RAB14

Summary

RAB14 (RAB14, member RAS oncogene family, HGNC:16524) is a protein-coding gene on chromosome 9q33.2, encoding Ras-related protein Rab-14 (P61106). The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes.

RAB14 belongs to the large RAB family of low molecular mass GTPases that are involved in intracellular membrane trafficking. These proteins act as molecular switches that flip between an inactive GDP-bound state and an active GTP-bound state in which they recruit downstream effector proteins onto membranes (Junutula et al., 2004 [PubMed 15004230]).

Source: NCBI Gene 51552 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Moderate, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 26 total
• Druggable target: yes
• MANE Select transcript: NM_016322

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16524
Approved symbol	RAB14
Name	RAB14, member RAS oncogene family
Location	9q33.2
Locus type	gene with protein product
Status	Approved
Aliases	FBP, RAB-14
Ensembl gene	ENSG00000119396
Ensembl biotype	protein_coding
OMIM	612673
Entrez	51552

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 10 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000373840, ENST00000451303, ENST00000703996, ENST00000703997, ENST00000703998, ENST00000703999, ENST00000704000, ENST00000704001, ENST00000901390, ENST00000917626, ENST00000917627, ENST00000972674

RefSeq mRNA: 1 — MANE Select: NM_016322 NM_016322

CCDS: CCDS6827

Canonical transcript exons

ENST00000373840 — 8 exons

Exon	Start	End
ENSE00000724451	121182930	121182960
ENSE00000724453	121183311	121183398
ENSE00000724454	121186953	121187019
ENSE00000806478	121190554	121190731
ENSE00000806482	121192171	121192224
ENSE00001461714	121178133	121181573
ENSE00001461727	121193361	121193419
ENSE00001461729	121201639	121201869

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 97.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 69.4029 / max 537.5614, expressed in 1826 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
102340	65.1239	1825
102339	3.8634	1517
102337	0.3180	121
102338	0.0976	33

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
nipple	UBERON:0002030	97.94	gold quality
inferior vagus X ganglion	UBERON:0005363	97.62	gold quality
mammary duct	UBERON:0001765	97.20	gold quality
mucosa of paranasal sinus	UBERON:0005030	97.13	gold quality
lower lobe of lung	UBERON:0008949	97.11	gold quality
pharyngeal mucosa	UBERON:0000355	97.05	gold quality
ventral tegmental area	UBERON:0002691	96.95	gold quality
cranial nerve II	UBERON:0000941	96.84	gold quality
frontal pole	UBERON:0002795	96.73	gold quality
superior vestibular nucleus	UBERON:0007227	96.62	gold quality
tongue squamous epithelium	UBERON:0006919	96.55	gold quality
renal medulla	UBERON:0000362	96.54	gold quality
trigeminal ganglion	UBERON:0001675	96.53	gold quality
endometrium epithelium	UBERON:0004811	96.52	gold quality
pons	UBERON:0000988	96.46	gold quality
pylorus	UBERON:0001166	96.44	gold quality
superior surface of tongue	UBERON:0007371	96.43	gold quality
dorsal root ganglion	UBERON:0000044	96.34	gold quality
cortical plate	UBERON:0005343	96.27	gold quality
middle frontal gyrus	UBERON:0002702	96.09	gold quality
corpus epididymis	UBERON:0004359	96.09	gold quality
trachea	UBERON:0003126	96.08	gold quality
paraflocculus	UBERON:0005351	96.07	gold quality
oral cavity	UBERON:0000167	96.06	gold quality
pericardium	UBERON:0002407	96.05	gold quality
subthalamic nucleus	UBERON:0001906	95.97	gold quality
epithelium of mammary gland	UBERON:0003244	95.85	gold quality
islet of Langerhans	UBERON:0000006	95.82	gold quality
mammalian vulva	UBERON:0000997	95.74	gold quality
corpus callosum	UBERON:0002336	95.70	gold quality

Single-cell (SCXA)

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

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

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

249 targeting RAB14, 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-98-3P	100.00	74.08	3907
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754

Literature-anchored findings (GeneRIF, showing 33)

