RAB21

Summary

RAB21 (RAB21, member RAS oncogene family, HGNC:18263) is a protein-coding gene on chromosome 12q21.1, encoding Ras-related protein Rab-21 (Q9UL25). The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes.

This gene belongs to the Rab family of monomeric GTPases, which are involved in the control of cellular membrane traffic. The encoded protein plays a role in the targeted trafficking of integrins via its association with integrin alpha tails. As a consequence, the encoded protein is involved in the regulation of cell adhesion and migration. Expression of this gene is associated with a poor prognosis for glioma patients. This gene is downregulated by the tumor suppressor miR-200b, and miRNA-200b is itself downregulated in glioma tissues.

Source: NCBI Gene 23011 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 31 total
• MANE Select transcript: NM_014999

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18263
Approved symbol	RAB21
Name	RAB21, member RAS oncogene family
Location	12q21.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0118
Ensembl gene	ENSG00000080371
Ensembl biotype	protein_coding
OMIM	612398
Entrez	23011

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 retained_intron, 2 protein_coding

ENST00000261263, ENST00000358546, ENST00000547246, ENST00000552686, ENST00000967018

RefSeq mRNA: 1 — MANE Select: NM_014999 NM_014999

CCDS: CCDS9003

Canonical transcript exons

ENST00000261263 — 7 exons

Exon	Start	End
ENSE00001098832	71769800	71769859
ENSE00001098835	71770592	71770699
ENSE00001194681	71754863	71755288
ENSE00001431792	71785531	71800286
ENSE00003481298	71782570	71782658
ENSE00003670280	71773959	71774022
ENSE00003677141	71782031	71782085

Expression profiles

Bgee: expression breadth ubiquitous, 300 present calls, max score 96.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 60.5580 / max 1918.8505, expressed in 1820 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
126829	58.5454	1820
126832	0.8445	521
126830	0.6744	294
126831	0.3921	125
206801	0.1016	37

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	96.52	gold quality
heart right ventricle	UBERON:0002080	96.37	gold quality
biceps brachii	UBERON:0001507	95.91	gold quality
esophagus squamous epithelium	UBERON:0006920	95.88	gold quality
gastrocnemius	UBERON:0001388	95.66	gold quality
adrenal tissue	UBERON:0018303	95.63	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	95.58	gold quality
calcaneal tendon	UBERON:0003701	95.57	gold quality
muscle of leg	UBERON:0001383	95.56	gold quality
amniotic fluid	UBERON:0000173	95.29	gold quality
gluteal muscle	UBERON:0002000	95.16	gold quality
popliteal artery	UBERON:0002250	95.16	gold quality
tibial artery	UBERON:0007610	95.16	gold quality
muscle organ	UBERON:0001630	95.13	gold quality
skeletal muscle organ	UBERON:0014892	95.13	gold quality
descending thoracic aorta	UBERON:0002345	94.76	gold quality
monocyte	CL:0000576	94.74	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.72	gold quality
aorta	UBERON:0000947	94.69	gold quality
heart left ventricle	UBERON:0002084	94.69	gold quality
cardiac ventricle	UBERON:0002082	94.66	gold quality
medial globus pallidus	UBERON:0002477	94.63	gold quality
mononuclear cell	CL:0000842	94.60	gold quality
islet of Langerhans	UBERON:0000006	94.56	gold quality
skeletal muscle tissue	UBERON:0001134	94.52	gold quality
right atrium auricular region	UBERON:0006631	94.51	gold quality
heart	UBERON:0000948	94.43	gold quality
leukocyte	CL:0000738	94.40	gold quality
vastus lateralis	UBERON:0001379	94.12	gold quality
colonic epithelium	UBERON:0000397	94.11	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)

355 targeting RAB21, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-1277-5P	100.00	73.95	5056
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-3662	99.99	73.82	5684
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-373-5P	99.98	75.36	4753

Literature-anchored findings (GeneRIF, showing 14)

