TBC1D3H

Summary

TBC1D3H (TBC1 domain family member 3H, HGNC:30708) is a protein-coding gene on chromosome 17q12, encoding TBC1 domain family member 3H (P0C7X1). Acts as a GTPase activating protein for RAB5.

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

Source: NCBI Gene 729877 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 37 total
• MANE Select transcript: NM_001123392

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30708
Approved symbol	TBC1D3H
Name	TBC1 domain family member 3H
Location	17q12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000274226
Ensembl biotype	protein_coding
OMIM	610811
Entrez	729877

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000610350

RefSeq mRNA: 1 — MANE Select: NM_001123392 NM_001123392

CCDS: CCDS45653

Canonical transcript exons

ENST00000610350 — 14 exons

Exon	Start	End
ENSE00003717616	36386576	36386661
ENSE00003718993	36388325	36388435
ENSE00003724782	36385254	36385293
ENSE00003725773	36379396	36379548
ENSE00003731960	36386824	36386896
ENSE00003733469	36384691	36384771
ENSE00003747768	36384140	36384247
ENSE00003752417	36377531	36378414
ENSE00003766368	36380482	36380547
ENSE00003768393	36382404	36382452
ENSE00003768617	36381740	36381860
ENSE00003769401	36383701	36383810
ENSE00003771827	36380932	36381026
ENSE00003773679	36379919	36380018

Expression profiles

Bgee: expression breadth broad, 100 present calls, max score 65.36.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	65.36	gold quality
right testis	UBERON:0004534	62.02	gold quality
testis	UBERON:0000473	51.18	gold quality
left testis	UBERON:0004533	50.94	gold quality
granulocyte	CL:0000094	50.08	silver quality
urinary bladder	UBERON:0001255	45.42	gold quality
colonic epithelium	UBERON:0000397	42.99	gold quality
bone marrow cell	CL:0002092	40.88	gold quality
right lung	UBERON:0002167	40.12	gold quality
adenohypophysis	UBERON:0002196	39.59	gold quality
bone marrow	UBERON:0002371	39.40	gold quality
right hemisphere of cerebellum	UBERON:0014890	38.59	gold quality
blood	UBERON:0000178	37.57	gold quality
cerebellar hemisphere	UBERON:0002245	36.91	gold quality
tonsil	UBERON:0002372	36.90	gold quality
sural nerve	UBERON:0015488	36.50	gold quality
cerebellar cortex	UBERON:0002129	36.49	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
cerebellum	UBERON:0002037	36.29	gold quality
amygdala	UBERON:0001876	35.69	gold quality
temporal lobe	UBERON:0001871	35.62	gold quality
liver	UBERON:0002107	35.56	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	34.98	gold quality
right lobe of liver	UBERON:0001114	34.83	gold quality
adult mammalian kidney	UBERON:0000082	34.71	gold quality
right frontal lobe	UBERON:0002810	34.51	gold quality
putamen	UBERON:0001874	34.36	gold quality
hypothalamus	UBERON:0001898	33.48	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.07

Regulation

Is transcription factor: no

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), TBC1D3D (ENSG00000274419), TBC1D3L (ENSG00000274512), TBC1D3 (ENSG00000274611)

Protein

Protein identifiers

TBC1 domain family member 3H — P0C7X1 (reviewed: P0C7X1)

All UniProt accessions (1): P0C7X1

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 heart.

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_001116864* (*=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-P0C7X1-F1	59.83	0.22

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: 16 (showing top): GOMF_ENZYME_ACTIVATOR_ACTIVITY, GOMF_NUCLEOSIDE_TRIPHOSPHATASE_REGULATOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY, MIR335_3P, MIR4743_3P, MIR5585_5P, MIR6888_3P, MIR519E_3P, MIR515_3P, MIR33B_3P, chr17q12, NAKAYA_B_CELL_FLUARIX_FLUVIRIN_AGE_18_50YO_7DY_UP, GOMF_MOLECULAR_FUNCTION_ACTIVATOR_ACTIVITY, WP_17Q12_COPY_NUMBER_VARIATION_SYNDROME, GOCC_ENDOSOME

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

188 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TBC1D3H	KRTAP2-2	Q9BYT5	512
TBC1D3H	ZNHIT3	Q15649	506
TBC1D3H	ERLN	P0DI80	479
TBC1D3H	C17orf50	Q8WW18	475
TBC1D3H	SCGB1C2	P0DMR2	471
TBC1D3H	KRTAP9-7	A8MTY7	447
TBC1D3H	TBC1D23	Q9NUY8	426
TBC1D3H	MTRNR2L1	P0CJ68	420
TBC1D3H	CDRT15L2	A8MXV6	419
TBC1D3H	SYNRG	Q9UMZ2	378
TBC1D3H	CFAP97D1	B2RV13	371
TBC1D3H	PIGW	Q7Z7B1	371
TBC1D3H	SPMAP1	A8MV24	369
TBC1D3H	KRTAP9-8	Q9BYQ0	367
TBC1D3H	SPEM2	Q0P670	357

IntAct

2 interactions, top by confidence:

A	B	Type	Score
SDCBP	TBC1D3H	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (3): TBC1D3H (Negative Genetic), TBC1D3H (Negative Genetic), TBC1D3H (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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	32
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2450 predictions. Top by Δscore:

Variant	Effect	Δscore
17:36378412:TGG:T	acceptor_gain	1.0000
17:36379914:CTTA:C	donor_loss	1.0000
17:36379915:TTACT:T	donor_loss	1.0000
17:36379916:TACTC:T	donor_loss	1.0000
17:36379917:A:AC	donor_gain	1.0000
17:36379918:C:CT	donor_gain	1.0000
17:36379918:CT:C	donor_gain	1.0000
17:36379918:CTCTG:C	donor_gain	1.0000
17:36383699:A:AC	donor_gain	1.0000
17:36383700:C:CC	donor_gain	1.0000
17:36384248:C:CC	acceptor_gain	1.0000
17:36378410:TTTGG:T	acceptor_gain	0.9900
17:36378411:TTGG:T	acceptor_gain	0.9900
17:36378413:GG:G	acceptor_gain	0.9900
17:36378415:C:CC	acceptor_gain	0.9900
17:36379751:A:C	acceptor_gain	0.9900
17:36379912:GACTT:G	donor_loss	0.9900
17:36379913:ACTT:A	donor_loss	0.9900
17:36379917:ACT:A	donor_gain	0.9900
17:36379918:CTC:C	donor_gain	0.9900
17:36379918:CTCT:C	donor_gain	0.9900
17:36380014:GAGAT:G	acceptor_gain	0.9900
17:36380016:GAT:G	acceptor_gain	0.9900
17:36380016:GATC:G	acceptor_loss	0.9900
17:36380017:ATCT:A	acceptor_loss	0.9900
17:36380018:TCT:T	acceptor_loss	0.9900
17:36380019:C:A	acceptor_loss	0.9900
17:36380019:C:CC	acceptor_gain	0.9900
17:36380020:T:G	acceptor_loss	0.9900
17:36381024:ATC:A	acceptor_gain	0.9900

AlphaMissense

3580 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:36381786:G:C	F207L	0.972
17:36381786:G:T	F207L	0.972
17:36381788:A:G	F207L	0.972
17:36379991:A:G	W286R	0.897
17:36379991:A:T	W286R	0.897
17:36384196:A:G	W111R	0.893
17:36384196:A:T	W111R	0.893
17:36383802:C:A	K132N	0.892
17:36383802:C:G	K132N	0.892
17:36383721:G:C	F159L	0.875
17:36383721:G:T	F159L	0.875
17:36383723:A:G	F159L	0.875
17:36381785:A:G	W208R	0.872
17:36381785:A:T	W208R	0.872
17:36384738:A:G	W78R	0.872
17:36384738:A:T	W78R	0.872
17:36381783:C:A	W208C	0.856
17:36381783:C:G	W208C	0.856
17:36384194:C:A	W111C	0.852
17:36384194:C:G	W111C	0.852
17:36384736:C:A	W78C	0.850
17:36384736:C:G	W78C	0.850
17:36384739:C:A	K77N	0.841
17:36384739:C:G	K77N	0.841
17:36381787:A:G	F207S	0.834
17:36384144:T:G	Y128S	0.817
17:36381791:C:G	A206P	0.816
17:36382449:C:A	Q167H	0.813
17:36382449:C:G	Q167H	0.813
17:36381022:A:C	F224L	0.809

dbSNP variants (sampled 300 via entrez): RS1001753333 (17:36389808 A>G,T), RS1008293676 (17:36385887 C>G), RS1008324956 (17:36388790 T>C), RS1010528138 (17:36385969 C>T), RS1019797225 (17:36385900 C>G), RS1021909415 (17:36389757 A>C,G), RS1022293948 (17:36385977 G>A,T), RS1028436580 (17:36385843 G>A,C,T), RS1030616923 (17:36388767 C>A,G), RS1034436569 (17:36390055 G>A,T), RS1037572768 (17:36385767 C>T), RS1037647273 (17:36388396 C>T), RS1041143898 (17:36388851 C>A,T), RS1050208482 (17:36388635 G>A,C,T), RS1056910811 (17:36385673 A>G)

Disease associations

OMIM: gene MIM:610811 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005951_15	Body mass index	3.000000e-13

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression	1
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Diethylhexyl Phthalate	increases expression	1
Smoke	decreases expression	1
Valproic Acid	increases methylation	1
Cyclosporine	increases expression	1

Clinical trials (associated diseases)

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