TBC1D16

Summary

TBC1D16 (TBC1 domain family member 16, HGNC:28356) is a protein-coding gene on chromosome 17q25.3, encoding TBC1 domain family member 16 (Q8TBP0). May act as a GTPase-activating protein for Rab family protein(s).

Enables GTPase activator activity. Involved in regulation of receptor recycling. Located in cytosol and early endosome.

Source: NCBI Gene 125058 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 174 total
• MANE Select transcript: NM_019020

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28356
Approved symbol	TBC1D16
Name	TBC1 domain family member 16
Location	17q25.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC25062, FLJ20748
Ensembl gene	ENSG00000167291
Ensembl biotype	protein_coding
OMIM	616637
Entrez	125058

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 27 protein_coding

ENST00000310924, ENST00000340848, ENST00000570373, ENST00000571872, ENST00000572862, ENST00000573782, ENST00000574241, ENST00000574427, ENST00000576768, ENST00000910404, ENST00000910405, ENST00000910406, ENST00000910407, ENST00000926252, ENST00000926253, ENST00000926254, ENST00000926255, ENST00000926256, ENST00000926257, ENST00000926258, ENST00000926259, ENST00000926260, ENST00000926261, ENST00000926262, ENST00000926263, ENST00000926264, ENST00000968563

RefSeq mRNA: 4 — MANE Select: NM_019020 NM_001271844, NM_001271845, NM_001271846, NM_019020

CCDS: CCDS11766, CCDS62351, CCDS62352, CCDS62353

Canonical transcript exons

ENST00000310924 — 12 exons

Exon	Start	End
ENSE00001111799	79948872	79949006
ENSE00001111800	79949717	79949865
ENSE00001111801	79950411	79950578
ENSE00001193121	79951450	79951597
ENSE00001226499	80010160	80010757
ENSE00001382516	80013367	80013609
ENSE00001390504	80035795	80035872
ENSE00001657540	79942060	79942206
ENSE00001774443	79944908	79945087
ENSE00002645055	79932343	79941107
ENSE00003596281	79952657	79952818
ENSE00003784957	79947645	79947831

Expression profiles

Bgee: expression breadth ubiquitous, 267 present calls, max score 96.78.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.3402 / max 299.1940, expressed in 1705 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
168600	19.7001	1677
168587	0.7212	83
168596	0.3207	127
168592	0.1064	33
168597	0.0970	34
168589	0.0801	32
168588	0.0744	27
168591	0.0646	26
168590	0.0611	14
168594	0.0459	23

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	96.78	gold quality
stromal cell of endometrium	CL:0002255	93.61	gold quality
colonic epithelium	UBERON:0000397	93.24	gold quality
renal medulla	UBERON:0000362	93.02	gold quality
tendon of biceps brachii	UBERON:0008188	92.66	gold quality
decidua	UBERON:0002450	92.12	gold quality
adrenal tissue	UBERON:0018303	90.69	gold quality
adipose tissue	UBERON:0001013	89.53	gold quality
metanephros cortex	UBERON:0010533	89.29	gold quality
subcutaneous adipose tissue	UBERON:0002190	89.18	gold quality
connective tissue	UBERON:0002384	88.97	gold quality
ganglionic eminence	UBERON:0004023	88.84	gold quality
thoracic mammary gland	UBERON:0005200	88.51	gold quality
mammary gland	UBERON:0001911	88.47	gold quality
mammary duct	UBERON:0001765	88.32	gold quality
epithelium of mammary gland	UBERON:0003244	88.03	gold quality
lateral nuclear group of thalamus	UBERON:0002736	87.83	gold quality
cortical plate	UBERON:0005343	87.65	gold quality
sural nerve	UBERON:0015488	87.57	gold quality
ventricular zone	UBERON:0003053	87.17	gold quality
right hemisphere of cerebellum	UBERON:0014890	87.10	gold quality
pericardium	UBERON:0002407	86.69	gold quality
cerebellar hemisphere	UBERON:0002245	86.66	gold quality
cerebellum	UBERON:0002037	86.65	gold quality
cerebellar cortex	UBERON:0002129	86.64	gold quality
layer of synovial tissue	UBERON:0007616	86.51	gold quality
tibia	UBERON:0000979	86.29	gold quality
embryo	UBERON:0000922	86.12	gold quality
adipose tissue of abdominal region	UBERON:0007808	85.95	gold quality
nucleus accumbens	UBERON:0001882	85.58	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.21
E-GEOD-137537	yes	5.26

