RAB11B

Summary

RAB11B (RAB11B, member RAS oncogene family, HGNC:9761) is a protein-coding gene on chromosome 19p13.2, encoding Ras-related protein Rab-11B (Q15907). The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes.

The Ras superfamily of small GTP-binding proteins, which includes the Ras (see MIM 190020), Ral (see MIM 179550), Rho (see MIM 165390), Rap (see MIM 179520), and Rab (see MIM 179508) families, is involved in controlling a diverse set of essential cellular functions. The Rab family, including RAB11B, appears to play a critical role in regulating exocytotic and endocytotic pathways (summary by Zhu et al., 1994 [PubMed 7811277]).

Source: NCBI Gene 9230 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matter (Strong, GenCC)
• Clinical variants (ClinVar): 259 total — 1 pathogenic, 3 likely-pathogenic
• MANE Select transcript: NM_004218

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9761
Approved symbol	RAB11B
Name	RAB11B, member RAS oncogene family
Location	19p13.2
Locus type	gene with protein product
Status	Approved
Aliases	H-YPT3
Ensembl gene	ENSG00000185236
Ensembl biotype	protein_coding
OMIM	604198
Entrez	9230

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 retained_intron

ENST00000328024, ENST00000594216, ENST00000598706, ENST00000600719, ENST00000601897, ENST00000896951, ENST00000896952, ENST00000949520

RefSeq mRNA: 1 — MANE Select: NM_004218 NM_004218

CCDS: CCDS12201

Canonical transcript exons

ENST00000328024 — 5 exons

Exon	Start	End
ENSE00001298946	8402485	8402565
ENSE00001321995	8403413	8404434
ENSE00003160480	8390360	8390456
ENSE00003536420	8402086	8402279
ENSE00003598791	8399863	8400058

Expression profiles

Bgee: expression breadth ubiquitous, 223 present calls, max score 99.02.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 75.5405 / max 454.8596, expressed in 1825 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
173658	75.5405	1825

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of thyroid gland	UBERON:0001119	99.02	gold quality
left lobe of thyroid gland	UBERON:0001120	98.98	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.42	gold quality
cortical plate	UBERON:0005343	98.41	gold quality
right uterine tube	UBERON:0001302	98.31	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.21	gold quality
right atrium auricular region	UBERON:0006631	98.20	gold quality
popliteal artery	UBERON:0002250	98.17	gold quality
tibial artery	UBERON:0007610	98.17	gold quality
ganglionic eminence	UBERON:0004023	98.14	gold quality
apex of heart	UBERON:0002098	98.10	gold quality
right frontal lobe	UBERON:0002810	98.08	gold quality
adenohypophysis	UBERON:0002196	97.97	gold quality
right coronary artery	UBERON:0001625	97.95	gold quality
body of stomach	UBERON:0001161	97.94	gold quality
mucosa of stomach	UBERON:0001199	97.93	gold quality
metanephros cortex	UBERON:0010533	97.92	gold quality
ascending aorta	UBERON:0001496	97.90	gold quality
thoracic aorta	UBERON:0001515	97.90	gold quality
left coronary artery	UBERON:0001626	97.87	gold quality
aorta	UBERON:0000947	97.83	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.81	gold quality
endocervix	UBERON:0000458	97.79	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.78	gold quality
lower esophagus	UBERON:0013473	97.77	gold quality
descending thoracic aorta	UBERON:0002345	97.76	gold quality
cerebellar hemisphere	UBERON:0002245	97.71	gold quality
body of pancreas	UBERON:0001150	97.55	gold quality
left ovary	UBERON:0002119	97.53	gold quality
cerebellar cortex	UBERON:0002129	97.51	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	14.29

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

86 targeting RAB11B, 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-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-98-3P	100.00	74.08	3907
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-4728-5P	99.85	69.39	4718

Literature-anchored findings (GeneRIF, showing 15)

