GOLPH3

Summary

GOLPH3 (golgi phosphoprotein 3, HGNC:15452) is a protein-coding gene on chromosome 5p13.3, encoding Golgi phosphoprotein 3 (Q9H4A6). Phosphatidylinositol-4-phosphate-binding protein that links Golgi membranes to the cytoskeleton and may participate in the tensile force required for vesicle budding from the Golgi.

The Golgi complex plays a key role in the sorting and modification of proteins exported from the endoplasmic reticulum. The protein encoded by this gene is a peripheral membrane protein of the Golgi stack and may have a regulatory role in Golgi trafficking. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of these variants has not been determined.

Source: NCBI Gene 64083 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 32 total
• MANE Select transcript: NM_022130

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15452
Approved symbol	GOLPH3
Name	golgi phosphoprotein 3
Location	5p13.3
Locus type	gene with protein product
Status	Approved
Aliases	GPP34, GOPP1, MIDAS, Vps74
Ensembl gene	ENSG00000113384
Ensembl biotype	protein_coding
OMIM	612207
Entrez	64083

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000265070, ENST00000503610, ENST00000512668, ENST00000856516, ENST00000961399, ENST00000961400

RefSeq mRNA: 1 — MANE Select: NM_022130 NM_022130

CCDS: CCDS3896

Canonical transcript exons

ENST00000265070 — 4 exons

Exon	Start	End
ENSE00001200437	32124716	32126636
ENSE00002031824	32173810	32174319
ENSE00003653193	32143749	32143880
ENSE00003657560	32135572	32135686

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.04.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 40.2286 / max 406.2253, expressed in 1817 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
61166	36.9150	1817
61165	2.6374	1422
61164	0.6762	292

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.04	gold quality
epithelium of nasopharynx	UBERON:0001951	98.50	gold quality
nasopharynx	UBERON:0001728	98.48	gold quality
caput epididymis	UBERON:0004358	98.47	gold quality
mammary duct	UBERON:0001765	98.24	gold quality
cauda epididymis	UBERON:0004360	98.05	gold quality
cardia of stomach	UBERON:0001162	98.02	gold quality
corpus epididymis	UBERON:0004359	98.00	gold quality
mucosa of sigmoid colon	UBERON:0004993	97.98	gold quality
pylorus	UBERON:0001166	97.93	gold quality
lower lobe of lung	UBERON:0008949	97.88	gold quality
epithelium of mammary gland	UBERON:0003244	97.82	gold quality
palpebral conjunctiva	UBERON:0001812	97.81	gold quality
colonic mucosa	UBERON:0000317	97.75	gold quality
seminal vesicle	UBERON:0000998	97.58	gold quality
trachea	UBERON:0003126	97.52	gold quality
gall bladder	UBERON:0002110	97.48	gold quality
parotid gland	UBERON:0001831	97.41	gold quality
oocyte	CL:0000023	97.35	gold quality
islet of Langerhans	UBERON:0000006	97.34	gold quality
mucosa of paranasal sinus	UBERON:0005030	97.33	gold quality
bronchial epithelial cell	CL:0002328	97.29	gold quality
nasal cavity epithelium	UBERON:0005384	97.29	gold quality
urethra	UBERON:0000057	97.23	gold quality
eye	UBERON:0000970	97.22	gold quality
type B pancreatic cell	CL:0000169	97.19	gold quality
jejunal mucosa	UBERON:0000399	97.16	gold quality
penis	UBERON:0000989	97.16	gold quality
nasal cavity mucosa	UBERON:0001826	97.16	gold quality
placenta	UBERON:0001987	97.14	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-7037	yes	124.96
E-CURD-112	no	3.02
E-HCAD-5	no	2.24
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

184 targeting GOLPH3, 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-3163	100.00	77.23	8605
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4775	99.98	75.00	6394
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753

Literature-anchored findings (GeneRIF, showing 40)

