RABGGTB

Summary

RABGGTB (Rab geranylgeranyltransferase subunit beta, HGNC:9796) is a protein-coding gene on chromosome 1p31.1, encoding Geranylgeranyl transferase type-2 subunit beta (P53611). Catalyzes the transfer of a geranylgeranyl moiety from geranylgeranyl diphosphate to both cysteines of Rab proteins with the C-terminal sequence -XXCC, -XCXC and -CCXX, such as RAB1A, RAB3A, RAB5A and RAB7A. It is a common-essential gene (DepMap: required in 98.9% of cancer cell lines).

This gene encodes the beta-subunit of the enzyme Rab geranylgeranyl-transferase (RabGGTase), which belongs to the protein prenyltransferase family. RabGGTase catalyzes the post-translational addition of geranylgeranyl groups to C-terminal cysteine residues of Rab GTPases. Three small nucleolar RNA genes are present in the intronic regions of this gene. Alternately spliced transcript variants have been observed for this gene. A pseudogene associated with this gene is located on chromosome 3.

Source: NCBI Gene 5876 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 50 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 98.9% of screened cell lines (common-essential)
• MANE Select transcript: NM_004582

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9796
Approved symbol	RABGGTB
Name	Rab geranylgeranyltransferase subunit beta
Location	1p31.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000137955
Ensembl biotype	protein_coding
OMIM	179080
Entrez	5876

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 19 protein_coding, 12 protein_coding_CDS_not_defined

ENST00000319942, ENST00000370826, ENST00000459697, ENST00000461653, ENST00000462042, ENST00000467748, ENST00000470201, ENST00000471759, ENST00000473406, ENST00000485459, ENST00000489450, ENST00000491266, ENST00000496055, ENST00000497648, ENST00000872421, ENST00000872422, ENST00000935144, ENST00000935145, ENST00000935146, ENST00000935147, ENST00000935148, ENST00000935149, ENST00000935150, ENST00000935151, ENST00000935152, ENST00000935153, ENST00000935154, ENST00000935155, ENST00000935156, ENST00000935157, ENST00000964019

RefSeq mRNA: 1 — MANE Select: NM_004582 NM_004582

CCDS: CCDS669

Canonical transcript exons

ENST00000319942 — 9 exons

Exon	Start	End
ENSE00001172570	75786256	75786274
ENSE00001221127	75794510	75795086
ENSE00003461091	75789159	75789356
ENSE00003475485	75792181	75792306
ENSE00003483781	75789952	75790057
ENSE00003486670	75791285	75791337
ENSE00003515027	75794084	75794233
ENSE00003664662	75787497	75787604
ENSE00003668254	75791461	75791571

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 35.4120 / max 489.7264, expressed in 1810 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
3549	28.5360	1801
3547	3.7230	1450
3548	1.2889	782
3551	1.0817	676
3550	0.6952	405
201552	0.0873	18

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.33	gold quality
germinal epithelium of ovary	UBERON:0001304	98.63	gold quality
tibia	UBERON:0000979	98.60	gold quality
cartilage tissue	UBERON:0002418	98.41	gold quality
pigmented layer of retina	UBERON:0001782	98.32	gold quality
body of pancreas	UBERON:0001150	98.18	gold quality
gingival epithelium	UBERON:0001949	98.12	gold quality
esophagus squamous epithelium	UBERON:0006920	98.02	gold quality
islet of Langerhans	UBERON:0000006	98.00	gold quality
pylorus	UBERON:0001166	97.97	gold quality
parietal pleura	UBERON:0002400	97.94	gold quality
epithelium of nasopharynx	UBERON:0001951	97.93	gold quality
visceral pleura	UBERON:0002401	97.84	gold quality
pancreas	UBERON:0001264	97.80	gold quality
superior surface of tongue	UBERON:0007371	97.80	gold quality
pleura	UBERON:0000977	97.71	gold quality
amniotic fluid	UBERON:0000173	97.70	gold quality
adrenal tissue	UBERON:0018303	97.69	gold quality
body of tongue	UBERON:0011876	97.66	gold quality
pericardium	UBERON:0002407	97.63	gold quality
squamous epithelium	UBERON:0006914	97.60	gold quality
corpus callosum	UBERON:0002336	97.46	gold quality
oocyte	CL:0000023	97.45	gold quality
rectum	UBERON:0001052	97.37	gold quality
tongue	UBERON:0001723	97.36	gold quality
endothelial cell	CL:0000115	97.35	gold quality
tendon of biceps brachii	UBERON:0008188	97.35	gold quality
pharyngeal mucosa	UBERON:0000355	97.33	gold quality
cardia of stomach	UBERON:0001162	97.29	gold quality
nephron tubule	UBERON:0001231	97.25	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.15

