TBC1D3G

Summary

TBC1D3G (TBC1 domain family member 3G, HGNC:29860) is a protein-coding gene on chromosome 17q12, encoding TBC1 domain family member 3G (Q6DHY5). Acts as a GTPase activating protein for RAB5.

Predicted to enable GTPase activator activity. Predicted to be located in plasma membrane.

Source: NCBI Gene 101060321 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• MANE Select transcript: NM_001291462

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29860
Approved symbol	TBC1D3G
Name	TBC1 domain family member 3G
Location	17q12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000260287
Ensembl biotype	protein_coding
OMIM	610810
Entrez	101060321

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000569055, ENST00000959385

RefSeq mRNA: 1 — MANE Select: NM_001291462 NM_001291462

CCDS: CCDS74040

Canonical transcript exons

ENST00000569055 — 14 exons

Exon	Start	End
ENSE00002578788	36329856	36329904
ENSE00002585669	36333876	36334759
ENSE00002587908	36330448	36330568
ENSE00002594912	36328498	36328607
ENSE00002601767	36331761	36331826
ENSE00002602496	36332760	36332912
ENSE00002607262	36327537	36327617
ENSE00002611521	36328061	36328168
ENSE00002615932	36331282	36331376
ENSE00002624475	36332290	36332389
ENSE00003507437	36325646	36325731
ENSE00003510663	36325411	36325483
ENSE00003527731	36327015	36327054
ENSE00003733528	36323884	36323982

Expression profiles

Bgee: expression breadth ubiquitous, 109 present calls, max score 84.16.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.16	silver quality
left testis	UBERON:0004533	82.97	gold quality
right testis	UBERON:0004534	82.40	gold quality
testis	UBERON:0000473	81.97	gold quality
right uterine tube	UBERON:0001302	81.70	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	65.76	gold quality
duodenum	UBERON:0002114	49.32	gold quality
right coronary artery	UBERON:0001625	42.44	gold quality
hindlimb stylopod muscle	UBERON:0004252	41.35	gold quality
skeletal muscle tissue	UBERON:0001134	39.41	gold quality
muscle tissue	UBERON:0002385	38.95	gold quality
bone marrow	UBERON:0002371	38.69	gold quality
smooth muscle tissue	UBERON:0001135	38.63	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
fallopian tube	UBERON:0003889	36.88	gold quality
metanephros cortex	UBERON:0010533	36.49	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
endocervix	UBERON:0000458	36.09	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
uterine cervix	UBERON:0000002	35.28	gold quality
blood	UBERON:0000178	35.06	gold quality
left uterine tube	UBERON:0001303	34.84	gold quality
muscle of leg	UBERON:0001383	33.33	gold quality
liver	UBERON:0002107	33.13	gold quality
gall bladder	UBERON:0002110	32.87	gold quality
placenta	UBERON:0001987	32.48	gold quality
cortex of kidney	UBERON:0001225	32.46	gold quality
gastrocnemius	UBERON:0001388	32.23	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.35

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

19 targeting TBC1D3G, 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-1250-3P	99.96	70.04	4038
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-12130	99.75	65.47	452
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-3940-5P	99.14	65.26	493
HSA-MIR-4507	99.14	65.27	515
HSA-MIR-421	98.90	67.04	1883
HSA-MIR-7155-5P	98.65	66.14	1290
HSA-MIR-8060	98.61	66.93	1187
HSA-MIR-5585-5P	97.95	68.80	1024
HSA-MIR-3135A	96.41	65.30	494
HSA-MIR-548AD-3P	94.39	66.04	350

Cross-species orthologs

0 orthologs

Paralogs (45): RABGAP1 (ENSG00000011454), TBC1D22A (ENSG00000054611), TBC1D22B (ENSG00000065491), TBC1D1 (ENSG00000065882), EVI5 (ENSG00000067208), TBC1D25 (ENSG00000068354), TBC1D2 (ENSG00000095383), TBC1D10A (ENSG00000099992), SGSM3 (ENSG00000100359), TBC1D17 (ENSG00000104946), TBC1D13 (ENSG00000107021), TBC1D12 (ENSG00000108239), TBC1D9 (ENSG00000109436), TBC1D30 (ENSG00000111490), TBC1D15 (ENSG00000121749), TBC1D5 (ENSG00000131374), TBC1D14 (ENSG00000132405), TBC1D8B (ENSG00000133138), TBC1D4 (ENSG00000136111), GRTP1 (ENSG00000139835), SGSM2 (ENSG00000141258), EVI5L (ENSG00000142459), TBCK (ENSG00000145348), USP6NL (ENSG00000148429), RABGAP1L (ENSG00000152061), SGSM1 (ENSG00000167037), TBC1D21 (ENSG00000167139), TBC1D2B (ENSG00000167202), TBC1D16 (ENSG00000167291), TBC1D10B (ENSG00000169221), TBC1D10C (ENSG00000175463), TBC1D28 (ENSG00000189375), TBC1D9B (ENSG00000197226), TBC1D8 (ENSG00000204634), TBC1D26 (ENSG00000214946), TBC1D3K (ENSG00000273513), TBC1D3H (ENSG00000274226), TBC1D3D (ENSG00000274419), TBC1D3L (ENSG00000274512), TBC1D3 (ENSG00000274611)