• MIDAS/GPP34 is involved in the regulation of mitochondrial lipids, leading to increases of total mitochondrial mass in response to mitochondrial dysfunction. (PMID:16263763)
• Gain- and loss-of-function studies in vitro and in vivo validated GOLPH3 as a potent oncogene (PMID:19553991)
• GOLPH3 links the Golgi network to mTOR signaling and human cancer (PMID:19624311)
• GOLPH3 bridges phosphatidylinositol-4-phosphate and actomyosin to stretch and shape the golgi to promote budding (PMID:19837035)
• The evidence suggests that GOLPH3 binds to phosphatidylinositol-4-phosphate-rich trans-Golgi membranes and MYO18A conveying a tensile force required for efficient tubule and vesicle formation. (PMID:19837035)
• Targeting of GOLPH3 to the Golgi apparatus requires ongoing synthesis of phosphatidylinositol (PtdIns) 4-phosphate (PtdIns4P) by the Pik1 PtdIns 4-kinase and that modulation of the levels and cellular location of PtdIns4P leads to mislocalization. (PMID:20026658)
• This study does not support the association of PDZD2, GOLPH3, and MTMR12 genes with schizophrenia. (PMID:21451436)
• High GOLPH3 is associated with gliomas. (PMID:21499727)
• Human rhabdomyosarcoma cell lines and biopsy specimens exhibited an increased expression of GOLPH3 and GOLPH3L. GOLPH3 and GOLPH3L knockdown by siRNA prevented the proliferation of human rhabdomyosarcoma cell lines. (PMID:21822541)
• Data indicate that golgi phosphoprotein 3 (GOLPH3) overexpression decreased FOXO1 transcriptional activity. (PMID:22675169)
• These studies establish the role of PI4P and its interacting protein GOLPH3 in HCV secretion and strengthen the significance of the Golgi secretory pathway in this process. (PMID:22745132)
• results suggest GOLPH3 overexpression is associated with poor prognosis for cN0 oral tongue cancer patients and may represent a novel and useful prognostic indicator for cN0 oral tongue cancer (PMID:22905766)
• Overexpression of Golgi phosphoprotein-3 is associated with glioblastoma multiforme. (PMID:22972189)
• Overexpression of GOLPH3 is associated with the transition of prostate cancer from hormone sensitive phase to hormone refractory phase. (PMID:23006319)
• GOLPH3 can regulate cell-cell interaction by controlling Golgi retention of C2GnT1. (PMID:23027862)
• Data indicate the potential involvement of GOLPH3 in the development, differentiation, and tumorigenesis of esophageal squamous cell cancer (ESCC), and suggest the possibility of its use as a diagnostic and prognostic marker in ESCC. (PMID:23056210)
• the overexpression of GOLPH3 is closely related to the progression of gastric cancer and might be regarded as an independent predictor of poor prognosis for gastric cancer (PMID:23132295)
• GOLPH3L differs critically from GOLPH3 in that it is largely unable to bind to MYO18A; data demonstrate that despite their similarities, unexpectedly, GOLPH3L antagonizes GOLPH3/MYO18A at the Golgi (PMID:23345592)
• GOLPH3 regulates the migration and invasion of glioma cells though regulation of RhoA. (PMID:23500462)
• PDZ module mediates direct binding of myosin-18A to GOLPH3, and this interaction in turn modulates the actin binding properties of the N-terminal extension. Thus, myosin-18A can act as an actin cross-linker with multiple regulatory modulators (PMID:23990465)