• Rab21 (and Rab5) associate with the cytoplasmic domains of alpha-integrin chains, and their expression influences the endo/exocytic traffic of integrins. This function of Rab21 is dependent on its GTP/GDP cycle and proper membrane targeting (PMID:16754960)
• Results show that targeted trafficking of integrins to and from the cleavage furrow is required for successful cytokinesis, and that this is regulated by Rab21. (PMID:18804435)
• show that TI-VAMP interacts with the Vps9 domain and ankyrin-repeat-containing protein Varp, a guanine nucleotide exchange factor of the small GTPase Rab21, through a specific domain herein called the interacting domain. (PMID:19745841)
• Taken together, these data suggest that Rab21 plays a negative role in the EGF-mediated MAPK signaling pathway. Overexpression of Rab21 attenuated EGF-mediated mitogen-activated protein kinase (MAPK) signaling by inducing EGFR degradation. (PMID:22525675)
• High RAB21 expression is associated with glioma. (PMID:24477653)
• Starvation-induced MTMR13 and RAB21 activity regulates VAMP8 to promote autophagosome-lysosome fusion. (PMID:25648148)
• we identified a novel gamma-secretase-associating protein Rab21 and illustrate that Rab21 promotes gamma-secretase internalization and translocation to late endosome/lysosome. Moreover, silencing of Rab21 decreases the gamma-secretase activity in APP processing thus production of Abeta. (PMID:28547526)
• Rab21 silencing can induce apoptosis and inhibit proliferation in human glioma cells. (PMID:29270202)
• Rab21 regulates LPS-induced pro-inflammatory responses by promoting TLR4 endosomal traffic and downstream signaling activation (PMID:30471852)
• Colorectal cancer cells respond differentially to autophagy inhibition in vivo. (PMID:31383875)
• Rab21 Protein Is Degraded by Both the Ubiquitin-Proteasome Pathway and the Autophagy-Lysosome Pathway. (PMID:35163051)
• Circular RNA Circ_0008043 promotes the proliferation and metastasis of hepatocellular carcinoma cells by regulating the microRNA (miR)-326/RAB21 axis. (PMID:35220907)
• RAB21 controls autophagy and cellular energy homeostasis by regulating retromer-mediated recycling of SLC2A1/GLUT1. (PMID:35993307)
• The Regulatory Mechanism of Rab21 in Human Diseases. (PMID:37369821)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rab21	ENSDARG00000100752
mus_musculus	Rab21	ENSMUSG00000020132
rattus_norvegicus	Rab21	ENSRNOG00000003923
drosophila_melanogaster	Rab21	FBGN0039966
caenorhabditis_elegans		WBGENE00004279

Paralogs (68): RAB27B (ENSG00000041353), RAB27A (ENSG00000069974), RAB7A (ENSG00000075785), RABL2B (ENSG00000079974), 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), 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-21 — Q9UL25 (reviewed: Q9UL25)

All UniProt accessions (1): Q9UL25

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. RAB21 is involved in membrane trafficking control. During the mitosis of adherent cells, controls the endosomal trafficking of integrins which is required for the successful completion of cytokinesis. Regulates integrin internalization and recycling, but does not influence the traffic of endosomally translocated receptors in general. As a result, may regulate cell adhesion and migration. Involved in neurite growth. Following SBF2/MTMT13-mediated activation in response to starvation-induced autophagy, binds to and regulates SNARE protein VAMP8 endolysosomal transport required for SNARE-mediated autophagosome-lysosome fusion. Modulates protein levels of the cargo receptors TMED2 and TMED10, and required for appropriate Golgi localization of TMED10.

Subunit / interactions. Interacts with the cytoplasmic tail of integrins ITGA1, ITGA2, ITGA5, ITGA6, ITGA11 and ITGB1. Interacts with RABGEF1 (via VPS9 domain). Interacts with ANKRD27. Interacts with VAMP7. Interacts (in GTP-bound form) with VAMP8 in response to starvation; the interaction probably regulates VAMP8 endolysosomal trafficking. Interacts (active GTP-bound form) with TMED10; the interaction is indirect and regulates TMED10 abundance and localization at the Golgi.

