LONP2

Summary

LONP2 (lon peptidase 2, peroxisomal, HGNC:20598) is a protein-coding gene on chromosome 16q12.1, encoding Lon protease homolog 2, peroxisomal (Q86WA8). ATP-dependent serine protease that mediates the selective degradation of misfolded and unassembled polypeptides in the peroxisomal matrix.

In human, peroxisomes function primarily to catalyze fatty acid beta-oxidation and, as a by-product, produce hydrogen peroxide and superoxide. The protein encoded by this gene is an ATP-dependent protease that likely plays a role in maintaining overall peroxisome homeostasis as well as proteolytically degrading peroxisomal proteins damaged by oxidation. The protein has an N-terminal Lon N substrate recognition domain, an ATPase domain, a proteolytic domain, and, in some isoforms, a C-terminal peroxisome targeting sequence. Alternative splicing results in multiple transcript variants encoding distinct isoforms.

Source: NCBI Gene 83752 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 123 total — 2 pathogenic, 15 likely-pathogenic
• MANE Select transcript: NM_031490

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20598
Approved symbol	LONP2
Name	lon peptidase 2, peroxisomal
Location	16q12.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC4840, LONP, LONPL
Ensembl gene	ENSG00000102910
Ensembl biotype	protein_coding
OMIM	617774
Entrez	83752

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 7 protein_coding, 3 nonsense_mediated_decay, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000285737, ENST00000416006, ENST00000535754, ENST00000564259, ENST00000565185, ENST00000565867, ENST00000566719, ENST00000566755, ENST00000570174, ENST00000894603, ENST00000967323, ENST00000967324, ENST00000967325

RefSeq mRNA: 3 — MANE Select: NM_031490 NM_001300948, NM_001348078, NM_031490

CCDS: CCDS10734, CCDS73880

Canonical transcript exons

ENST00000285737 — 15 exons

Exon	Start	End
ENSE00001020602	48262778	48262872
ENSE00001126174	48351581	48357349
ENSE00001142479	48258618	48258740
ENSE00001142486	48256610	48256741
ENSE00001142495	48252131	48252365
ENSE00001202129	48261424	48261587
ENSE00001825343	48244300	48244621
ENSE00003484399	48348100	48348290
ENSE00003485086	48299662	48299788
ENSE00003500124	48277338	48277479
ENSE00003548227	48270016	48270274
ENSE00003630517	48334216	48334358
ENSE00003640917	48296015	48296165
ENSE00003668059	48347507	48347714
ENSE00003678256	48303172	48303305

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 97.38.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 38.4966 / max 292.9659, expressed in 1820 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
153949	37.8579	1820
153950	0.6388	334

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	97.38	gold quality
right lobe of liver	UBERON:0001114	96.55	gold quality
pituitary gland	UBERON:0000007	96.23	gold quality
adenohypophysis	UBERON:0002196	96.19	gold quality
liver	UBERON:0002107	95.42	gold quality
left lobe of thyroid gland	UBERON:0001120	94.86	gold quality
thyroid gland	UBERON:0002046	94.74	gold quality
caput epididymis	UBERON:0004358	94.64	gold quality
right lobe of thyroid gland	UBERON:0001119	94.48	gold quality
left ovary	UBERON:0002119	94.47	gold quality
tibia	UBERON:0000979	94.20	gold quality
adrenal tissue	UBERON:0018303	94.07	gold quality
right ovary	UBERON:0002118	93.46	gold quality
secondary oocyte	CL:0000655	93.19	gold quality
islet of Langerhans	UBERON:0000006	93.10	gold quality
epithelium of mammary gland	UBERON:0003244	92.83	gold quality
left uterine tube	UBERON:0001303	92.81	gold quality
endocervix	UBERON:0000458	92.78	gold quality
corpus epididymis	UBERON:0004359	92.74	gold quality
gall bladder	UBERON:0002110	92.72	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	92.72	gold quality
lower lobe of lung	UBERON:0008949	92.62	gold quality
calcaneal tendon	UBERON:0003701	92.59	gold quality
cerebellar hemisphere	UBERON:0002245	92.52	gold quality
mammary duct	UBERON:0001765	92.51	gold quality
ventricular zone	UBERON:0003053	92.48	gold quality
right hemisphere of cerebellum	UBERON:0014890	92.40	gold quality
cerebellar cortex	UBERON:0002129	92.39	gold quality
body of pancreas	UBERON:0001150	92.32	gold quality
body of uterus	UBERON:0009853	92.31	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-135922	yes	20.46
E-ANND-3	yes	9.63
E-MTAB-6058	no	873.05

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

70 targeting LONP2, 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-5011-5P	100.00	83.46	5820
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-199A-3P	99.75	70.48	929
HSA-MIR-199B-3P	99.75	70.48	929

Literature-anchored findings (GeneRIF, showing 2)

• The proteolytic activity of oligomeric Tysnd1 is in turn controlled by self-cleavage of Tysnd1 and degradation of Tysnd1 cleavage products by PsLon. (PMID:22002062)
• Findings suggest that LONP2 promotes cervical tumorigenesis via oxidative stress. (PMID:29502128)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	lonp2	ENSDARG00000101438
mus_musculus	Lonp2	ENSMUSG00000047866
rattus_norvegicus	Lonp2	ENSRNOG00000015162
caenorhabditis_elegans		WBGENE00013541

Paralogs (1): LONP1 (ENSG00000196365)

Protein

Protein identifiers

Lon protease homolog 2, peroxisomal — Q86WA8 (reviewed: Q86WA8)

Alternative names: Lon protease-like protein 2, Peroxisomal Lon protease

All UniProt accessions (5): Q86WA8, E7EN44, H3BPF7, H3BQ67, H3BUW8

UniProt curated annotations — full annotation on UniProt →

Function. ATP-dependent serine protease that mediates the selective degradation of misfolded and unassembled polypeptides in the peroxisomal matrix. Necessary for type 2 peroxisome targeting signal (PTS2)-containing protein processing and facilitates peroxisome matrix protein import. May indirectly regulate peroxisomal fatty acid beta-oxidation through degradation of the self-processed forms of TYSND1.

Subunit / interactions. Interacts with PEX5. Interacts with TYSND1. May interact with enzymes involved in beta-oxidation of fatty acids, including ACOX1/AOX.

Subcellular location. Peroxisome matrix.

Tissue specificity. Widely expressed, with high levels in the liver, kidney and pancreas.

Similarity. Belongs to the peptidase S16 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q86WA8-1	1	yes
Q86WA8-2	2

RefSeq proteins (3): NP_001287877, NP_001335007, NP_113678* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003111	Lon_prtase_N	Domain
IPR003593	AAA+_ATPase	Domain
IPR003959	ATPase_AAA_core	Domain
IPR004815	Lon_bac/euk-typ	Family
IPR008268	Peptidase_S16_AS	Active_site
IPR008269	Lon_proteolytic	Domain
IPR014721	Ribsml_uS5_D2-typ_fold_subgr	Homologous_superfamily
IPR015947	PUA-like_sf	Homologous_superfamily
IPR020568	Ribosomal_Su5_D2-typ_SF	Homologous_superfamily
IPR027065	Lon_Prtase	Family
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR027501	Lonp2_euk	Family
IPR046336	Lon_prtase_N_sf	Homologous_superfamily
IPR054594	Lon_lid	Domain

Pfam: PF00004, PF02190, PF05362, PF22667

UniProt features (14 total): mutagenesis site 2, sequence conflict 2, domain 2, active site 2, initiator methionine 1, chain 1, short sequence motif 1, binding site 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86WA8-F1	77.33	0.18

Functional residue map

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

Catalytic / active sites (2): 743; 786

Ligand- & substrate-binding residues (1): 375–382

Post-translational modifications (1): 2

Mutagenesis-validated functional residues (2):

Position	Phenotype
743	reduces degradation of self-processed forms of tysnd1. loss of acox1-processing.
850–852	loss of peroxisomal localization.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-390471	Association of TriC/CCT with target proteins during biosynthesis
R-HSA-9033241	Peroxisomal protein import
R-HSA-390466	Chaperonin-mediated protein folding
R-HSA-391251	Protein folding
R-HSA-392499	Metabolism of proteins
R-HSA-9609507	Protein localization

MSigDB gene sets: 206 (showing top): GOBP_LIPID_MODIFICATION, GOBP_FATTY_ACID_CATABOLIC_PROCESS, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, YANG_BREAST_CANCER_ESR1_BULK_UP, GOBP_PROTEIN_TARGETING, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_KETONE_METABOLIC_PROCESS, GOBP_REGULATION_OF_FATTY_ACID_METABOLIC_PROCESS, GOBP_REGULATION_OF_LIPID_METABOLIC_PROCESS, GOBP_PROTEIN_MATURATION, UEDA_PERIFERAL_CLOCK, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_REGULATION_OF_KETONE_METABOLIC_PROCESS

GO Biological Process (8): protein quality control for misfolded or incompletely synthesized proteins (GO:0006515), protein targeting to peroxisome (GO:0006625), peroxisome organization (GO:0007031), protein processing (GO:0016485), protein import into peroxisome matrix (GO:0016558), regulation of fatty acid beta-oxidation (GO:0031998), proteolysis (GO:0006508), protein catabolic process (GO:0030163)

GO Molecular Function (11): protease binding (GO:0002020), ATP-dependent peptidase activity (GO:0004176), serine-type endopeptidase activity (GO:0004252), ATP binding (GO:0005524), peptidase activity (GO:0008233), ATP hydrolysis activity (GO:0016887), enzyme binding (GO:0019899), nucleotide binding (GO:0000166), protein binding (GO:0005515), serine-type peptidase activity (GO:0008236), hydrolase activity (GO:0016787)

GO Cellular Component (6): nucleus (GO:0005634), peroxisome (GO:0005777), peroxisomal matrix (GO:0005782), cytosol (GO:0005829), membrane (GO:0016020), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Chaperonin-mediated protein folding	1
Protein localization	1
Protein folding	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
establishment of protein localization to peroxisome	2
protein metabolic process	2
peptidase activity	2
ATP-dependent activity	2
protein catabolic process	1
protein targeting	1
organelle organization	1
proteolysis	1
protein maturation	1
peroxisomal membrane transport	1
protein transmembrane import into intracellular organelle	1
protein localization to peroxisome	1
fatty acid beta-oxidation	1
regulation of fatty acid oxidation	1
regulation of lipid catabolic process	1
macromolecule catabolic process	1
enzyme binding	1
endopeptidase activity	1
serine-type peptidase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
ribonucleoside triphosphate phosphatase activity	1
protein binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
serine hydrolase activity	1
catalytic activity	1
intracellular membrane-bounded organelle	1
microbody	1
peroxisome	1
microbody lumen	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2096 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LONP2	CRBN	Q96SW2	855
LONP2	TYSND1	Q2T9J0	718
LONP2	CLPP	Q16740	644
LONP2	HSPD1	P10809	642
LONP2	CLPX	O76031	641
LONP2	PEX5	P50542	550
LONP2	KCNMA1	Q12791	548
LONP2	CLPB	Q9H078	530
LONP2	YME1L1	Q96TA2	520
LONP2	AFG3L2	Q9Y4W6	513
LONP2	HSPE1	P61604	491
LONP2	BTBD2	Q9BX70	489
LONP2	SH2D4B	Q5SQS7	478
LONP2	OMA1	Q96E52	466
LONP2	DNAJA3	Q96EY1	465

IntAct

97 interactions, top by confidence:

A	B	Type	Score
RB1CC1	ATG13	psi-mi:“MI:0914”(association)	0.820
RSPH9	LONP2	psi-mi:“MI:0915”(physical association)	0.740
OS9	HSP90B1	psi-mi:“MI:0914”(association)	0.640
TYSND1	TYSND1	psi-mi:“MI:0914”(association)	0.580
LONP2	SYCE1	psi-mi:“MI:0915”(physical association)	0.560
OS9	AGRN	psi-mi:“MI:0914”(association)	0.530
DKK3	NME4	psi-mi:“MI:0914”(association)	0.530
RSPH9	EIF3H	psi-mi:“MI:0914”(association)	0.530
IL17A	IL2	psi-mi:“MI:0914”(association)	0.530
IGFBP4	CETN3	psi-mi:“MI:0914”(association)	0.530
LIMK1	LIMK2	psi-mi:“MI:0914”(association)	0.530
IGFBP4	MYCBP2	psi-mi:“MI:0914”(association)	0.530
IL1R2	EXOC5	psi-mi:“MI:0914”(association)	0.530
PCDHA3	CYP51A1	psi-mi:“MI:0914”(association)	0.530
CAT	NUDT19	psi-mi:“MI:0914”(association)	0.420
MAPK6		psi-mi:“MI:0914”(association)	0.350
M2	IPO5	psi-mi:“MI:0914”(association)	0.350
M2	AGPS	psi-mi:“MI:0914”(association)	0.350
MKI67	ARHGAP10	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
PCDHA4	TMEM223	psi-mi:“MI:0914”(association)	0.350
SUCLA2	GTPBP10	psi-mi:“MI:0914”(association)	0.350
PCDHA12	KLRG2	psi-mi:“MI:0914”(association)	0.350
CDC16	KRBA1	psi-mi:“MI:0914”(association)	0.350

BioGRID (89): LONP2 (Affinity Capture-MS), LONP2 (Affinity Capture-MS), LONP2 (Affinity Capture-MS), LONP2 (Affinity Capture-MS), LONP2 (Affinity Capture-MS), LONP2 (Affinity Capture-MS), LONP2 (Affinity Capture-MS), LONP2 (Affinity Capture-MS), LONP2 (Affinity Capture-MS), LONP2 (Affinity Capture-MS), LONP2 (Affinity Capture-MS), LONP2 (Affinity Capture-MS), LONP2 (Affinity Capture-MS), LONP2 (Affinity Capture-MS), LONP2 (Affinity Capture-MS)

ESM2 similar proteins: A0A384JAD8, A2Y8X2, B7FSL4, O42945, O59921, O74878, O74932, O82627, O94213, P04713, P09842, P0C585, P31688, P40387, P53993, P78875, P93655, Q00075, Q00217, Q00764, Q00775, Q07158, Q0DEV5, Q3MIB4, Q3SY69, Q42857, Q42919, Q42968, Q43092, Q43134, Q43784, Q4WHW0, Q4WLM9, Q50167, Q54K57, Q54NU9, Q5R6M5, Q6C3K2, Q86WA8, Q8LL05

Diamond homologs: A0LEE9, A0LG61, A0RJ87, A4J7L6, A4XJL4, A5EWF3, A5FG89, A6LD45, A7HK39, A7NM80, A8F811, A8HYF7, A8ZX50, A9B3R2, A9B5N1, A9ETZ9, A9F8L0, A9GBF1, A9GIS9, A9WGB5, B0S2N4, B0TFI9, B0TZA7, B1GZQ6, B2KCC0, B2RII6, B2TFQ5, B2V6N0, B3CLB3, B3E7K2, B3ERM8, B3QSJ7, B4RI01, B5EDX8, B5Y8Q8, B5YFG2, B7GXS7, B8BDV1, B8CY71, B8EMF2

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
LONP2	“down-regulates quantity by destabilization”	TYSND1	cleavage

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 117 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
Peroxisomal protein import	9	20.0×	2e-07
RHOB GTPase cycle	6	11.9×	2e-03
RHOQ GTPase cycle	5	11.6×	7e-03
RHOA GTPase cycle	7	6.7×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	15
Uncertain significance	92
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (17)

Variant ID	HGVS	Classification
1082503	NM_003031.4(SIAH1):c.502A>G (p.Thr168Ala)	Pathogenic
1082506	NM_003031.4(SIAH1):c.121T>G (p.Cys41Gly)	Pathogenic
1082508	NM_003031.4(SIAH1):c.149C>T (p.Pro50Leu)	Likely pathogenic
1685439	NM_003031.4(SIAH1):c.484G>A (p.Asp162Asn)	Likely pathogenic
1711958	NM_003031.4(SIAH1):c.455A>G (p.His152Arg)	Likely pathogenic
1712904	NM_003031.4(SIAH1):c.226C>T (p.Arg76Trp)	Likely pathogenic
3235937	NM_003031.4(SIAH1):c.361dup (p.Cys121fs)	Likely pathogenic
3359032	NM_003031.4(SIAH1):c.15_16insA (p.Ala6fs)	Likely pathogenic
3385363	NM_003031.4(SIAH1):c.19dup (p.Thr7fs)	Likely pathogenic
3385364	NM_003031.4(SIAH1):c.71_75del (p.Ala24fs)	Likely pathogenic
3385365	NM_003031.4(SIAH1):c.104T>A (p.Leu35Ter)	Likely pathogenic
3385366	NM_003031.4(SIAH1):c.165T>A (p.Cys55Ter)	Likely pathogenic
3385367	NM_003031.4(SIAH1):c.337_338del (p.Glu113fs)	Likely pathogenic
3602262	NM_003031.4(SIAH1):c.140A>G (p.Tyr47Cys)	Likely pathogenic
4057265	NM_003031.4(SIAH1):c.288C>G (p.Phe96Leu)	Likely pathogenic
4072245	NM_003031.4(SIAH1):c.23dup (p.Leu9fs)	Likely pathogenic
4814210	NM_003031.4(SIAH1):c.260T>C (p.Met87Thr)	Likely pathogenic

SpliceAI

2927 predictions. Top by Δscore:

Variant	Effect	Δscore
16:48244617:CACAG:C	donor_loss	1.0000
16:48244619:CAGGT:C	donor_loss	1.0000
16:48244620:AGG:A	donor_loss	1.0000
16:48244621:GGTA:G	donor_loss	1.0000
16:48244623:T:G	donor_loss	1.0000
16:48252125:TTTCA:T	acceptor_loss	1.0000
16:48252127:TCAG:T	acceptor_loss	1.0000
16:48252128:CA:C	acceptor_loss	1.0000
16:48252129:A:AC	acceptor_loss	1.0000
16:48252129:AG:A	acceptor_gain	1.0000
16:48252130:GG:G	acceptor_gain	1.0000
16:48252130:GGATT:G	acceptor_gain	1.0000
16:48252361:TAC:T	donor_gain	1.0000
16:48252361:TACAA:T	donor_gain	1.0000
16:48252362:ACA:A	donor_gain	1.0000
16:48252362:ACAA:A	donor_gain	1.0000
16:48252362:ACAAG:A	donor_loss	1.0000
16:48252363:CAAG:C	donor_loss	1.0000
16:48252364:AA:A	donor_gain	1.0000
16:48252366:G:GG	donor_gain	1.0000
16:48252366:G:T	donor_loss	1.0000
16:48256608:A:AG	acceptor_gain	1.0000
16:48256608:AGTT:A	acceptor_gain	1.0000
16:48256609:G:GG	acceptor_gain	1.0000
16:48256609:GTT:G	acceptor_gain	1.0000
16:48256609:GTTG:G	acceptor_gain	1.0000
16:48258616:A:AG	acceptor_gain	1.0000
16:48258617:G:GG	acceptor_gain	1.0000
16:48258617:GA:G	acceptor_gain	1.0000
16:48258733:A:G	donor_gain	1.0000

AlphaMissense

5554 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:48262780:T:C	L297P	1.000
16:48262849:T:C	L320P	1.000
16:48262854:T:A	W322R	1.000
16:48262854:T:C	W322R	1.000
16:48270214:G:C	R394P	1.000
16:48270265:G:C	R411P	1.000
16:48270267:G:A	G412R	1.000
16:48270267:G:C	G412R	1.000
16:48270268:G:A	G412E	1.000
16:48270268:G:T	G412V	1.000
16:48270273:A:G	R414G	1.000
16:48270274:G:C	R414T	1.000
16:48270274:G:T	R414M	1.000
16:48277338:G:C	R414S	1.000
16:48277338:G:T	R414S	1.000
16:48277339:C:A	R415S	1.000
16:48277345:T:C	Y417H	1.000
16:48277349:T:A	V418D	1.000
16:48277351:G:C	G419R	1.000
16:48277352:G:A	G419D	1.000
16:48277354:A:C	S420R	1.000
16:48277356:C:A	S420R	1.000
16:48277356:C:G	S420R	1.000
16:48277363:G:C	G423R	1.000
16:48277364:G:A	G423D	1.000
16:48277364:G:T	G423V	1.000
16:48277420:G:C	D442H	1.000
16:48277421:A:T	D442V	1.000
16:48277423:G:A	E443K	1.000
16:48277424:A:T	E443V	1.000

dbSNP variants (sampled 300 via entrez): RS1000005538 (16:48248215 A>G), RS1000021775 (16:48329963 A>G), RS1000046088 (16:48291584 A>G), RS1000058018 (16:48338152 A>G), RS1000088400 (16:48276506 A>G), RS1000104744 (16:48298174 G>A,T), RS1000125300 (16:48344955 G>A,C), RS1000136108 (16:48297857 G>A), RS1000151842 (16:48248925 C>A), RS1000222114 (16:48346220 C>T), RS1000314842 (16:48260771 G>T), RS1000326940 (16:48359860 G>T), RS1000345590 (16:48260628 A>G), RS1000375224 (16:48343882 G>T), RS1000383539 (16:48312345 G>C)

Disease associations

OMIM: gene MIM:617774 | disease phenotypes: MIM:619314

GenCC curated gene-disease

Mondo (3): Buratti-Harel syndrome (MONDO:0859144), neurodevelopmental disorder (MONDO:0700092), prostate cancer (MONDO:0008315)

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

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625
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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	3
Acetaminophen	decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
uranyl acetate	increases expression	1
bisphenol A	affects methylation, affects cotreatment	1
sodium arsenate	decreases expression	1
trichostatin A	increases expression	1
benzo(e)pyrene	increases methylation	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	increases methylation	1
jinfukang	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Fulvestrant	affects cotreatment, affects methylation	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation	1
Caffeine	decreases phosphorylation	1
Carbamazepine	affects expression	1
Cisplatin	increases expression	1
Ivermectin	decreases expression	1
Lead	affects methylation	1
Methapyrilene	increases methylation	1
Methyl Methanesulfonate	increases expression	1
Phenylmercuric Acetate	affects cotreatment, increases expression	1
Plant Extracts	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
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