TBC1D3D

Summary

TBC1D3D (TBC1 domain family member 3D, HGNC:28944) is a protein-coding gene on chromosome 17q12, encoding TBC1 domain family member 3D (A0A087WVF3). Acts as a GTPase activating protein for RAB5.

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

Source: NCBI Gene 101060389 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_001291465

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28944
Approved symbol	TBC1D3D
Name	TBC1 domain family member 3D
Location	17q12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000274419
Ensembl biotype	protein_coding
OMIM	610807
Entrez	101060389

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000616101, ENST00000886872

RefSeq mRNA: 1 — MANE Select: NM_001291465 NM_001291465

CCDS: CCDS74044

Canonical transcript exons

ENST00000616101 — 14 exons

Exon	Start	End
ENSE00003713821	38007686	38007766
ENSE00003719170	38011910	38011975
ENSE00003721075	38008210	38008317
ENSE00003721446	38005795	38005880
ENSE00003725034	38008647	38008756
ENSE00003727777	38005560	38005632
ENSE00003730655	38012909	38013061
ENSE00003734255	38010597	38010717
ENSE00003741666	38012439	38012538
ENSE00003746622	38003976	38004131
ENSE00003751231	38010005	38010053
ENSE00003751942	38007164	38007203
ENSE00003752305	38011431	38011525
ENSE00003978342	38014025	38014908

Expression profiles

Bgee: expression breadth ubiquitous, 127 present calls, max score 98.50.

Top tissues by expression

133 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	98.50	gold quality
mucosa of stomach	UBERON:0001199	81.60	gold quality
granulocyte	CL:0000094	70.63	gold quality
superior frontal gyrus	UBERON:0002661	69.11	gold quality
sural nerve	UBERON:0015488	67.10	gold quality
right adrenal gland	UBERON:0001233	65.12	gold quality
adenohypophysis	UBERON:0002196	62.62	gold quality
stromal cell of endometrium	CL:0002255	61.87	gold quality
right ovary	UBERON:0002118	61.23	gold quality
cerebellar cortex	UBERON:0002129	60.73	gold quality
cerebellum	UBERON:0002037	60.43	gold quality
skin of abdomen	UBERON:0001416	60.22	gold quality
apex of heart	UBERON:0002098	60.19	gold quality
right hemisphere of cerebellum	UBERON:0014890	60.13	gold quality
cerebellar hemisphere	UBERON:0002245	59.94	gold quality
zone of skin	UBERON:0000014	59.91	gold quality
skin of leg	UBERON:0001511	59.77	gold quality
right adrenal gland cortex	UBERON:0035827	58.17	gold quality
hindlimb stylopod muscle	UBERON:0004252	58.01	gold quality
left adrenal gland	UBERON:0001234	57.96	gold quality
esophagus mucosa	UBERON:0002469	57.87	gold quality
ectocervix	UBERON:0012249	57.86	gold quality
primary visual cortex	UBERON:0002436	57.62	gold quality
cortex of kidney	UBERON:0001225	57.56	gold quality
minor salivary gland	UBERON:0001830	57.17	gold quality
fundus of stomach	UBERON:0001160	57.08	gold quality
vagina	UBERON:0000996	57.03	gold quality
small intestine Peyer’s patch	UBERON:0003454	56.47	gold quality
prostate gland	UBERON:0002367	56.40	gold quality
left testis	UBERON:0004533	56.05	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.58

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

17 targeting TBC1D3D, 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-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-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), TBC1D3L (ENSG00000274512), TBC1D3 (ENSG00000274611)

Protein

Protein identifiers

TBC1 domain family member 3D — A0A087WVF3 (reviewed: A0A087WVF3)

All UniProt accessions (1): A0A087WVF3

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_001278394* (*=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-A0A087WVF3-F1	60.43	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: 9 (showing top): GOMF_ENZYME_ACTIVATOR_ACTIVITY, GOMF_NUCLEOSIDE_TRIPHOSPHATASE_REGULATOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY, MIR335_3P, MIR5585_5P, chr17q12, GOMF_MOLECULAR_FUNCTION_ACTIVATOR_ACTIVITY, 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

192 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TBC1D3D	OR4X2	Q8NGF9	573
TBC1D3D	KRTAP2-2	Q9BYT5	478
TBC1D3D	ZNHIT3	Q15649	448
TBC1D3D	ERLN	P0DI80	444
TBC1D3D	C17orf50	Q8WW18	432
TBC1D3D	SCGB1C2	P0DMR2	419
TBC1D3D	KRTAP9-7	A8MTY7	416
TBC1D3D	GEMIN8	Q9NWZ8	392
TBC1D3D	MTRNR2L1	P0CJ68	390
TBC1D3D	TBC1D23	Q9NUY8	389
TBC1D3D	CDRT15L2	A8MXV6	380
TBC1D3D	ADGRG4	Q8IZF6	350
TBC1D3D	SYNRG	Q9UMZ2	345
TBC1D3D	SLC6A18	Q96N87	342
TBC1D3D	CFAP97D1	B2RV13	338

IntAct

2 interactions, top by confidence:

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

BioGRID (3): LOC101060389 (Negative Genetic), LOC101060389 (Negative Genetic), LOC101060389 (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

3577 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:38010669:T:C	F207L	0.980
17:38010671:C:A	F207L	0.980
17:38010671:C:G	F207L	0.980
17:38012466:T:A	W286R	0.910
17:38012466:T:C	W286R	0.910
17:38008261:T:A	W111R	0.909
17:38008261:T:C	W111R	0.909
17:38008655:G:C	K132N	0.908
17:38008655:G:T	K132N	0.908
17:38007719:T:A	W78R	0.905
17:38007719:T:C	W78R	0.905
17:38008734:T:C	F159L	0.898
17:38008736:C:A	F159L	0.898
17:38008736:C:G	F159L	0.898
17:38007721:G:C	W78C	0.880
17:38007721:G:T	W78C	0.880
17:38010670:T:C	F207S	0.878
17:38010672:T:A	W208R	0.877
17:38010672:T:C	W208R	0.877
17:38010674:G:C	W208C	0.877
17:38010674:G:T	W208C	0.877
17:38010666:G:C	A206P	0.872
17:38008263:G:C	W111C	0.871
17:38008263:G:T	W111C	0.871
17:38007718:G:C	K77N	0.861
17:38007718:G:T	K77N	0.861
17:38007742:G:C	W85C	0.847
17:38007742:G:T	W85C	0.847
17:38008313:A:C	Y128S	0.840
17:38010667:C:A	A206E	0.838

dbSNP variants (sampled 300 via entrez): RS1159177292 (17:38014394 C>A), RS1161170712 (17:38014666 G>A,C), RS1166355511 (17:38012819 C>T), RS1166378746 (17:38013533 G>A), RS1167072337 (17:38014632 T>G), RS1171636188 (17:38013895 T>A), RS1172907781 (17:38012824 C>A), RS1173958132 (17:38015146 A>G), RS1178504761 (17:38014859 G>C), RS1182084779 (17:38015165 G>A), RS1182117084 (17:38015227 C>T), RS1182841057 (17:38013926 A>G), RS1186272759 (17:38012847 G>A,T), RS1187132172 (17:38014462 G>A), RS1187927088 (17:38012723 G>A)

Disease associations

OMIM: gene MIM:610807 | 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

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	decreases expression, affects cotreatment	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
perfluorooctanoic acid	affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	decreases expression, affects cotreatment	1
abrine	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	affects cotreatment, decreases expression	1
perfluorobutanesulfonic acid	decreases expression, affects cotreatment	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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