TBC1D3E

Summary

TBC1D3E (TBC1 domain family member 3E, HGNC:27071) is a protein-coding gene on chromosome 17q12, encoding TBC1 domain family member 3E (A0A087X179). Acts as a GTPase activating protein for RAB5.

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

Source: NCBI Gene 102723859 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_001291466

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27071
Approved symbol	TBC1D3E
Name	TBC1 domain family member 3E
Location	17q12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000278599
Ensembl biotype	protein_coding
OMIM	610808
Entrez	102723859

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000621587

RefSeq mRNA: 1 — MANE Select: NM_001291466 NM_001291466

CCDS: CCDS77009

Canonical transcript exons

ENST00000618095 — 0 exons

Expression profiles

Bgee: expression breadth ubiquitous, 102 present calls, max score 76.89.

Top tissues by expression

129 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	76.89	gold quality
mucosa of stomach	UBERON:0001199	75.31	gold quality
bone marrow cell	CL:0002092	44.38	gold quality
gall bladder	UBERON:0002110	44.32	gold quality
bone marrow	UBERON:0002371	42.06	gold quality
tonsil	UBERON:0002372	40.91	silver quality
fundus of stomach	UBERON:0001160	40.64	gold quality
blood	UBERON:0000178	38.98	gold quality
ganglionic eminence	UBERON:0004023	37.70	silver quality
lymph node	UBERON:0000029	37.49	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
mucosa of transverse colon	UBERON:0004991	36.06	gold quality
left testis	UBERON:0004533	35.47	gold quality
testis	UBERON:0000473	35.18	gold quality
right uterine tube	UBERON:0001302	33.55	gold quality
adult mammalian kidney	UBERON:0000082	33.50	gold quality
liver	UBERON:0002107	33.03	gold quality
right hemisphere of cerebellum	UBERON:0014890	32.40	gold quality
cerebellar hemisphere	UBERON:0002245	32.15	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
cerebellar cortex	UBERON:0002129	32.07	gold quality
cerebellum	UBERON:0002037	32.06	gold quality
urinary bladder	UBERON:0001255	32.04	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
prefrontal cortex	UBERON:0000451	30.78	gold quality
muscle of leg	UBERON:0001383	30.67	gold quality
left uterine tube	UBERON:0001303	30.62	gold quality
kidney	UBERON:0002113	30.23	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.65

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

19 targeting TBC1D3E, 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), TBC1D3G (ENSG00000260287), TBC1D3K (ENSG00000273513), TBC1D3H (ENSG00000274226), TBC1D3D (ENSG00000274419), TBC1D3L (ENSG00000274512)

Protein

Protein identifiers

TBC1 domain family member 3E — A0A087X179 (reviewed: A0A087X179)

All UniProt accessions (1): A0A087X179

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.

Tissue specificity. Expressed in pancreas, thymus and testis.

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_001278395* (*=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 (6 total): lipid moiety-binding region 2, chain 1, domain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A0A087X179-F1	60.44	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: 8 (showing top): GOMF_ENZYME_ACTIVATOR_ACTIVITY, GOMF_NUCLEOSIDE_TRIPHOSPHATASE_REGULATOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY, chr17q12, GOMF_MOLECULAR_FUNCTION_ACTIVATOR_ACTIVITY, WP_17Q12_COPY_NUMBER_VARIATION_SYNDROME, GOCC_ENDOSOME, GOMF_GTPASE_ACTIVATOR_ACTIVITY

GO Biological Process (0):

GO Molecular Function (1): GTPase activator activity (GO:0005096)

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
endomembrane system	1
cytoplasmic vesicle	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

10 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TBC1D3E	ADHFE1	Q8IWW8	322
TBC1D3E	RDH5	Q92781	270
TBC1D3E	GPR32	O75388	0
TBC1D3E	ERVFRD-1	P60508	0
TBC1D3E	CCDC7	Q96M83	0

IntAct

2 interactions, top by confidence:

A	B	Type	Score
M		psi-mi:“MI:0914”(association)	0.350

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

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS111549784 (17:38124224 T>A), RS111638343 (17:38123005 A>C,G,T), RS111660355 (17:38125216 T>G), RS112933293 (17:38122554 A>G), RS11550750 (17:38132229 T>A), RS1156353835 (17:38135058 G>A), RS1156489671 (17:38135111 C>T), RS1156720073 (17:38136860 C>T), RS1156855602 (17:38126674 C>G,T), RS1157054282 (17:38123793 G>T), RS1157167244 (17:38133541 G>A), RS1157458146 (17:38127888 C>A), RS1157772065 (17:38133879 T>G), RS1157789417 (17:38124503 A>G), RS1157853376 (17:38128463 A>G)

Disease associations

OMIM: gene MIM:610808 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

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

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
triphenyl phosphate	affects expression	1
2-methyl-4-isothiazolin-3-one	decreases expression	1
sodium arsenite	decreases expression, increases abundance	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
di-n-butylphosphoric acid	affects expression	1
abrine	increases expression	1
bisphenol S	increases expression	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Methapyrilene	increases methylation	1
Smoke	decreases expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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