SPATA18

Summary

SPATA18 (spermatogenesis associated 18, HGNC:29579) is a protein-coding gene on chromosome 4q12, encoding Mitochondria-eating protein (Q8TC71). Key regulator of mitochondrial quality that mediates the repairing or degradation of unhealthy mitochondria in response to mitochondrial damage.

This gene encodes a p53-inducible protein that is able to induce lysosome-like organelles within mitochondria that eliminate oxidized mitochondrial proteins, thereby contributing to mitochondrial quality control. Dysregulation of mitochondrial quality control is associated with cancer and degenerative diseases. The encoded protein mediates accumulation of the lysosome-like mitochondrial organelles through interaction with B cell lymphoma 2 interacting protein 3 and B cell lymphoma 2 interacting protein 3 like at the outer mitochondrial membrane, which allows translocation of lysosomal proteins to the mitochondrial matrix from the cytosol. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 132671 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 114 total
• MANE Select transcript: NM_145263

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29579
Approved symbol	SPATA18
Name	spermatogenesis associated 18
Location	4q12
Locus type	gene with protein product
Status	Approved
Aliases	FLJ32906
Ensembl gene	ENSG00000163071
Ensembl biotype	protein_coding
OMIM	612814
Entrez	132671

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 13 protein_coding, 4 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay, 2 retained_intron

ENST00000295213, ENST00000419395, ENST00000503055, ENST00000505038, ENST00000505320, ENST00000506829, ENST00000508915, ENST00000510549, ENST00000511028, ENST00000514670, ENST00000851873, ENST00000851874, ENST00000851875, ENST00000851876, ENST00000851877, ENST00000851878, ENST00000851879, ENST00000928447, ENST00000928448, ENST00000957035, ENST00000957036

RefSeq mRNA: 4 — MANE Select: NM_145263 NM_001297608, NM_001346102, NM_001346103, NM_145263

CCDS: CCDS3489, CCDS75124

Canonical transcript exons

ENST00000295213 — 13 exons

Exon	Start	End
ENSE00001071338	52082387	52082510
ENSE00001852064	52094880	52097299
ENSE00002072159	52051304	52051791
ENSE00003494894	52069821	52069916
ENSE00003544732	52062220	52062332
ENSE00003559824	52094527	52094572
ENSE00003570877	52060782	52060897
ENSE00003607657	52078735	52078893
ENSE00003622459	52071917	52072156
ENSE00003637491	52076779	52077040
ENSE00003664203	52060419	52060524
ENSE00003672557	52079744	52079919
ENSE00003674055	52084916	52084999

Expression profiles

Bgee: expression breadth ubiquitous, 214 present calls, max score 99.87.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.7377 / max 187.2003, expressed in 1181 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
47606	4.7377	1181

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	99.87	gold quality
bronchial epithelial cell	CL:0002328	99.27	gold quality
oviduct epithelium	UBERON:0004804	98.89	gold quality
bronchus	UBERON:0002185	98.72	gold quality
right uterine tube	UBERON:0001302	97.89	gold quality
mucosa of paranasal sinus	UBERON:0005030	97.52	gold quality
left testis	UBERON:0004533	94.44	gold quality
right testis	UBERON:0004534	94.43	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.43	gold quality
testis	UBERON:0000473	92.61	gold quality
epithelium of nasopharynx	UBERON:0001951	92.07	gold quality
fallopian tube	UBERON:0003889	90.79	gold quality
nasal cavity epithelium	UBERON:0005384	89.04	gold quality
nasal cavity mucosa	UBERON:0001826	88.31	gold quality
epithelial cell of pancreas	CL:0000083	85.13	gold quality
calcaneal tendon	UBERON:0003701	83.58	gold quality
adult organism	UBERON:0007023	83.58	gold quality
trachea	UBERON:0003126	82.38	gold quality
skin of hip	UBERON:0001554	81.55	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.98	gold quality
right adrenal gland cortex	UBERON:0035827	80.36	gold quality
endometrium	UBERON:0001295	79.93	gold quality
epithelium of mammary gland	UBERON:0003244	79.43	gold quality
mammary duct	UBERON:0001765	79.40	gold quality
minor salivary gland	UBERON:0001830	79.38	gold quality
gall bladder	UBERON:0002110	79.23	gold quality
descending thoracic aorta	UBERON:0002345	78.89	gold quality
caput epididymis	UBERON:0004358	78.80	gold quality
saliva-secreting gland	UBERON:0001044	78.50	gold quality
esophagus squamous epithelium	UBERON:0006920	77.84	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-114	yes	60.84
E-MTAB-10287	yes	25.17
E-ANND-3	yes	9.45