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

43 targeting RABGGTB, 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-3924	100.00	72.09	2394
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-568	99.98	69.86	2084
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-607	99.97	73.62	5593
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-6516-3P	99.65	68.57	1238
HSA-MIR-5197-5P	99.64	69.08	1494
HSA-MIR-8061	99.63	69.44	1411
HSA-MIR-891B	99.59	69.81	1083
HSA-MIR-2113	99.58	71.22	1521
HSA-MIR-543	99.52	69.03	2595

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 98.9% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 3)

• an interaction between a transmembrane receptor and RGGTA (PMID:21990357)
• This study reports the identification of a previously unknown human prenyltransferase complex consisting of an orphan prenyltransferase alpha subunit, PTAR1, and the catalytic beta-subunit of GGTase2, RabGGTB. (PMID:31209342)
• A SNARE geranylgeranyltransferase essential for the organization of the Golgi apparatus. (PMID:32128853)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rabggtb	ENSDARG00000068587
mus_musculus	Rabggtb	ENSMUSG00000038975
rattus_norvegicus	Rabggtb	ENSRNOG00000009992
drosophila_melanogaster	RabGGTb	FBGN0028970
caenorhabditis_elegans		WBGENE00015099

Paralogs (2): PGGT1B (ENSG00000164219), FNTB (ENSG00000257365)

Protein

Protein identifiers

Geranylgeranyl transferase type-2 subunit beta — P53611 (reviewed: P53611)

Alternative names: Geranylgeranyl transferase type II subunit beta, Rab geranyl-geranyltransferase subunit beta, Rab geranylgeranyltransferase subunit beta, Type II protein geranyl-geranyltransferase subunit beta

All UniProt accessions (3): P53611, Q5T4U8, Q6IB63

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the transfer of a geranylgeranyl moiety from geranylgeranyl diphosphate to both cysteines of Rab proteins with the C-terminal sequence -XXCC, -XCXC and -CCXX, such as RAB1A, RAB3A, RAB5A and RAB7A. Catalytic subunit of the geranylgeranyl transferase type 3 (GGTase-3) complex. The GGTase-3 complex geranylgeranylates and targets FBXL2 to the cellular membranes, where FBXL2 forms part of the E3 ubiquitin-protein ligase complex SCF(FBXL2) that mediates the degradation of membrane-anchored proteins. The GGTase-3 complex geranylgeranylates Golgi v-SNARE protein YKT6 at ‘Cys-194’ and this prenylation is required for Golgi SNARE complex assembly.

Subunit / interactions. Heterotrimer composed of RABGGTA, RABGGTB and CHM; within this trimer, RABGGTA and RABGGTB form the catalytic component B, while CHM (component A) mediates peptide substrate binding. The Rab GGTase dimer (RGGT) interacts with CHM (component A) prior to Rab protein binding; the association is stabilized by geranylgeranyl pyrophosphate (GGpp). The CHM:RGGT:Rab complex is destabilized by GGpp. Interaction of RABGGTB with prenylated PTP4A2 precludes its association with RABGGTA and inhibits enzyme activity. Part of the GGTase-3 complex, composed of PTAR1 and RABGGTB; this complex geranylgeranylates FBXL2 and YKT6. Interacts with CHODL. Interacts with non-phosphorylated form of RAB8A; phosphorylation of RAB8A at ‘Thr-72’ disrupts this interaction.