• High GOLPH3 expression is associated growth and metastasis of esophageal squamous cancer. (PMID:24175832)
• In this review, GOLPH3 is described as an oncoprotein involved in cell signal transduction. (PMID:24395131)
• GOLPH3 is associated with prognosis in colorectal cancer patients treated with postoperative 5-fluorouracil-based adjuvant chemotherapy. (PMID:24444035)
• GOLPH3 gene expression might play a role in tumorigenesis in epithelial ovarian carcinoma as upregulation of GOLPH3 expression is associated with a more aggressive tumor phenotype. (PMID:24458516)
• Identification of the DNA-damage-induced Golgi response reveals an unexpected pathway through DNA-PK, GOLPH3, and MYO18A that regulates cell survival following DNA damage. (PMID:24485452)
• These results suggest that GOLPH3 expression is likely to have important roles in renal cell carcinoma (RCC) development and progression, and that GOLPH3 is a prognostic biomarker and a promising therapeutic target for RCC. (PMID:24595000)
• Data indicate that Golgi phosphoprotein 3 (GOLPH3) binds to and controls the Golgi localization of protein O-linked mannose beta-1,2-N-acetlyglucosaminyltransferase 1 (POMGnT1). (PMID:24733390)
• The DNA copy number variations disrupt PDZD2 and GOLPH3 genes predominantly expressed in placenta, and it may represent a novel risk factor for recurrent miscarriage. (PMID:24827138)
• Data indicate that Golgi phosphoprotein 3 (GOLPH3) was overexpressed in hepatocellular carcinoma (HCC) at both the mRNA and protein levels, and high expression of GOLPH3 could be served as a novel and potential prognostic biomarker for HCC patients. (PMID:24867097)
• These results are the first direct demonstration of the role of GOLPH3 in N-glycosylation to regulate cell biological functions. (PMID:24895123)
• Results show that in esophageal squamous cell carcinoma (ESCC), miR-126 was downregulated and IRS-1 and GOLPH3, overexpressed suggesting a tumor suppression role of miR-126 via the regulation of IRS-1 and GOLPH3. (PMID:25017784)
• High GOLPH3 expression is associated with metastasis in non-small cell lung cancer. (PMID:25081375)
• High expression of the GOLPH3 protein is common in early-stage Non-Small-Cell Lung Carcinoma, and is closely associated with tumor progression, increased tumor angiogenesis, and poor survival. (PMID:25081702)
• Study demonstrated that overexpression of GOLPH3 was associated with poor survival in patients with pancreatic ductal adenocarcinoma. (PMID:25104140)
• GOLPH3 promotes glioblastoma cell migration and invasion via the mTOR-YB1pathway. (PMID:25156912)
• overexpression of GOLPH3 protein is closely related to poorer prognosis in patients with epithelial ovarian cancer. (PMID:25204671)
• Both PKD2 and GOLPH3 play important roles in the progression of human gliomas by promoting cell proliferation. (PMID:25218347)
• GOLPH3 has a role in triggering signal-mediated incorporation of glycosyltransferases into coatomer-coated vesicles (PMID:25246532)
• The GOPLH3 expression level is highly correlated with Akt/mTOR signaling in human gastric cancer samples. (PMID:25286393)
• Golgi phosphoprotein 3 (GOLPH3) promotes hepatocellular carcinoma cell aggressiveness by activating the NF-kappaB pathway. (PMID:25385148)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Golph3	ENSMUSG00000022200
rattus_norvegicus	Golph3	ENSRNOG00000012186