• identifies the class I Rab11-FIPs as the first putative effector proteins for the Rab14 GTPase (PMID:19702578)
• These findings suggest that Rab14 and Rab4 act sequentially, together with RUFY1. (PMID:20534812)
• Data show that Rab14 facilitates the delivery of sphingolipids required for bacterial development and replication from the Golgi to chlamydial inclusions. (PMID:21124879)
• Data suggest that targeting with the miR-451/RAB14 interaction might serve as a novel therapeutic application to treat NSCLC patients. (PMID:21358675)
• FAM116 and Rab14 therefore define an endocytic recycling pathway needed for ADAM protease trafficking and regulation of cell-cell junctions. (PMID:22595670)
• findings support a model for HIV-1 Env incorporation in which specific targeting to the particle assembly microdomain on the plasma membrane is mediated by FIP1C and Rab14 (PMID:23592992)
• Rab5a, Rab8a and Rab14 are major regulators of MT1-MMP trafficking and invasive migration of primary human macrophages. (PMID:23606746)
• Data indicate taht the parasitophorous vacuole (PV), marked with Rab14, Rab30, or Rab43, colocalize with host-derived sphingolipids in the vacuolar space. (PMID:23615442)
• Data indicate that myosin Va interacted with multiple new Rab subfamilies including Rab6, Rab14 and Rab39B. (PMID:24006491)
• the miR-451/RAB14 interaction plays an important role in the enhancement of radiosensitivity in NPC cells. (PMID:25201065)
• RAB14 is a direct target of both MIR144 and MIR451. As MIR144 and MIR451 expression increased during human erythropoiesis, RAB14 protein expression decreased. RAB14 as a novel physiological inhibitor of human erythropoiesis. (PMID:25312678)
• PKCiota binds to Rab14 and that PKCiota requires Rab14 for its correct distribution in cells. As with Rab14, PKCiota protects claudin-2 from lysosomal degradation and, in consequence, modulates epithelial barrier. (PMID:25694446)
• We find that Rab14 indeed binds to RCP, albeit with reduced affinity relative to conventional Rab11-FIP and Rab25-FIP complexes. However, in vivo, Rab11 recruits RCP onto biological membranes. (PMID:26032412)
• Rab14-specific siRNA-induced downregulation of Rab14 increases the sensitivity to cisplatin, while forced expression of Rab14 lacking 3’-UTR abrogated the pro-apoptotic function of miR-148a in renal cancer cells. miR-148a acts as a tumor suppressor and holds great potential for renal cancer therapy by directly targeting Rab14. (PMID:28098870)
• acst as oncogene and Induces proliferation of gastric cancer cells via AKT signaling pathway (PMID:28107526)
• Phosphorylation of RCP at Ser(435) by Lemur tyrosine kinase-3 (LMTK3) and of EphA2 at Ser(897) by Akt are both necessary to promote Rab14-dependent (and Rab11-independent) trafficking of EphA2 which generates cell:cell repulsion events that drive tumour cells apart. (PMID:28294115)
• RAB14 was identified as a direct target gene of miR-320a, according to the results of bioinformatics analysis and a luciferase reporter assay. Downregulation of RAB14 by RAB14-small interfering RNA inhibited the viability of Gastric Cancer cells, which was similar to the phenotype of miR-320a mimics. (PMID:28713899)
• The results from this analysis indicated that Rab11a, Rab11c(Rab25) and Rab14 were expressed in a wide range of cell lines, including the human placental trophoblastic BeWo cell line. (PMID:28922401)
• Colorectal carcinoma (CRC) patients with elevated miR4903p amounts had prolonged overall survival. Ectopic expression of miR4903p in CRC cells resulted in decreased expression of RAB14, which was directly targeted by miR4903p, interacting with its 3’UTR. (PMID:29916545)
• Rab14 was overexpressed in pancreatic cancer and promotes growth and gemcitabine resistance, possibly through regulation of mitochondrial function and Bcl-2. (PMID:30267303)
• RAB14 acts as a tumor promoter and modulates the invasion and metastatic potential of bladder cancer cells via activating the MAPK pathway. (PMID:30809635)
• The KCNQ1OT1 promoted oral squamous cell carcinoma (OSCC) tumorigenesis via the modulation of miR-185-5p/Rab14 axis, which may serve as a therapeutic target for the treatment of OSCC. (PMID:31755091)
• LINC00963 predicts poor prognosis and promotes esophageal cancer cells invasion via targeting miR-214-5p/RAB14 axis. (PMID:31957829)
• Roles of Interaction between CCN2 and Rab14 in Aggrecan Production by Chondrocytes. (PMID:32316324)
• Proximity proteomics identifies novel function of Rab14 in trafficking of Ebola virus matrix protein VP40. (PMID:32327259)
• Long Noncoding RNA MALAT1 Promotes Colorectal Cancer Progression by Acting as a ceRNA of miR-508-5p to Regulate RAB14 Expression. (PMID:33344634)
• Rab14/MACF2 complex regulates endosomal targeting during cytokinesis. (PMID:33566684)
• Long noncoding RNA SNHG20 regulates cell migration, invasion, and proliferation via the microRNA-19b-3p/RAB14 axis in oral squamous cell carcinoma. (PMID:34282711)
• The endocytic pathway taken by cationic substances requires Rab14 but not Rab5 and Rab7. (PMID:34731620)
• Mevalonate pathway orchestrates insulin signaling via RAB14 geranylgeranylation-mediated phosphorylation of AKT to regulate hepatic glucose metabolism. (PMID:34995578)
• MiR-214-3p targets Ras-related protein 14 (RAB14) to inhibit cellular migration and invasion in esophageal Cancer cells. (PMID:36471277)
• AMPK boosts ADAM10 shedding activity in human aortic endothelial cells by promoting Rab14-dependent ADAM10 cell surface translocation. (PMID:37451218)
• Circular RNA IARS modulates the progression and ferroptosis of osteosarcoma via sponging miR-188-5p from RAB14. (PMID:38958715)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rab14	ENSDARG00000074246
mus_musculus	Rab14	ENSMUSG00000026878
rattus_norvegicus	Rab14	ENSRNOG00000071747
drosophila_melanogaster	Rab14	FBGN0015791
caenorhabditis_elegans		WBGENE00004276

