GRTP1

Summary

GRTP1 (growth hormone regulated TBC protein 1, HGNC:20310) is a protein-coding gene on chromosome 13q34, encoding Growth hormone-regulated TBC protein 1 (Q5TC63). May act as a GTPase-activating protein for Rab family protein(s).

Predicted to enable GTPase activator activity. Predicted to be active in cytoplasm and plasma membrane.

Source: NCBI Gene 79774 — RefSeq curated summary.

At a glance

• GWAS associations: 13
• Clinical variants (ClinVar): 105 total — 1 pathogenic
• MANE Select transcript: NM_024719

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20310
Approved symbol	GRTP1
Name	growth hormone regulated TBC protein 1
Location	13q34
Locus type	gene with protein product
Status	Approved
Aliases	FLJ22474, TBC1D6
Ensembl gene	ENSG00000139835
Ensembl biotype	protein_coding
OMIM	620890
Entrez	79774

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 12 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000326039, ENST00000375430, ENST00000375431, ENST00000476439, ENST00000620217, ENST00000896924, ENST00000896925, ENST00000896926, ENST00000896927, ENST00000896928, ENST00000927042, ENST00000927043, ENST00000927044

RefSeq mRNA: 4 — MANE Select: NM_024719 NM_001286732, NM_001286733, NM_001411029, NM_024719

CCDS: CCDS66591, CCDS73606, CCDS91839, CCDS9534

Canonical transcript exons

ENST00000375431 — 8 exons

Exon	Start	End
ENSE00000940358	113350849	113350973
ENSE00000940359	113344863	113344959
ENSE00000940360	113325919	113326091
ENSE00001467056	113324163	113324577
ENSE00001467058	113325661	113325846
ENSE00001467065	113364020	113364130
ENSE00001594382	113355323	113355481
ENSE00003672850	113363762	113363910

Expression profiles

Bgee: expression breadth ubiquitous, 224 present calls, max score 99.32.

FANTOM5 (CAGE): breadth broad, TPM avg 4.3132 / max 116.2168, expressed in 912 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
138340	3.3711	837
138341	0.6674	421
138339	0.2747	162

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	99.32	gold quality
secondary oocyte	CL:0000655	99.15	gold quality
right lobe of liver	UBERON:0001114	95.56	gold quality
mucosa of transverse colon	UBERON:0004991	94.30	gold quality
jejunal mucosa	UBERON:0000399	93.67	gold quality
lower esophagus mucosa	UBERON:0035834	90.74	gold quality
transverse colon	UBERON:0001157	89.89	gold quality
skin of abdomen	UBERON:0001416	89.10	gold quality
mucosa of sigmoid colon	UBERON:0004993	89.05	gold quality
colonic mucosa	UBERON:0000317	89.03	gold quality
duodenum	UBERON:0002114	88.93	gold quality
small intestine Peyer’s patch	UBERON:0003454	88.53	gold quality
liver	UBERON:0002107	88.32	gold quality
skin of leg	UBERON:0001511	87.83	gold quality
small intestine	UBERON:0002108	87.42	gold quality
esophagus mucosa	UBERON:0002469	87.42	gold quality
esophagus squamous epithelium	UBERON:0006920	87.25	gold quality
palpebral conjunctiva	UBERON:0001812	86.96	gold quality
upper leg skin	UBERON:0004262	86.62	gold quality
left adrenal gland cortex	UBERON:0035825	86.57	gold quality
zone of skin	UBERON:0000014	86.41	gold quality
right adrenal gland	UBERON:0001233	86.27	gold quality
intestine	UBERON:0000160	86.01	gold quality
left adrenal gland	UBERON:0001234	85.93	gold quality
right adrenal gland cortex	UBERON:0035827	85.79	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.77	gold quality
large intestine	UBERON:0000059	85.75	gold quality
colon	UBERON:0001155	85.69	gold quality
rectum	UBERON:0001052	85.57	gold quality
epithelium of nasopharynx	UBERON:0001951	85.25	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.79

