RAB36

Summary

RAB36 (RAB36, member RAS oncogene family, HGNC:9775) is a protein-coding gene on chromosome 22q11.23, encoding Ras-related protein Rab-36 (O95755). The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes.

Predicted to enable GTP binding activity and GTPase activity. Predicted to be involved in vesicle-mediated transport. Predicted to be located in Golgi membrane.

Source: NCBI Gene 9609 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 63 total
• MANE Select transcript: NM_004914

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9775
Approved symbol	RAB36
Name	RAB36, member RAS oncogene family
Location	22q11.23
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000100228
Ensembl biotype	protein_coding
OMIM	605662
Entrez	9609

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000263116, ENST00000341989, ENST00000420895, ENST00000857885, ENST00000857886, ENST00000857887

RefSeq mRNA: 3 — MANE Select: NM_004914 NM_001349877, NM_001349878, NM_004914

CCDS: CCDS13805

Canonical transcript exons

ENST00000263116 — 11 exons

Exon	Start	End
ENSE00000651221	23146605	23146685
ENSE00000651223	23150063	23150154
ENSE00000651225	23152461	23152526
ENSE00000651226	23153033	23153134
ENSE00000651228	23155968	23156032
ENSE00000651231	23157992	23158043
ENSE00000651232	23158898	23158979
ENSE00000651234	23159163	23159253
ENSE00000651236	23160879	23160998
ENSE00000879414	23145477	23145551
ENSE00001386696	23161500	23165663

Expression profiles

Bgee: expression breadth ubiquitous, 201 present calls, max score 95.81.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.4052 / max 55.2450, expressed in 1126 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
191301	3.1348	1100
191302	0.2703	136

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	95.81	gold quality
epithelium of bronchus	UBERON:0002031	93.29	gold quality
bronchial epithelial cell	CL:0002328	93.01	gold quality
bronchus	UBERON:0002185	92.46	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	86.02	gold quality
secondary oocyte	CL:0000655	84.99	gold quality
pituitary gland	UBERON:0000007	83.85	gold quality
adenohypophysis	UBERON:0002196	83.82	gold quality
mucosa of paranasal sinus	UBERON:0005030	83.17	gold quality
right lobe of thyroid gland	UBERON:0001119	82.88	gold quality
left lobe of thyroid gland	UBERON:0001120	81.82	gold quality
thyroid gland	UBERON:0002046	81.55	gold quality
ventricular zone	UBERON:0003053	81.33	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.29	gold quality
nasal cavity epithelium	UBERON:0005384	81.28	gold quality
epithelium of nasopharynx	UBERON:0001951	81.07	gold quality
oocyte	CL:0000023	78.80	gold quality
metanephros cortex	UBERON:0010533	77.99	gold quality
middle temporal gyrus	UBERON:0002771	76.73	silver quality
right frontal lobe	UBERON:0002810	76.60	gold quality
prefrontal cortex	UBERON:0000451	76.46	gold quality
caput epididymis	UBERON:0004358	76.40	gold quality
cingulate cortex	UBERON:0003027	76.29	gold quality
Brodmann (1909) area 23	UBERON:0013554	76.21	silver quality
anterior cingulate cortex	UBERON:0009835	76.15	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.14	gold quality
right adrenal gland cortex	UBERON:0035827	76.02	gold quality
stromal cell of endometrium	CL:0002255	75.85	gold quality
nasal cavity mucosa	UBERON:0001826	75.74	gold quality
right adrenal gland	UBERON:0001233	75.55	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-114	yes	11.32
E-ANND-3	yes	9.22

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CUX1

miRNA regulators (miRDB)

115 targeting RAB36, 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-3120-5P	100.00	65.56	965
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6842-5P	99.80	67.54	1587

Literature-anchored findings (GeneRIF, showing 4)

• Rab36 may regulate the spatial distribution of late endosomes and lysosomes through a similar mechanism to Rab34. (PMID:19961360)
• These data show that RUTBC2 can act as a Rab36 GAP in cells and suggest that RUTBC2 links Rab9A function to Rab36 function in the endosomal system. (PMID:22637480)
• these results provide the first clues regarding the role of miR-1247 might be a potential therapeutic agent and diagnostic marker of bladder cancer by inhibiting RAB36 expression. (PMID:29872024)
• Novel genetic markers for chronic kidney disease in a geographically isolated population of Indigenous Australians: Individual and multiple phenotype genome-wide association study. (PMID:38347632)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	rab36	ENSDARG00000014058
mus_musculus	Rab36	ENSMUSG00000020175
rattus_norvegicus	Rab36	ENSRNOG00000001311
drosophila_melanogaster	RabX5	FBGN0035255

Paralogs (68): RAB27B (ENSG00000041353), RAB27A (ENSG00000069974), RAB7A (ENSG00000075785), RABL2B (ENSG00000079974), RAB21 (ENSG00000080371), RAB10 (ENSG00000084733), RAB18 (ENSG00000099246), 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-36 — O95755 (reviewed: O95755)

All UniProt accessions (2): O95755, H7C0Z1

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.

