TBC1D3B

Summary

TBC1D3B (TBC1 domain family member 3B, HGNC:27011) is a protein-coding gene on chromosome 17q12, encoding TBC1 domain family member 3B (A6NDS4). Acts as a GTPase activating protein for RAB5.

This gene encodes a protein that is similar to TBC1 domain family, member 3. This protein contains a TBC (Tre-2, Bub2p, and Cdc16p) domain, which is found in proteins involved in RAB GTPase signaling and vesicle trafficking. There are multiple copies of this gene located within a cluster of chemokine genes on chromosome 17q.

Source: NCBI Gene 414059 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 13 total
• MANE Select transcript: NM_001001417

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27011
Approved symbol	TBC1D3B
Name	TBC1 domain family member 3B
Location	17q12
Locus type	gene with protein product
Status	Approved
Aliases	PRC17
Ensembl gene	ENSG00000274808
Ensembl biotype	protein_coding
OMIM	610144
Entrez	414059

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000610580, ENST00000611257, ENST00000616006, ENST00000622280

RefSeq mRNA: 1 — MANE Select: NM_001001417 NM_001001417

CCDS: CCDS42300

Canonical transcript exons

ENST00000611257 — 14 exons

Exon	Start	End
ENSE00003714371	36167544	36167696
ENSE00003719657	36172845	36172925
ENSE00003722621	36174731	36174816
ENSE00003725969	36168067	36168166
ENSE00003731394	36168630	36168695
ENSE00003731999	36165683	36166563
ENSE00003732139	36174979	36175051
ENSE00003736903	36176480	36176636
ENSE00003737259	36173408	36173447
ENSE00003741862	36169080	36169174
ENSE00003752013	36169891	36170011
ENSE00003754257	36170555	36170603
ENSE00003754753	36171855	36171964
ENSE00003788875	36172294	36172401

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 90.83.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	90.83	gold quality
cerebellar hemisphere	UBERON:0002245	90.19	gold quality
cerebellar cortex	UBERON:0002129	90.09	gold quality
cerebellum	UBERON:0002037	90.01	gold quality
left testis	UBERON:0004533	89.89	gold quality
right testis	UBERON:0004534	89.48	gold quality
right uterine tube	UBERON:0001302	89.40	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.22	gold quality
testis	UBERON:0000473	89.07	gold quality
skin of leg	UBERON:0001511	87.97	gold quality
lower esophagus mucosa	UBERON:0035834	87.70	gold quality
zone of skin	UBERON:0000014	87.37	gold quality
skin of abdomen	UBERON:0001416	86.66	gold quality
pituitary gland	UBERON:0000007	86.50	gold quality
esophagus mucosa	UBERON:0002469	86.48	gold quality
metanephros cortex	UBERON:0010533	86.45	gold quality
vagina	UBERON:0000996	86.42	gold quality
right frontal lobe	UBERON:0002810	85.74	gold quality
right adrenal gland cortex	UBERON:0035827	85.50	gold quality
right adrenal gland	UBERON:0001233	85.17	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.45	gold quality
left adrenal gland	UBERON:0001234	84.20	gold quality
left adrenal gland cortex	UBERON:0035825	84.16	gold quality
blood	UBERON:0000178	84.06	gold quality
esophagus	UBERON:0001043	83.89	gold quality
adenohypophysis	UBERON:0002196	83.82	gold quality
prostate gland	UBERON:0002367	83.82	gold quality
minor salivary gland	UBERON:0001830	83.59	gold quality
mucosa of stomach	UBERON:0001199	83.33	gold quality
ectocervix	UBERON:0012249	83.20	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.78

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

18 targeting TBC1D3B, 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-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-12130	99.75	65.47	452
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-8054	99.48	70.81	2084
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-6895-3P	98.79	65.69	996
HSA-MIR-7155-5P	98.65	66.14	1290
HSA-MIR-6812-5P	97.56	65.39	1059
HSA-MIR-424-3P	97.20	65.86	385
HSA-MIR-101-5P	96.84	65.66	649
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 3B — A6NDS4 (reviewed: A6NDS4)

All UniProt accessions (3): A0A087WU82, A0A087WVG1, A6NDS4

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_001001417* (*=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 (9 total): sequence conflict 3, 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-A6NDS4-F1	60.26	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: 17 (showing top): MIDORIKAWA_AMPLIFIED_IN_LIVER_CANCER, 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, MIR335_3P, MIR12123, MIR548AV_5P_MIR548K, MIR8054, MIR5585_5P, chr17q12, HOEK_NEUTROPHIL_2011_2012_TIV_ADULT_1DY_DN, GOMF_MOLECULAR_FUNCTION_ACTIVATOR_ACTIVITY, WP_17Q12_COPY_NUMBER_VARIATION_SYNDROME

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

270 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TBC1D3B	USP32	Q8NFA0	747
TBC1D3B	CDRT15L2	A8MXV6	570
TBC1D3B	TBC1D22B	Q9NU19	530
TBC1D3B	CCDC144A	A2RUR9	452
TBC1D3B	SLC35G3	Q8N808	447
TBC1D3B	SLC35G6	P0C7Q6	447
TBC1D3B	SGSM2	O43147	433
TBC1D3B	SPDYE4	A6NLX3	432
TBC1D3B	OR3A2	P47893	432
TBC1D3B	CHCT1	Q86WR6	419
TBC1D3B	TBC1D21	Q8IYX1	419
TBC1D3B	RAB5A	P20339	418
TBC1D3B	LRRC3C	A6NJW4	398
TBC1D3B	KRTAP2-2	Q9BYT5	398
TBC1D3B	FBXW10B	O95170	396

IntAct

3 interactions, top by confidence:

A	B	Type	Score
TBC1D3B	WDR83	psi-mi:“MI:0915”(physical association)	0.400
TBC1D3B	HSPB1	psi-mi:“MI:0915”(physical association)	0.370

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	4
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

4811 predictions. Top by Δscore:

Variant	Effect	Δscore
17:36166561:TGG:T	acceptor_gain	1.0000
17:36168065:A:AC	donor_gain	1.0000
17:36168066:C:CC	donor_gain	1.0000
17:36168066:CT:C	donor_gain	1.0000
17:36168066:CTCTG:C	donor_gain	1.0000
17:36171853:A:AC	donor_gain	1.0000
17:36171854:C:CC	donor_gain	1.0000
17:36172402:C:CC	acceptor_gain	1.0000
17:36256006:A:AC	donor_gain	1.0000
17:36256007:C:CC	donor_gain	1.0000
17:36256007:CT:C	donor_gain	1.0000
17:36256007:CTCTG:C	donor_gain	1.0000
17:36260337:C:CC	acceptor_gain	1.0000
17:36166559:TTTGG:T	acceptor_gain	0.9900
17:36166560:TTGG:T	acceptor_gain	0.9900
17:36166562:GG:G	acceptor_gain	0.9900
17:36166564:C:CC	acceptor_gain	0.9900
17:36168060:GACTT:G	donor_loss	0.9900
17:36168061:ACTTA:A	donor_loss	0.9900
17:36168062:CTTA:C	donor_loss	0.9900
17:36168063:TT:T	donor_loss	0.9900
17:36168064:TA:T	donor_loss	0.9900
17:36168066:C:CA	donor_loss	0.9900
17:36168163:AGATC:A	acceptor_loss	0.9900
17:36168164:GATC:G	acceptor_loss	0.9900
17:36168165:ATC:A	acceptor_loss	0.9900
17:36168165:ATCT:A	acceptor_loss	0.9900
17:36168166:TC:T	acceptor_loss	0.9900
17:36168166:TCTG:T	acceptor_loss	0.9900
17:36168167:C:A	acceptor_loss	0.9900

AlphaMissense

3582 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:36169937:G:C	F207L	0.981
17:36169937:G:T	F207L	0.981
17:36169939:A:G	F207L	0.981
17:36172892:A:G	W78R	0.945
17:36172892:A:T	W78R	0.945
17:36172350:A:G	W111R	0.944
17:36172350:A:T	W111R	0.944
17:36168139:A:G	W286R	0.931
17:36168139:A:T	W286R	0.931
17:36172890:C:A	W78C	0.922
17:36172890:C:G	W78C	0.922
17:36169938:A:G	F207S	0.905
17:36169936:A:G	W208R	0.901
17:36169936:A:T	W208R	0.901
17:36172348:C:A	W111C	0.900
17:36172348:C:G	W111C	0.900
17:36172893:C:A	K77N	0.896
17:36172893:C:G	K77N	0.896
17:36171875:G:C	F159L	0.887
17:36171875:G:T	F159L	0.887
17:36171877:A:G	F159L	0.887
17:36169934:C:A	W208C	0.873
17:36169934:C:G	W208C	0.873
17:36168136:C:G	D287H	0.869
17:36171956:C:A	K132N	0.867
17:36171956:C:G	K132N	0.867
17:36169942:C:G	A206P	0.866
17:36172391:C:G	R97P	0.856
17:36172869:C:A	W85C	0.849
17:36172869:C:G	W85C	0.849

dbSNP variants (sampled 300 via entrez): RS1000026591 (17:36165942 G>A), RS1003582909 (17:36171565 T>C), RS1005516113 (17:36177457 A>G), RS1012715465 (17:36171415 G>A,C), RS1017007022 (17:36172458 A>G,T), RS1024204657 (17:36167399 T>C), RS1024651833 (17:36171450 C>A,T), RS1025630293 (17:36171691 C>T), RS1029818742 (17:36178150 G>A,C), RS1032925980 (17:36165378 G>C), RS1039398197 (17:36165665 G>A,T), RS1041363119 (17:36171161 T>A,C), RS1041450170 (17:36165729 C>T), RS1045564809 (17:36176576 C>G,T), RS1054104445 (17:36171240 C>A,G,T)

Disease associations

OMIM: gene MIM:610144 | 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
GCST006291_70	Spherical equivalent or myopia (age of diagnosis)	4.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004847	age at onset

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression	2
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	decreases expression	1
pentanal	decreases expression	1
Cadmium	decreases expression	1
Folic Acid	decreases expression	1
Smoke	decreases expression	1
Valproic Acid	increases methylation	1
Cyclosporine	increases expression	1
Aflatoxin B1	increases expression	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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