Activity regulation. The enzymatic reaction requires the aid of a Rab escort protein (also called component A).

Cofactor. Binds 1 zinc ion per subunit.

Similarity. Belongs to the protein prenyltransferase subunit beta family.

RefSeq proteins (1): NP_004573* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001330	Prenyltrans	Domain
IPR008930	Terpenoid_cyclase/PrenylTrfase	Homologous_superfamily
IPR026873	Ptb1	Family
IPR045089	PGGT1B-like	Family

Pfam: PF00432

Enzyme classification (BRENDA):

• EC 2.5.1.60 — protein geranylgeranyltransferase type II (BRENDA: 9 organisms, 44 substrates, 88 inhibitors, 7 Km, 2 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
GERANYLGERANYL DIPHOSPHATE	—	2
RAB3A	—	1
YPT1P	0.0011	1
RAB PROTEIN	—	0

Catalyzed reactions (Rhea), 1 shown:

• geranylgeranyl diphosphate + L-cysteinyl-[protein] = S-geranylgeranyl-L-cysteinyl-[protein] + diphosphate (RHEA:21240)

UniProt features (49 total): helix 20, strand 8, repeat 6, binding site 5, sequence conflict 3, modified residue 2, turn 2, initiator methionine 1, chain 1, mutagenesis site 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
6O60	X-RAY DIFFRACTION	2.5
6J7X	X-RAY DIFFRACTION	2.75
6J7F	X-RAY DIFFRACTION	2.88
6J6X	X-RAY DIFFRACTION	2.96
6J74	X-RAY DIFFRACTION	3.21

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P53611-F1	96.69	0.93

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 (5): 240; 241–244; 290; 190–192; 238

Post-translational modifications (2): 2, 3

Mutagenesis-validated functional residues (1):

Position	Phenotype
49	abolishes geranylgeranylation of ykt6.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-6803205	TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain
R-HSA-8873719	RAB geranylgeranylation

MSigDB gene sets: 200 (showing top): YAGI_AML_WITH_INV_16_TRANSLOCATION, TGCGCANK_UNKNOWN, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, SWEET_KRAS_ONCOGENIC_SIGNATURE, GCM_NPM1, MORF_SNRP70, PID_PRL_SIGNALING_EVENTS_PATHWAY, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, KYNG_DNA_DAMAGE_DN, KYNG_DNA_DAMAGE_BY_4NQO, TGACCTY_ERR1_Q2, GOBP_VESICLE_MEDIATED_TRANSPORT, GOMF_GTPASE_BINDING, WEI_MYCN_TARGETS_WITH_E_BOX

GO Biological Process (4): endoplasmic reticulum to Golgi vesicle-mediated transport (GO:0006888), visual perception (GO:0007601), protein geranylgeranylation (GO:0018344), protein modification process (GO:0036211)

GO Molecular Function (10): Rab geranylgeranyltransferase activity (GO:0004663), zinc ion binding (GO:0008270), small GTPase binding (GO:0031267), catalytic activity (GO:0003824), prenyltransferase activity (GO:0004659), protein geranylgeranyltransferase activity (GO:0004661), protein binding (GO:0005515), protein prenyltransferase activity (GO:0008318), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (4): cytosol (GO:0005829), plasma membrane (GO:0005886), Rab-protein geranylgeranyltransferase complex (GO:0005968), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
TP53 Regulates Transcription of Cell Death Genes	1
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	3
cellular anatomical structure	2
intercellular transport	1
intracellular transport	1
Golgi vesicle transport	1
sensory perception of light stimulus	1
protein prenylation	1
protein metabolic process	1
macromolecule modification	1
protein geranylgeranyltransferase activity	1
transition metal ion binding	1
GTPase binding	1
molecular_function	1
transferase activity, transferring alkyl or aryl (other than methyl) groups	1
protein prenyltransferase activity	1
binding	1
prenyltransferase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
cation binding	1
membrane	1
cell periphery	1
transferase complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1364 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RABGGTB	RABGGTA	Q92696	986
RABGGTB	PTAR1	Q7Z6K3	820
RABGGTB	FNTA	P49354	818
RABGGTB	RAB1A	P11476	805
RABGGTB	CHML	P26374	738
RABGGTB	RAB3A	P20336	670
RABGGTB	FBXL2	Q9UKC9	615
RABGGTB	GGT1	P19440	591
RABGGTB	CHM	P24386	572
RABGGTB	FBXL17	Q9UF56	524
RABGGTB	RWDD1	Q9H446	503
RABGGTB	WDR47	O94967	488
RABGGTB	ERLEC1	Q96DZ1	478
RABGGTB	DNPH1	O43598	458
RABGGTB	NME6	O75414	458