Subcellular location. Golgi apparatus membrane.

Tissue specificity. Ubiquitously present in all tissues examined.

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).

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 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.

Isoforms (2)

UniProt ID	Names	Canonical?
O95755-1	1	yes
O95755-2	2

RefSeq proteins (3): NP_001336806, NP_001336807, NP_004905* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001806	Small_GTPase	Family
IPR005225	Small_GTP-bd	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR050227	Rab	Family

Pfam: PF00071

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (26 total): binding site 17, short sequence motif 2, lipid moiety-binding region 2, sequence variant 2, chain 1, region of interest 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95755-F1	86.27	0.66

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 (17): 83; 86; 89; 89; 112; 115; 172; 174; 203; 204; 205; 68 …

Post-translational modifications (2): 266, 267

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-6811438	Intra-Golgi traffic
R-HSA-8873719	RAB geranylgeranylation

MSigDB gene sets: 81 (showing top): SHEPARD_BMYB_MORPHOLINO_UP, HOFFMANN_SMALL_PRE_BII_TO_IMMATURE_B_LYMPHOCYTE_DN, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, KYNG_RESPONSE_TO_H2O2, GOMF_GTPASE_ACTIVITY, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ACID_ANHYDRIDES, DODD_NASOPHARYNGEAL_CARCINOMA_DN, REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, NOUSHMEHR_GBM_SILENCED_BY_METHYLATION, PILON_KLF1_TARGETS_UP, REACTOME_VESICLE_MEDIATED_TRANSPORT, REACTOME_INTRA_GOLGI_TRAFFIC, REACTOME_INTRA_GOLGI_AND_RETROGRADE_GOLGI_TO_ER_TRAFFIC, REACTOME_RAB_GERANYLGERANYLATION

GO Biological Process (2): protein transport (GO:0015031), vesicle-mediated transport (GO:0016192)

GO Molecular Function (7): GTPase activity (GO:0003924), G protein activity (GO:0003925), GTP binding (GO:0005525), metal ion binding (GO:0046872), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (3): Golgi membrane (GO:0000139), Golgi apparatus (GO:0005794), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Intra-Golgi and retrograde Golgi-to-ER traffic	1
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	2
intracellular protein localization	1
establishment of protein localization	1
cellular process	1
ribonucleoside triphosphate phosphatase activity	1
GTPase activity	1
molecular function regulator activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
Golgi apparatus	1
bounding membrane of organelle	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1044 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RAB36	RSPH14	Q9UHP6	979
RAB36	RILPL2	Q969X0	731
RAB36	MICALL1	Q8N3F8	685
RAB36	RILP	Q96NA2	656
RAB36	RABGAP1	Q9Y3P9	613
RAB36	GCC2	Q8IWJ2	556
RAB36	COG6	Q9Y2V7	553
RAB36	SGSM1	Q2NKQ1	541
RAB36	DCTN1	Q14203	510
RAB36	SGSM2	O43147	477
RAB36	GNAZ	P19086	470
RAB36	RAB10	P61026	454
RAB36	MLPH	Q9BV36	446
RAB36	TEX22	C9J3V5	439
RAB36	UNC13B	O14795	430

IntAct

4 interactions, top by confidence:

A	B	Type	Score
HSF2BP	RAB36	psi-mi:“MI:0915”(physical association)	0.560
RAB36	HSF2BP	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (6): HSF2BP (Two-hybrid), RAB36 (Co-fractionation), RAB36 (Co-fractionation), RAB36 (Co-fractionation), RAB36 (Two-hybrid), Ccdc64b (Affinity Capture-Western)

ESM2 similar proteins: A0A142I740, A2QM49, A5PK65, A6NHG4, A9SDL4, A9V2Y9, B2RXM4, B4G653, C5WU23, D3ZVR1, D4AWH0, D7PHZ1, F7D4X9, G0R6S7, K2RU68, O35215, O95755, O96347, P0DO34, P30046, P30111, P80254, P90835, P9WEP2, Q08CY5, Q0CS96, Q0DDI1, Q0IHU5, Q11177, Q18785, Q25313, Q28J83, Q4WQZ6, Q567W6, Q59750, Q5AXB0, Q5MFW3, Q5PQA5, Q5VVY1, Q5ZC83

Diamond homologs: A6QR46, C4YL11, F1PTE3, O04486, O18333, O18334, O35509, O42819, O80501, O95755, P07560, P0CY30, P0CY31, P10536, P11620, P16976, P17608, P17609, P17610, P19892, P20340, P22125, P22129, P25766, P31584, P33723, P34139, P34213, P35279, P35286, P35288, P36410, P36861, P38555, P40393, P46638, P51153, P51996, P53994, P59279

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	44
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2641 predictions. Top by Δscore:

Variant	Effect	Δscore
22:23150061:A:AG	acceptor_gain	1.0000
22:23150062:G:GG	acceptor_gain	1.0000
22:23153132:GAT:G	donor_gain	1.0000
22:23153133:AT:A	donor_gain	1.0000
22:23153134:TG:T	donor_loss	1.0000
22:23153135:G:GA	donor_loss	1.0000
22:23153135:G:GG	donor_gain	1.0000
22:23153136:T:A	donor_loss	1.0000
22:23153137:AAGTT:A	donor_loss	1.0000
22:23155959:A:AG	acceptor_gain	1.0000
22:23156031:GG:G	donor_gain	1.0000
22:23156032:GG:G	donor_gain	1.0000
22:23157981:C:A	acceptor_gain	1.0000
22:23157982:G:A	acceptor_gain	1.0000
22:23157990:A:AG	acceptor_gain	1.0000
22:23157990:AGT:A	acceptor_gain	1.0000
22:23157991:G:GG	acceptor_gain	1.0000
22:23157991:GT:G	acceptor_gain	1.0000
22:23157991:GTG:G	acceptor_gain	1.0000
22:23158041:CAGGT:C	donor_loss	1.0000
22:23158043:GGT:G	donor_loss	1.0000
22:23158044:G:GG	donor_gain	1.0000
22:23158044:GTA:G	donor_loss	1.0000
22:23158891:A:AG	acceptor_gain	1.0000
22:23158892:C:G	acceptor_gain	1.0000
22:23158894:CCAGG:C	acceptor_loss	1.0000
22:23158895:CAGGC:C	acceptor_loss	1.0000
22:23158896:A:AG	acceptor_gain	1.0000
22:23158896:AG:A	acceptor_gain	1.0000
22:23158897:G:GG	acceptor_gain	1.0000

AlphaMissense

2167 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:23155973:A:C	D178A	0.999
22:23155993:T:C	F185L	0.999
22:23155995:C:A	F185L	0.999
22:23155995:C:G	F185L	0.999
22:23155969:T:A	W177R	0.998
22:23155969:T:C	W177R	0.998
22:23155972:G:C	D178H	0.998
22:23155973:A:G	D178G	0.998
22:23155973:A:T	D178V	0.998
22:23155974:C:A	D178E	0.998
22:23155974:C:G	D178E	0.998
22:23152511:C:T	T137I	0.997
22:23153077:G:A	G157E	0.997
22:23153085:T:C	F160L	0.997
22:23153087:T:A	F160L	0.997
22:23153087:T:G	F160L	0.997
22:23158967:G:C	K238N	0.997
22:23158967:G:T	K238N	0.997
22:23152507:A:C	K136Q	0.996
22:23152508:A:T	K136M	0.996
22:23153049:T:C	F148L	0.996
22:23153051:T:A	F148L	0.996
22:23153051:T:G	F148L	0.996
22:23153074:T:A	I156N	0.996
22:23153128:T:C	L174P	0.996
22:23155971:G:C	W177C	0.996
22:23155971:G:T	W177C	0.996
22:23155994:T:C	F185S	0.996
22:23158006:T:C	F203L	0.996
22:23158008:T:A	F203L	0.996

dbSNP variants (sampled 300 via entrez): RS1000012092 (22:23144527 A>T), RS1000259754 (22:23150697 G>A), RS1000403512 (22:23158423 G>A), RS1000422446 (22:23152486 G>T), RS1000545553 (22:23165130 C>T), RS1000598061 (22:23165470 G>C), RS1000697543 (22:23154626 G>C), RS1000752425 (22:23160670 A>T), RS1000860648 (22:23158617 G>A), RS1000861756 (22:23149532 G>C), RS1001018035 (22:23143338 T>A,G), RS1001140430 (22:23157260 T>C), RS1001265058 (22:23164407 A>T), RS1001447242 (22:23169224 C>G), RS1001549484 (22:23164052 C>A,T)

Disease associations

OMIM: gene MIM:605662 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST003074_24	Cerebral amyloid deposition in APOEe4 non-carriers (PET imaging)	9.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007707	cerebral amyloid deposition measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	3
Air Pollutants	increases abundance, increases expression	2
Estradiol	affects expression, affects binding, increases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
Valproic Acid	affects expression, increases expression	2
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
terbufos	increases methylation	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	decreases expression	1
manganese chloride	increases abundance, increases expression	1
benzo(e)pyrene	increases methylation	1
ferrous chloride	decreases expression	1
aflatoxin B2	increases methylation	1
Resveratrol	affects cotreatment, decreases expression	1
Arsenic	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Fonofos	increases methylation	1
Manganese	increases abundance, increases expression	1
Methapyrilene	increases methylation	1
Parathion	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Rotenone	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	decreases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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