• structural analysis shows Rab11 isoforms may possess different GTP hydrolysis rates (PMID:16545962)
• This is the first report detailing apical CFTR recycling in a native expression system and to demonstrate that Rab11b regulates apical recycling in polarized epithelial cells. (PMID:19244346)
• propose a model where Rab11B specifically transports vesicles derived from the Golgi to the immature Inner Membrane Complex of the growing daughter parasites. (PMID:20686666)
• These data introduce Rab11b as a crucial regulator and Rip11 as mediator of acidosis-induced V-ATPase traffic in duct cells of submandibular gland. (PMID:20717956)
• These findings reveal a novel role for Rab11b in limiting, rather than promoting, the plasma membrane expression of Cav1.2 L-type Ca2+ channels. (PMID:21248079)
• Data show that the cAMP/PKA/CREB signaling pathway initiates acidosis-induced V-ATPase trafficking in salivary ducts via regulation of Rab11b expression. (PMID:22561749)
• the predominant mechanism of melanin transfer is keratinocyte-induced exocytosis, mediated by Rab11b through remodeling of the melanosome membrane, followed by subsequent endocytosis by keratinocytes (PMID:24141907)
• Upon Rab11b depletion, FGFR4 is trapped in the pericentriolar recycling compartment. (PMID:24589086)
• we determined a crystal structure of the PKG II LZ-Rab11b complex. The PKG II LZ domain presents a mostly nonpolar surface onto which Rab11b docks, through van der Waals interactions (PMID:25070890)
• Rab11A and Rab11B differentially regulate intracellular trafficking of PAR1 through distinct endosomal sorting mechanisms (PMID:26635365)
• High RAB11B expression is associated with pancreatic cancer. (PMID:27481517)
• Recurrent de novo mutations disturbing the GTP/GDP binding pocket of RAB11B cause intellectual disability and a distinctive brain phenotype. (PMID:29106825)
• Expression of wild-type Rab11a in Rab11a knockout cells rescued the late endosome/lysosome phenotype. Overall, these results indicate that Rab11a and Rab11b have overlapping and distinct functions and that Rab11a, unexpectedly, plays a central role in the homeostasis of endosomal-lysosomal biogenesis. (PMID:30981667)
• Rab11b-mediated integrin recycling promotes brain metastatic adaptation and outgrowth. (PMID:32541798)
• Rab11-mediated post-Golgi transport of the sialyltransferase ST3GAL4 suggests a new mechanism for regulating glycosylation. (PMID:33524390)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rab11ba	ENSDARG00000041878
mus_musculus	Rab11b	ENSMUSG00000077450
caenorhabditis_elegans	rab-11.1	WBGENE00004274

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), 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)

Protein

Protein identifiers

Ras-related protein Rab-11B — Q15907 (reviewed: Q15907)

Alternative names: GTP-binding protein YPT3

All UniProt accessions (3): Q15907, M0R2D0, M0R377

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. RAB11B plays a role in endocytic recycling, regulating apical recycling of several transmembrane proteins including cystic fibrosis transmembrane conductance regulator/CFTR, epithelial sodium channel/ENaC, potassium voltage-gated channel, and voltage-dependent L-type calcium channel. May also regulate constitutive and regulated secretion, like insulin granule exocytosis. Required for melanosome transport and release from melanocytes. Also regulates V-ATPase intracellular transport in response to extracellular acidosis. Promotes Rabin8/RAB3IP preciliary vesicular trafficking to mother centriole by forming a ciliary targeting complex containing Rab11, ASAP1, Rabin8/RAB3IP, RAB11FIP3 and ARF4, thereby regulating ciliogenesis initiation. On the contrary, upon LPAR1 receptor signaling pathway activation, interaction with phosphorylated WDR44 prevents Rab11-RAB3IP-RAB11FIP3 complex formation and cilia growth. Also interacts with RABL3 to promote ciliary vesicle formation.

Subunit / interactions. Interacts with KCNMA1. Interacts with RAB11FIP1, RAB11FIP2, RAB11FIP3 and RAB11FIP4. May interact with TBC1D14. Interacts with ATP6V1E1. Interacts with PI4KB. Interacts (GDP-bound form) with ZFYVE27. Interacts (GDP-bound form) with KIF5A in a ZFYVE27-dependent manner. Interacts with RELCH. Interacts (in GTP-bound form) with TBC1D8B (via domain Rab-GAP TBC). Forms a complex containing RAB11B, ASAP1, Rabin8/RAB3IP, RAP11FIP3 and ARF4. Interacts with WDR44.

Subcellular location. Recycling endosome membrane. Cytoplasmic vesicle. Secretory vesicle. Synaptic vesicle membrane. Phagosome membrane.

Post-translational modifications. Citrullinated by PADI4. (Microbial infection) Glycosylated on arginine residues by S.typhimurium protein Ssek3.

Disease relevance. Neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matter (NDAGSCW) [MIM:617807] An autosomal dominant neurodevelopmental disorder apparent in infancy and characterized by severe intellectual disability with absent speech, epilepsy, and hypotonia. Additionally, visual problems, musculoskeletal abnormalities, and microcephaly can be present. Brain imaging shows decreased cortical white matter, often with decreased cerebellar white matter, thin corpus callosum, and thin brainstem. The disease is caused by variants affecting the gene represented in this entry.

