_loss	1.0000
3:120698422:C:CC	donor_gain	1.0000
3:120705994:GCTCA:G	donor_loss	1.0000
3:120705995:CTCA:C	donor_loss	1.0000
3:120705996:TCACC:T	donor_loss	1.0000
3:120705997:CACC:C	donor_loss	1.0000
3:120705998:A:AC	donor_gain	1.0000
3:120705998:A:T	donor_loss	1.0000
3:120705998:AC:A	donor_gain	1.0000
3:120705999:C:CC	donor_gain	1.0000
3:120705999:CC:C	donor_gain	1.0000
3:120706112:TAC:T	acceptor_gain	1.0000
3:120706113:ACC:A	acceptor_loss	1.0000
3:120706115:C:CC	acceptor_gain	1.0000
3:120709775:TTTA:T	donor_loss	1.0000
3:120709776:TTA:T	donor_loss	1.0000
3:120709777:TACCA:T	donor_loss	1.0000
3:120709778:A:T	donor_loss	1.0000
3:120709779:C:CA	donor_loss	1.0000
3:120709779:CCAT:C	donor_gain	1.0000
3:120709909:CCTAA:C	acceptor_loss	1.0000
3:120709911:T:G	acceptor_loss	1.0000
3:120730694:A:AC	donor_gain	1.0000
3:120730695:C:CC	donor_gain	1.0000
3:120730695:CT:C	donor_gain	1.0000

AlphaMissense

1535 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:120706114:C:T	G90D	0.999
3:120730775:G:A	S20F	0.999
3:120730778:T:A	K19I	0.999
3:120730781:C:T	G18E	0.999
3:120730782:C:A	G18W	0.999
3:120730782:C:G	G18R	0.999
3:120730782:C:T	G18R	0.999
3:120742470:C:A	G13V	0.999
3:120742470:C:T	G13E	0.999
3:120742471:C:G	G13R	0.999
3:120742471:C:T	G13R	0.999
3:120694172:A:G	L196P	0.998
3:120698514:T:A	K148I	0.998
3:120698521:C:A	G146W	0.998
3:120706058:A:G	W109R	0.998
3:120706058:A:T	W109R	0.998
3:120706102:A:T	V94E	0.998
3:120709780:C:G	G90R	0.998
3:120709851:T:C	D66G	0.998
3:120709851:T:G	D66A	0.998
3:120709855:A:G	W65R	0.998
3:120709855:A:T	W65R	0.998
3:120730713:A:G	C41R	0.998
3:120730760:A:G	L25P	0.998
3:120730776:A:G	S20P	0.998
3:120730777:T:A	K19N	0.998
3:120730777:T:G	K19N	0.998
3:120730779:T:G	K19Q	0.998
3:120730781:C:A	G18V	0.998
3:120694163:A:G	F199S	0.997

dbSNP variants (sampled 300 via entrez): RS1000058954 (3:120731384 A>G), RS1000115570 (3:120704032 A>G), RS1000156141 (3:120725346 G>A), RS1000175752 (3:120711397 A>C), RS1000209354 (3:120725538 G>C,T), RS1000262939 (3:120695812 C>T), RS1000300924 (3:120740381 C>T), RS1000319841 (3:120721042 A>G), RS1000341372 (3:120717732 G>A), RS1000371446 (3:120715576 G>A,T), RS1000406960 (3:120730986 C>G,T), RS1000444797 (3:120704281 C>A,T), RS1000445156 (3:120715800 TC>T), RS1000492855 (3:120724028 A>T), RS1000587927 (3:120744408 G>A)

Disease associations

OMIM: gene MIM:618542 | disease phenotypes: MIM:608456, MIM:618680

GenCC curated gene-disease

Disease	Classification	Inheritance
familial pancreatic carcinoma	Supportive	Autosomal dominant
pancreatic cancer, susceptibility to, 5	Limited	Autosomal dominant

Mondo (3): familial adenomatous polyposis 2 (MONDO:0012041), pancreatic cancer, susceptibility to, 5 (MONDO:0032867), familial pancreatic carcinoma (MONDO:0015278)

Orphanet (2): Attenuated familial adenomatous polyposis (Orphanet:220460), MUTYH-related polyposis (Orphanet:247798)