Protein

Protein identifiers

TBC1 domain family member 3G — Q6DHY5 (reviewed: Q6DHY5)

All UniProt accessions (1): Q6DHY5

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a GTPase activating protein for RAB5. Does not act on RAB4 or RAB11.

Subcellular location. Cell membrane.

Post-translational modifications. Ubiquitinated by a CUL7-based E3 ligase, which leads to proteasomal degradation. Palmitoylation is required for membrane localization and protects TBC1D3 from ubiquitination.

Miscellaneous. TBC1D3 is encoded by a collection of very similar paralogs with multiple copies of each paralog, some human genomes encoding well over 50 copies depending on ethnic origin of the donor.

RefSeq proteins (1): NP_001278391* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000195	Rab-GAP-TBC_dom	Domain
IPR035969	Rab-GAP_TBC_sf	Homologous_superfamily
IPR050302	Rab_GAP_TBC_domain	Family

Pfam: PF00566

UniProt features (12 total): sequence conflict 5, region of interest 2, lipid moiety-binding region 2, chain 1, domain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6DHY5-F1	60.54	0.25

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 318, 325

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 11 (showing top): ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, GOMF_ENZYME_ACTIVATOR_ACTIVITY, GOMF_NUCLEOSIDE_TRIPHOSPHATASE_REGULATOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY, WANG_RESPONSE_TO_GSK3_INHIBITOR_SB216763_UP, chr17q12, THAKAR_PBMC_INACTIVATED_INFLUENZA_AGE_21_30YO_RESPONDERS_28DY_DN, GOMF_MOLECULAR_FUNCTION_ACTIVATOR_ACTIVITY, WP_17Q12_COPY_NUMBER_VARIATION_SYNDROME, GOCC_ENDOSOME, GOMF_GTPASE_ACTIVATOR_ACTIVITY

GO Biological Process (0):

GO Molecular Function (2): GTPase activator activity (GO:0005096), protein binding (GO:0005515)

GO Cellular Component (3): endosome (GO:0005768), plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
binding	1
endomembrane system	1
cytoplasmic vesicle	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

216 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TBC1D3G	CDRT15L2	A8MXV6	580
TBC1D3G	OR4X2	Q8NGF9	507
TBC1D3G	CCDC144A	A2RUR9	479
TBC1D3G	SLC35G3	Q8N808	476
TBC1D3G	SLC35G6	P0C7Q6	476
TBC1D3G	ZNF670	Q9BS34	474
TBC1D3G	CHCT1	Q86WR6	447
TBC1D3G	SPDYE4	A6NLX3	447
TBC1D3G	OR3A2	P47893	447
TBC1D3G	OR5M11	Q96RB7	447
TBC1D3G	ZNF669	Q96BR6	432
TBC1D3G	LRRC3C	A6NJW4	419
TBC1D3G	FBXW10B	O95170	419
TBC1D3G	KRTAP2-2	Q9BYT5	419
TBC1D3G	C17orf78	Q8N4C9	418

IntAct

29 interactions, top by confidence:

A	B	Type	Score
TBC1D3G	ZRANB1	psi-mi:“MI:0915”(physical association)	0.560
TBC1D3G	MDFI	psi-mi:“MI:0915”(physical association)	0.560
BAG3	TBC1D3G	psi-mi:“MI:0915”(physical association)	0.560
PSMD2	TBC1D3G	psi-mi:“MI:0915”(physical association)	0.560
GRB2	TBC1D3G	psi-mi:“MI:0915”(physical association)	0.560
GEM	TBC1D3G	psi-mi:“MI:0915”(physical association)	0.560
BAG4	TBC1D3G	psi-mi:“MI:0915”(physical association)	0.560
TBC1D3G	GTPBP3	psi-mi:“MI:0915”(physical association)	0.560
TBC1D3G	PPM1G	psi-mi:“MI:0914”(association)	0.350
TBC1D3G	ZRANB1	psi-mi:“MI:0915”(physical association)	0.000
TBC1D3G	MDFI	psi-mi:“MI:0915”(physical association)	0.000
BAG3	TBC1D3G	psi-mi:“MI:0915”(physical association)	0.000
PSMD2	TBC1D3G	psi-mi:“MI:0915”(physical association)	0.000
GRB2	TBC1D3G	psi-mi:“MI:0915”(physical association)	0.000
GEM	TBC1D3G	psi-mi:“MI:0915”(physical association)	0.000
BAG4	TBC1D3G	psi-mi:“MI:0915”(physical association)	0.000
GTPBP3	TBC1D3G	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (10): LOC101060321 (Two-hybrid), LOC101060321 (Two-hybrid), LOC101060321 (Two-hybrid), LOC101060321 (Two-hybrid), LOC101060321 (Two-hybrid), LOC101060321 (Two-hybrid), LOC101060321 (Two-hybrid), LOC101060321 (Two-hybrid), LOC101060321 (Negative Genetic), LOC101060321 (Negative Genetic)