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) 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.

Induction. Up-regulated by extracellular acidosis and down-regulated by alkalosis (at protein level).

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q15907-1	1	yes
Q15907-2	2

RefSeq proteins (1): NP_004209* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF00071

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (57 total): binding site 20, helix 9, strand 6, sequence conflict 5, modified residue 3, region of interest 3, lipid moiety-binding region 2, sequence variant 2, mutagenesis site 2, initiator methionine 1, chain 1, propeptide 1, splice variant 1, turn 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
2F9L	X-RAY DIFFRACTION	1.55
2F9M	X-RAY DIFFRACTION	1.95
4OJK	X-RAY DIFFRACTION	2.66

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15907-F1	86.14	0.68

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 (20): 25; 25; 26; 37; 38; 40; 42; 43; 43; 66; 69; 124 …

Post-translational modifications (5): 2, 4, 215, 214, 215

Mutagenesis-validated functional residues (2):

Position	Phenotype
25	dominant negative mutant locked in the inactive gdp-bound form; alters apical recycling. does not interact with zfyv2e a
70	constitutively active mutant locked in the active gtp-bound form; alters apical recycling.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-8854214	TBC/RABGAPs
R-HSA-8873719	RAB geranylgeranylation

MSigDB gene sets: 341 (showing top): E2F_Q4, E2F_Q4_01, GOBP_PIGMENT_GRANULE_LOCALIZATION, GOBP_VESICLE_LOCALIZATION, GOBP_TRANSITION_METAL_ION_TRANSPORT, SP3_Q3, GOBP_INSULIN_SECRETION, GOBP_CELLULAR_RESPONSE_TO_CARBOHYDRATE_STIMULUS, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_CELLULAR_PIGMENTATION, GOBP_HORMONE_TRANSPORT, KYNG_DNA_DAMAGE_DN, KYNG_DNA_DAMAGE_BY_4NQO, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING

GO Biological Process (16): receptor recycling (GO:0001881), melanosome transport (GO:0032402), endocytic recycling (GO:0032456), transferrin transport (GO:0033572), insulin secretion involved in cellular response to glucose stimulus (GO:0035773), regulation of monoatomic anion transport (GO:0044070), constitutive secretory pathway (GO:0045054), regulated exocytosis (GO:0045055), cellular response to acidic pH (GO:0071468), establishment of protein localization to membrane (GO:0090150), amyloid-beta clearance by transcytosis (GO:0150093), regulation of cilium assembly (GO:1902017), regulation of protein localization to cell surface (GO:2000008), regulation of endocytic recycling (GO:2001135), protein transport (GO:0015031), vesicle-mediated transport to the plasma membrane (GO:0098876)

GO Molecular Function (9): GTPase activity (GO:0003924), G protein activity (GO:0003925), GTP binding (GO:0005525), GDP binding (GO:0019003), myosin V binding (GO:0031489), cadherin binding (GO:0045296), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (14): Golgi apparatus (GO:0005794), cytosol (GO:0005829), synaptic vesicle (GO:0008021), phagocytic vesicle membrane (GO:0030670), synaptic vesicle membrane (GO:0030672), phagocytic vesicle (GO:0045335), recycling endosome (GO:0055037), recycling endosome membrane (GO:0055038), extracellular exosome (GO:0070062), cytoplasm (GO:0005737), endosome (GO:0005768), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-2 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
exocytosis	3
cytoplasm	3
cellular anatomical structure	3
establishment of protein localization	2
localization within membrane	2
guanyl ribonucleotide binding	2
endomembrane system	2
endocytosis	1
receptor metabolic process	1
melanosome localization	1
establishment of melanosome localization	1
pigment granule transport	1
endosomal transport	1
vesicle-mediated transport to the plasma membrane	1
iron ion transport	1
protein transport	1
insulin secretion	1
establishment of localization in cell	1
cellular response to glucose stimulus	1
monoatomic anion transport	1
regulation of monoatomic ion transport	1
response to acidic pH	1
cellular response to pH	1
transcytosis	1
amyloid-beta clearance	1
cilium assembly	1
regulation of plasma membrane bounded cell projection assembly	1
regulation of organelle assembly	1
regulation of protein localization	1
protein localization to cell surface	1
regulation of intracellular transport	1
endocytic recycling	1
regulation of vesicle-mediated transport	1
transport	1
intracellular protein localization	1
vesicle-mediated transport	1
ribonucleoside triphosphate phosphatase activity	1
GTPase activity	1
molecular function regulator activity	1
purine ribonucleoside triphosphate binding	1