HPO phenotypes

25 total (25 of 25 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000819	Diabetes mellitus
HP:0000952	Jaundice
HP:0001433	Hepatosplenomegaly
HP:0001738	Exocrine pancreatic insufficiency
HP:0001824	Weight loss
HP:0002017	Nausea and vomiting
HP:0002027	Abdominal pain
HP:0002039	Anorexia
HP:0002254	Intermittent diarrhea
HP:0002716	Lymphadenopathy
HP:0002861	Melanoma
HP:0002896	Neoplasm of the liver
HP:0002910	Elevated circulating hepatic transaminase concentration
HP:0003002	Breast carcinoma
HP:0003003	Colon cancer
HP:0003418	Back pain
HP:0004389	Intestinal pseudo-obstruction
HP:0004396	Poor appetite
HP:0005249	Functional intestinal obstruction
HP:0006725	Pancreatic adenocarcinoma
HP:0012334	Extrahepatic cholestasis
HP:0012432	Chronic fatigue
HP:0025318	Ovarian carcinoma
HP:0100592	Peritoneal abscess

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001762_465	Obesity-related traits	2.000000e-07
GCST001762_569	Obesity-related traits	1.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004736	aspartate aminotransferase measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C563924	Colorectal Adenomatous Polyposis, Autosomal Recessive (supp.)
C535837	Pancreatic carcinoma, familial (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105853 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 2,395 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL3301622	GILTERITINIB	4	2,395

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

ChEMBL bioactivities

3 potent at pChembl≥5 of 5 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.39	Kd	4027	nM	CHEMBL3752910
5.39	ED50	4037	nM	CHEMBL3752910
5.32	Kd	4830	nM	GILTERITINIB

PubChem BioAssay actives

2 with measured affinity, of 218 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149181: Binding affinity to human RABL3 incubated for 45 mins by Kinobead based pull down assay	kd	4.0273	uM
Gilteritinib	1425151: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	4.8300	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
dicrotophos	decreases expression	1
bufotalin	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	increases expression	1
butyraldehyde	decreases expression	1
ochratoxin A	affects binding	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
cylindrospermopsin	increases expression	1
CGP 52608	affects binding, increases reaction	1
monomethylarsonous acid	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Allergens	increases expression, affects cotreatment, increases abundance	1
Atrazine	decreases expression	1
Vehicle Emissions	affects cotreatment, increases abundance, increases expression	1
Cadmium	decreases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Coal	decreases expression, increases abundance	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	decreases expression	1
Formaldehyde	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Silicon Dioxide	decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3991864	Binding	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by ma	The target landscape of clinical kinase drugs. — Science

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00835133	Not specified	ACTIVE_NOT_RECRUITING	Collecting Blood and Tissue Samples From Family Members of Patients With Pancreatic Diseases, Pancreatic Cancer, and Melanoma
NCT02070705	Not specified	TERMINATED	DCE MRI in Patients With Pancreatic Cancer
NCT02078245	Not specified	UNKNOWN	Quality Control Study of MR Based Screening of Individual With Increased Risk for Pancreas Cancer.
NCT02206360	Not specified	ACTIVE_NOT_RECRUITING	Pancreatic Cancer Early Detection Program
NCT02560896	Not specified	COMPLETED	Understanding Genetic Incidental Findings in Your Family (UNIFY Study)
NCT03693378	Not specified	COMPLETED	A Study of IMMray™ PanCan-d Test for Early Detection of Pancreatic Cancer in High-risk Groups
NCT04095195	Not specified	RECRUITING	Registry of Subjects at Risk of Pancreatic Cancer
NCT04104230	Not specified	UNKNOWN	Quebec Pancreas Cancer Study
NCT04247503	Not specified	ACTIVE_NOT_RECRUITING	Cohort Study of Pancreatic Cancer Risk
NCT04743479	Not specified	RECRUITING	Artificial Intelligence-based Early Screening of Pancreatic Cancer and High Risk Tracing (ESPRIT-AI)
NCT05740111	Not specified	ENROLLING_BY_INVITATION	The PREPAIRD Study: Personalized Surveillance for Early Detection of Pancreatic Cancer in High Risk Individuals
NCT06760741	Not specified	NOT_YET_RECRUITING	PREVENPANC Project: a Spanish Multicenter Study for Pancreatic Cancer Prevention
NCT07307664	Not specified	RECRUITING	Increasing Germline Genetic Testing for Patients With Cancer
NCT02198092	Not specified	COMPLETED	Preliminary Evaluation of Septin9 in Patients With Hereditary Colon Cancer Syndromes
NCT03847532	Not specified	UNKNOWN	MUTYH-associated Polyposis
NCT06163365	Not specified	UNKNOWN	Inherited Cancer Early Diagnosis (ICED) Study
NCT07461246	Not specified	ACTIVE_NOT_RECRUITING	Familial Adenomatous Poliposys Italian Network (Rete Italiana Poliposi Adenomatosa Familiare)