Paralogs (68): RAB27B (ENSG00000041353), RAB27A (ENSG00000069974), RAB7A (ENSG00000075785), RABL2B (ENSG00000079974), RAB21 (ENSG00000080371), RAB10 (ENSG00000084733), RAB18 (ENSG00000099246), RAB36 (ENSG00000100228), IFT27 (ENSG00000100360), RAB40AL (ENSG00000102128), RAB11A (ENSG00000103769), RAB2A (ENSG00000104388), RAB3D (ENSG00000105514), RAB3A (ENSG00000105649), RAB5C (ENSG00000108774), RAB34 (ENSG00000109113), RAB5B (ENSG00000111540), RAB35 (ENSG00000111737), RAB23 (ENSG00000112210), DNAJC27 (ENSG00000115137), RAB29 (ENSG00000117280), RAB32 (ENSG00000118508), RAB9B (ENSG00000123570), RAB9A (ENSG00000123595), RAB38 (ENSG00000123892), RAB22A (ENSG00000124209), RAB17 (ENSG00000124839), RAB2B (ENSG00000129472), RAB25 (ENSG00000132698), RAB33A (ENSG00000134594), RAB30 (ENSG00000137502), RAB1A (ENSG00000138069), RAB20 (ENSG00000139832), RAB15 (ENSG00000139998), RAB40B (ENSG00000141542), RAB13 (ENSG00000143545), RABL2A (ENSG00000144134), RAB5A (ENSG00000144566), RAB19 (ENSG00000146955), RAB41 (ENSG00000147127)

Protein

Protein identifiers

Ras-related protein Rab-14 — P61106 (reviewed: P61106)

All UniProt accessions (5): P61106, A0A994J451, A0A994J4B9, A0A994J774, X6RFL8

UniProt curated annotations — full annotation on UniProt →

Function. The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different set of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. RAB14 is involved in membrane trafficking between the Golgi complex and endosomes during early embryonic development. Regulates the Golgi to endosome transport of FGFR-containing vesicles during early development, a key process for developing basement membrane and epiblast and primitive endoderm lineages during early postimplantation development. May act by modulating the kinesin KIF16B-cargo association to endosomes. Regulates, together with its guanine nucleotide exchange factor DENND6A, the specific endocytic transport of ADAM10, N-cadherin/CDH2 shedding and cell-cell adhesion. Mediates endosomal tethering and fusion through the interaction with RUFY1 and RAB4B. Interaction with RAB11FIP1 may function in the process of neurite formation.