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53, TP63

miRNA regulators (miRDB)

91 targeting SPATA18, 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-4795-3P	100.00	74.62	4024
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-8067	99.86	69.59	2260

Literature-anchored findings (GeneRIF, showing 12)

• beta-sarcoglycan and SPATA18 may have a role in limb-girdle muscular dystrophy type 2E (PMID:16088906)
• Mieap induces intramitochondrial lysosome-like organella that plays a critical role in mitochondrial quality control by eliminating oxidized mitochondrial proteins (PMID:21264221)
• Mieap induced vacuole-like structures (designated as MIV for Mieap-induced vacuole), which engulfed and degraded the unhealthy mitochondria by accumulating lysosomes (PMID:21264228)
• show that SPATA18 transcription is induced by p53 in a variety of cell types of both human and mouse origin (PMID:21300779)
• The physical interaction of Mieap, BNIP3 and NIX at the mitochondrial outer membrane may play a critical role in the translocation of lysosomal proteins from the cytoplasm to the mitochondrial matrix. (PMID:22292033)
• Results show that Mieap induced caspase-dependent mitochondrial apoptosis in breast cancer (BC) cells. Mieap protein was downregulated and its promoter methylated in BC with more aggressive and malignant phenotypes. (PMID:30290054)
• Mieap-induced accumulation of lysosomes within mitochondria (MALM) regulates gastric cancer cell invasion under hypoxia by suppressing reactive oxygen species accumulation. (PMID:30808977)
• DNA damage invokes mitophagy through a pathway involving Spata18. (PMID:32453416)
• Causative role for defective expression of mitochondria-eating protein in accumulation of mitochondria in thyroid oncocytic cell tumors. (PMID:32458504)
• p53/Mieap-regulated mitochondrial quality control plays an important role as a tumor suppressor in gastric and esophageal cancers. (PMID:32736677)
• SPATA18 Expression Predicts Favorable Clinical Outcome in Colorectal Cancer. (PMID:35269894)
• High SPATA18 Expression and its Diagnostic and Prognostic Value in Clear Cell Renal Cell Carcinoma. (PMID:36751118)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	spata18	ENSDARG00000052343
mus_musculus	Spata18	ENSMUSG00000029155
rattus_norvegicus	Spata18	ENSRNOG00000002120
drosophila_melanogaster	CG11498	FBGN0039749

Protein

Protein identifiers

Mitochondria-eating protein — Q8TC71 (reviewed: Q8TC71)

Alternative names: Spermatogenesis-associated protein 18

All UniProt accessions (4): A0A140VKF4, D6RGI2, E7EVV3, Q8TC71

UniProt curated annotations — full annotation on UniProt →

Function. Key regulator of mitochondrial quality that mediates the repairing or degradation of unhealthy mitochondria in response to mitochondrial damage. Mediator of mitochondrial protein catabolic process (also named MALM) by mediating the degradation of damaged proteins inside mitochondria by promoting the accumulation in the mitochondrial matrix of hydrolases that are characteristic of the lysosomal lumen. Also involved in mitochondrion degradation of damaged mitochondria by promoting the formation of vacuole-like structures (named MIV), which engulf and degrade unhealthy mitochondria by accumulating lysosomes. The physical interaction of SPATA18/MIEAP, BNIP3 and BNIP3L/NIX at the mitochondrial outer membrane regulates the opening of a pore in the mitochondrial double membrane in order to mediate the translocation of lysosomal proteins from the cytoplasm to the mitochondrial matrix. Binds cardiolipin. May form molecular condensates (non-membrane-bounded organelles) within mitochondria that compartmentalize and promote cardiolipin metabolism.

Subunit / interactions. Interacts (via coiled-coil domains) with BNIP3L (via BH3 domain). Interacts (via coiled-coil domains) with BNIP3 (via BH3 domain). Interacts with YWHAG/14-3-3 protein gamma; a protein that also plays a role in MALM. Interacts with YWHAG/14-3-3 protein gamma; a protein that also plays a role in MALM.

Subcellular location. Cytoplasm. Cytosol. Mitochondrion outer membrane. Mitochondrion matrix Cytoplasm. Mitochondrion matrix.

Induction. By p53/TP53 and p63/TP63. Directly activated by p53/TP53.