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1

miRNA regulators (miRDB)

315 targeting TBC1D16, 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-6867-5P	100.00	82.21	3464
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-1236-3P	99.94	68.04	1695

Literature-anchored findings (GeneRIF, showing 8)

• TBC1D16 and RAB27A, were identified known drivers of melanoma both are involved in the regulation of vesicular trafficking, which highlights this process as important for proliferation in melanoma. (PMID:21129771)
• TBC1D16 is a GTPase activating protein for Rab4A that regulates transferrin receptor recycling and EGFR trafficking and signaling. (PMID:23019362)
• RAB5C is identified as a new TBC1D16 target and showed that it regulates EGFR in melanoma cells. (PMID:26030178)
• Bipolar disorder participants with a history of Suicidal behavior showed less overall methylation in the intron 3 of TRE2/BUB2/CDC16 domain family member 16 (TBC1D16). (PMID:28276657)
• TBC1D16 is a predictive marker for favorable prognosis of Epithelial ovarian cancer. (PMID:29962380)
• Findings suggest characteristic DNA methylation changes in TBC1D16 is relatively common tumor-associated epigenetic events in multiple tumor types, which is consistent with a potential role as more general drivers of tumor progression. (PMID:31383000)
• TBC1D16 predicts chemosensitivity and prognosis in adult acute myeloid leukemia (AML) patients. (PMID:33476656)
• Novel Host Protein TBC1D16, a GTPase Activating Protein of Rab5C, Inhibits Prototype Foamy Virus Replication. (PMID:34367131)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tbc1d16	ENSDARG00000036994
mus_musculus	Tbc1d16	ENSMUSG00000039976
rattus_norvegicus	Tbc1d16	ENSRNOG00000049758
drosophila_melanogaster	TBC1D16	FBGN0032249
caenorhabditis_elegans		WBGENE00018639

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), TBC1D10B (ENSG00000169221), TBC1D10C (ENSG00000175463), TBC1D28 (ENSG00000189375), TBC1D9B (ENSG00000197226), TBC1D8 (ENSG00000204634), TBC1D26 (ENSG00000214946), TBC1D3G (ENSG00000260287), TBC1D3K (ENSG00000273513), TBC1D3H (ENSG00000274226), TBC1D3D (ENSG00000274419), TBC1D3L (ENSG00000274512), TBC1D3 (ENSG00000274611)

Protein

Protein identifiers

TBC1 domain family member 16 — Q8TBP0 (reviewed: Q8TBP0)

All UniProt accessions (6): Q8TBP0, I3L0U9, I3L0V9, I3L235, I3L4T6, I3L4U4

UniProt curated annotations — full annotation on UniProt →

Function. May act as a GTPase-activating protein for Rab family protein(s).

Isoforms (4)

UniProt ID	Names	Canonical?
Q8TBP0-1	1	yes
Q8TBP0-2	2
Q8TBP0-3	3
Q8TBP0-4	4

RefSeq proteins (4): NP_001258773, NP_001258774, NP_001258775, NP_061893* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF00566

UniProt features (15 total): splice variant 6, region of interest 3, compositionally biased region 3, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TBP0-F1	70.14	0.35

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-8854214	TBC/RABGAPs
R-HSA-199991	Membrane Trafficking
R-HSA-5653656	Vesicle-mediated transport
R-HSA-9007101	Rab regulation of trafficking

MSigDB gene sets: 206 (showing top): ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, REACTOME_MEMBRANE_TRAFFICKING, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, EFC_Q6, ZHAN_MULTIPLE_MYELOMA_CD1_UP, CEBP_Q2, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, ONKEN_UVEAL_MELANOMA_UP, GOBP_CILIUM_ORGANIZATION, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, GOBP_RECEPTOR_METABOLIC_PROCESS, GOBP_ORGANELLE_ASSEMBLY, CYTAGCAAY_UNKNOWN, GOBP_REGULATION_OF_CILIUM_ASSEMBLY, RFX1_02

GO Biological Process (1): regulation of receptor recycling (GO:0001919)

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

GO Cellular Component (2): early endosome (GO:0005769), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Rab regulation of trafficking	1
Vesicle-mediated transport	1
Membrane Trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
receptor recycling	1
regulation of signaling	1
regulation of macromolecule metabolic process	1
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
binding	1
endosome	1
cytoplasm	1
cellular anatomical structure	1