Subunit / interactions. Interacts with ZFYVE20. Interacts with KIF16B. Interacts (GTP-bound form) with RUFY1; the interaction recruits RUFY1 onto endosomal membranes. Interacts (GTP-bound form) with RAB11FIP1 (via its C-terminus); the interactions doesn’t mediate RAB11FIP1 rectruitment to membranes. Interacts with RAB11FIP2.

Subcellular location. Recycling endosome. Early endosome membrane. Golgi apparatus membrane. Golgi apparatus. trans-Golgi network membrane. Cytoplasmic vesicle. Phagosome.

Activity regulation. Regulated by guanine nucleotide exchange factors (GEFs) including DENND6A and DENND6B which promote the exchange of bound GDP for free GTP. Regulated by GTPase activating proteins (GAPs) which increase the GTP hydrolysis activity. Inhibited by GDP dissociation inhibitors (GDIs) which prevent Rab-GDP dissociation.

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 drives 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 (1): NP_057406* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001806	Small_GTPase	Family
IPR005225	Small_GTP-bd	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR030702	Rab14	Family
IPR050209	Rab_GTPases_membrane_traffic	Family

Pfam: PF00071

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (58 total): binding site 31, helix 8, strand 6, region of interest 3, modified residue 2, lipid moiety-binding region 2, mutagenesis site 2, initiator methionine 1, chain 1, sequence variant 1, turn 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
1Z0F	X-RAY DIFFRACTION	2.15
4DRZ	X-RAY DIFFRACTION	2.3
4D0G	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P61106-F1	85.58	0.63

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 (31): 23; 24; 24; 25; 25; 25; 26; 26; 38; 39; 40; 42 …

Post-translational modifications (4): 2, 215, 213, 215

Mutagenesis-validated functional residues (2):

Position	Phenotype
25	dominant-negative mutant (gdp-bound form). loss of interaction with rufy1.
70	constitutively active mutant (gtp-bound form). interacts with rufy1.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-1445148	Translocation of SLC2A4 (GLUT4) to the plasma membrane
R-HSA-1660499	Synthesis of PIPs at the plasma membrane
R-HSA-6798695	Neutrophil degranulation
R-HSA-8873719	RAB geranylgeranylation
R-HSA-8876198	RAB GEFs exchange GTP for GDP on RABs

MSigDB gene sets: 338 (showing top): GGGACCA_MIR133A_MIR133B, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_VACUOLE_ORGANIZATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOCC_VACUOLAR_MEMBRANE, GOCC_SECRETORY_GRANULE, GOBP_VESICLE_ORGANIZATION, GOBP_MEMBRANE_FUSION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GTTAAAG_MIR302B, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, IIZUKA_LIVER_CANCER_PROGRESSION_L1_G1_UP, ATGTTAA_MIR302C, GOBP_PHAGOLYSOSOME_ASSEMBLY

GO Biological Process (14): phagolysosome assembly (GO:0001845), intracellular protein transport (GO:0006886), Golgi to endosome transport (GO:0006895), fibroblast growth factor receptor signaling pathway (GO:0008543), vesicle-mediated transport (GO:0016192), endocytic recycling (GO:0032456), regulation of protein localization (GO:0032880), endosomal vesicle fusion (GO:0034058), early endosome to Golgi transport (GO:0034498), defense response to bacterium (GO:0042742), regulation of embryonic development (GO:0045995), intracellular transport (GO:0046907), phagosome maturation (GO:0090382), protein transport (GO:0015031)