Paralogs (1): GOLPH3L (ENSG00000143457)

Protein

Protein identifiers

Golgi phosphoprotein 3 — Q9H4A6 (reviewed: Q9H4A6)

Alternative names: Coat protein GPP34, Mitochondrial DNA absence factor

All UniProt accessions (2): D6REM1, Q9H4A6

UniProt curated annotations — full annotation on UniProt →

Function. Phosphatidylinositol-4-phosphate-binding protein that links Golgi membranes to the cytoskeleton and may participate in the tensile force required for vesicle budding from the Golgi. Thereby, may play a role in Golgi membrane trafficking and could indirectly give its flattened shape to the Golgi apparatus. May also bind to the coatomer to regulate Golgi membrane trafficking. May play a role in anterograde transport from the Golgi to the plasma membrane and regulate secretion. Has also been involved in the control of the localization of Golgi enzymes through interaction with their cytoplasmic part. May play an indirect role in cell migration. Has also been involved in the modulation of mTOR signaling. May also be involved in the regulation of mitochondrial lipids biosynthesis.

Subunit / interactions. Homodimer. Interacts with the coatomer complex. Interacts with MYO18A; the interaction is direct and may link Golgi membranes to the actin cytoskeleton. Interacts with GCNT1; may control its retention in the Golgi. Interacts with VPS35.

Subcellular location. Golgi apparatus. Golgi stack membrane. trans-Golgi network membrane. Mitochondrion intermembrane space. Cell membrane. Endosome.

Tissue specificity. Detected in muscle fibers of patients with mitochondrial diseases; not detected in normal muscle fibers.

Post-translational modifications. Phosphorylated.

Induction. Activated by depletion of mitochondrial DNA.

Miscellaneous. Modulates sensitivity to rapamycin. Tumors expressing this protein are more sensitive to rapamycin in vivo.

Similarity. Belongs to the GOLPH3/VPS74 family.

RefSeq proteins (1): NP_071413* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008628	GPP34-like	Family
IPR038261	GPP34-like_sf	Homologous_superfamily

Pfam: PF05719

UniProt features (41 total): helix 13, mutagenesis site 7, strand 6, binding site 4, turn 3, region of interest 2, modified residue 2, compositionally biased region 2, chain 1, disulfide bond 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
3KN1	X-RAY DIFFRACTION	2.9
9QPQ	ELECTRON MICROSCOPY	7.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H4A6-F1	84.06	0.69

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (4): 81; 90; 171; 174

Post-translational modifications (2): 36, 35

Disulfide bonds (1): 84–108

Mutagenesis-validated functional residues (7):

Position	Phenotype
7	altered binding to coatomer.
14–15	loss of binding to coatomer.
81	abolishes phosphoinositide binding and localization to the golgi apparatus; when associated with a-90.
90	abolishes phosphoinositide binding and localization to the golgi apparatus; when associated with a-81.
90	loss of function in vesicle budding, abolishes phosphoinositide binding and localization to the golgi apparatus.
171	abolishes phosphoinositide binding and localization to the golgi apparatus; when associated with a-174.
174	abolishes phosphoinositide binding and localization to the golgi apparatus; when associated with a-171 or l-171.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 242 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_ESTABLISHMENT_OF_EPITHELIAL_CELL_POLARITY, GOBP_VESICLE_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_TOR_SIGNALING, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_PROTEIN_TARGETING, KYNG_DNA_DAMAGE_DN, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS

GO Biological Process (21): retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum (GO:0006890), Golgi organization (GO:0007030), glycoprotein biosynthetic process (GO:0009101), protein secretion (GO:0009306), gene expression (GO:0010467), regulation of mitochondrion organization (GO:0010821), cell migration (GO:0016477), lamellipodium assembly (GO:0030032), positive regulation of TOR signaling (GO:0032008), Golgi to plasma membrane protein transport (GO:0043001), negative regulation of apoptotic process (GO:0043066), protein retention in Golgi apparatus (GO:0045053), Golgi vesicle budding (GO:0048194), positive regulation of protein secretion (GO:0050714), leukocyte tethering or rolling (GO:0050901), cell adhesion molecule production (GO:0060352), cellular response to rapamycin (GO:0072752), Golgi ribbon formation (GO:0090161), asymmetric Golgi ribbon formation (GO:0090164), protein targeting to Golgi apparatus (GO:0140450), protein transport (GO:0015031)

GO Molecular Function (5): enzyme binding (GO:0019899), phosphatidylinositol-4-phosphate binding (GO:0070273), cargo adaptor activity (GO:0140312), protein binding (GO:0005515), lipid binding (GO:0008289)

GO Cellular Component (11): Golgi membrane (GO:0000139), mitochondrion (GO:0005739), mitochondrial intermembrane space (GO:0005758), endosome (GO:0005768), Golgi apparatus (GO:0005794), trans-Golgi network (GO:0005802), cytosol (GO:0005829), plasma membrane (GO:0005886), Golgi cisterna (GO:0031985), Golgi cisterna membrane (GO:0032580), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	3
Golgi vesicle transport	2
macromolecule biosynthetic process	2
protein transport	2
binding	2
intracellular membrane-bounded organelle	2
endomembrane system	2
Golgi apparatus subcompartment	2
cellular anatomical structure	2
organelle organization	1
endomembrane system organization	1
glycoprotein metabolic process	1
carbohydrate derivative biosynthetic process	1
secretion by cell	1
establishment of protein localization to extracellular region	1
protein localization to extracellular region	1
mitochondrion organization	1
regulation of organelle organization	1
cell motility	1
lamellipodium organization	1
plasma membrane bounded cell projection assembly	1
TOR signaling	1
regulation of TOR signaling	1
positive regulation of intracellular signal transduction	1
Golgi to plasma membrane transport	1
establishment of protein localization to plasma membrane	1
protein localization to plasma membrane	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
maintenance of protein location in cell	1
protein localization to Golgi apparatus	1
Golgi membrane	1
vesicle budding from membrane	1
protein secretion	1
regulation of protein secretion	1
positive regulation of protein transport	1
positive regulation of secretion by cell	1
cellular extravasation	1
leukocyte adhesion to vascular endothelial cell	1

Protein interactions and networks

STRING

3744 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GOLPH3	SEC24B	O95487	946
GOLPH3	MYO18A	Q92614	942
GOLPH3	ARF1	P10947	937
GOLPH3	PPEF1	O14829	918
GOLPH3	CD4	P01730	905
GOLPH3	GOLGA2	Q08379	902
GOLPH3	COPB1	P53618	890
GOLPH3	SEC13	P55735	861
GOLPH3	SEC24A	O95486	847
GOLPH3	SAR1A	Q9NR31	843
GOLPH3	SEC24C	P53992	840
GOLPH3	STK25	O00506	838
GOLPH3	SEC16A	O15027	818
GOLPH3	GORASP1	Q9BQQ3	817
GOLPH3	USO1	O60763	814

IntAct

149 interactions, top by confidence:

A	B	Type	Score
MYO18A	GOLPH3	psi-mi:“MI:0915”(physical association)	0.720
GOLPH3	MYO18A	psi-mi:“MI:0407”(direct interaction)	0.720
MYO18A	GOLPH3	psi-mi:“MI:0403”(colocalization)	0.720
	GOLPH3	psi-mi:“MI:0407”(direct interaction)	0.680
	GOLPH3	psi-mi:“MI:0915”(physical association)	0.680
COQ8A	COQ9	psi-mi:“MI:0914”(association)	0.670
TNFSF14	TMEM11	psi-mi:“MI:0914”(association)	0.670
GOLPH3	RCC1L	psi-mi:“MI:0914”(association)	0.640
SDHAF3	NDUFAB1	psi-mi:“MI:0914”(association)	0.640
STX12	SNAP23	psi-mi:“MI:0914”(association)	0.640
GCNT1	GOLPH3	psi-mi:“MI:0915”(physical association)	0.610
GOLPH3	GCNT1	psi-mi:“MI:0915”(physical association)	0.610
GOLPH3	GCNT1	psi-mi:“MI:0403”(colocalization)	0.610
GOLPH3	GCNT1	psi-mi:“MI:0407”(direct interaction)	0.610
ARL6IP1	GOLPH3	psi-mi:“MI:0915”(physical association)	0.560
GOLPH3	ARL6IP1	psi-mi:“MI:0915”(physical association)	0.560
vpr	GOLPH3	psi-mi:“MI:0915”(physical association)	0.560
GOLPH3	XRCC5	psi-mi:“MI:0915”(physical association)	0.540

BioGRID (213): GOLPH3 (Two-hybrid), COP1 (Reconstituted Complex), SEC26 (Reconstituted Complex), SEC27 (Reconstituted Complex), SEC21 (Reconstituted Complex), RET2 (Reconstituted Complex), SEC28 (Reconstituted Complex), GOLPH3 (Affinity Capture-MS), GOLPH3 (Affinity Capture-MS), GOLPH3 (Affinity Capture-MS), GMPPB (Affinity Capture-MS), GMPPA (Affinity Capture-MS), WBSCR16 (Affinity Capture-MS), FAM20B (Affinity Capture-MS), TSR3 (Affinity Capture-MS)

ESM2 similar proteins: A0JPI4, A6H7F6, A8WZU5, A8XEZ1, A8XYX3, D8WUA4, F4JIN3, F4JMJ3, O14205, O74737, P0C5E7, P46555, P62583, Q06385, Q0VCR7, Q14156, Q23541, Q3V3R1, Q4VBT2, Q54J20, Q5PPU5, Q5SPP5, Q5U4Q6, Q61T02, Q641A2, Q66H74, Q6C710, Q6FLD4, Q6FPH9, Q6ZQ18, Q75B51, Q8AVH4, Q8BG67, Q8GWG2, Q8IGJ0, Q8R088, Q8STE5, Q8VZM7, Q8WT44, Q96TA2

Diamond homologs: A0JPI4, A6H7F6, O14205, P62583, Q06385, Q5PPU5, Q5U4Q6, Q66H74, Q8R088, Q9CRA5, Q9ERE4, Q9H4A5, Q9H4A6, Q9VQ93

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
GOLPH3	“up-regulates activity”	MTOR
GOLPH3	“up-regulates activity”	mTORC1
GOLPH3	“up-regulates activity”	mTORC2
PRKDC	“up-regulates activity”	GOLPH3	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 174 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
Antigen processing-Cross presentation	5	12.8×	5e-03
ER-Phagosome pathway	8	8.4×	1e-03
Class A/1 (Rhodopsin-like receptors)	11	6.6×	6e-04
GPCR ligand binding	11	5.7×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	8	11.2×	6e-04
monoatomic ion transport	8	8.0×	2e-03
phospholipase C-activating G protein-coupled receptor signaling pathway	9	7.6×	2e-03
positive regulation of cytosolic calcium ion concentration	9	6.8×	2e-03
G protein-coupled receptor signaling pathway	16	3.7×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	19
Likely benign	2
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

1015 predictions. Top by Δscore:

Variant	Effect	Δscore
5:32126632:CTCAC:C	acceptor_gain	1.0000
5:32135565:AGCTT:A	donor_loss	1.0000
5:32135566:GCTTA:G	donor_loss	1.0000
5:32135567:CTT:C	donor_loss	1.0000
5:32135568:TTA:T	donor_loss	1.0000
5:32135570:A:AC	donor_gain	1.0000
5:32135571:C:CC	donor_gain	1.0000
5:32135571:CCA:C	donor_gain	1.0000
5:32135683:TTAC:T	acceptor_gain	1.0000
5:32173817:T:TA	donor_gain	1.0000
5:32173841:T:TA	donor_gain	1.0000
5:32126633:TCAC:T	acceptor_gain	0.9900
5:32126634:CAC:C	acceptor_gain	0.9900
5:32126634:CACC:C	acceptor_gain	0.9900
5:32135570:AC:A	donor_gain	0.9900
5:32135571:CC:C	donor_gain	0.9900
5:32135571:CCACT:C	donor_gain	0.9900
5:32135687:C:CC	acceptor_gain	0.9900
5:32143743:TCTTA:T	donor_loss	0.9900
5:32143744:CTTA:C	donor_loss	0.9900
5:32143745:TTA:T	donor_loss	0.9900
5:32143746:TACCT:T	donor_loss	0.9900
5:32143747:A:AG	donor_loss	0.9900
5:32143748:CCTTT:C	donor_gain	0.9900
5:32143880:CCTAT:C	acceptor_gain	0.9900
5:32173842:C:A	donor_gain	0.9900
5:32173865:T:A	donor_gain	0.9900
5:32126635:AC:A	acceptor_gain	0.9800
5:32126636:CC:C	acceptor_gain	0.9800
5:32126637:C:CC	acceptor_gain	0.9800