ESM2 similar proteins: A0A087WVF3, A0A087WXS9, A0A087X179, A0A087X1G2, A6NDS4, A6NER0, A6QPT6, B9A6J9, M3WHG5, O14771, O15482, O15553, O19110, O76081, P0C7X1, P0C7X3, P0C7X4, P35125, P48778, P48967, P79209, Q13670, Q15697, Q2TBC4, Q3T191, Q3UZD7, Q4R2Z8, Q5DRQ5, Q5SSQ6, Q5XFX8, Q69ZB3, Q6DHY5, Q6IPX1, Q6ZMN8, Q8BLR5, Q8BWA8, Q8IYF1, Q8IZP1, Q8JZW5, Q8N7G0

Diamond homologs: A0A087WVF3, A0A087WXS9, A0A087X179, A0A087X1G2, A2AWA9, A6H6A9, A6NDS4, A6NER0, B9A6J9, H2KZZ6, P0C7X1, P35125, Q2M2D7, Q5RAN1, Q5SVR0, Q66K14, Q6DHY5, Q6IPX1, Q80XC3, Q86UD7, Q8IZP1, Q92738, Q9UFV1, Q9Y3P9, A3KGB4, A6QP29, B0R0W9, B7ZAP0, O60343, O60447, O95759, O97790, P58802, P97366, Q0IIM8, Q10496, Q12317, Q12344, Q28CB1, Q3UYK3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

3581 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:36330520:T:C	F207L	0.979
17:36330522:C:A	F207L	0.979
17:36330522:C:G	F207L	0.979
17:36332317:T:A	W286R	0.933
17:36332317:T:C	W286R	0.933
17:36328112:T:A	W111R	0.920
17:36328112:T:C	W111R	0.920
17:36327570:T:A	W78R	0.919
17:36327570:T:C	W78R	0.919
17:36327572:G:C	W78C	0.897
17:36327572:G:T	W78C	0.897
17:36330523:T:A	W208R	0.885
17:36330523:T:C	W208R	0.885
17:36328585:T:C	F159L	0.884
17:36328587:C:A	F159L	0.884
17:36328587:C:G	F159L	0.884
17:36330521:T:C	F207S	0.883
17:36327569:G:C	K77N	0.875
17:36327569:G:T	K77N	0.875
17:36328114:G:C	W111C	0.872
17:36328114:G:T	W111C	0.872
17:36328506:G:C	K132N	0.871
17:36328506:G:T	K132N	0.871
17:36328163:T:G	Y128D	0.862
17:36328164:A:C	Y128S	0.856
17:36330525:G:C	W208C	0.851
17:36330525:G:T	W208C	0.851
17:36327593:G:C	W85C	0.845
17:36327593:G:T	W85C	0.845
17:36332319:G:C	W286C	0.840

dbSNP variants (sampled 300 via entrez): RS1156281886 (17:36314978 T>C), RS1156387044 (17:36321661 T>C), RS1156476344 (17:36317939 C>T), RS1156573549 (17:36452051 AGCG>A), RS1156739599 (17:36326258 G>A), RS1156910969 (17:36323202 G>A), RS1157026296 (17:36452759 C>A), RS1157039151 (17:36327768 C>T), RS1157051932 (17:36332362 A>C), RS1157358423 (17:36333086 C>T), RS1157518568 (17:36330610 T>G), RS1157897020 (17:36452525 G>C,T), RS1157907490 (17:36326730 C>T), RS1157956010 (17:36332675 C>T), RS1158091702 (17:36258681 ACT>A)

Disease associations

OMIM: gene MIM:610810 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST005951_15	Body mass index	3.000000e-13
GCST009159_13	Blood protein levels	7.000000e-21

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004747	protein measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance	1
benzo(e)pyrene	decreases methylation	1
indeno(1,2,3-cd)pyrene	decreases expression	1
abrine	increases expression	1
Arsenic	increases abundance, decreases expression	1
Estradiol	affects cotreatment, decreases expression	1
Methapyrilene	decreases methylation	1
Smoke	decreases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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