Protein interactions and networks

STRING

2789 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RAB11B	CAGE1	Q8TC20	791
RAB11B	DKKL1	Q9UK85	722
RAB11B	LRPAP1	P30533	608
RAB11B	EXOC6	Q8TAG9	588
RAB11B	CEACAM5	P06731	506
RAB11B	GDI1	P31150	500
RAB11B	ACRBP	Q8NEB7	477
RAB11B	CNDP2	Q96KP4	438
RAB11B	ZFYVE27	Q5T4F4	424
RAB11B	VPS45	Q9NRW7	394
RAB11B	EXOC7	Q9UPT5	381
RAB11B	VAMP1	P23763	380
RAB11B	TRAPPC8	Q9Y2L5	378
RAB11B	ARF6	P26438	366
RAB11B	CD63	P08962	357

IntAct

144 interactions, top by confidence:

A	B	Type	Score
IKBKG	IKBKB	psi-mi:“MI:0914”(association)	0.980
PIK3CA	PIK3R2	psi-mi:“MI:0914”(association)	0.900
RAB11B	RAB11FIP2	psi-mi:“MI:0915”(physical association)	0.840
IFIT2	IFIT3	psi-mi:“MI:0914”(association)	0.780
RAB11B	SH3BP5L	psi-mi:“MI:0915”(physical association)	0.740
RAB11FIP1	YWHAH	psi-mi:“MI:0914”(association)	0.740
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
RAB11B	SH3BP5	psi-mi:“MI:0914”(association)	0.640
DYNLL2	BLTP3B	psi-mi:“MI:0914”(association)	0.640
MMAB	DBT	psi-mi:“MI:0914”(association)	0.620
RAB11B	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
RAB11B	MYO5B	psi-mi:“MI:0915”(physical association)	0.560
FOS	RAB11B	psi-mi:“MI:0915”(physical association)	0.560
GRB2	RAB11B	psi-mi:“MI:0915”(physical association)	0.560
GRIA1	RAB11B	psi-mi:“MI:0915”(physical association)	0.560
SRC	RAB11B	psi-mi:“MI:0915”(physical association)	0.560
TSC1	RAB11B	psi-mi:“MI:0915”(physical association)	0.560
RAB11B	WFS1	psi-mi:“MI:0915”(physical association)	0.560
SPRED1	RAB11B	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (273): RAB11B (Affinity Capture-MS), RAB11FIP1 (Affinity Capture-MS), RAB11FIP2 (Affinity Capture-MS), WDR44 (Affinity Capture-MS), CHML (Affinity Capture-MS), CHM (Affinity Capture-MS), SH3BP5L (Affinity Capture-MS), RAB25 (Affinity Capture-MS), SH3BP5 (Affinity Capture-MS), S100A3 (Affinity Capture-MS), SERPINB5 (Affinity Capture-MS), SELENBP1 (Affinity Capture-MS), RAB11FIP5 (Affinity Capture-MS), LYG2 (Affinity Capture-MS), LRRC15 (Affinity Capture-MS)

ESM2 similar proteins: E2RQ15, O01803, O04486, O23561, O35509, P17610, P19892, P22129, P25766, P28185, P28187, P36412, P46638, P62490, P62491, P62492, P62493, P62494, Q01111, Q15907, Q1PEX3, Q2TA29, Q39222, Q39434, Q39572, Q3MHP2, Q40191, Q40193, Q40195, Q40520, Q40522, Q40523, Q40723, Q52NJ1, Q58DW6, Q5R9M7, Q5ZJN2, Q96283, Q9FE79, Q9FGK5

Diamond homologs: A2WSI7, A2Y7R5, A2YEQ6, H9BW96, O17915, O76742, O97572, P09527, P18067, P22127, P22129, P24408, P28748, P32835, P32836, P33519, P34139, P35288, P36019, P36411, P36864, P38542, P38543, P38544, P38545, P38546, P38547, P38548, P41914, P41915, P41916, P41917, P41918, P41919, P42558, P46638, P51149, P51150, P51151, P52301

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 159 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
Signaling by ERBB2 ECD mutants	6	35.4×	2e-06
Signaling by FLT3 ITD and TKD mutants	5	33.4×	2e-05
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	7	31.9×	3e-07
Tie2 Signaling	6	31.6×	3e-06
Constitutive Signaling by EGFRvIII	5	31.3×	2e-05
GRB2 events in ERBB2 signaling	5	27.8×	4e-05
Downstream signal transduction	8	26.7×	3e-07
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	5	25.0×	5e-05