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

19 targeting GRTP1, 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-656-3P	100.00	72.15	2788
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-6733-3P	99.54	67.80	1281
HSA-MIR-4519	99.48	66.10	859
HSA-MIR-548AV-3P	99.43	68.50	1721
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-5697	99.39	67.74	1249
HSA-MIR-133A-3P	99.27	71.53	1270
HSA-MIR-133B	99.27	71.53	1270
HSA-MIR-4650-3P	99.01	68.39	1062
HSA-MIR-518C-5P	98.53	69.20	1640
HSA-MIR-320E	97.49	65.96	865
HSA-MIR-514A-5P	96.94	65.49	801
HSA-MIR-4280	96.44	67.69	473

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	grtp1a	ENSDARG00000029936
danio_rerio	grtp1b	ENSDARG00000030269
mus_musculus	Grtp1	ENSMUSG00000038515

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), 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), TBC1D3 (ENSG00000274611)

Protein

Protein identifiers

Growth hormone-regulated TBC protein 1 — Q5TC63 (reviewed: Q5TC63)

Alternative names: TBC1 domain family member 6

All UniProt accessions (2): Q5TC63, A0A087X0Y1

UniProt curated annotations — full annotation on UniProt →

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q5TC63-1	1	yes
Q5TC63-2	2
Q5TC63-3	3

RefSeq proteins (4): NP_001273661, NP_001273662, NP_001397958, NP_078995* (*=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 (5 total): splice variant 2, chain 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5TC63-F1	94.83	0.91

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 59 (showing top): PEREZ_TP63_TARGETS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, chr13q34, PEREZ_TP53_AND_TP63_TARGETS, MODULE_342, RAY_TUMORIGENESIS_BY_ERBB2_CDC25A_DN, GOMF_ENZYME_ACTIVATOR_ACTIVITY, GOMF_NUCLEOSIDE_TRIPHOSPHATASE_REGULATOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY, MEISSNER_BRAIN_HCP_WITH_H3K4ME3_AND_H3K27ME3, MEISSNER_NPC_HCP_WITH_H3K4ME2, WAMUNYOKOLI_OVARIAN_CANCER_LMP_UP, FIGUEROA_AML_METHYLATION_CLUSTER_6_DN, TORCHIA_TARGETS_OF_EWSR1_FLI1_FUSION_UP

GO Biological Process (0):

GO Molecular Function (1): GTPase activator activity (GO:0005096)

GO Cellular Component (2): cytoplasm (GO:0005737), plasma membrane (GO:0005886)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
intracellular anatomical structure	1
cellular anatomical structure	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1364 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GRTP1	SLC9D1	Q6UWJ1	616
GRTP1	TBC1D22A	Q8WUA7	588
GRTP1	DCUN1D2	Q6PH85	544
GRTP1	ADPRHL1	Q8NDY3	542
GRTP1	ZNF780A	O75290	537
GRTP1	TBC1D5	Q92609	524
GRTP1	PCID2	Q5JVF3	479
GRTP1	MYOZ3	Q8TDC0	475
GRTP1	MICOS10	Q5TGZ0	474
GRTP1	TBC1D13	Q9NVG8	474
GRTP1	TBC1D20	Q96BZ9	470
GRTP1	TIMM21	Q9BVV7	455
GRTP1	DHRS4	Q9BTZ2	449
GRTP1	TBC1D32	Q96NH3	438
GRTP1	FBXO15	Q8NCQ5	427

IntAct

9 interactions, top by confidence:

A	B	Type	Score
GJB7	PALM3	psi-mi:“MI:0914”(association)	0.530
FBXL19	MED19	psi-mi:“MI:0914”(association)	0.530
NES	RPL10	psi-mi:“MI:0914”(association)	0.350
	HLA-C	psi-mi:“MI:0914”(association)	0.350
MAGEA3	PALM3	psi-mi:“MI:0914”(association)	0.350
TBRG1	APOD	psi-mi:“MI:0914”(association)	0.350
PCDHGC3	FYN	psi-mi:“MI:0914”(association)	0.350
GRTP1	UBB	psi-mi:“MI:0914”(association)	0.350

BioGRID (16): GRTP1 (Affinity Capture-MS), GRTP1 (Affinity Capture-MS), GRTP1 (Affinity Capture-MS), FAM63A (Affinity Capture-MS), UBB (Affinity Capture-MS), ATP2A1 (Affinity Capture-MS), GRTP1 (Affinity Capture-RNA), GRTP1 (Affinity Capture-MS), UBB (Affinity Capture-MS), GRTP1 (Affinity Capture-MS), GRTP1 (Affinity Capture-MS), GRTP1 (Affinity Capture-MS), GRTP1 (Affinity Capture-MS), FAM63A (Affinity Capture-MS), GRTP1 (Affinity Capture-MS)

ESM2 similar proteins: A0A3L7I2I8, A6H6A9, A7YWD2, O08593, O60733, O94829, P15498, P27870, P49638, P49754, P54100, P97570, P97819, Q02384, Q07889, Q07890, Q28HW9, Q2KIX2, Q2T9Q1, Q3UBZ5, Q4QQU7, Q4R678, Q5F361, Q5KU39, Q5R974, Q5TC63, Q5ZIC8, Q5ZJ17, Q62245, Q66H63, Q6AXU7, Q6GL87, Q6GLZ0, Q6NRC7, Q6PBU5, Q8AYC9, Q8BM85, Q8CA95, Q8K0C1, Q8R3D1

Diamond homologs: A0A087WVF3, A0A087WXS9, A0A087X179, A0A087X1G2, A2AWA9, A3KGB4, A6H6A9, A6NDS4, A6NER0, A6QP29, B0R0W9, B7ZAP0, B9A6J9, H2KZZ6, O60343, O60447, O95759, O97790, P0C7X1, P35125, P58802, P97366, Q0IIM8, Q10496, Q12317, Q12344, Q28CB1, Q3UYK3, Q4KMP7, Q5R372, Q5RAN1, Q5RCW6, Q5SVR0, Q5TC63, Q5ZJ17, Q60949, Q66K14, Q6DHY5, Q6IPX1, Q6ZT07

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	68
Likely benign	21
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
625813	GRCh37/hg19 13q33.1-34(chr13:101881803-115091330)	Pathogenic

SpliceAI

1532 predictions. Top by Δscore:

Variant	Effect	Δscore
13:113325718:A:AC	donor_gain	1.0000
13:113325718:AT:A	donor_gain	1.0000
13:113325843:CTGT:C	acceptor_gain	1.0000
13:113325914:CTCA:C	donor_loss	1.0000
13:113325915:TCAC:T	donor_loss	1.0000
13:113325916:CACC:C	donor_loss	1.0000
13:113325917:A:T	donor_loss	1.0000
13:113325918:C:CA	donor_loss	1.0000
13:113326091:TCTGC:T	acceptor_loss	1.0000
13:113326092:C:CC	acceptor_gain	1.0000
13:113326100:CAA:C	acceptor_gain	1.0000
13:113326102:A:AC	acceptor_gain	1.0000
13:113326102:A:C	acceptor_gain	1.0000
13:113326104:G:C	acceptor_gain	1.0000
13:113326104:G:GC	acceptor_gain	1.0000
13:113350969:CAGGT:C	acceptor_gain	1.0000
13:113350974:C:CC	acceptor_gain	1.0000
13:113363855:T:TA	donor_gain	1.0000
13:113324573:ATTTT:A	acceptor_gain	0.9900
13:113324574:TTTT:T	acceptor_gain	0.9900
13:113325694:C:CA	donor_gain	0.9900
13:113325705:T:C	donor_gain	0.9900
13:113325718:ATCG:A	donor_gain	0.9900
13:113325719:T:C	donor_gain	0.9900
13:113325746:T:TA	donor_gain	0.9900
13:113325913:GCTCA:G	donor_loss	0.9900
13:113325917:A:AC	donor_gain	0.9900
13:113325917:ACCT:A	donor_gain	0.9900
13:113325918:C:CC	donor_gain	0.9900
13:113325918:CCT:C	donor_gain	0.9900

AlphaMissense

2183 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:113325828:C:G	D252H	0.996
13:113325957:A:G	W233R	0.996
13:113325957:A:T	W233R	0.996
13:113344900:A:C	F175L	0.996
13:113344900:A:T	F175L	0.996
13:113344902:A:G	F175L	0.996
13:113325831:A:G	W251R	0.995
13:113325831:A:T	W251R	0.995
13:113344951:A:C	N158K	0.995
13:113344951:A:T	N158K	0.995
13:113355431:A:G	W78R	0.995
13:113355431:A:T	W78R	0.995
13:113363807:A:G	W46R	0.995
13:113363807:A:T	W46R	0.995
13:113363892:G:C	F17L	0.995
13:113363892:G:T	F17L	0.995
13:113363894:A:G	F17L	0.995
13:113344940:C:T	G162E	0.994
13:113350939:G:C	F125L	0.994
13:113350939:G:T	F125L	0.994
13:113350941:A:G	F125L	0.994
13:113350964:C:G	R117P	0.994
13:113344959:C:G	G156R	0.993
13:113344959:C:T	G156R	0.993
13:113350857:A:G	Y153H	0.993
13:113350892:A:G	L141P	0.993
13:113355443:G:T	R74S	0.993
13:113363805:C:A	W46C	0.993
13:113363805:C:G	W46C	0.993
13:113325827:T:A	D252V	0.992

dbSNP variants (sampled 300 via entrez): RS1000003737 (13:113362403 A>G), RS1000088162 (13:113325625 C>T), RS1000105289 (13:113366029 G>A), RS1000105767 (13:113328820 C>T), RS1000125609 (13:113340149 C>A,T), RS1000181540 (13:113343327 G>C), RS1000189404 (13:113339597 T>A), RS1000227597 (13:113328226 CTG>C), RS1000371466 (13:113354604 C>G), RS1000384029 (13:113360922 C>A), RS1000415073 (13:113329039 G>A,C,T), RS1000427020 (13:113354807 G>A), RS1000588463 (13:113333315 G>A), RS1000695417 (13:113333223 T>C), RS1000757596 (13:113343521 A>G)

Disease associations

OMIM: gene MIM:620890 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST001335_25	Mean platelet volume	8.000000e-12
GCST004599_159	Mean platelet volume	2.000000e-40
GCST004603_132	Platelet count	8.000000e-17
GCST004616_53	Platelet distribution width	5.000000e-09
GCST004616_54	Platelet distribution width	4.000000e-45
GCST007998_16	Intraocular pressure	8.000000e-17
GCST90002395_163	Mean platelet volume	9.000000e-48
GCST90002395_165	Mean platelet volume	2.000000e-78
GCST90002401_66	Platelet distribution width	2.000000e-37
GCST90002401_67	Platelet distribution width	9.000000e-14
GCST90002401_68	Platelet distribution width	2.000000e-86
GCST90002402_224	Platelet count	2.000000e-22
GCST90002402_225	Platelet count	4.000000e-50

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0007984	platelet component distribution width
EFO:0004695	intraocular pressure measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects binding, increases expression, affects cotreatment, decreases expression	4
Valproic Acid	increases expression	3
methylmercuric chloride	increases expression	2
Acetaminophen	decreases expression	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Cyclosporine	decreases expression	2
Aflatoxin B1	affects expression, increases methylation	2
sodium arsenite	decreases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases expression, decreases reaction	1
jinfukang	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Fulvestrant	increases methylation	1
Vehicle Emissions	decreases expression, decreases reaction	1
Cadmium	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Nickel	decreases expression	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1
Acrylamide	increases expression	1
Particulate Matter	decreases expression, decreases reaction	1

Clinical trials (associated diseases)

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