AlphaMissense

1934 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:32126503:A:C	H202Q	1.000
5:32126503:A:T	H202Q	1.000
5:32126505:G:C	H202D	1.000
5:32126518:A:C	F197L	1.000
5:32126518:A:T	F197L	1.000
5:32126519:A:C	F197C	1.000
5:32126519:A:G	F197S	1.000
5:32126520:A:G	F197L	1.000
5:32126527:G:C	F194L	1.000
5:32126527:G:T	F194L	1.000
5:32126528:A:C	F194C	1.000
5:32126528:A:G	F194S	1.000
5:32126529:A:G	F194L	1.000
5:32126549:A:C	L187W	1.000
5:32126567:A:G	L181P	1.000
5:32126572:T:A	K179N	1.000
5:32126572:T:G	K179N	1.000
5:32126573:T:A	K179I	1.000
5:32126574:T:C	K179E	1.000
5:32126576:G:T	A178D	1.000
5:32126582:C:G	R176P	1.000
5:32126626:C:A	W161C	1.000
5:32126626:C:G	W161C	1.000
5:32126628:A:G	W161R	1.000
5:32126628:A:T	W161R	1.000
5:32126636:C:A	G158V	1.000
5:32126636:C:T	G158D	1.000
5:32135572:C:G	G158R	1.000
5:32135577:A:G	L156P	1.000
5:32135590:A:G	W152R	1.000

dbSNP variants (sampled 300 via entrez): RS1000011598 (5:32137157 C>G), RS1000063813 (5:32139978 G>A,C,T), RS1000067752 (5:32143617 T>C,G), RS1000165975 (5:32131207 G>T), RS1000254989 (5:32152336 A>G), RS1000307881 (5:32158109 A>C), RS1000317580 (5:32166189 A>G), RS1000350404 (5:32165760 T>C,G), RS1000401975 (5:32125866 T>C), RS1000468221 (5:32136871 T>C), RS1000505917 (5:32132819 A>G), RS1000519893 (5:32140277 G>A), RS1000559627 (5:32132540 C>T), RS1000644373 (5:32171195 C>T), RS1000681635 (5:32167025 A>G)

Disease associations

OMIM: gene MIM:612207 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): primary ovarian failure (MONDO:0005387)

Orphanet (1): NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009391_863	Metabolite levels	1.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010534	suberic acid measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases reaction, increases expression, decreases expression	2
sodium arsenite	decreases expression, increases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	decreases expression	1
ochratoxin A	decreases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
1-(4-(6-bromobenzo(1,3)dioxol-5-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta(c)quinolin-8-yl)ethanone	increases expression	1
4-(6-bromo-1,3-benzodioxol-5-yl)-3a,4,5,9b-3H-cyclopenta(c)quinoline	decreases reaction, increases expression	1
Sunitinib	increases response to substance	1
Arsenic Trioxide	decreases reaction, affects binding	1
Acetaminophen	decreases expression	1
Gemcitabine	increases response to substance	1
Acrolein	increases oxidation, increases abundance, affects cotreatment	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Fluorouracil	increases response to substance	1
Ivermectin	decreases expression	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Tobacco Smoke Pollution	increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SQ27	HAP1 GOLPH3 (-) 1	Cancer cell line	Male
CVCL_SQ28	HAP1 GOLPH3 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT00001951	PHASE2	COMPLETED	Hormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019	PHASE2	WITHDRAWN	Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494	PHASE2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852	PHASE2	SUSPENDED	The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467	PHASE2	UNKNOWN	Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982	PHASE2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
NCT02912104	PHASE1	COMPLETED	A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure
NCT03178695	PHASE1	COMPLETED	Inovium Ovarian Rejuvenation Trials
NCT04815213	PHASE1	ACTIVE_NOT_RECRUITING	The Use of Expandeded Mesenchymal Stromal Cells (MSC) in Premature Ovarian Failure (POF) in Adult Humans
NCT05138367	PHASE1	COMPLETED	Effects of UCA-PSCs in Women With POF
NCT06132542	PHASE1	UNKNOWN	Autologous ADMSC Transplantation in Patients With POI
NCT00948857	PHASE2/PHASE3	TERMINATED	Dehydroepiandrosterone (DHEA) Treatment and Premature Ovarian Failure (POF)
NCT04031456	PHASE2/PHASE3	RECRUITING	Autologous PRP Infusion May Restore Ovarian Function and May Promote Folliculogenesis in POI Patients
NCT02043743	PHASE1/PHASE2	UNKNOWN	Autologous Stem Cells Transplantation in Patients With Idiopathic and Drug Induced Premature Ovarian Failure
NCT02062931	PHASE1/PHASE2	UNKNOWN	Autologous Mesenchymal Stem Cells Transplantation In Women With Premature Ovarian Failure
NCT02151890	PHASE1/PHASE2	COMPLETED	Pregnancy After Stem Cell Transplantation in Premature Ovarian Failure
NCT02372474	PHASE1/PHASE2	COMPLETED	It is a Real The First Baby Of Autologous Stem Cell Therapy in Premature Ovarian Failure
NCT02603744	PHASE1/PHASE2	UNKNOWN	Autologous Adipose Derived Mesenchymal Stromal Cells Transplantation in Women With Premature Ovarian Failure (POF)
NCT02644447	PHASE1/PHASE2	COMPLETED	Transplantation of HUC-MSCs With Injectable Collagen Scaffold for POF
NCT03069209	PHASE1/PHASE2	UNKNOWN	Autologous Bone Marrow-Derived Stem Cell Transplantation in Patients With Premature Ovarian Failure (POF)
NCT03985462	PHASE1/PHASE2	WITHDRAWN	Very Small Embryonic-like Stem Cells for Ovary
NCT04009473	PHASE1/PHASE2	UNKNOWN	Stem Cell Therapy and Growth Factor Ovarian in Vitro Activation
NCT04071574	PHASE1/PHASE2	COMPLETED	Comparative Study on the Efficacy of Ovarian Stimulation Protocols on the Success Rate of ICSI in Female Infertility
NCT04922398	PHASE1/PHASE2	UNKNOWN	Ovarian Injection of PRP (Platelet -Rich Plasma) Vs Normal Saline in Premature Ovarian Insufficiency
NCT05462379	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Autologous Heterotopic Fresh Ovarian Graft in Woman With LACC Eligible for Pelvic Radiotherapy Treatment.
NCT06202547	PHASE1/PHASE2	UNKNOWN	Intra-ovarian Injection of MSC-EVs in Idiopathic Premature Ovarian Failure
NCT01129947	EARLY_PHASE1	WITHDRAWN	The Use of DHEA in Women With Premature Ovarian Failure
NCT05522634	EARLY_PHASE1	UNKNOWN	A Clinical Study of Chinese Herbal Compound TJAOA101 in the Treatment of Premature Ovarian Insufficiency
NCT07308327	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	The Influence of Gut Microbiota on Ovarian Function: A Single-center, Randomized,Double Blind, Parallel-controlled, Exploratory Clinical Trial
NCT00001275	Not specified	COMPLETED	Ovarian Follicle Function in Patients With Primary Ovarian Failure
NCT00001306	Not specified	COMPLETED	Steroid Therapy in Autoimmune Premature Ovarian Failure
NCT00006156	Not specified	COMPLETED	Feasibility Study for Development of an Early Test for Ovarian Failure
NCT00119925	Not specified	UNKNOWN	‘SPRING’-Study: Subfertility Guidelines: Patient Related Implementation in the Netherlands Among Gynaecologists