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of Rac protein signal transduction	5	22.5×	1e-03
vesicle fusion	5	20.9×	1e-03
substrate adhesion-dependent cell spreading	5	11.9×	7e-03
epidermal growth factor receptor signaling pathway	6	10.3×	4e-03
exocytosis	9	9.5×	3e-04
Ras protein signal transduction	6	8.6×	7e-03
T cell receptor signaling pathway	7	7.4×	6e-03
endocytosis	9	6.0×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	3
Uncertain significance	74
Likely benign	130
Benign	33

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
4813460	NM_004218.4(RAB11B):c.64G>T (p.Val22Leu)	Pathogenic
2770910	NM_004218.4(RAB11B):c.220C>G (p.Arg74Gly)	Likely pathogenic
3235921	NM_004218.4(RAB11B):c.85T>C (p.Ser29Pro)	Likely pathogenic
3337505	NM_004218.4(RAB11B):c.196G>T (p.Asp66Tyr)	Likely pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

1431 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:8399869:T:C	L16P	1.000
19:8399874:G:A	G18R	1.000
19:8399874:G:C	G18R	1.000
19:8399874:G:T	G18W	1.000
19:8399875:G:A	G18E	1.000
19:8399875:G:T	G18V	1.000
19:8399889:G:C	G23R	1.000
19:8399889:G:T	G23C	1.000
19:8399890:G:A	G23D	1.000
19:8399890:G:T	G23V	1.000
19:8399892:A:C	K24Q	1.000
19:8399893:A:T	K24M	1.000
19:8399894:G:C	K24N	1.000
19:8399894:G:T	K24N	1.000
19:8399896:G:T	S25I	1.000
19:8399902:T:C	L27P	1.000
19:8399905:T:C	L28P	1.000
19:8399911:G:C	R30P	1.000
19:8399928:T:C	F36L	1.000
19:8399929:T:C	F36S	1.000
19:8399930:C:A	F36L	1.000
19:8399930:C:G	F36L	1.000
19:8399950:C:T	T43I	1.000
19:8399953:T:A	I44N	1.000
19:8399955:G:C	G45R	1.000
19:8399956:G:A	G45D	1.000
19:8399964:T:C	F48L	1.000
19:8399965:T:C	F48S	1.000
19:8399965:T:G	F48C	1.000
19:8399966:C:A	F48L	1.000

dbSNP variants (sampled 300 via entrez): RS1000080334 (19:8390701 G>A), RS1000346951 (19:8389922 A>T), RS1000392208 (19:8403734 G>A,C), RS1000462076 (19:8400746 C>T), RS1000553048 (19:8394741 C>G,T), RS1000978014 (19:8396833 C>G), RS1000989067 (19:8394895 A>T), RS1001067710 (19:8404691 G>A,T), RS1001807732 (19:8393063 C>A), RS1001965475 (19:8389547 G>T), RS1002091008 (19:8393265 C>T), RS1002343921 (19:8397812 C>T), RS1002379240 (19:8398139 A>G), RS1002530230 (19:8402666 T>TTTTTG,TTTTTGTTTTTTTC), RS1002563441 (19:8397056 G>A)

Disease associations

OMIM: gene MIM:604198 | disease phenotypes: MIM:617807

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matter	Strong	Autosomal dominant

Mondo (1): neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matter (MONDO:0060624)

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases abundance, increases expression	2
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
bisphenol A	increases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
ochratoxin A	affects binding	1
ochratoxin B	affects binding	1
epigallocatechin gallate	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
bisphenol B	increases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	increases expression	1
Vorinostat	decreases expression	1
Cannabidiol	affects cotreatment, decreases expression	1
Cuprizone	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Drugs, Chinese Herbal	increases expression	1
Ivermectin	decreases expression	1
Naphthoquinones	increases expression	1
Ouabain	increases expression	1
Selenium	increases expression	1
Smoke	increases abundance, increases expression	1
Theophylline	increases expression	1
Tobacco Smoke Pollution	affects expression	1
Tretinoin	increases expression	1
Urethane	increases expression	1
Valproic Acid	increases methylation	1
Gold Compounds	decreases methylation, increases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TH94	HAP1 RAB11B (-) 1	Cancer cell line	Male
CVCL_XS07	HAP1 RAB11B (-) 2	Cancer cell line	Male
CVCL_XS08	HAP1 RAB11B (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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