Subcellular location. Endoplasmic reticulum membrane. Golgi apparatus. trans-Golgi network. Golgi apparatus membrane. Early endosome membrane. Cytoplasmic vesicle membrane. Cleavage furrow. Cell projection. Neuron projection.

Tissue specificity. Widely expressed. In jejunal tissue, predominantly expressed in the apical region of the epithelial cell layer of the villi, weak expression, if any, in the crypt epithelium. Capillary endothelium and some cell types in the lamina propria also show expression.

Activity regulation. Regulated by guanine nucleotide exchange factors (GEFs) including ANKRD27 and RABGEF1, 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).

Domain organisation. Switch 1, switch 2 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 (1): NP_055814* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001806	Small_GTPase	Family
IPR005225	Small_GTP-bd	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR041833	Rab21	Family

Pfam: PF00071

Enzyme classification (BRENDA):

• EC 3.6.5.2 — small monomeric GTPase (BRENDA: 49 organisms, 138 substrates, 55 inhibitors, 5 Km, 1 kcat entries)

Substrate kinetics (BRENDA)

1 substrates with measured Km, best-characterized 1. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
GTP	—	0

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (48 total): binding site 19, helix 9, strand 7, modified residue 2, lipid moiety-binding region 2, mutagenesis site 2, short sequence motif 2, initiator methionine 1, chain 1, propeptide 1, region of interest 1, turn 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
1Z08	X-RAY DIFFRACTION	1.8
1YZT	X-RAY DIFFRACTION	2.05
2OT3	X-RAY DIFFRACTION	2.1
1Z0I	X-RAY DIFFRACTION	2.33
1YZU	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UL25-F1	83.89	0.62

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 (19): 33; 34; 45; 46; 48; 50; 51; 51; 74; 77; 132; 133 …

Post-translational modifications (4): 2, 222, 221, 222

Mutagenesis-validated functional residues (2):

Position	Phenotype
33	defects in gtp-binding. abolishes the interaction with vamp8 in response to starvation. abolishes the interaction with t
78	defects in gtp hydrolysis. does not affect the interaction with vamp8 in response to starvation. does not affect the int

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-8873719	RAB geranylgeranylation
R-HSA-8876198	RAB GEFs exchange GTP for GDP on RABs

MSigDB gene sets: 342 (showing top): GOBP_DENDRITE_DEVELOPMENT, AAGCAAT_MIR137, GOBP_AXO_DENDRITIC_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_NEURON_PROJECTION_EXTENSION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_REGULATION_OF_DENDRITE_MORPHOGENESIS, GOBP_GROWTH, GOBP_REGULATION_OF_EXOCYTOSIS, GOBP_NEUROGENESIS, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, REACTOME_MEMBRANE_TRAFFICKING

GO Biological Process (10): intracellular protein transport (GO:0006886), anterograde axonal transport (GO:0008089), regulation of exocytosis (GO:0017157), regulation of axon extension (GO:0030516), Rab protein signal transduction (GO:0032482), positive regulation of receptor-mediated endocytosis (GO:0048260), positive regulation of dendrite morphogenesis (GO:0050775), protein stabilization (GO:0050821), positive regulation of early endosome to late endosome transport (GO:2000643), protein transport (GO:0015031)

GO Molecular Function (7): GTPase activity (GO:0003924), G protein activity (GO:0003925), GTP binding (GO:0005525), GDP binding (GO:0019003), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (24): Golgi membrane (GO:0000139), endosome (GO:0005768), early endosome (GO:0005769), endoplasmic reticulum membrane (GO:0005789), trans-Golgi network (GO:0005802), cytosol (GO:0005829), focal adhesion (GO:0005925), cytoplasmic side of plasma membrane (GO:0009898), endomembrane system (GO:0012505), vesicle membrane (GO:0012506), early endosome membrane (GO:0031901), cleavage furrow (GO:0032154), Golgi cisterna membrane (GO:0032580), synapse (GO:0045202), extracellular exosome (GO:0070062), cytoplasmic side of early endosome membrane (GO:0098559), axon cytoplasm (GO:1904115), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), membrane (GO:0016020), cytoplasmic vesicle membrane (GO:0030659), cytoplasmic vesicle (GO:0031410), cell projection (GO:0042995), neuron projection (GO:0043005)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Post-translational protein modification	1
Rab regulation of trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
endomembrane system	3
organelle membrane	3
cytoplasm	3
cellular anatomical structure	3
intracellular protein localization	2
guanyl ribonucleotide binding	2
plasma membrane	2
intracellular membrane-bounded organelle	2
protein transport	1
intracellular transport	1
axonal transport	1
axon cytoplasm	1
exocytosis	1
regulation of vesicle-mediated transport	1
regulation of secretion by cell	1
regulation of developmental growth	1
axon extension	1
regulation of extent of cell growth	1
small GTPase-mediated signal transduction	1
receptor-mediated endocytosis	1
positive regulation of endocytosis	1
regulation of receptor-mediated endocytosis	1
positive regulation of cell morphogenesis	1
positive regulation of cell projection organization	1
dendrite morphogenesis	1
regulation of dendrite morphogenesis	1
positive regulation of neurogenesis	1
regulation of protein stability	1
positive regulation of intracellular transport	1
early endosome to late endosome transport	1
regulation of early endosome to late endosome 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
nucleoside phosphate binding	1
heterocyclic compound binding	1

Protein interactions and networks

STRING

1290 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RAB21	RABGEF1	Q9UJ41	911
RAB21	ANKRD27	Q96NW4	801
RAB21	ITGB1	P05556	747
RAB21	SBF2	Q86WG5	668
RAB21	VAMP7	P51809	617
RAB21	RABIF	P47224	608
RAB21	RIC1	Q4ADV7	574
RAB21	RAB5A	P20339	560
RAB21	RBSN	Q9H1K0	557
RAB21	ARF6	P26438	556
RAB21	GIPC1	O14908	552
RAB21	EEA1	Q15075	548
RAB21	NISCH	Q9Y2I1	527
RAB21	DENND1B	Q6P3S1	521
RAB21	RABEP1	Q15276	512

IntAct

123 interactions, top by confidence:

A	B	Type	Score
GDI1	RAB4A	psi-mi:“MI:0914”(association)	0.820
LDHA	LDHC	psi-mi:“MI:0914”(association)	0.770
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
RABGEF1	RAB21	psi-mi:“MI:0407”(direct interaction)	0.590
IGF1R	PIK3R2	psi-mi:“MI:2364”(proximity)	0.590
VSIG2	TTI1	psi-mi:“MI:0914”(association)	0.530
P2RX1	ATE1	psi-mi:“MI:0914”(association)	0.530
SLC22A16	APBA3	psi-mi:“MI:0914”(association)	0.530
FANCE	ENPP1	psi-mi:“MI:0914”(association)	0.530
IL1R2	EXOC5	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
RAB21	MACF1	psi-mi:“MI:0915”(physical association)	0.480
RAB21	MACF1	psi-mi:“MI:0403”(colocalization)	0.480
	AP3D1	psi-mi:“MI:0914”(association)	0.460
RAB21	APPL1	psi-mi:“MI:0407”(direct interaction)	0.440
APPL1	RAB21	psi-mi:“MI:0407”(direct interaction)	0.440
TUBA1A	TUBAL3	psi-mi:“MI:2364”(proximity)	0.420
ITGB1	RAB21	psi-mi:“MI:0915”(physical association)	0.400
RAB21	MACF1	psi-mi:“MI:0915”(physical association)	0.400
	RAB21	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (187): RAB21 (Affinity Capture-MS), RAB21 (Affinity Capture-MS), RAB21 (Affinity Capture-MS), RAB21 (Affinity Capture-MS), RAB21 (Affinity Capture-MS), RAB21 (Affinity Capture-MS), RAB21 (Affinity Capture-MS), RAB21 (Affinity Capture-MS), RAB21 (Affinity Capture-MS), RAB21 (Affinity Capture-MS), RAB21 (Affinity Capture-MS), RAB21 (Affinity Capture-MS), RAB21 (Affinity Capture-MS), RAB21 (Affinity Capture-MS), RAB21 (Affinity Capture-MS)

ESM2 similar proteins: A6QR46, C4YL11, O00194, O18334, O23657, O49841, O80501, P0CY30, P0CY31, P10949, P17608, P20340, P34213, P35279, P35289, P35293, P36017, P55745, P59190, P61294, P62823, P62824, P90726, Q05976, Q0IIG8, Q17R06, Q1KME6, Q1RMR4, Q22782, Q54DA7, Q55FK2, Q5R5H5, Q5RAV6, Q5ZLG1, Q6DHC1, Q8CG50, Q8HZJ5, Q8K386, Q8MXS1, Q96E17

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

3 interactions.

A	Effect	B	Mechanism
RAB21	“form complex”	“Early Endosome”	binding
“1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate”	“down-regulates activity”	RAB21	binding
RAB21	up-regulates	“Early macropinosomes”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 148 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
RAF activation	5	16.1×	1e-03
Signaling by RAF1 mutants	5	13.4×	2e-03
Signaling by moderate kinase activity BRAF mutants	5	12.2×	2e-03
Paradoxical activation of RAF signaling by kinase inactive BRAF	5	12.2×	2e-03
Signaling downstream of RAS mutants	5	12.2×	2e-03
Translocation of SLC2A4 (GLUT4) to the plasma membrane	6	8.9×	2e-03
RAB geranylgeranylation	5	8.3×	5e-03
Signaling by BRAF and RAF1 fusions	5	8.2×	5e-03

GO biological processes:

GO term	Partners	Fold	FDR
vesicle-mediated transport	9	6.6×	4e-03
positive regulation of MAPK cascade	10	6.1×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	14
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1022 predictions. Top by Δscore:

Variant	Effect	Δscore
12:71755286:CAGGT:C	donor_loss	1.0000
12:71755287:AGGTG:A	donor_loss	1.0000
12:71755288:GGTG:G	donor_loss	1.0000
12:71755289:GT:G	donor_loss	1.0000
12:71755290:T:G	donor_loss	1.0000
12:71769794:TTTTA:T	acceptor_loss	1.0000
12:71769796:TTAGG:T	acceptor_loss	1.0000
12:71769798:A:AC	acceptor_loss	1.0000
12:71769798:A:AG	acceptor_gain	1.0000
12:71769799:G:A	acceptor_loss	1.0000
12:71769799:G:GT	acceptor_gain	1.0000
12:71769799:GGC:G	acceptor_gain	1.0000
12:71769856:ATGGG:A	donor_loss	1.0000
12:71769858:GG:G	donor_gain	1.0000
12:71769858:GGGT:G	donor_loss	1.0000
12:71769859:GG:G	donor_gain	1.0000
12:71769859:GGTA:G	donor_loss	1.0000
12:71769860:G:C	donor_loss	1.0000
12:71769860:G:GG	donor_gain	1.0000
12:71769861:TAAG:T	donor_loss	1.0000
12:71774019:GTTG:G	donor_gain	1.0000
12:71782081:GAGTC:G	donor_gain	1.0000
12:71782083:GTC:G	donor_gain	1.0000
12:71782086:G:GG	donor_gain	1.0000
12:71782565:TTAA:T	acceptor_loss	1.0000
12:71782568:A:AC	acceptor_loss	1.0000
12:71782569:G:GA	acceptor_loss	1.0000
12:71782626:GAAT:G	donor_gain	1.0000
12:71782657:AA:A	donor_gain	1.0000
12:71782657:AAG:A	donor_loss	1.0000

AlphaMissense

1456 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:71755205:G:A	G26R	1.000
12:71755205:G:C	G26R	1.000
12:71755205:G:T	G26W	1.000
12:71755206:G:A	G26E	1.000
12:71755220:G:A	G31R	1.000
12:71755220:G:C	G31R	1.000
12:71755220:G:T	G31W	1.000
12:71755221:G:A	G31E	1.000
12:71755221:G:T	G31V	1.000
12:71755223:A:C	K32Q	1.000
12:71755227:C:T	T33M	1.000
12:71755259:T:C	F44L	1.000
12:71755261:T:A	F44L	1.000
12:71755261:T:G	F44L	1.000
12:71769806:T:C	F56L	1.000
12:71769808:C:A	F56L	1.000
12:71769808:C:G	F56L	1.000
12:71769849:T:C	L70P	1.000
12:71769855:T:A	I72K	1.000
12:71769855:T:G	I72R	1.000
12:71769857:T:A	W73R	1.000
12:71769857:T:C	W73R	1.000
12:71769859:G:C	W73C	1.000
12:71769859:G:T	W73C	1.000
12:71770592:G:A	D74N	1.000
12:71770592:G:C	D74H	1.000
12:71770592:G:T	D74Y	1.000
12:71770593:A:C	D74A	1.000
12:71770593:A:G	D74G	1.000
12:71770593:A:T	D74V	1.000

dbSNP variants (sampled 300 via entrez): RS1000034152 (12:71799628 A>G), RS1000094144 (12:71754856 G>A), RS1000125020 (12:71795926 A>G), RS1000154877 (12:71772308 G>T), RS1000193831 (12:71767502 TTG>T), RS1000227127 (12:71773631 T>C), RS1000251013 (12:71760709 A>G), RS1000256672 (12:71755048 C>G,T), RS1000345938 (12:71773694 T>C,G), RS1000373940 (12:71783956 T>C), RS1000386304 (12:71789650 A>C,G), RS1000584017 (12:71782934 G>A), RS1000682047 (12:71784285 T>C), RS1000794918 (12:71765544 A>G), RS1000848692 (12:71794922 G>C)

Disease associations

OMIM: gene MIM:612398 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST006269_1231	General cognitive ability	5.000000e-08
GCST008129_59	Body mass index	1.000000e-09
GCST010204_208	Low density lipoprotein cholesterol levels	4.000000e-15
GCST010243_149	Apolipoprotein B levels	1.000000e-08
GCST010245_91	LDL cholesterol levels	1.000000e-08
GCST010988_497	Adult body size	3.000000e-08
GCST011418_2	HDL cholesterol levels	6.000000e-07

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0004340	body mass index
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004615	apolipoprotein B measurement
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, decreases methylation	4
bisphenol A	increases expression	3
Tobacco Smoke Pollution	increases expression, affects expression	3
sodium arsenite	affects cotreatment, increases abundance, increases expression	2
manganese chloride	decreases expression, affects cotreatment, increases abundance, increases expression	2
Air Pollutants	affects expression, increases abundance, decreases expression	2
Manganese	affects cotreatment, increases abundance, increases expression, decreases expression	2
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
cobaltous chloride	increases expression	1
K 7174	increases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
bisphenol S	increases expression	1
PCI 5002	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Arsenic Trioxide	increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Demecolcine	increases expression	1
Doxorubicin	affects expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ethyl Methanesulfonate	increases expression	1
Fluorouracil	affects expression	1
Formaldehyde	increases expression	1
Furaldehyde	affects cotreatment, affects localization, decreases expression	1
Hydrogen Peroxide	affects cotreatment, increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TI04	HAP1 RAB21 (-) 1	Cancer cell line	Male
CVCL_TI05	HAP1 RAB21 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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