IntAct

97 interactions, top by confidence:

A	B	Type	Score
PTAR1	RABGGTB	psi-mi:“MI:0914”(association)	0.920
PTAR1	RABGGTB	psi-mi:“MI:0915”(physical association)	0.920
RABGGTB	PTAR1	psi-mi:“MI:0914”(association)	0.920
RABGGTB	PTAR1	psi-mi:“MI:0915”(physical association)	0.920
RABGGTB	PTAR1	psi-mi:“MI:0407”(direct interaction)	0.920
RABGGTA	RABGGTB	psi-mi:“MI:0914”(association)	0.880
RABGGTB	RABGGTA	psi-mi:“MI:0915”(physical association)	0.880
RABGGTB	YKT6	psi-mi:“MI:0914”(association)	0.740
RABGGTB	YKT6	psi-mi:“MI:0915”(physical association)	0.740
WDR4	RABGGTB	psi-mi:“MI:0915”(physical association)	0.720
RABGGTB	B4GALT7	psi-mi:“MI:0915”(physical association)	0.720
RABGGTB	WDR4	psi-mi:“MI:0915”(physical association)	0.720
B4GALT7	RABGGTB	psi-mi:“MI:0915”(physical association)	0.720
RAB31	CHM	psi-mi:“MI:0914”(association)	0.640
RAB9A	CHM	psi-mi:“MI:0914”(association)	0.610
RAB8A	WDR91	psi-mi:“MI:0914”(association)	0.600

BioGRID (207): WDR4 (Two-hybrid), B4GALT7 (Two-hybrid), TMEM25 (Two-hybrid), RAB37 (Two-hybrid), FAM19A1 (Two-hybrid), RABGGTB (Affinity Capture-MS), RABGGTB (Affinity Capture-MS), INPP5A (Affinity Capture-MS), PRRC2C (Affinity Capture-MS), PIPSL (Affinity Capture-MS), PIP5K1C (Affinity Capture-MS), PIP5K1A (Affinity Capture-MS), AKAP11 (Affinity Capture-MS), PALM (Affinity Capture-MS), NOTCH3 (Affinity Capture-MS)

ESM2 similar proteins: A0A0E0SP71, A0A348FUE1, A3LQF9, B0G172, C4YSU5, O13782, O80642, O93830, P0DPA1, P18898, P20133, P22007, P32073, P32434, P38604, P41992, P46960, P49355, P49356, P53609, P53610, P53611, P53612, Q02293, Q04782, Q04903, Q08603, Q10231, Q2V0C9, Q38920, Q4WES9, Q54MJ7, Q55D51, Q55D85, Q55DA3, Q55FS0, Q59LF2, Q59M69, Q5E9B3, Q5EAD5

Diamond homologs: B0G172, O13782, O93830, P20133, P41992, P46960, P53609, P53610, P53611, P53612, Q02293, Q08603, Q5E9B3, Q5EAD5, Q84J75, Q8BUY9, Q8K2I1, Q9LHL5, G4MY67, P22007, P49355, P49356, Q04903, Q38920, O80642, P32434, Q55DA3, P18898, Q55D51

