RAB5C

Summary

RAB5C (RAB5C, member RAS oncogene family, HGNC:9785) is a protein-coding gene on chromosome 17q21.2, encoding Ras-related protein Rab-5C (P51148). The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. It is a selective cancer dependency (DepMap: 10.8% of cell lines).

Members of the Rab protein family are small GTPases of the Ras superfamily that are thought to ensure fidelity in the process of docking and/or fusion of vesicles with their correct acceptor compartment (Han et al., 1996 [PubMed 8646882]).

Source: NCBI Gene 5878 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Strong, GenCC)
• GWAS associations: 9
• Clinical variants (ClinVar): 43 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 10.8% of screened cell lines
• MANE Select transcript: NM_004583

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9785
Approved symbol	RAB5C
Name	RAB5C, member RAS oncogene family
Location	17q21.2
Locus type	gene with protein product
Status	Approved
Aliases	RAB5CL
Ensembl gene	ENSG00000108774
Ensembl biotype	protein_coding
OMIM	604037
Entrez	5878

Gene structure

Transcript identifiers

Ensembl transcripts: 37 — 35 protein_coding, 2 retained_intron

ENST00000346213, ENST00000393860, ENST00000546881, ENST00000547517, ENST00000550013, ENST00000550406, ENST00000550504, ENST00000551338, ENST00000552162, ENST00000909835, ENST00000909836, ENST00000909837, ENST00000909838, ENST00000909839, ENST00000909840, ENST00000909841, ENST00000909842, ENST00000909843, ENST00000909844, ENST00000909845, ENST00000909846, ENST00000909847, ENST00000909848, ENST00000909851, ENST00000911957, ENST00000911958, ENST00000911959, ENST00000911960, ENST00000911961, ENST00000949315, ENST00000949316, ENST00000949317, ENST00000949318, ENST00000949319, ENST00000949320, ENST00000949321, ENST00000949322

RefSeq mRNA: 3 — MANE Select: NM_004583 NM_001252039, NM_004583, NM_201434

CCDS: CCDS11419, CCDS58551

Canonical transcript exons

ENST00000346213 — 6 exons

Exon	Start	End
ENSE00000000204	42154893	42154989
ENSE00002339421	42126755	42126848
ENSE00002414688	42124979	42125898
ENSE00003534295	42128261	42128383
ENSE00003620371	42130337	42130590
ENSE00003634781	42128649	42128800

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 98.26.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 81.1676 / max 681.5587, expressed in 1824 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
166107	80.1812	1823
166104	0.9765	641
166105	0.0100	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	98.26	gold quality
granulocyte	CL:0000094	98.08	gold quality
right lung	UBERON:0002167	98.06	gold quality
upper lobe of left lung	UBERON:0008952	98.03	gold quality
metanephros cortex	UBERON:0010533	98.00	gold quality
right adrenal gland cortex	UBERON:0035827	98.00	gold quality
right adrenal gland	UBERON:0001233	97.96	gold quality
leukocyte	CL:0000738	97.93	gold quality
body of stomach	UBERON:0001161	97.90	gold quality
mononuclear cell	CL:0000842	97.89	gold quality
left adrenal gland	UBERON:0001234	97.86	gold quality
right coronary artery	UBERON:0001625	97.82	gold quality
gall bladder	UBERON:0002110	97.82	gold quality
right lobe of thyroid gland	UBERON:0001119	97.75	gold quality
left uterine tube	UBERON:0001303	97.75	gold quality
omental fat pad	UBERON:0010414	97.74	gold quality
mucosa of stomach	UBERON:0001199	97.73	gold quality
peritoneum	UBERON:0002358	97.73	gold quality
left adrenal gland cortex	UBERON:0035825	97.72	gold quality
left lobe of thyroid gland	UBERON:0001120	97.65	gold quality
descending thoracic aorta	UBERON:0002345	97.64	gold quality
stromal cell of endometrium	CL:0002255	97.62	gold quality
thoracic aorta	UBERON:0001515	97.59	gold quality
transverse colon	UBERON:0001157	97.56	gold quality
left coronary artery	UBERON:0001626	97.56	gold quality
ascending aorta	UBERON:0001496	97.55	gold quality
mucosa of transverse colon	UBERON:0004991	97.50	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.47	gold quality
aorta	UBERON:0000947	97.46	gold quality
popliteal artery	UBERON:0002250	97.46	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	43.62
E-ANND-3	yes	13.99
E-CURD-88	yes	4.70
E-GEOD-106540	no	448.08
E-MTAB-6379	no	28.93

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

94 targeting RAB5C, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-570-3P	99.96	72.41	4910
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-4698	99.84	71.41	4303

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 10.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 17)

• GTP-Rab5c also bound to AMAP1, and activation of Rab5c by EGFR signaling was necessary to promote the intracellular association of AMAP1 and PRKD2 (PMID:22734003)
• Rab5C modulates Rac1-mediated cell motility. (PMID:24587345)
• PLP2 and RAB5C are binding partners of TPD52. (PMID:24604726)
• Enforced miR-509 expression in NALM6 cells reduced RAB5C mRNA and protein levels, and RAB5C was demonstrated to be a direct target of miR-509. (PMID:25368993)
• Rab5C and EEA1 in the early endosomal pathway, and Rab7A and lysobisphosphatidic acid in the late endosomal pathway, are important for trafficking of phosphorothioate Antisense oligonucleotides and facilitate their escape from endolysosomal compartments after Stabilin-mediated internalization. (PMID:29437530)
• We identify RAB5C as a new candidate gene for type-2 diabetes risk with a functional role in endosomal type-2 diabetes module. Functional analysis shows that RAB5C is tyrosine phosphorylated. Data analysis reveals a tyrosine phosphorylation motif in the GTP binding site of RAB5C which may be targeted by insulin receptor. Insulin-dependent tyrosine phosphorylation of RAB5C is inhibited by overexpression of HACD3 (PTPLAD1). (PMID:30300385)
• ASO rapidly trafficked to the late endosome/lysosome in poor productive uptake cells compared to those with more robust knockdown. An siRNA screen identified several factors mechanistically involved in productive ASO uptake, including the endosomal GTPase Rab5C (PMID:30927008)
• Rab5C orchestrates a mechanism of radioresistance in rectal adenocarcinoma cell. (PMID:30968159)
• The results reveal that FAK activates Rab5, leading to cell migration. (PMID:31292193)
• MiR-145 functions as a tumor suppressor in Papillary Thyroid Cancer by inhibiting RAB5C. (PMID:32788878)
• The endosomal RIN2/Rab5C machinery prevents VEGFR2 degradation to control gene expression and tip cell identity during angiogenesis. (PMID:33983539)
• Novel Host Protein TBC1D16, a GTPase Activating Protein of Rab5C, Inhibits Prototype Foamy Virus Replication. (PMID:34367131)
• RAB5C, a new mRNA binding target of HuR, regulates breast cancer cell proliferation. (PMID:36480789)
• Long Non-Coding RNA BCAR4 Promotes Oxaliplatin Resistance in Colorectal Cancer by Modulating miR-484-3p/RAB5C Expression. (PMID:36657426)
• Effects of miR-145 targeting rab5c and regulating MAPK / ERK signaling pathway on proliferation and invasion of thyroid papillary carcinoma cells. (PMID:37213158)
• Macrocephaly and developmental delay caused by missense variants in RAB5C. (PMID:37552066)
• Rab5c promotes RSV and ADV replication by autophagy in respiratory epithelial cells. (PMID:38242290)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	rab5c	ENSDARG00000026712
mus_musculus	Rab5c	ENSMUSG00000019173
rattus_norvegicus	AABR07009572.1	ENSRNOG00000013038
rattus_norvegicus	Rab5c	ENSRNOG00000018568
drosophila_melanogaster	Rab5	FBGN0014010
caenorhabditis_elegans	rab-5	WBGENE00004268

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), RAB34 (ENSG00000109113), RAB5B (ENSG00000111540), RAB35 (ENSG00000111737), RAB23 (ENSG00000112210), DNAJC27 (ENSG00000115137), RAB29 (ENSG00000117280), RAB32 (ENSG00000118508), RAB14 (ENSG00000119396), 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-5C — P51148 (reviewed: P51148)

Alternative names: L1880, RAB5L

All UniProt accessions (5): P51148, F8VSF8, F8VVK3, F8VWU4, K7ENY4

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 sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. Involved in early endocytic trafficking. Required for EEA1 recruitment to early endosomes. Required for EGF and transferrin endocytosis and trafficking through early endosomes.

Subunit / interactions. Interacts with EEA1. Interacts with INCA1. Interacts with GDI1, GDI2, CHML and CHM; phosphorylation at Ser-85 disrupts this interaction. Interacts (GTP-bound) with SGSM3; SGSM3 acts as a GAP.

Subcellular location. Cell membrane. Early endosome membrane. Melanosome.

Post-translational modifications. Phosphorylation of Ser-85 in the switch II region by LRRK2 prevents the association of RAB regulatory proteins, including CHM, CHML and RAB GDP dissociation inhibitors GDI1 and GDI2. (Microbial infection) Glycosylated on arginine residues by S.typhimurium protein Ssek3.

Activity regulation. Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP. Regulated by GTPase activating proteins (GAPs) including SGSM3, which increase the GTP hydrolysis activity. Inhibited by GDP dissociation inhibitors (GDIs).

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.

Isoforms (2)

UniProt ID	Names	Canonical?
P51148-1	1	yes
P51148-2	2

RefSeq proteins (3): NP_001238968, NP_004574, NP_958842 (=MANE)

Domains & families (InterPro)

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

Pfam: PF00071

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (45 total): binding site 18, helix 7, strand 6, region of interest 3, lipid moiety-binding region 2, mutagenesis site 2, chain 1, modified residue 1, splice variant 1, sequence variant 1, sequence conflict 1, compositionally biased region 1, turn 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4KYI	X-RAY DIFFRACTION	3.08

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P51148-F1	85.39	0.75

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 (18): 35; 36; 47; 48; 53; 53; 76; 79; 134; 135; 137; 165 …

Post-translational modifications (3): 85, 213, 214

Mutagenesis-validated functional residues (2):

Position	Phenotype
85	loss of phosphorylation. no effect on gdi1, gdi2, chml and chm binding.
85	phosphomimetic mutant. loss of gdi1, gdi2, chml and chm binding.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-432722	Golgi Associated Vesicle Biogenesis
R-HSA-6798695	Neutrophil degranulation
R-HSA-8854214	TBC/RABGAPs
R-HSA-8856828	Clathrin-mediated endocytosis
R-HSA-8873719	RAB geranylgeranylation
R-HSA-8876198	RAB GEFs exchange GTP for GDP on RABs
R-HSA-9820960	Respiratory syncytial virus (RSV) attachment and entry

MSigDB gene sets: 268 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, GCACCTT_MIR18A_MIR18B, RNGTGGGC_UNKNOWN, FXR_IR1_Q6, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_ENDOSOME_ORGANIZATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOCC_VACUOLAR_MEMBRANE, GOCC_SECRETORY_GRANULE, LFA1_Q6, GOBP_VESICLE_ORGANIZATION, MODULE_45, MCBRYAN_PUBERTAL_TGFB1_TARGETS_UP, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING

GO Biological Process (7): intracellular protein transport (GO:0006886), endocytosis (GO:0006897), endosome organization (GO:0007032), endosomal transport (GO:0016197), regulation of endocytosis (GO:0030100), plasma membrane to endosome transport (GO:0048227), 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), metal ion binding (GO:0046872), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (12): lysosomal membrane (GO:0005765), endosome (GO:0005768), early endosome (GO:0005769), lipid droplet (GO:0005811), plasma membrane (GO:0005886), endomembrane system (GO:0012505), endocytic vesicle (GO:0030139), early endosome membrane (GO:0031901), azurophil granule membrane (GO:0035577), melanosome (GO:0042470), extracellular exosome (GO:0070062), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Rab regulation of trafficking	2
trans-Golgi Network Vesicle Budding	1
Innate Immune System	1
Membrane Trafficking	1
Post-translational protein modification	1
Respiratory Syncytial Virus Infection Pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
vesicle-mediated transport	3
intracellular protein localization	2
intracellular transport	2
guanyl ribonucleotide binding	2
cytoplasmic vesicle	2
cellular anatomical structure	2
protein transport	1
vesicle budding from membrane	1
membrane invagination	1
import into cell	1
endomembrane system organization	1
vesicle organization	1
endocytosis	1
regulation of cellular component organization	1
regulation of vesicle-mediated transport	1
transport	1
establishment of protein localization	1
ribonucleoside triphosphate phosphatase activity	1
GTPase activity	1
molecular function regulator activity	1
purine ribonucleoside triphosphate binding	1
anion binding	1
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
lysosome	1
lytic vacuole membrane	1
endomembrane system	1
endosome	1
intracellular membraneless organelle	1
membrane	1
cell periphery	1
vacuole	1
plasma membrane	1
early endosome	1
endosome membrane	1
lysosomal membrane	1
secretory granule membrane	1

Protein interactions and networks

STRING

2128 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RAB5C	EEA1	Q15075	832
RAB5C	RAB5B	P35239	643
RAB5C	AP2M1	P20172	586
RAB5C	VAMP3	Q15836	528
RAB5C	HSPA8	P11142	512
RAB5C	RABGEF1	Q9UJ41	504
RAB5C	STAB2	Q8WWQ8	501
RAB5C	AP2A1	O95782	493
RAB5C	NCBP2L	A6PVI3	493
RAB5C	VAMP2	P19065	484
RAB5C	RAB10	P61026	476
RAB5C	SNAP23	O00161	475
RAB5C	RABEP1	Q15276	465
RAB5C	RBSN	Q9H1K0	460
RAB5C	GOLGA2	Q08379	460

IntAct

210 interactions, top by confidence:

A	B	Type	Score
GDI1	RAB4A	psi-mi:“MI:0914”(association)	0.820
RAB5C	APPL2	psi-mi:“MI:0915”(physical association)	0.780
APPL2	RAB5C	psi-mi:“MI:0915”(physical association)	0.780
RAB5C	EEA1	psi-mi:“MI:0915”(physical association)	0.730
EEA1	RAB5C	psi-mi:“MI:0403”(colocalization)	0.730
EEA1	RAB5C	psi-mi:“MI:0915”(physical association)	0.730
EEA1	RAB5C	psi-mi:“MI:0407”(direct interaction)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
vipD	RAB5C	psi-mi:“MI:0407”(direct interaction)	0.680
vipD	RAB5C	psi-mi:“MI:0403”(colocalization)	0.680
CHM	RAB5C	psi-mi:“MI:0914”(association)	0.640
RAB5C	RBSN	psi-mi:“MI:0915”(physical association)	0.610
RBSN	RAB5C	psi-mi:“MI:0407”(direct interaction)	0.610
RAB5C	ALS2CL	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (755): APPL2 (Two-hybrid), RAB5C (Affinity Capture-RNA), RAB5C (Affinity Capture-RNA), RAB5C (Affinity Capture-MS), RAB5C (Affinity Capture-MS), ARF1 (Co-fractionation), ARL8A (Co-fractionation), ETFA (Co-fractionation), LDHA (Co-fractionation), LDHAL6A (Co-fractionation), LDHAL6B (Co-fractionation), LDHB (Co-fractionation), PSMC2 (Co-fractionation), RAB1A (Co-fractionation), RAB1B (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: A4FV54, A6QR46, M0RC99, O18333, O18334, O80501, P05712, P11023, P16976, P17608, P18066, P20336, P20339, P20340, P22127, P22128, P24409, P25228, P29687, P31582, P31583, P34213, P35276, P35278, P35279, P35280, P35292, P36017, P36586, P36863, P49103, P49104, P51147, P51148, P53994, P55258, P61006, P61007, P61019, P61020

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
LYST	“down-regulates activity”	RAB5C	binding
RAB5C	“up-regulates activity”	EEA1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 186 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
ER-Phagosome pathway	8	8.6×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
protein transport	14	3.9×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	26
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1340 predictions. Top by Δscore:

Variant	Effect	Δscore
17:42125894:CTTAG:C	acceptor_gain	1.0000
17:42125895:TTAG:T	acceptor_gain	1.0000
17:42125895:TTAGC:T	acceptor_loss	1.0000
17:42125896:TAG:T	acceptor_gain	1.0000
17:42125897:AG:A	acceptor_gain	1.0000
17:42125898:GC:G	acceptor_loss	1.0000
17:42125899:C:CA	acceptor_loss	1.0000
17:42125899:C:CC	acceptor_gain	1.0000
17:42126750:CTGA:C	donor_loss	1.0000
17:42126751:TGA:T	donor_loss	1.0000
17:42126752:GAC:G	donor_loss	1.0000
17:42126753:A:AC	donor_gain	1.0000
17:42126753:A:C	donor_loss	1.0000
17:42126754:C:CC	donor_gain	1.0000
17:42126754:C:CG	donor_loss	1.0000
17:42126757:ATTG:A	donor_gain	1.0000
17:42126846:TTC:T	acceptor_gain	1.0000
17:42126846:TTCC:T	acceptor_loss	1.0000
17:42126847:TC:T	acceptor_gain	1.0000
17:42126848:CC:C	acceptor_gain	1.0000
17:42126849:C:CC	acceptor_gain	1.0000
17:42126849:CTG:C	acceptor_loss	1.0000
17:42126850:T:A	acceptor_loss	1.0000
17:42126854:T:C	acceptor_gain	1.0000
17:42126854:T:TC	acceptor_gain	1.0000
17:42126858:A:AC	acceptor_gain	1.0000
17:42126858:A:C	acceptor_gain	1.0000
17:42126864:G:C	acceptor_gain	1.0000
17:42126864:G:GC	acceptor_gain	1.0000
17:42128379:GTATC:G	acceptor_gain	1.0000

AlphaMissense

1418 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:42128297:C:A	K135N	1.000
17:42128297:C:G	K135N	1.000
17:42128299:T:C	K135E	1.000
17:42128300:G:C	N134K	1.000
17:42128300:G:T	N134K	1.000
17:42128304:C:T	G133D	1.000
17:42128346:A:G	L119P	1.000
17:42128357:C:A	W115C	1.000
17:42128357:C:G	W115C	1.000
17:42128359:A:G	W115R	1.000
17:42128359:A:T	W115R	1.000
17:42128677:G:T	A97D	1.000
17:42128678:C:G	A97P	1.000
17:42128680:G:T	A96D	1.000
17:42128681:C:G	A96P	1.000
17:42128686:G:T	A94D	1.000
17:42128692:C:G	R92P	1.000
17:42128699:A:G	Y90H	1.000
17:42128707:G:T	A87D	1.000
17:42128710:A:G	L86P	1.000
17:42128710:A:T	L86Q	1.000
17:42128720:A:G	Y83H	1.000
17:42128731:C:A	G79V	1.000
17:42128731:C:T	G79E	1.000
17:42128732:C:G	G79R	1.000
17:42128732:C:T	G79R	1.000
17:42128734:G:T	A78D	1.000
17:42128739:G:C	D76E	1.000
17:42128739:G:T	D76E	1.000
17:42128740:T:A	D76V	1.000

dbSNP variants (sampled 300 via entrez): RS1000011607 (17:42136637 G>A), RS1000031940 (17:42143955 T>G), RS1000176774 (17:42143356 G>A), RS1000265129 (17:42131331 TA>T,TAA), RS1000313219 (17:42143671 C>T), RS1000343677 (17:42154684 G>C,T), RS1000491043 (17:42148719 A>G), RS1000541427 (17:42136915 C>T), RS1000548157 (17:42147892 T>A,G), RS1000599370 (17:42129844 TA>T), RS1000676693 (17:42153541 T>A), RS1000874582 (17:42153273 G>A,C), RS1000915603 (17:42142637 G>A), RS1000935453 (17:42156275 A>C), RS1000999829 (17:42129553 A>T)

Disease associations

OMIM: gene MIM:604037 | disease phenotypes: MIM:615637

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Strong	Autosomal dominant

Mondo (2): macrocephaly-developmental delay syndrome (MONDO:0014289), neurodevelopmental disorder (MONDO:0700092)

Orphanet (1): Macrocephaly-developmental delay syndrome (Orphanet:397612)

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST003194_33	Fibrinogen levels	6.000000e-09
GCST004121_12	Fibrinogen levels	5.000000e-09
GCST004122_11	Fibrinogen levels	2.000000e-09
GCST004785_17	Vitiligo	7.000000e-10
GCST005195_68	Coronary artery disease	7.000000e-09
GCST007447_1	vWF and FVIII levels	5.000000e-08
GCST007932_4	Medication use (thyroid preparations)	2.000000e-14
GCST90002392_16	Mean corpuscular volume	1.000000e-11
GCST90002407_136	White blood cell count	6.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004630	factor VIII measurement
EFO:0009933	Thyroid preparation use 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): CHEMBL6066876 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases oxidation, affects expression, increases expression, affects cotreatment, increases abundance	3
Ozone	affects cotreatment, increases oxidation, increases abundance, affects expression	3
bisphenol A	increases expression, affects cotreatment	2
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	2
Acrolein	affects cotreatment, increases oxidation, increases abundance	2
Caffeine	decreases expression, increases phosphorylation	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Tretinoin	increases expression	2
Valproic Acid	affects expression, increases expression	2
Particulate Matter	increases abundance, increases expression, affects cotreatment	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
propionaldehyde	increases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
ochratoxin A	affects binding	1
ochratoxin B	affects binding	1
epigallocatechin gallate	decreases expression	1
tamibarotene	increases expression	1
K 7174	decreases expression	1
torcetrapib	increases expression	1
ICG 001	affects expression	1
2-amino-14,16-dimethyloctadecan-3-ol	decreases expression	1
bisphenol S	increases expression	1
bisphenol AF	increases 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
CHEMBL5652219	Binding	Binding affinity to human RAB5C 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

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D3U3	HAP1 RAB5C (-) 1	Cancer cell line	Male
CVCL_D3U4	HAP1 RAB5C (-) 2	Cancer cell line	Male
CVCL_D3U5	HAP1 RAB5C (-) 3	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