GO Molecular Function (8): GTPase activity (GO:0003924), G protein activity (GO:0003925), GTP binding (GO:0005525), GDP binding (GO:0019003), myosin V binding (GO:0031489), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (25): Golgi membrane (GO:0000139), lysosome (GO:0005764), lysosomal membrane (GO:0005765), early endosome (GO:0005769), late endosome (GO:0005770), rough endoplasmic reticulum (GO:0005791), Golgi stack (GO:0005795), trans-Golgi network (GO:0005802), cytosol (GO:0005829), plasma membrane (GO:0005886), endomembrane system (GO:0012505), trans-Golgi network transport vesicle (GO:0030140), early endosome membrane (GO:0031901), nuclear outer membrane-endoplasmic reticulum membrane network (GO:0042175), phagocytic vesicle (GO:0045335), perinuclear region of cytoplasm (GO:0048471), recycling endosome (GO:0055037), recycling endosome membrane (GO:0055038), extracellular exosome (GO:0070062), tertiary granule membrane (GO:0070821), endosome (GO:0005768), Golgi apparatus (GO:0005794), membrane (GO:0016020), cytoplasmic vesicle membrane (GO:0030659), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Membrane Trafficking	1
PI Metabolism	1
Innate Immune System	1
Post-translational protein modification	1
Rab regulation of trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular protein localization	3
transport	3
endosome	3
cellular anatomical structure	3
guanyl ribonucleotide binding	2
Golgi apparatus subcompartment	2
cytoplasm	2
membrane	2
endosome membrane	2
phagocytosis	1
lysosome organization	1
vesicle organization	1
organelle assembly	1
phagosome maturation	1
protein transport	1
intracellular transport	1
post-Golgi vesicle-mediated transport	1
intercellular transport	1
cytosolic transport	1
cell surface receptor protein tyrosine kinase signaling pathway	1
cellular response to fibroblast growth factor stimulus	1
cellular process	1
endosomal transport	1
vesicle-mediated transport to the plasma membrane	1
regulation of localization	1
vesicle fusion	1
retrograde transport, endosome to Golgi	1
Golgi vesicle transport	1
defense response	1
response to bacterium	1
embryo development	1
regulation of multicellular organismal development	1
intracellular anatomical structure	1
cellular localization	1
establishment of localization in cell	1
phagolysosome assembly	1
exocytosis	1
organelle organization	1
establishment of protein localization	1
ribonucleoside triphosphate phosphatase activity	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

174 interactions, top by confidence:

A	B	Type	Score
GDI1	RAB4A	psi-mi:“MI:0914”(association)	0.820
RAB14	EXOC5	psi-mi:“MI:0915”(physical association)	0.720
EXOC5	RAB14	psi-mi:“MI:0915”(physical association)	0.720
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
SPTLC1	SPTLC2	psi-mi:“MI:0914”(association)	0.680
CHM	RAB5C	psi-mi:“MI:0914”(association)	0.640
SEC13	SEC16A	psi-mi:“MI:0914”(association)	0.640
RAB14	OCRL	psi-mi:“MI:0915”(physical association)	0.590
OCRL	RAB14	psi-mi:“MI:0915”(physical association)	0.590
RAB14	OCRL	psi-mi:“MI:0407”(direct interaction)	0.590
GARIN6	RAB14	psi-mi:“MI:0915”(physical association)	0.560
RAB14	SH3BP5L	psi-mi:“MI:0915”(physical association)	0.560
RAB14	GARIN6	psi-mi:“MI:0915”(physical association)	0.560
rep	AGPS	psi-mi:“MI:0914”(association)	0.530
NUFIP1	PDE2A	psi-mi:“MI:0914”(association)	0.530
TIMMDC1	NDUFS8	psi-mi:“MI:0914”(association)	0.530
SLC15A4	PGRMC1	psi-mi:“MI:0914”(association)	0.530
SLC1A5	GPR89A	psi-mi:“MI:0914”(association)	0.530

BioGRID (365): RAB14 (Two-hybrid), RAB14 (Affinity Capture-MS), RAB14 (Affinity Capture-MS), RAB14 (Affinity Capture-MS), RAB14 (Reconstituted Complex), RAB14 (Affinity Capture-MS), RAB14 (Affinity Capture-MS), RAB14 (Affinity Capture-MS), RAB14 (Affinity Capture-MS), RAB14 (Affinity Capture-MS), RAB14 (Affinity Capture-MS), RAB14 (Affinity Capture-RNA), ATP6V1C1 (Co-fractionation), RAB14 (Co-fractionation), RAB14 (Co-fractionation)

ESM2 similar proteins: M0RC99, O24466, P05714, P11023, P18066, P20336, P20339, P29687, P31582, P31583, P35278, P36586, P51147, P51148, P56371, P61020, P61021, P61106, P61107, P61271, P62823, P63011, P63012, Q06AU3, Q06AU6, Q0IIG7, Q0ILQ6, Q40191, Q40520, Q40522, Q4R4R9, Q52NJ6, Q53B90, Q58DS9, Q5R7L7, Q5R8Z8, Q5RBG1, Q5ZHW4, Q5ZKU5, Q68EK7

Diamond homologs: A5D7F5, F1PTE3, H9BW96, O18333, O23561, O24461, P05712, P05714, P10536, P16976, P17609, P20338, P20791, P22125, P24409, P31022, P31584, P34140, P35282, P35286, P36409, P36410, P36411, P36861, P36862, P36863, P36864, P41924, P49103, P49104, P51146, P51153, P53994, P55745, P56371, P59279, P61017, P61018, P61019, P61026

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
RAB14	“form complex”	“Early Endosome”	binding
RAB14	“up-regulates activity”	RUFY1	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 196 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
RAB geranylgeranylation	10	13.6×	2e-06
COPII-mediated vesicle transport	7	9.0×	2e-03
RHOQ GTPase cycle	6	8.6×	8e-03
RAB GEFs exchange GTP for GDP on RABs	8	7.8×	2e-03
Neutrophil degranulation	18	3.3×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
post-Golgi vesicle-mediated transport	5	32.1×	1e-04
vesicle fusion	5	18.4×	2e-03
exocytosis	12	11.1×	1e-06
Ras protein signal transduction	7	8.8×	3e-03
vesicle-mediated transport	12	7.0×	7e-05
endocytosis	9	5.2×	7e-03
protein transport	18	4.8×	3e-05
intracellular protein transport	11	4.3×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1667 predictions. Top by Δscore:

Variant	Effect	Δscore
9:121186951:A:AC	donor_gain	1.0000
9:121186952:C:CC	donor_gain	1.0000
9:121187020:C:CC	acceptor_gain	1.0000
9:121190727:CATAA:C	acceptor_gain	1.0000
9:121190729:TAA:T	acceptor_gain	1.0000
9:121190732:C:CC	acceptor_gain	1.0000
9:121191771:A:AC	donor_gain	1.0000
9:121192164:AACTT:A	donor_loss	1.0000
9:121192166:CTT:C	donor_loss	1.0000
9:121192169:A:AC	donor_gain	1.0000
9:121192169:A:AT	donor_loss	1.0000
9:121192170:C:CC	donor_gain	1.0000
9:121192170:CA:C	donor_gain	1.0000
9:121192170:CAT:C	donor_gain	1.0000
9:121192170:CATT:C	donor_gain	1.0000
9:121192170:CATTT:C	donor_gain	1.0000
9:121192222:CCC:C	acceptor_gain	1.0000
9:121192223:CCC:C	acceptor_gain	1.0000
9:121192223:CCCTG:C	acceptor_loss	1.0000
9:121192225:C:A	acceptor_loss	1.0000
9:121192225:C:CC	acceptor_gain	1.0000
9:121192226:T:C	acceptor_loss	1.0000
9:121192625:A:AC	donor_gain	1.0000
9:121192626:C:CC	donor_gain	1.0000
9:121193354:AACTT:A	donor_loss	1.0000
9:121193355:ACTT:A	donor_loss	1.0000
9:121193356:CTT:C	donor_loss	1.0000
9:121193357:TTACC:T	donor_loss	1.0000
9:121193358:TA:T	donor_loss	1.0000
9:121193359:A:AC	donor_gain	1.0000

AlphaMissense

1416 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:121181549:G:C	F165L	1.000
9:121181549:G:T	F165L	1.000
9:121181551:A:G	F165L	1.000
9:121183322:G:T	A143D	1.000
9:121183349:A:T	V134D	1.000
9:121183375:T:A	K125N	1.000
9:121183375:T:G	K125N	1.000
9:121183376:T:A	K125I	1.000
9:121183377:T:C	K125E	1.000
9:121183382:C:T	G123E	1.000
9:121186979:C:G	A109P	1.000
9:121186989:C:A	W105C	1.000
9:121186989:C:G	W105C	1.000
9:121186991:A:G	W105R	1.000
9:121186991:A:T	W105R	1.000
9:121190563:T:A	D92V	1.000
9:121190581:C:T	G86E	1.000
9:121190587:G:T	A84D	1.000
9:121190593:C:A	R82I	1.000
9:121190611:A:T	V76D	1.000
9:121190619:A:C	F73L	1.000
9:121190619:A:T	F73L	1.000
9:121190620:A:C	F73C	1.000
9:121190620:A:G	F73S	1.000
9:121190621:A:C	F73V	1.000
9:121190621:A:G	F73L	1.000
9:121190621:A:T	F73I	1.000
9:121190632:C:A	G69V	1.000
9:121190632:C:T	G69E	1.000
9:121190633:C:G	G69R	1.000

dbSNP variants (sampled 300 via entrez): RS1000050717 (9:121181975 T>C), RS1000147702 (9:121194564 C>T), RS1000368914 (9:121188727 C>T), RS1000384046 (9:121188520 T>A), RS1000402065 (9:121181715 G>A), RS1000405468 (9:121200445 T>A,C,G), RS1000681222 (9:121201351 C>A,T), RS1000734519 (9:121201237 G>A), RS1000800894 (9:121188600 A>G), RS1000853161 (9:121188829 C>G), RS1000984776 (9:121186767 A>C,T), RS1001137480 (9:121189896 C>G), RS1001152941 (9:121193196 CA>C), RS1001189761 (9:121190111 G>A), RS1001417605 (9:121197003 A>C)

Disease associations

OMIM: gene MIM:612673 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Moderate	Autosomal dominant

Mondo (1): neurodevelopmental disorder (MONDO:0700092)

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001538_20	Immune reponse to smallpox (secreted IFN-alpha)	4.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004645	response to vaccine
EFO:0004873	cytokine measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067416 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.54	Kd	2882	nM	CHEMBL3752910
5.54	ED50	2882	nM	CHEMBL3752910
5.35	Kd	4443	nM	CHEMBL5653589
5.35	ED50	4443	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 4 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	2149169: Binding affinity to human RAB14 incubated for 45 mins by Kinobead based pull down assay	kd	2.8823	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149169: Binding affinity to human RAB14 incubated for 45 mins by Kinobead based pull down assay	kd	4.4430	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, affects cotreatment	2
FR900359	increases phosphorylation	1
testosterone enanthate	affects expression	1
sodium arsenate	decreases expression	1
ochratoxin A	affects binding	1
ochratoxin B	affects binding	1
pentanal	decreases expression	1
mitomycin C-DNA adduct	increases expression	1
microcystin RR	increases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
bisphenol B	increases expression	1
2-amino-14,16-dimethyloctadecan-3-ol	decreases expression	1
jinfukang	decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Coumestrol	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Isoniazid	increases expression	1
Ivermectin	decreases expression	1
Phenolsulfonphthalein	increases expression, affects cotreatment	1
Ribonucleotides	affects binding	1
Rotenone	increases expression	1
Selenium	decreases expression	1
Tobacco Smoke Pollution	affects expression	1
Tretinoin	increases expression	1
Valproic Acid	decreases methylation	1
Vitamin E	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	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
CHEMBL5652211	Binding	Binding affinity to human RAB14 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

2 cell lines: 1 transformed cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3FJ	Abcam HEK293T RAB14 KO	Transformed cell line	Female
CVCL_TH98	HAP1 RAB14 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice