TBC1D19

Summary

TBC1D19 (TBC1 domain family member 19, HGNC:25624) is a protein-coding gene on chromosome 4p15.2, encoding TBC1 domain family member 19 (Q8N5T2). May act as a GTPase-activating protein for Rab family protein(s).

Predicted to enable GTPase activator activity.

Source: NCBI Gene 55296 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 71 total
• MANE Select transcript: NM_018317

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25624
Approved symbol	TBC1D19
Name	TBC1 domain family member 19
Location	4p15.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ11082
Ensembl gene	ENSG00000109680
Ensembl biotype	protein_coding
Entrez	55296

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 9 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000264866, ENST00000502873, ENST00000504442, ENST00000505206, ENST00000511789, ENST00000512840, ENST00000513455, ENST00000513596, ENST00000515568, ENST00000892672, ENST00000892673, ENST00000951249

RefSeq mRNA: 2 — MANE Select: NM_018317 NM_001292054, NM_018317

CCDS: CCDS3439, CCDS75115

Canonical transcript exons

ENST00000264866 — 21 exons

Exon	Start	End
ENSE00001122317	26753820	26753890
ENSE00001150862	26754873	26756223
ENSE00002033133	26584084	26584292
ENSE00003464482	26683675	26683749
ENSE00003464792	26672149	26672187
ENSE00003471688	26620613	26620688
ENSE00003478567	26720081	26720125
ENSE00003481499	26640141	26640187
ENSE00003483421	26748411	26748526
ENSE00003493461	26717933	26718017
ENSE00003510562	26659597	26659707
ENSE00003528012	26742508	26742599
ENSE00003566055	26614408	26614453
ENSE00003569351	26688345	26688407
ENSE00003574456	26673776	26673888
ENSE00003587087	26613169	26613241
ENSE00003602845	26735455	26735487
ENSE00003625483	26637211	26637285
ENSE00003639241	26666333	26666405
ENSE00003653812	26638771	26638834
ENSE00003668053	26739864	26739973

Expression profiles

Bgee: expression breadth ubiquitous, 198 present calls, max score 87.32.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.7886 / max 278.3680, expressed in 1732 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
47194	13.5018	1723
47193	1.1391	649
47191	0.1020	52
47192	0.0458	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	87.32	gold quality
adrenal tissue	UBERON:0018303	86.67	gold quality
calcaneal tendon	UBERON:0003701	86.05	gold quality
stromal cell of endometrium	CL:0002255	85.78	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.38	gold quality
male germ cell	CL:0000015	84.14	silver quality
cortical plate	UBERON:0005343	82.71	gold quality
gall bladder	UBERON:0002110	81.91	gold quality
right adrenal gland	UBERON:0001233	81.66	gold quality
right adrenal gland cortex	UBERON:0035827	81.54	gold quality
islet of Langerhans	UBERON:0000006	81.40	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.93	gold quality
buccal mucosa cell	CL:0002336	80.91	silver quality
ganglionic eminence	UBERON:0004023	80.57	gold quality
ventricular zone	UBERON:0003053	80.17	gold quality
colonic epithelium	UBERON:0000397	80.00	gold quality
body of uterus	UBERON:0009853	79.19	gold quality
left adrenal gland	UBERON:0001234	79.16	gold quality
smooth muscle tissue	UBERON:0001135	79.03	gold quality
adrenal gland	UBERON:0002369	78.65	gold quality
left adrenal gland cortex	UBERON:0035825	78.37	gold quality
left ovary	UBERON:0002119	78.00	gold quality
right ovary	UBERON:0002118	77.42	gold quality
choroid plexus epithelium	UBERON:0003911	76.72	gold quality
adrenal cortex	UBERON:0001235	76.58	gold quality
right atrium auricular region	UBERON:0006631	76.53	gold quality
ovary	UBERON:0000992	76.12	gold quality
endocervix	UBERON:0000458	76.00	gold quality
right uterine tube	UBERON:0001302	75.74	gold quality
prefrontal cortex	UBERON:0000451	75.60	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.05

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

107 targeting TBC1D19, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-6772-5P	99.94	67.01	577
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-374A-5P	99.90	71.34	2923

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tbc1d19	ENSDARG00000013842
mus_musculus	Tbc1d19	ENSMUSG00000039178
rattus_norvegicus	Tbc1d19	ENSRNOG00000003003
drosophila_melanogaster	CG7742	FBGN0031690

Protein

Protein identifiers

TBC1 domain family member 19 — Q8N5T2 (reviewed: Q8N5T2)

All UniProt accessions (5): Q8N5T2, D6RA60, D6RA74, D6RD52, D6RDZ1

UniProt curated annotations — full annotation on UniProt →

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q8N5T2-1	1	yes
Q8N5T2-2	2

RefSeq proteins (2): NP_001278983, NP_060787* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000195	Rab-GAP-TBC_dom	Domain
IPR035969	Rab-GAP_TBC_sf	Homologous_superfamily
IPR042507	TBC1D19	Family

Pfam: PF00566

UniProt features (6 total): sequence variant 2, chain 1, domain 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N5T2-F1	92.11	0.81

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 183 (showing top): AAGCAAT_MIR137, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, SMID_BREAST_CANCER_RELAPSE_IN_LUNG_DN, CTATGCA_MIR153, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, MODULE_205, FREAC3_01, GOBP_CILIUM_ORGANIZATION, GOBP_ORGANELLE_ASSEMBLY, ATCATGA_MIR433, GOBP_REGULATION_OF_CILIUM_ASSEMBLY, POU3F2_02, GOBP_CELL_PROJECTION_ORGANIZATION

GO Biological Process (0):

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

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
binding	1

Protein interactions and networks

STRING

404 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TBC1D19	TBC1D21	Q8IYX1	665
TBC1D19	TBC1D13	Q9NVG8	641
TBC1D19	DNAAF9	Q5TEA3	616
TBC1D19	TBC1D10C	Q8IV04	592
TBC1D19	TBC1D14	Q9P2M4	591
TBC1D19	TBC1D17	Q9HA65	576
TBC1D19	TBC1D22B	Q9NU19	573
TBC1D19	TBC1D10A	Q9BXI6	566
TBC1D19	FEZ2	Q9UHY8	564
TBC1D19	TBC1D7	Q9P0N9	549
TBC1D19	TBC1D12	O60347	546
TBC1D19	TBC1D20	Q96BZ9	536
TBC1D19	TBC1D2B	Q9UPU7	530
TBC1D19	RAB12	Q6IQ22	522
TBC1D19	TBC1D22A	Q8WUA7	522

IntAct

28 interactions, top by confidence:

A	B	Type	Score
NICN1	TTLL1	psi-mi:“MI:0914”(association)	0.640
TTLL1	CDC27	psi-mi:“MI:0914”(association)	0.640
NICN1	TPGS2	psi-mi:“MI:0914”(association)	0.640
MAGEA12	TBC1D19	psi-mi:“MI:0915”(physical association)	0.560
TBC1D19	MAGEA12	psi-mi:“MI:0915”(physical association)	0.560
MBD3	TBC1D19	psi-mi:“MI:0915”(physical association)	0.560
LRRC49	SNAP29	psi-mi:“MI:0914”(association)	0.530
TBC1D19		psi-mi:“MI:0915”(physical association)	0.370
PPP1CC	TBC1D19	psi-mi:“MI:0915”(physical association)	0.370
IGHA1	PLG	psi-mi:“MI:0914”(association)	0.350
LRRC49	PCM1	psi-mi:“MI:0914”(association)	0.350
ROS1	ODAD3	psi-mi:“MI:0914”(association)	0.350
TPGS1	PPFIA3	psi-mi:“MI:0914”(association)	0.350
CSTPP1	CRYGS	psi-mi:“MI:0914”(association)	0.350
CSTPP1	PEX5	psi-mi:“MI:0914”(association)	0.350
TTLL1	CAMK2B	psi-mi:“MI:0914”(association)	0.350
LRRC49	ASS1	psi-mi:“MI:0914”(association)	0.350
CSTPP1	KRBA1	psi-mi:“MI:0914”(association)	0.350
NICN1	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
TTLL1	RGS12	psi-mi:“MI:0914”(association)	0.350
CEP135	CCDC66	psi-mi:“MI:2364”(proximity)	0.270
CAT	PSMD12	psi-mi:“MI:2364”(proximity)	0.270
MBD3	TBC1D19	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (24): TBC1D19 (Two-hybrid), TBC1D19 (Affinity Capture-MS), TBC1D19 (Proximity Label-MS), TBC1D19 (Affinity Capture-MS), TBC1D19 (Affinity Capture-MS), TBC1D19 (Affinity Capture-MS), TBC1D19 (Affinity Capture-RNA), TBC1D19 (Proximity Label-MS), TBC1D19 (Two-hybrid), TBC1D19 (Proximity Label-MS), TBC1D19 (Proximity Label-MS), TBC1D19 (Proximity Label-MS), TBC1D19 (Proximity Label-MS), TBC1D19 (Affinity Capture-MS), TBC1D19 (Affinity Capture-MS)

ESM2 similar proteins: A1A5K6, A6H8I2, A7E2V1, F1QWA8, H2LP95, O02697, O97790, P0CI65, P48736, Q08CX5, Q28CB1, Q29RJ2, Q2KI13, Q3U487, Q3UUG6, Q3UYK3, Q3V3E1, Q4QR86, Q5R8B7, Q5SVR0, Q5T447, Q5ZJX5, Q66K14, Q6AZT7, Q6DDI6, Q6DEY8, Q6NXY1, Q6P6R7, Q6ZT07, Q7T2D0, Q7Z494, Q8BGG7, Q8N5T2, Q8R5A6, Q8TC07, Q8TF42, Q8VCZ6, Q8WUA7, Q8WZA2, Q91WS7

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 28 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Carboxyterminal post-translational modifications of tubulin	5	59.5×	4e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	46
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

4782 predictions. Top by Δscore:

Variant	Effect	Δscore
4:26614452:GT:G	donor_gain	1.0000
4:26614454:G:GG	donor_gain	1.0000
4:26659708:G:GG	donor_gain	1.0000
4:26663041:G:GT	donor_gain	1.0000
4:26663088:G:GG	donor_gain	1.0000
4:26683667:A:AG	acceptor_gain	1.0000
4:26683668:A:AG	acceptor_gain	1.0000
4:26683670:TTTAG:T	acceptor_loss	1.0000
4:26683671:TTAG:T	acceptor_loss	1.0000
4:26683673:A:G	acceptor_loss	1.0000
4:26683673:AG:A	acceptor_gain	1.0000
4:26683674:G:A	acceptor_loss	1.0000
4:26683674:GG:G	acceptor_gain	1.0000
4:26683674:GGAT:G	acceptor_gain	1.0000
4:26683745:ATAAA:A	donor_gain	1.0000
4:26683746:TAAA:T	donor_gain	1.0000
4:26683746:TAAAG:T	donor_loss	1.0000
4:26683747:AAA:A	donor_gain	1.0000
4:26683747:AAAGT:A	donor_loss	1.0000
4:26683748:AA:A	donor_gain	1.0000
4:26683749:AGT:A	donor_loss	1.0000
4:26683750:G:T	donor_loss	1.0000
4:26683750:GTAA:G	donor_gain	1.0000
4:26683751:T:TG	donor_loss	1.0000
4:26683752:A:AG	donor_loss	1.0000
4:26720078:TAG:T	acceptor_loss	1.0000
4:26720079:A:AG	acceptor_gain	1.0000
4:26720079:A:AT	acceptor_loss	1.0000
4:26720080:G:GG	acceptor_gain	1.0000
4:26720124:TGG:T	donor_loss	1.0000

AlphaMissense

3435 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:26637217:T:A	W101R	1.000
4:26637217:T:C	W101R	1.000
4:26638807:T:A	W136R	1.000
4:26638807:T:C	W136R	1.000
4:26640162:T:A	V152D	1.000
4:26640176:G:C	D157H	1.000
4:26640177:A:C	D157A	1.000
4:26640177:A:G	D157G	1.000
4:26640177:A:T	D157V	1.000
4:26673853:T:A	W261R	1.000
4:26673853:T:C	W261R	1.000
4:26683739:T:C	L294P	1.000
4:26688381:T:C	F310L	1.000
4:26688382:T:C	F310S	1.000
4:26688382:T:G	F310C	1.000
4:26688383:T:A	F310L	1.000
4:26688383:T:G	F310L	1.000
4:26688387:T:C	F312L	1.000
4:26688389:T:A	F312L	1.000
4:26688389:T:G	F312L	1.000
4:26688393:G:C	D314H	1.000
4:26717952:G:C	R325P	1.000
4:26735473:G:A	G368E	1.000
4:26742578:T:C	L433P	1.000
4:26748430:T:A	W447R	1.000
4:26748430:T:C	W447R	1.000
4:26748484:T:A	W465R	1.000
4:26748484:T:C	W465R	1.000
4:26753859:T:C	L492P	1.000
4:26753886:C:A	A501D	1.000

dbSNP variants (sampled 300 via entrez): RS1000003672 (4:26771590 T>C), RS1000009745 (4:26672676 G>T), RS10000211 (4:26627038 C>A,G,T), RS10000377 (4:26627043 G>A,C), RS1000050246 (4:26763149 G>A), RS1000051301 (4:26642041 A>C), RS1000054191 (4:26814391 A>G), RS1000070427 (4:26836266 G>A), RS1000111186 (4:26617586 T>C), RS1000113931 (4:26594893 G>A), RS10001152 (4:26854794 T>A,C), RS1000122422 (4:26850083 G>A,T), RS1000145677 (4:26663376 A>G), RS1000151200 (4:26731314 C>T), RS1000157528 (4:26781797 G>C)

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

3 associations (top):

Study	Trait	p-value
GCST007267_26	Systolic blood pressure	3.000000e-12
GCST007930_44	Medication use (agents acting on the renin-angiotensin system)	4.000000e-10
GCST009391_526	Metabolite levels	7.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0009931	Agents acting on the renin-angiotensin system use measurement
EFO:0010117	pyruvate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression	3
potassium chromate(VI)	affects cotreatment, decreases expression	2
Estradiol	affects cotreatment, increases expression, decreases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	decreases expression, increases expression	1
sodium arsenite	decreases expression, increases abundance, affects cotreatment	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
chromium hexavalent ion	decreases expression	1
ICG 001	increases expression	1
jinfukang	decreases expression, affects cotreatment	1
Temozolomide	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Atrazine	increases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	affects cotreatment, decreases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Methyl Methanesulfonate	increases expression	1
Progesterone	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Urethane	increases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	decreases expression	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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