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
CHM	“down-regulates activity”	RABGGTB	binding
RABGGTB	“up-regulates activity”	RAB5A	lipidation
RABGGTB	“up-regulates activity”	RAB3A	lipidation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 49 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
RAB geranylgeranylation	13	60.8×	2e-18
TBC/RABGAPs	5	35.1×	3e-05
RAB GEFs exchange GTP for GDP on RABs	10	33.5×	3e-11

GO biological processes:

GO term	Partners	Fold	FDR
retrograde transport, endosome to Golgi	5	23.4×	4e-04
MAPK cascade	5	17.4×	9e-04
positive regulation of MAPK cascade	5	9.2×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	28
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1415 predictions. Top by Δscore:

Variant	Effect	Δscore
1:75787605:G:GG	donor_gain	1.0000
1:75790150:A:AG	acceptor_gain	1.0000
1:75790151:G:GT	acceptor_gain	1.0000
1:75790151:GGTCC:G	acceptor_gain	1.0000
1:75790270:A:G	donor_gain	1.0000
1:75790270:ATAAG:A	donor_gain	1.0000
1:75790275:G:GG	donor_gain	1.0000
1:75790513:GTAGG:G	donor_gain	1.0000
1:75791279:TTGTA:T	acceptor_loss	1.0000
1:75791280:TGTA:T	acceptor_loss	1.0000
1:75791281:GTA:G	acceptor_loss	1.0000
1:75791282:TAG:T	acceptor_loss	1.0000
1:75791283:A:C	acceptor_loss	1.0000
1:75791284:G:C	acceptor_loss	1.0000
1:75791334:GTTG:G	donor_gain	1.0000
1:75791336:TGGT:T	donor_loss	1.0000
1:75791338:G:GG	donor_gain	1.0000
1:75791338:GTAA:G	donor_loss	1.0000
1:75791339:T:A	donor_loss	1.0000
1:75791452:T:TA	acceptor_gain	1.0000
1:75791457:GTA:G	acceptor_loss	1.0000
1:75791458:TA:T	acceptor_loss	1.0000
1:75791459:A:AG	acceptor_gain	1.0000
1:75791459:A:T	acceptor_loss	1.0000
1:75791459:AG:A	acceptor_gain	1.0000
1:75791459:AGG:A	acceptor_gain	1.0000
1:75791459:AGGG:A	acceptor_gain	1.0000
1:75791460:G:A	acceptor_loss	1.0000
1:75791460:G:GA	acceptor_gain	1.0000
1:75791460:GG:G	acceptor_gain	1.0000

AlphaMissense

2177 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:75791558:C:T	S189F	1.000
1:75792266:G:C	R222P	1.000
1:75792293:G:A	G231E	1.000
1:75792296:G:C	R232T	1.000
1:75792296:G:T	R232M	1.000
1:75792297:G:C	R232S	1.000
1:75792297:G:T	R232S	1.000
1:75794096:T:C	C240R	1.000
1:75794097:G:A	C240Y	1.000
1:75794098:C:G	C240W	1.000
1:75794099:T:C	Y241H	1.000
1:75794108:T:A	W244R	1.000
1:75794108:T:C	W244R	1.000
1:75794522:C:A	H290N	1.000
1:75794522:C:G	H290D	1.000
1:75789189:A:C	S48R	0.999
1:75789191:T:A	S48R	0.999
1:75789191:T:G	S48R	0.999
1:75789201:T:A	W52R	0.999
1:75789201:T:C	W52R	0.999
1:75789345:A:C	S100R	0.999
1:75789347:T:A	S100R	0.999
1:75789347:T:G	S100R	0.999
1:75791293:G:C	D142H	0.999
1:75791294:A:T	D142V	0.999
1:75791300:G:C	R144T	0.999
1:75791300:G:T	R144I	0.999
1:75791301:A:C	R144S	0.999
1:75791301:A:T	R144S	0.999
1:75791302:T:C	F145L	0.999

dbSNP variants (sampled 300 via entrez): RS1000387919 (1:75793442 A>G), RS1000398920 (1:75793047 C>T), RS1000443143 (1:75785854 G>C), RS1000689542 (1:75792344 C>T), RS1000794329 (1:75791414 T>C), RS1001005787 (1:75791678 C>A,G,T), RS1001038088 (1:75786209 G>A), RS1001090932 (1:75784779 C>T), RS1001116289 (1:75793344 G>A), RS1001374931 (1:75791008 T>G), RS1002091111 (1:75791749 C>T), RS1002122134 (1:75792167 G>A), RS1002303389 (1:75784904 CG>C), RS1002362233 (1:75785305 C>T), RS1002675466 (1:75785128 C>A,T)

Disease associations

OMIM: gene MIM:179080 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST003518_71	Daytime sleep phenotypes	8.000000e-07
GCST003518_98	Daytime sleep phenotypes	3.000000e-06
GCST006249_15	Serum metabolite levels	8.000000e-28
GCST006249_16	Serum metabolite levels	1.000000e-24
GCST006249_5	Serum metabolite levels	4.000000e-32
GCST006249_6	Serum metabolite levels	6.000000e-30
GCST006249_71	Serum metabolite levels	3.000000e-19
GCST006249_72	Serum metabolite levels	1.000000e-18
GCST006249_81	Serum metabolite levels	5.000000e-16
GCST006249_82	Serum metabolite levels	4.000000e-15

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007828	daytime rest measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523994 (PROTEIN COMPLEX)

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

ChEMBL bioactivities

11 potent at pChembl≥5 of 11 total, top 10 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.87	Ki	1360	nM	CHEMBL1221574
5.68	IC50	2100	nM	CHEMBL1221574
5.66	IC50	2200	nM	CHEMBL1221575
5.51	IC50	3100	nM	CHEMBL4558573
5.44	IC50	3600	nM	CHEMBL4518286
5.35	IC50	4500	nM	CHEMBL1221621
5.33	IC50	4700	nM	CHEMBL4443727
5.32	IC50	4800	nM	CHEMBL4456846
5.16	IC50	7000	nM	CHEMBL4469845
5.16	IC50	7000	nM	CHEMBL4467525

PubChem BioAssay actives

1 with measured affinity, of 23 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2R,3R,4S,5R)-2-(4-bromophenyl)-4-hexylsulfanyl-1-(4-methylphenyl)sulfonyl-5-propylpyrrolidine-3-carboxylic acid	1920874: Inhibition of Geranylgeranyl transferase type-2 in human NIH3T3 cells assessed as inhibition of Rab geranylgeranylation incubated for 48 hrs by immunoblotting assay	ic50	2.1000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases methylation	4
bisphenol A	decreases methylation, decreases expression, affects expression, affects cotreatment	3
Tetrachlorodibenzodioxin	decreases expression	3
Benzo(a)pyrene	decreases expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Rotenone	increases expression	2
Tretinoin	decreases expression, increases reaction	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	increases expression	1
uranyl acetate	affects expression	1
trichostatin A	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	increases expression	1
manganese chloride	decreases expression, increases abundance	1
beta-methylcholine	affects expression	1
tamibarotene	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
pentabromodiphenyl ether	increases expression	1
chloropicrin	increases expression	1
deguelin	increases expression	1
nickel acetate	affects expression	1
monomethylarsonous acid	decreases expression	1
K 7174	increases expression	1
GW 4064	affects cotreatment, decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
6-(4-chlorophenyl)imidazo(2,1-b)(1,3)thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime	affects cotreatment, increases expression	1
pyrimidifen	increases expression	1
abrine	increases expression	1

ChEMBL screening assays

23 unique, capped per target: 23 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4315908	Binding	Inhibition of GGtase-2 in human cells assessed as minimum effective dose required for increase in intracellular lambda chain level after 48 hrs by ELISA	Novel benzimidazole phosphonates as potential inhibitors of protein prenylation. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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