Protein interactions and networks

STRING

680 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TBC1D16	RAB4A	P20338	576
TBC1D16	TBC1D20	Q96BZ9	553
TBC1D16	TBC1D23	Q9NUY8	535
TBC1D16	CDC16	Q13042	509
TBC1D16	TBC1D1	Q86TI0	487
TBC1D16	TBC1D8	O95759	476
TBC1D16	TBC1D19	Q8N5T2	473
TBC1D16	TBC1D7	Q9P0N9	460
TBC1D16	CARD14	Q9BXL6	443
TBC1D16	PPM1L	Q5SGD2	434
TBC1D16	TBC1D10C	Q8IV04	427
TBC1D16	FAM174B	Q3ZCQ3	425
TBC1D16	DGKE	P52429	415
TBC1D16	EVI5	O60447	413
TBC1D16	WDR64	B1ANS9	399

IntAct

7 interactions, top by confidence:

A	B	Type	Score
TBC1D16	NOTCH2NLA	psi-mi:“MI:0915”(physical association)	0.370
HDAC6	GLOD5	psi-mi:“MI:0914”(association)	0.350
TBC1D16	CTSC	psi-mi:“MI:0914”(association)	0.350
Cxxc5	TNRC18	psi-mi:“MI:0914”(association)	0.350
Eif3e	RPSA	psi-mi:“MI:0914”(association)	0.350

BioGRID (32): TBC1D16 (Two-hybrid), TBC1D16 (Two-hybrid), TBC1D16 (Two-hybrid), TBC1D16 (Two-hybrid), TBC1D16 (Two-hybrid), TBC1D16 (Two-hybrid), TBC1D16 (Two-hybrid), TBC1D16 (Two-hybrid), KRT40 (Two-hybrid), KRTAP10-9 (Two-hybrid), KRTAP10-5 (Two-hybrid), KRTAP10-8 (Two-hybrid), NOTCH2NL (Two-hybrid), TBC1D16 (Affinity Capture-RNA), TBC1D16 (Affinity Capture-RNA)

ESM2 similar proteins: A2A690, A2AWP8, A2RRU4, F1LQY6, F1LTE0, F1LXF1, O88842, O94827, O95267, P11274, P49797, Q0P5I0, Q14161, Q14CM0, Q29RM4, Q3B7L5, Q3UHE1, Q5JSP0, Q5R5M3, Q5R5T1, Q5T6S3, Q5XIS9, Q66H91, Q66T02, Q68FF6, Q6PAJ1, Q6RFZ7, Q6ZN54, Q6ZPY2, Q6ZR37, Q76JQ2, Q7Z6G3, Q80YA9, Q8BZ03, Q8R1S4, Q8TBP0, Q8TCU6, Q8WXI2, Q91ZP9, Q96JH8

Diamond homologs: A1A5B6, O43147, P09379, P48365, Q2NKQ1, Q3MII6, Q6FWI1, Q80U12, Q8BPQ7, Q8BYH7, Q8TBP0, Q8TC07, Q94BY9, Q9CXF4, Q9HA65, Q9UUH7, I2HAA0, Q09830, Q6BU76, A6H8I2, O95759, P48566, P53258, P87234, Q12317, Q28CB1, Q3UYK3, Q4QQU7, Q5SVR0, Q5TC63, Q66K14, Q6GL87, Q6GLZ0, Q6P6R7, Q6PBU5, Q6ZT07, Q7T2D0, Q8C9V1, Q8VCZ6, Q96HU1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	144
Likely benign	9
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

3746 predictions. Top by Δscore:

Variant	Effect	Δscore
17:79942054:CCTCA:C	donor_loss	1.0000
17:79942055:CTCA:C	donor_loss	1.0000
17:79942056:TCACC:T	donor_loss	1.0000
17:79942057:CACCT:C	donor_loss	1.0000
17:79942058:A:AT	donor_loss	1.0000
17:79942058:ACCTT:A	donor_gain	1.0000
17:79942059:C:A	donor_loss	1.0000
17:79942059:CCTTC:C	donor_gain	1.0000
17:79942062:T:A	donor_gain	1.0000
17:79942203:CCGT:C	acceptor_gain	1.0000
17:79942204:CGTC:C	acceptor_gain	1.0000
17:79947639:CCTCA:C	donor_loss	1.0000
17:79947640:CTCAC:C	donor_loss	1.0000
17:79947641:TCA:T	donor_loss	1.0000
17:79947642:CA:C	donor_loss	1.0000
17:79947643:A:AC	donor_gain	1.0000
17:79947643:ACC:A	donor_loss	1.0000
17:79947644:C:CC	donor_gain	1.0000
17:79947827:TCCTC:T	acceptor_gain	1.0000
17:79947828:CCTCC:C	acceptor_gain	1.0000
17:79947833:T:C	acceptor_loss	1.0000
17:79947841:G:T	acceptor_gain	1.0000
17:79948676:C:A	donor_gain	1.0000
17:79949711:GGTTA:G	donor_loss	1.0000
17:79949712:GTTA:G	donor_loss	1.0000
17:79949713:TTA:T	donor_loss	1.0000
17:79949714:TACC:T	donor_loss	1.0000
17:79949715:ACCT:A	donor_loss	1.0000
17:79949716:C:CG	donor_loss	1.0000
17:79949850:C:CT	acceptor_gain	1.0000

AlphaMissense

5016 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:79949820:A:G	W435R	1.000
17:79949820:A:T	W435R	1.000
17:79944968:C:A	K616N	0.999
17:79944968:C:G	K616N	0.999
17:79944988:A:G	W610R	0.999
17:79944988:A:T	W610R	0.999
17:79947779:C:G	G532R	0.999
17:79947779:C:T	G532R	0.999
17:79947788:A:G	Y529H	0.999
17:79948941:T:A	D491V	0.999
17:79948941:T:G	D491A	0.999
17:79948942:C:G	D491H	0.999
17:79949818:C:A	W435C	0.999
17:79949818:C:G	W435C	0.999
17:80010698:A:G	W81R	0.999
17:80010698:A:T	W81R	0.999
17:80013417:A:T	V44D	0.999
17:79944922:A:G	W632R	0.998
17:79944922:A:T	W632R	0.998
17:79944934:A:G	W628R	0.998
17:79944934:A:T	W628R	0.998
17:79944994:G:C	H608D	0.998
17:79944998:G:C	F606L	0.998
17:79944998:G:T	F606L	0.998
17:79945000:A:G	F606L	0.998
17:79945071:A:G	L582P	0.998
17:79947716:A:G	C553R	0.998
17:79947766:A:G	L536P	0.998
17:79947769:T:A	D535V	0.998
17:79947769:T:C	D535G	0.998

dbSNP variants (sampled 300 via entrez): RS1000032390 (17:80020020 G>A), RS1000043338 (17:79986553 C>G), RS1000113250 (17:79943522 C>A), RS1000120125 (17:80027415 G>A), RS1000122371 (17:79950355 G>A,C), RS1000146359 (17:79939170 A>G), RS1000180694 (17:80036583 C>A,G,T), RS1000181966 (17:79952347 C>A), RS1000242780 (17:79938302 G>C), RS1000290714 (17:80030783 G>A), RS1000298539 (17:79972196 A>G), RS1000341637 (17:79947552 A>G), RS1000350716 (17:80023966 A>G,T), RS1000380845 (17:80017359 AT>A), RS1000384536 (17:79976875 A>C)

Disease associations

OMIM: gene MIM:616637 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST005987_5	Albumin-globulin ratio	3.000000e-10
GCST005989_30	Serum total protein levels	3.000000e-09
GCST005990_22	Non-albumin protein levels	2.000000e-11
GCST008962_4	Hematology traits	2.000000e-07
GCST90002396_678	Mean reticulocyte volume	7.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005128	albumin:globulin ratio measurement
EFO:0004587	lymphocyte count
EFO:0010701	mean reticulocyte volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

52 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	3
Valproic Acid	increases expression, decreases expression	3
Aflatoxin B1	decreases expression, decreases methylation, increases methylation	3
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
Tunicamycin	decreases expression, increases expression	2
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	affects cotreatment, increases methylation, decreases methylation	1
trichostatin A	affects expression	1
beta-lapachone	decreases expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
cobaltous chloride	decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
CGP 52608	affects binding, increases reaction	1
oxamflatin	increases expression	1
apicidin	increases expression	1
2-palmitoylglycerol	increases expression	1
scriptaid	increases expression	1
abrine	decreases expression	1
suberoyl bis-hydroxamic acid	increases expression	1
jinfukang	increases expression	1
NSC 689534	affects binding, decreases expression	1
Zoledronic Acid	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Vorinostat	increases expression	1
Panobinostat	increases expression	1
Acrolein	increases abundance, affects cotreatment, increases oxidation	1
Air Pollutants	increases oxidation, affects cotreatment, increases abundance	1

Clinical trials (associated diseases)

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