Similarity. Belongs to the MIEAP family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8TC71-1	1, Alpha, Mieap-alpha	yes
Q8TC71-2	2, Beta, Mieap-beta

RefSeq proteins (4): NP_001284537, NP_001333031, NP_001333032, NP_660306* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026169	MIEAP	Family
IPR031981	MIEAP_C	Domain

Pfam: PF16026

UniProt features (21 total): compositionally biased region 5, modified residue 5, region of interest 4, sequence variant 2, coiled-coil region 2, chain 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TC71-F1	75.51	0.40

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 (5): 85, 156, 159, 287, 509

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 96 (showing top): GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, HNF1_Q6, GOBP_PHOSPHATIDYLGLYCEROL_METABOLIC_PROCESS, GOBP_REGULATION_OF_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GOBP_REGULATION_OF_LIPID_METABOLIC_PROCESS, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, ATF1_Q6, ROZANOV_MMP14_TARGETS_UP, GOBP_POSITIVE_REGULATION_OF_PHOSPHORUS_METABOLIC_PROCESS, HFH4_01, GOCC_MITOCHONDRIAL_ENVELOPE, GOBP_GLYCEROPHOSPHOLIPID_METABOLIC_PROCESS

GO Biological Process (6): mitochondrial protein catabolic process (GO:0035694), mitophagy by internal vacuole formation (GO:0035695), positive regulation of cardiolipin metabolic process (GO:1900210), CDP-diacylglycerol biosynthetic process (GO:0016024), cardiolipin biosynthetic process (GO:0032049), cardiolipin acyl-chain remodeling (GO:0035965)

GO Molecular Function (5): identical protein binding (GO:0042802), molecular condensate scaffold activity (GO:0140693), cardiolipin binding (GO:1901612), protein binding (GO:0005515), lipid binding (GO:0008289)

GO Cellular Component (9): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), mitochondrial matrix (GO:0005759), cytosol (GO:0005829), intracellular membrane-bounded organelle (GO:0043231), membrane (GO:0016020), intracellular membraneless organelle (GO:0043232)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cardiolipin metabolic process	3
intracellular anatomical structure	3
mitochondrion	2
binding	2
cytoplasm	2
intracellular organelle	2
mitochondrion organization	1
protein catabolic process	1
autophagy of mitochondrion	1
regulation of cardiolipin metabolic process	1
positive regulation of phospholipid metabolic process	1
CDP-diacylglycerol metabolic process	1
glycerophospholipid biosynthetic process	1
phosphatidylglycerol biosynthetic process	1
protein binding	1
protein-macromolecule adaptor activity	1
phosphatidylglycerol binding	1
nuclear lumen	1
intracellular membrane-bounded organelle	1
mitochondrial membrane	1
organelle outer membrane	1
intracellular organelle lumen	1
membrane-bounded organelle	1
membraneless organelle	1

Protein interactions and networks

STRING

888 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPATA18	SGCB	Q16585	786
SPATA18	BNIP3L	O60238	747
SPATA18	BNIP3	Q12983	628
SPATA18	SPATA45	Q537H7	626
SPATA18	SPATA19	Q7Z5L4	607
SPATA18	OR1E1	P30953	600
SPATA18	SPATA6	Q9NWH7	563
SPATA18	UNC45B	Q8IWX7	541
SPATA18	CFAP161	Q6P656	538
SPATA18	SPATA3	Q8NHX4	534
SPATA18	SPINK14	Q6IE38	527
SPATA18	CCDC146	Q8IYE0	520
SPATA18	SPMIP10	Q6ZNM6	515
SPATA18	SSPN	Q14714	497
SPATA18	OAZ3	Q9UMX2	487

IntAct

53 interactions, top by confidence:

A	B	Type	Score
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
SPATA18	LRIF1	psi-mi:“MI:0915”(physical association)	0.560
GOLGA2	SPATA18	psi-mi:“MI:0915”(physical association)	0.560
PIBF1	SPATA18	psi-mi:“MI:0915”(physical association)	0.560
SPATA18	MAD1L1	psi-mi:“MI:0915”(physical association)	0.560
AIMP2	SPATA18	psi-mi:“MI:0915”(physical association)	0.560
SPATA18	TACC3	psi-mi:“MI:0915”(physical association)	0.560
SPATA18	CARD10	psi-mi:“MI:0915”(physical association)	0.560
CCDC102B	SPATA18	psi-mi:“MI:0915”(physical association)	0.560
EFHC2	SPATA18	psi-mi:“MI:0915”(physical association)	0.560
SPATA18	TGM7	psi-mi:“MI:0915”(physical association)	0.560
GAS8	SPATA18	psi-mi:“MI:0915”(physical association)	0.560
SPATA18	SPATA18	psi-mi:“MI:0915”(physical association)	0.560
HOXA1	SPATA18	psi-mi:“MI:0915”(physical association)	0.560
LRIF1	SPATA18	psi-mi:“MI:0915”(physical association)	0.560
YWHAG	SHTN1	psi-mi:“MI:0914”(association)	0.560
YWHAB	SHTN1	psi-mi:“MI:0914”(association)	0.530
YWHAE	SHTN1	psi-mi:“MI:0914”(association)	0.530
YWHAZ	SHTN1	psi-mi:“MI:0914”(association)	0.530
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350
YWHAH	SHTN1	psi-mi:“MI:0914”(association)	0.350
YWHAQ	SHTN1	psi-mi:“MI:0914”(association)	0.350
YWHAE	DEPDC5	psi-mi:“MI:0914”(association)	0.350
YWHAG	BRAF	psi-mi:“MI:0914”(association)	0.350
YWHAH	FOXO6	psi-mi:“MI:0914”(association)	0.350
ODF2	DDX3X	psi-mi:“MI:2364”(proximity)	0.270
CEP128	CCDC66	psi-mi:“MI:2364”(proximity)	0.270
SPATA18	PIBF1	psi-mi:“MI:0915”(physical association)	0.000
SPATA18	MAD1L1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (33): SPATA18 (Proximity Label-MS), SPATA18 (Proximity Label-MS), SPATA18 (Affinity Capture-MS), SPATA18 (Affinity Capture-MS), SPATA18 (Affinity Capture-MS), SPATA18 (Two-hybrid), SPATA18 (Two-hybrid), SPATA18 (Two-hybrid), SPATA18 (Two-hybrid), SPATA18 (Two-hybrid), SPATA18 (Two-hybrid), SPATA18 (Two-hybrid), SPATA18 (Two-hybrid), SPATA18 (Two-hybrid), SPATA18 (Two-hybrid)

ESM2 similar proteins: A0JP43, A2RRS8, A2RV61, A4IG66, A9ZLX4, D5K8A2, E1BLK7, E1BW58, E9Q9R9, E9QHE3, P79457, Q02225, Q0P557, Q155Q3, Q2VUH7, Q3B7T8, Q3U6K5, Q3ULM0, Q498J5, Q4G0A6, Q4R7V1, Q503Q1, Q5JTW2, Q5RDE3, Q5RF72, Q5U465, Q68EF0, Q6AYB8, Q6AYL6, Q7TP65, Q80TB7, Q80Z25, Q86VD1, Q8C115, Q8C5W4, Q8IY21, Q8IYT8, Q8NAN2, Q8NG08, Q8NHQ1

Diamond homologs: D5K8A2, E1BLK7, E1BW58, Q0P557, Q498J5, Q503Q1, Q6AYL6, Q8TC71, Q95K37

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 29 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
Activation of BAD and translocation to mitochondria	6	240.4×	4e-12
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	6	212.1×	5e-12
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	6	212.1×	5e-12
Activation of BH3-only proteins	6	156.8×	3e-11
RHO GTPases activate PKNs	6	100.2×	4e-10
Intrinsic Pathway for Apoptosis	6	92.5×	6e-10
Transcriptional and post-translational regulation of MITF-M expression and activity	6	56.4×	1e-08
SARS-CoV-1-host interactions	6	55.5×	1e-08

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	70.5×	1e-06
intracellular protein localization	8	32.2×	2e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	95
Likely benign	6
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1915 predictions. Top by Δscore:

Variant	Effect	Δscore
4:52060521:GAAG:G	donor_gain	1.0000
4:52060522:AAGGT:A	donor_loss	1.0000
4:52060523:AGG:A	donor_loss	1.0000
4:52060525:G:GA	donor_loss	1.0000
4:52060526:T:G	donor_loss	1.0000
4:52062204:T:A	acceptor_gain	1.0000
4:52062328:GACGA:G	donor_gain	1.0000
4:52062331:GA:G	donor_gain	1.0000
4:52062333:G:GG	donor_gain	1.0000
4:52062340:G:GT	donor_gain	1.0000
4:52062341:A:T	donor_gain	1.0000
4:52069914:GCA:G	donor_gain	1.0000
4:52069917:G:GG	donor_gain	1.0000
4:52072110:G:GT	donor_gain	1.0000
4:52072153:G:GT	donor_gain	1.0000
4:52072154:A:T	donor_gain	1.0000
4:52077038:GTG:G	donor_gain	1.0000
4:52077041:G:GG	donor_gain	1.0000
4:52078894:G:GG	donor_gain	1.0000
4:52079738:TTTCA:T	acceptor_loss	1.0000
4:52079739:TTCA:T	acceptor_loss	1.0000
4:52079740:TCAG:T	acceptor_loss	1.0000
4:52079741:CA:C	acceptor_loss	1.0000
4:52079743:GGAT:G	acceptor_gain	1.0000
4:52079828:GAGA:G	donor_gain	1.0000
4:52079916:GCAA:G	donor_gain	1.0000
4:52079920:G:GG	donor_gain	1.0000
4:52079942:C:G	donor_gain	1.0000
4:52079948:G:T	donor_gain	1.0000
4:52094521:TTCCA:T	acceptor_loss	1.0000

AlphaMissense

3543 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:52082442:T:A	W471R	1.000
4:52082442:T:C	W471R	1.000
4:52082481:G:A	G484R	1.000
4:52082481:G:C	G484R	1.000
4:52082482:G:A	G484E	1.000
4:52082394:C:A	R455S	0.999
4:52082397:A:C	S456R	0.999
4:52082399:C:A	S456R	0.999
4:52082399:C:G	S456R	0.999
4:52082428:T:A	V466D	0.999
4:52082482:G:T	G484V	0.999
4:52076960:C:A	R314S	0.998
4:52077018:G:C	R333P	0.998
4:52078738:G:C	A342P	0.998
4:52082388:T:C	Y453H	0.998
4:52082406:T:C	S459P	0.998
4:52082436:C:G	H469D	0.998
4:52082444:G:C	W471C	0.998
4:52082444:G:T	W471C	0.998
4:52082446:C:A	P472H	0.998
4:52082446:C:G	P472R	0.998
4:52082449:C:A	A473D	0.998
4:52082452:T:A	L474H	0.998
4:52082488:C:A	A486D	0.998
4:52077033:C:A	A338D	0.997
4:52078741:T:C	F343L	0.997
4:52078743:C:A	F343L	0.997
4:52078743:C:G	F343L	0.997
4:52082388:T:G	Y453D	0.997
4:52082407:C:G	S459W	0.997

dbSNP variants (sampled 300 via entrez): RS1000032921 (4:52083732 A>G), RS10000556 (4:52085278 G>T), RS1000083111 (4:52085093 T>A), RS1000092787 (4:52063955 C>T), RS1000107032 (4:52079756 G>A,T), RS10001290 (4:52077794 C>T), RS1000136674 (4:52084232 G>A), RS1000175872 (4:52073489 C>A), RS1000214856 (4:52090300 T>C), RS1000246031 (4:52090729 C>A), RS1000283773 (4:52066926 C>T), RS1000423041 (4:52096914 A>G), RS1000449769 (4:52086303 A>G), RS1000466420 (4:52083974 C>T), RS1000491264 (4:52052709 T>C)

Disease associations

OMIM: gene MIM:612814 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): prostate cancer (MONDO:0008315)

Orphanet (1): Familial prostate cancer (Orphanet:1331)

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST005991_9	Platelet count	2.000000e-14
GCST006462_18	Uterine fibroids	1.000000e-08
GCST006867_32	Type 2 diabetes	2.000000e-08
GCST008156_81	Hip circumference adjusted for BMI	6.000000e-06
GCST008839_51	Height	2.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, decreases methylation	5
Valproic Acid	affects cotreatment, decreases expression, affects expression	5
Aflatoxin B1	affects expression, increases expression	4
Air Pollutants	increases expression, decreases expression, increases abundance	3
Doxorubicin	affects expression, increases expression	3
Dactinomycin	affects cotreatment, increases expression	2
Etoposide	increases expression	2
Indomethacin	decreases expression, affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Cyclosporine	decreases expression, increases expression	2
Cadmium Chloride	decreases expression	2
6,7-dimethoxy-2-(pyrrolidin-1-yl)-N-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine	increases expression	1
bisphenol F	affects cotreatment, increases expression	1
sotorasib	affects cotreatment, increases expression	1
quercitrin	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment, increases expression	1
nutlin 3	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression, decreases expression	1
trametinib	affects cotreatment, increases expression	1
NVP-BKM120	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Decitabine	affects expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Caffeine	increases phosphorylation	1
Camptothecin	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer