TBC1D3I

Summary

TBC1D3I (TBC1 domain family member 3I, HGNC:32709) is a protein-coding gene on chromosome 17q12, encoding TBC1 domain family member 3I (A0A087WXS9). Acts as a GTPase activating protein for RAB5.

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

Source: NCBI Gene 102724862 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_001291463

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32709
Approved symbol	TBC1D3I
Name	TBC1 domain family member 3I
Location	17q12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000274933
Ensembl biotype	protein_coding
Entrez	102724862

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000616671, ENST00000618620, ENST00000621034

RefSeq mRNA: 1 — MANE Select: NM_001291463 NM_001291463

CCDS: CCDS74039

Canonical transcript exons

ENST00000618421 — 0 exons

Expression profiles

Bgee: expression breadth ubiquitous, 129 present calls, max score 79.78.

Top tissues by expression

134 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	79.78	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.46	gold quality
lower esophagus mucosa	UBERON:0035834	76.84	gold quality
left testis	UBERON:0004533	74.20	gold quality
testis	UBERON:0000473	73.68	gold quality
right testis	UBERON:0004534	72.95	gold quality
right uterine tube	UBERON:0001302	69.21	gold quality
granulocyte	CL:0000094	66.47	gold quality
esophagus mucosa	UBERON:0002469	66.08	gold quality
blood	UBERON:0000178	65.39	gold quality
stromal cell of endometrium	CL:0002255	65.34	gold quality
right hemisphere of cerebellum	UBERON:0014890	65.08	gold quality
cerebellum	UBERON:0002037	64.23	gold quality
cerebellar hemisphere	UBERON:0002245	64.07	gold quality
cerebellar cortex	UBERON:0002129	63.98	gold quality
adenohypophysis	UBERON:0002196	63.76	gold quality
vagina	UBERON:0000996	63.22	gold quality
pituitary gland	UBERON:0000007	62.93	gold quality
tonsil	UBERON:0002372	62.91	gold quality
mucosa of transverse colon	UBERON:0004991	62.76	gold quality
right lobe of liver	UBERON:0001114	62.60	gold quality
endocervix	UBERON:0000458	62.32	gold quality
esophagus	UBERON:0001043	62.06	gold quality
right adrenal gland	UBERON:0001233	62.00	gold quality
prostate gland	UBERON:0002367	61.97	gold quality
ectocervix	UBERON:0012249	61.85	gold quality
apex of heart	UBERON:0002098	61.69	gold quality
left adrenal gland	UBERON:0001234	61.47	gold quality
primary visual cortex	UBERON:0002436	61.44	gold quality
uterine cervix	UBERON:0000002	61.17	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.26

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

18 targeting TBC1D3I, 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

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 3I — A0A087WXS9 (reviewed: A0A087WXS9)

All UniProt accessions (2): A0A087WXS9, A0A0B4J2F4

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_001278392* (*=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 (7 total): 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-A0A087WXS9-F1	60.13	0.24

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, MIR335_3P, MIR5585_5P, 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

26 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TBC1D3I	TBC1D20	Q96BZ9	166
TBC1D3I	BBS9	P78514	164
TBC1D3I	TBC1D22A	Q8WUA7	133
TBC1D3I	TBC1D22B	Q9NU19	133
TBC1D3I	ALG3	Q92685	109
TBC1D3I	SARAF	Q96BY9	72
TBC1D3I	BIN3	Q9NQY0	72
TBC1D3I	BIN1	O00499	72
TBC1D3I	AMPH	P49418	72
TBC1D3I	BIN2	Q9UBW5	72
TBC1D3I	GPR32	O75388	0
TBC1D3I	ERVFRD-1	P60508	0
TBC1D3I	CCDC7	Q96M83	0

IntAct

0 interactions, top by confidence:

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): RS1156397786 (17:36264585 G>A), RS1158091702 (17:36258681 ACT>A), RS1158209801 (17:36254460 G>A), RS1158468433 (17:36260292 G>A), RS1158805655 (17:36253901 G>A,C), RS1158900733 (17:36258537 G>A), RS1158918147 (17:36257543 G>A), RS1158994273 (17:36257041 G>A), RS1159334106 (17:36254473 A>C), RS1159685156 (17:36258120 GC>G), RS1159928007 (17:36265384 A>G), RS1160083215 (17:36262117 C>T), RS1160665676 (17:36264679 G>T), RS1160830360 (17:36260508 G>T), RS1161516484 (17:36262018 ATGGGCTTCTGGC>A)

Disease associations

OMIM: gene `` | 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

3 total (human), top 3 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	increases expression	1
Smoke	decreases expression	1
S-Nitrosoglutathione	increases expression	1

Clinical trials (associated diseases)

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