PDSS2

Summary

PDSS2 (decaprenyl diphosphate synthase subunit 2, HGNC:23041) is a protein-coding gene on chromosome 6q21, encoding All trans-polyprenyl-diphosphate synthase PDSS2 (Q86YH6). Heterotetrameric enzyme that catalyzes the condensation of farnesyl diphosphate (FPP), which acts as a primer, and isopentenyl diphosphate (IPP) to produce prenyl diphosphates of varying chain lengths and participates in the determination of the side chain of ubiquinone.

The protein encoded by this gene is an enzyme that synthesizes the prenyl side-chain of coenzyme Q, or ubiquinone, one of the key elements in the respiratory chain. The gene product catalyzes the formation of all trans-polyprenyl pyrophosphates from isopentyl diphosphate in the assembly of polyisoprenoid side chains, the first step in coenzyme Q biosynthesis. Defects in this gene are a cause of coenzyme Q10 deficiency.

Source: NCBI Gene 57107 — RefSeq curated summary.

At a glance

• Gene–disease (curated): coenzyme Q10 deficiency, primary, 3 (Definitive, GenCC) — +2 more curated relationships
• GWAS associations: 7
• Clinical variants (ClinVar): 290 total — 3 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 14
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_020381

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23041
Approved symbol	PDSS2
Name	decaprenyl diphosphate synthase subunit 2
Location	6q21
Locus type	gene with protein product
Status	Approved
Aliases	bA59I9.3, COQ1B
Ensembl gene	ENSG00000164494
Ensembl biotype	protein_coding
OMIM	610564
Entrez	57107

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 13 protein_coding

ENST00000369031, ENST00000369037, ENST00000449027, ENST00000900079, ENST00000900080, ENST00000900081, ENST00000900082, ENST00000900083, ENST00000900084, ENST00000900085, ENST00000900086, ENST00000934234, ENST00000962908

RefSeq mRNA: 1 — MANE Select: NM_020381 NM_020381

CCDS: CCDS5059

Canonical transcript exons

ENST00000369037 — 8 exons

Exon	Start	End
ENSE00001084760	107210439	107210570
ENSE00001084763	107193822	107193854
ENSE00001448665	107152562	107154777
ENSE00001878295	107458990	107459564
ENSE00002437709	107212109	107212282
ENSE00002457666	107334198	107334332
ENSE00002528929	107245548	107245619
ENSE00002532059	107274029	107274227

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 94.00.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.0424 / max 110.7990, expressed in 1797 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
74928	10.6838	1790
74927	1.1866	854
74926	0.7433	466
74925	0.3475	160
74924	0.0811	18

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	94.00	gold quality
nephron tubule	UBERON:0001231	92.97	gold quality
secondary oocyte	CL:0000655	92.38	gold quality
oocyte	CL:0000023	90.67	gold quality
tibia	UBERON:0000979	90.55	gold quality
renal glomerulus	UBERON:0000074	90.28	gold quality
esophagus squamous epithelium	UBERON:0006920	90.20	gold quality
metanephric glomerulus	UBERON:0004736	89.95	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.94	gold quality
visceral pleura	UBERON:0002401	89.73	gold quality
kidney epithelium	UBERON:0004819	89.62	gold quality
parietal pleura	UBERON:0002400	89.30	gold quality
endothelial cell	CL:0000115	88.47	silver quality
pleura	UBERON:0000977	88.46	gold quality
pancreatic ductal cell	CL:0002079	88.16	silver quality
right adrenal gland	UBERON:0001233	88.15	gold quality
right adrenal gland cortex	UBERON:0035827	88.04	gold quality
epithelium of esophagus	UBERON:0001976	87.35	gold quality
squamous epithelium	UBERON:0006914	87.25	gold quality
choroid plexus epithelium	UBERON:0003911	87.17	gold quality
left adrenal gland	UBERON:0001234	86.76	gold quality
tendon of biceps brachii	UBERON:0008188	86.40	silver quality
left adrenal gland cortex	UBERON:0035825	86.24	gold quality
gingival epithelium	UBERON:0001949	86.16	silver quality
palpebral conjunctiva	UBERON:0001812	85.93	gold quality
adrenal cortex	UBERON:0001235	85.88	gold quality
adrenal gland	UBERON:0002369	85.65	gold quality
right lobe of liver	UBERON:0001114	85.04	gold quality
germinal epithelium of ovary	UBERON:0001304	84.97	gold quality
liver	UBERON:0002107	84.91	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.44

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

128 targeting PDSS2, 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-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-302C-5P	99.97	72.56	3642
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
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 14)

• murine and human solanesyl and decaprenyl diphosphate synthases are heterotetramers composed of newly characterized hDPS1 (mSPS1) and hDLP1 (mDLP1). (PMID:16262699)
• Expression of PDSS2 is downregulated in human gastric cancer. PDSS2 may be a potent gastric cancer growth suppressor in vitro acting through apoptosis pathways. (PMID:19209031)
• Data show that expression of either dlp1 or dps1 recovered the thermo-sensitive growth of an E. coli ispB(R321A) mutant and restored IspB activity and production of Coenzyme Q-8. (PMID:20051244)
• Loss of PDSS2 expression is associated with non-small cell lung cancer. (PMID:23312889)
• Human PDSS2 polymorphisms are associated with podocyte diseases. A deficiency of coenzyme Q10 is manifested in lymphoblastoid cell lines derived from focal segmental glomerulosclerosis patients. (PMID:23926186)
• PDSS2 has tumor-suppressing activity in human lung cancer cells by enhancing apoptosis and inhibiting tumorigenic capacity. (PMID:24608273)
• Decreased PDSS2 mRNA levels were detected in HCC tissues of 56 patients, correlated with shorter disease-specific survival, and was identified as an independent prognostic factor (PMID:25189544)
• PDSS2 encodes a putative tumor suppressor, and its expression is regulated by hypermethylation of its promoter in gastric cancer cells. (PMID:25330808)
• Decreased PDSS2 expression is an unfavorable prognostic factor for hepatocellular carcinoma, and PDSS2 has potent anticancer activity in HCC tissues and HepG2 cells. (PMID:25780306)
• Results indicate PDSS2 gene which regulates coffee consumption by regulating the expression of the genes linked to caffeine metabolism. (PMID:27561104)
• Knockdown of PDSS2 induced chromosomal instability in the MIHA immortalized human liver cell line. Furthermore, knockdown of PDSS2 in MIHA induced malignant transformation. Overall, our findings indicate that PDSS2 deficiency might be a novel driving factor in hepatocellular carcinoma (HCC) development (PMID:29967258)
• Study identified the promoter region of the PDSS2 gene for the first time and demonstrated that Sp1 transcription factor could directly regulate the transcription of PDSS2. Also, the expression of Sp1 and PDSS2 are negatively correlated, and higher Sp1 expression with low PDSS2 expression is significantly associated with poor prognosis in lung cancer. (PMID:31783675)
• PDSS2-Del2, a new variant of PDSS2, promotes tumor cell metastasis and angiogenesis in hepatocellular carcinoma via activating NF-kappaB. (PMID:33064899)
• PDSS2 Inhibits the Ferroptosis of Vascular Endothelial Cells in Atherosclerosis by Activating Nrf2. (PMID:33929387)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	pdss2	ENSDARG00000012563
mus_musculus	Pdss2	ENSMUSG00000038240
rattus_norvegicus	Pdss2	ENSRNOG00000042962
drosophila_melanogaster	Pdss2	FBGN0037044

Paralogs (2): PDSS1 (ENSG00000148459), GGPS1 (ENSG00000152904)

Protein

Protein identifiers

All trans-polyprenyl-diphosphate synthase PDSS2 — Q86YH6 (reviewed: Q86YH6)

Alternative names: All-trans-decaprenyl-diphosphate synthase subunit 2, Candidate tumor suppressor protein, Decaprenyl pyrophosphate synthase subunit 2, Decaprenyl-diphosphate synthase subunit 2, Solanesyl-diphosphate synthase subunit 2

All UniProt accessions (3): Q86YH6, B4DKU5, Q5JRD6

UniProt curated annotations — full annotation on UniProt →

Function. Heterotetrameric enzyme that catalyzes the condensation of farnesyl diphosphate (FPP), which acts as a primer, and isopentenyl diphosphate (IPP) to produce prenyl diphosphates of varying chain lengths and participates in the determination of the side chain of ubiquinone. Supplies nona and decaprenyl diphosphate, the precursors for the side chain of the isoprenoid quinones ubiquinone-9 (Q9) and ubiquinone-10 (Q10) respectively. The enzyme adds isopentenyl diphosphate molecules sequentially to farnesyl diphosphate with trans stereochemistry. May play a role during cerebellar development. May regulate mitochondrial respiratory chain function.

Subunit / interactions. Heterotetramer composed of 2 PDSS1/DPS1 and 2 PDSS2/DLP1 subunits.

Subcellular location. Mitochondrion.

Disease relevance. Coenzyme Q10 deficiency, primary, 3 (COQ10D3) [MIM:614652] A fatal encephalomyopathic form of coenzyme Q10 deficiency with nephrotic syndrome. Coenzyme Q10 deficiency is an autosomal recessive disorder with variable manifestations consistent with 5 major phenotypes. The phenotypes include an encephalomyopathic form with seizures and ataxia; a multisystem infantile form with encephalopathy, cardiomyopathy and renal failure; a predominantly cerebellar form with ataxia and cerebellar atrophy; Leigh syndrome with growth retardation; and an isolated myopathic form. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Cofactor biosynthesis; ubiquinone biosynthesis.

Similarity. Belongs to the FPP/GGPP synthase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q86YH6-1	1	yes
Q86YH6-2	2

RefSeq proteins (1): NP_065114* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000092	Polyprenyl_synt	Family
IPR008949	Isoprenoid_synthase_dom_sf	Homologous_superfamily

Pfam: PF00348

Enzyme classification (BRENDA):

• EC 2.5.1.91 — all-trans-decaprenyl-diphosphate synthase (BRENDA: 11 organisms, 23 substrates, 0 inhibitors, 54 Km, 12 kcat entries)

Substrate kinetics (BRENDA)

9 substrates with measured Km, best-characterized 9. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
(2E,6E)-FARNESYL DIPHOSPHATE	0.0001–0.084	22
(2E,6E,10E)-GERANYLGERANYL DIPHOSPHATE	0.0001–0.04	12
GERANYLGERANYL DIPHOSPHATE	0.0001–0.0037	9
GERANYL DIPHOSPHATE	0.005–0.49	5
ISOPENTENYL DIPHOSPHATE	0.0138–0.089	2
(2E,6Z)-FARNESYL DIPHOSPHATE	0.29	1
ALL-E-GERANYLGERANYL DIPHOSPHATE	0.0029	1
GERANYL GERANYL DIPHOSPHATE	0.0115	1
NERYL DIPHOSPHATE	0.029	1

Catalyzed reactions (Rhea), 2 shown:

• 7 isopentenyl diphosphate + (2E,6E)-farnesyl diphosphate = all-trans-decaprenyl diphosphate + 7 diphosphate (RHEA:27802)
• 6 isopentenyl diphosphate + (2E,6E)-farnesyl diphosphate = all-trans-nonaprenyl diphosphate + 6 diphosphate (RHEA:55364)

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

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86YH6-F1	80.28	0.53

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-2142789	Ubiquinol biosynthesis

MSigDB gene sets: 167 (showing top): GOBP_HINDBRAIN_DEVELOPMENT, GOBP_METENCEPHALON_DEVELOPMENT, GOBP_KETONE_METABOLIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, CATTTCA_MIR203, AML_Q6, BLALOCK_ALZHEIMERS_DISEASE_UP, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, KEGG_TERPENOID_BACKBONE_BIOSYNTHESIS, GOCC_MITOCHONDRIAL_ENVELOPE, TATCTGG_MIR488, GOBP_LIPID_METABOLIC_PROCESS, GOBP_HEAD_DEVELOPMENT, GOBP_KETONE_BIOSYNTHETIC_PROCESS, GOBP_LIPID_BIOSYNTHETIC_PROCESS

GO Biological Process (5): ubiquinone biosynthetic process (GO:0006744), isoprenoid biosynthetic process (GO:0008299), cerebellum development (GO:0021549), regulation of body fluid levels (GO:0050878), lipid metabolic process (GO:0006629)

GO Molecular Function (6): prenyltransferase activity (GO:0004659), protein heterodimerization activity (GO:0046982), all-trans-nonaprenyl-diphosphate synthase (geranyl-diphosphate specific) activity (GO:0052923), all-trans-decaprenyl-diphosphate synthase activity (GO:0097269), protein binding (GO:0005515), transferase activity (GO:0016740)

GO Cellular Component (7): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), cytosol (GO:0005829), polyprenyl diphosphate synthase complex (GO:0032476), heterotetrameric polyprenyl diphosphate synthase complex (GO:0032478), ubiquinone biosynthesis complex (GO:0110142), transferase complex (GO:1990234)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Metabolism of cofactors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
prenyl diphosphate synthase activity	2
cytoplasm	2
catalytic complex	2
ubiquinone metabolic process	1
quinone biosynthetic process	1
isoprenoid metabolic process	1
lipid biosynthetic process	1
metencephalon development	1
anatomical structure development	1
regulation of biological quality	1
primary metabolic process	1
transferase activity, transferring alkyl or aryl (other than methyl) groups	1
protein dimerization activity	1
binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1
cellular anatomical structure	1
transferase complex	1
polyprenyl diphosphate synthase complex	1
inner mitochondrial membrane protein complex	1

Protein interactions and networks

STRING

2342 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PDSS2	COQ2	Q96H96	980
PDSS2	COQ8A	Q8NI60	969
PDSS2	COQ9	O75208	968
PDSS2	COQ6	Q9Y2Z9	913
PDSS2	COQ4	Q9Y3A0	874
PDSS2	COQ8B	Q96D53	859
PDSS2	COQ7	Q99807	843
PDSS2	COQ5	Q5HYK3	811
PDSS2	APTX	Q7Z2E3	803
PDSS2	PDSS1	Q5T2R2	800
PDSS2	COQ3	Q9NZJ6	794
PDSS2	ETFDH	Q16134	711
PDSS2	MAGOHB	Q96A72	687
PDSS2	MAGOH	P50606	687
PDSS2	IPO5	O00410	667

IntAct

33 interactions, top by confidence:

A	B	Type	Score
SDHA	SDHB	psi-mi:“MI:0914”(association)	0.820
FDPS	ZMPSTE24	psi-mi:“MI:0914”(association)	0.530
COX5B	COX7A2L	psi-mi:“MI:0914”(association)	0.530
ACAD9	PPL	psi-mi:“MI:0914”(association)	0.530
ACAT1	PDSS2	psi-mi:“MI:0915”(physical association)	0.400
PDSS2	ispB	psi-mi:“MI:0915”(physical association)	0.400
ACAD9	A2ML1	psi-mi:“MI:0914”(association)	0.350
OXLD1	NUDT19	psi-mi:“MI:0914”(association)	0.350
THEM4	KIAA0391	psi-mi:“MI:0914”(association)	0.350
UQCRFS1	VWA8	psi-mi:“MI:0914”(association)	0.350
NPTN	RTL8C	psi-mi:“MI:0914”(association)	0.350
MRPS24	NUDT19	psi-mi:“MI:0914”(association)	0.350
ISCA1	BACH1	psi-mi:“MI:0914”(association)	0.350
OXLD1	PRORP	psi-mi:“MI:0914”(association)	0.350
THEM4	PRORP	psi-mi:“MI:0914”(association)	0.350
H2AP	GNPAT	psi-mi:“MI:0914”(association)	0.350
LINC02872	NMT2	psi-mi:“MI:0914”(association)	0.350
MRPS25	ZNF865	psi-mi:“MI:0914”(association)	0.350
PCSK1N	CLTCL1	psi-mi:“MI:0914”(association)	0.350
MCCD1	USP4	psi-mi:“MI:0914”(association)	0.350
FECH	GTPBP10	psi-mi:“MI:0914”(association)	0.350
AKT1	PDSS2	psi-mi:“MI:2364”(proximity)	0.270
BRAF	PDSS2	psi-mi:“MI:2364”(proximity)	0.270
SMAD4	PDSS2	psi-mi:“MI:2364”(proximity)	0.270
PDSS2	SMAD4	psi-mi:“MI:2364”(proximity)	0.270
PDSS2	SPOP	psi-mi:“MI:2364”(proximity)	0.270
SPOP	PDSS2	psi-mi:“MI:2364”(proximity)	0.270
EGFR	PDSS2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (39): PDSS2 (Affinity Capture-MS), PDSS2 (Affinity Capture-MS), PDSS2 (Affinity Capture-MS), PDSS2 (Affinity Capture-MS), PDSS2 (Affinity Capture-MS), PDSS2 (Affinity Capture-MS), PDSS2 (Negative Genetic), PDSS2 (Positive Genetic), PDSS2 (Positive Genetic), SNRPG (Negative Genetic), TIMELESS (Negative Genetic), PDSS2 (Proximity Label-MS), PDSS2 (Proximity Label-MS), PDSS2 (Affinity Capture-RNA), PDSS2 (Affinity Capture-MS)

ESM2 similar proteins: B2RTY4, E7EZG2, E7F3F0, F4I507, F4JIU4, F4K0A6, O23653, O43502, O43795, O81770, P00860, P09057, P11926, P21271, P27117, P27118, P27119, P27120, P46735, P70569, Q02440, Q05096, Q13459, Q33DR3, Q5VQ09, Q63358, Q6ZLP5, Q86YH6, Q8C170, Q8R2J9, Q8W0Z9, Q99104, Q9FL12, Q9FZ06, Q9FZL4, Q9LFG8, Q9LHE9, Q9LPC6, Q9LYU8, Q9M8Z7

Diamond homologs: A0A0A7GEY4, A0A0U3BRC5, A0A0U5G0B1, A0A1B4XBK0, A0A1V1FVQ6, A0A2Z6AQX6, A0A348FUE1, A0A7D0AGU9, B1XJV9, C9K2Q3, K2SUY0, O04046, O05572, O06428, O22043, O24743, O26156, O43091, O50410, O66126, O66952, P0A5H9, P0AD57, P0AD58, P17060, P21684, P22939, P31114, P31171, P34802, P39464, P44916, P45204, P48368, P51268, P54383, P55539, P55785, P72580, P80042

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 42 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
Respiratory electron transport	6	19.7×	7e-05
Aerobic respiration and respiratory electron transport	5	15.3×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	4
Uncertain significance	134
Likely benign	112
Benign	17

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
1200	NM_020381.4(PDSS2):c.964C>T (p.Gln322Ter)	Pathogenic
214994	NM_020381.4(PDSS2):c.877-2A>G	Pathogenic
685834	GRCh37/hg19 6q21(chr6:107573260-107767076)x1	Pathogenic
214995	NM_020381.4(PDSS2):c.874A>G (p.Lys292Glu)	Likely pathogenic
3592875	NM_020381.4(PDSS2):c.401_402del (p.Asn134fs)	Likely pathogenic
3592877	NM_020381.4(PDSS2):c.183dup (p.Tyr62fs)	Likely pathogenic
3592878	NM_020381.4(PDSS2):c.129dup (p.Lys44fs)	Likely pathogenic

SpliceAI

3189 predictions. Top by Δscore:

Variant	Effect	Δscore
6:107154774:GCAA:G	acceptor_gain	1.0000
6:107154775:CAAC:C	acceptor_gain	1.0000
6:107154776:AA:A	acceptor_gain	1.0000
6:107154778:C:CC	acceptor_gain	1.0000
6:107193817:CCTAC:C	donor_loss	1.0000
6:107193819:TACCT:T	donor_loss	1.0000
6:107193820:A:AG	donor_loss	1.0000
6:107193821:C:T	donor_loss	1.0000
6:107193855:C:CA	acceptor_loss	1.0000
6:107193855:C:CC	acceptor_gain	1.0000
6:107212104:AGTAC:A	donor_loss	1.0000
6:107212105:GTACC:G	donor_loss	1.0000
6:107212106:TAC:T	donor_loss	1.0000
6:107212107:A:AG	donor_loss	1.0000
6:107212108:CCT:C	donor_loss	1.0000
6:107212138:A:AC	donor_gain	1.0000
6:107212139:C:CC	donor_gain	1.0000
6:107212153:TCTGA:T	donor_gain	1.0000
6:107212278:CTTTC:C	acceptor_gain	1.0000
6:107212279:TTTC:T	acceptor_gain	1.0000
6:107212280:TTC:T	acceptor_gain	1.0000
6:107212281:TC:T	acceptor_gain	1.0000
6:107212281:TCC:T	acceptor_loss	1.0000
6:107212282:CC:C	acceptor_gain	1.0000
6:107212283:C:CC	acceptor_gain	1.0000
6:107212283:CTAAA:C	acceptor_loss	1.0000
6:107212289:A:AC	acceptor_gain	1.0000
6:107212289:A:C	acceptor_gain	1.0000
6:107212291:G:C	acceptor_gain	1.0000
6:107245617:AACCT:A	acceptor_loss	1.0000

AlphaMissense

2607 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:107212199:G:C	S262R	0.995
6:107212199:G:T	S262R	0.995
6:107212201:T:G	S262R	0.995
6:107212192:C:G	A265P	0.994
6:107212198:A:G	C263R	0.993
6:107334276:A:G	L118P	0.993
6:107459120:C:G	A56P	0.993
6:107274086:A:C	S191R	0.992
6:107274086:A:T	S191R	0.992
6:107274088:T:G	S191R	0.992
6:107334265:C:G	A122P	0.992
6:107212135:C:A	G284W	0.990
6:107274064:C:G	A199P	0.990
6:107334276:A:T	L118H	0.990
6:107154705:C:G	A372P	0.989
6:107274075:A:G	L195P	0.989
6:107274214:C:G	A149P	0.989
6:107274198:A:G	L154P	0.988
6:107212134:C:T	G284E	0.987
6:107212196:G:C	C263W	0.986
6:107274063:G:T	A199D	0.986
6:107274081:T:G	D193A	0.986
6:107274213:G:T	A149E	0.986
6:107334279:A:G	L117P	0.986
6:107154656:A:G	L388S	0.985
6:107212138:A:C	Y283D	0.985
6:107212115:A:C	S290R	0.984
6:107212115:A:T	S290R	0.984
6:107212117:T:G	S290R	0.984
6:107212146:G:T	A280E	0.984

dbSNP variants (sampled 300 via entrez): RS1000014071 (6:107182656 G>C), RS1000028575 (6:107394814 T>A,C), RS1000029408 (6:107226962 C>T), RS1000035961 (6:107424843 C>T), RS1000036732 (6:107246396 C>A,G), RS1000047114 (6:107202359 C>T), RS1000050414 (6:107338182 C>A), RS1000059200 (6:107439812 C>G,T), RS1000061333 (6:107394520 C>A), RS1000061597 (6:107182348 A>C), RS1000067681 (6:107274326 C>T), RS1000074530 (6:107205446 G>A), RS1000079236 (6:107417065 A>G), RS1000087510 (6:107387810 C>T), RS1000089999 (6:107245804 T>C)

Disease associations

OMIM: gene MIM:610564 | disease phenotypes: MIM:614652

GenCC curated gene-disease

Disease	Classification	Inheritance
coenzyme Q10 deficiency, primary, 3	Definitive	Autosomal recessive
Leigh syndrome with nephrotic syndrome	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Leigh syndrome	Moderate	AR

Mondo (5): coenzyme Q10 deficiency, primary, 3 (MONDO:0013838), nephrotic syndrome (MONDO:0005377), kidney disorder (MONDO:0005240), focal segmental glomerulosclerosis (MONDO:0100313), (MONDO:0016816)

Orphanet (1): Leigh syndrome with nephrotic syndrome (Orphanet:255249)

HPO phenotypes

14 total (14 of 14 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000093	Proteinuria
HP:0000100	Nephrotic syndrome
HP:0000969	Edema
HP:0001319	Neonatal hypotonia
HP:0002151	Increased circulating lactate concentration
HP:0003073	Hypoalbuminemia
HP:0003623	Neonatal onset
HP:0007183	Focal T2 hyperintense basal ganglia lesion
HP:0007334	Bilateral tonic-clonic seizure with focal onset
HP:0011968	Feeding difficulties
HP:0032663	Focal motor status epilepticus
HP:0034369	Decreased level of coenzyme Q10 in skeletal muscle
HP:0100704	Cerebral visual impairment

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002724_13	Airway responsiveness in chronic obstructive pulmonary disease	1.000000e-06
GCST002724_21	Airway responsiveness in chronic obstructive pulmonary disease	2.000000e-06
GCST002986_2	Childhood and early adolescence aggressive behavior	1.000000e-06
GCST003253_6	Microalbuminuria	9.000000e-06
GCST004800_3	Forced expiratory volume in 1 second (environmental tobacco smoke interaction)	8.000000e-06
GCST005175_49	Coronary artery calcified atherosclerotic plaque (90 or 130 HU threshold) in type 2 diabetes	9.000000e-07
GCST009391_685	Metabolite levels	4.000000e-06

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0006897	airway responsiveness measurement
EFO:0004314	forced expiratory volume
EFO:0008361	environmental tobacco smoke exposure measurement
EFO:0004723	coronary artery calcification
EFO:0008529	kynurenine measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D005923	Glomerulosclerosis, Focal Segmental	C12.050.351.968.419.570.363.640; C12.200.777.419.570.363.660; C12.950.419.570.363.640
D007674	Kidney Diseases	C12.050.351.968.419; C12.200.777.419; C12.950.419
D009404	Nephrotic Syndrome	C12.050.351.968.419.630.643; C12.200.777.419.630.643; C12.950.419.630.643

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
Benzo(a)pyrene	decreases expression, increases methylation	7
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	5
Hydrogen Peroxide	affects expression, affects cotreatment, increases expression	3
Aflatoxin B1	affects expression, decreases expression	3
Nickel	decreases expression	2
aristolochic acid I	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
deoxynivalenol	increases expression	1
trichostatin A	increases expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
triacsin C	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	decreases expression	1
Atrazine	decreases expression	1
Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone	increases expression	1
Cisplatin	decreases expression	1
Doxorubicin	decreases expression	1
Formaldehyde	decreases expression	1
Phenobarbital	affects expression	1
Plant Extracts	affects cotreatment, increases expression	1
Quercetin	decreases expression	1
Selenium	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E2GL	HAP1 PDSS2 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00308321	PHASE4	UNKNOWN	Long Term Tapering or Standard Steroids for Nephrotic Syndrome
NCT01021540	PHASE4	COMPLETED	Prospective Study Evaluating the Effect of Repository Corticotropin in the Treatment of Various Nephrotic Syndromes
NCT01028287	PHASE4	COMPLETED	Adrenocorticotropic Hormone (ACTH) Treatment of Nephrotic Range Proteinuria in Diabetic Nephropathy (NRDN)
NCT01162005	PHASE4	COMPLETED	Therapeutic Effect of Tacrolimus on Primary Nephrotic Syndrome in Children
NCT01895894	PHASE4	COMPLETED	Mycophenolate Mofetil in Pediatric Steroid Dependent Nephrotic Syndrome
NCT02238418	PHASE4	COMPLETED	Efficacy of Usual Vitamin D Supplementation and Its Impact on Children and Adolescents Calciuria.
NCT02382575	PHASE4	UNKNOWN	Efficacy and Safety of Rituximab to That of Calcineurin Inhibitors in Children With Steroid Resistant Nephrotic Syndrome
NCT02427880	PHASE4	COMPLETED	Role of Acetazolamide and Hydrochlorothiazide Followed by Furosemide in Treating Nephrotic Edema
NCT03210688	PHASE4	COMPLETED	Active Vitamin D And Reduced Dose Prednisolone for Treatment in Minimal Change Nephropathy
NCT03347357	PHASE4	COMPLETED	Pharmacokinetics of Tacrolimus in Children
NCT05696977	PHASE4	UNKNOWN	Effect of Obesity on Cyclosporine Blood Trough Level in Nephrotic Syndrome Patients
NCT05966818	PHASE4	UNKNOWN	Effect of Dapagliflozin in Non-Diabetic Patients With Nephrotic Syndrome.
NCT06026787	PHASE4	COMPLETED	Clinical Value of Adding Dapagliflozin in Patients With Nephrotic Syndrome
NCT00067990	PHASE4	COMPLETED	Angiotensin II Blockade for Chronic Allograft Nephropathy
NCT00117078	PHASE4	COMPLETED	Aranesp® Monthly Preference Study - 2
NCT00117130	PHASE4	COMPLETED	Study to Evaluate Effectiveness of Aranesp®
NCT00132431	PHASE4	COMPLETED	START: Sensipar Treatment Algorithm to Reach K/DOQI Targets in Chronic Kidney Disease Subjects With Secondary Hyperparathyroidism
NCT00140985	PHASE4	COMPLETED	Antiproteinuric Efficacy of Losartan Potassium in Patients With Non-Diabetic Proteinuric Renal Diseases (0954-213)
NCT00246129	PHASE4	COMPLETED	CamTac Trial:Campath-Tacrolimus vs IL2R MoAb/Tacrolimus/MMF in Renal Transplantation
NCT00275535	PHASE4	COMPLETED	The Comparison of Tacrolimus and Sirolimus Immunosuppression Based Drug Regimens in Kidney Transplant Recipients
NCT00282217	PHASE4	COMPLETED	Study Evaluating Sirolimus in the Treatment of Kidney Transplant
NCT00289614	PHASE4	COMPLETED	Patients With Renal Impairment and Diabetes Undergoing Computed Tomography (CT)
NCT00290069	PHASE4	UNKNOWN	Renal Function Optimization With Mycophenolate Mofetil (MMF) Immunosuppressor Regimes (ALHAMBRA)
NCT00338468	PHASE4	TERMINATED	A Study to Assess Disability in Anemic Elderly Patients With Kidney Disease Receiving PROCRIT (Epoetin Alfa)
NCT00368901	PHASE4	COMPLETED	STAAR-2 Clinical Study
NCT00369733	PHASE4	COMPLETED	STAAR-3 Clinical Study
NCT00369772	PHASE4	COMPLETED	STAAR-1 Clinical Study
NCT00379899	PHASE4	COMPLETED	ADVANCE: Study to Evaluate Cinacalcet Plus Low Dose Vitamin D on Vascular Calcification in Subjects With Chronic Kidney Disease Receiving Hemodialysis
NCT00443508	PHASE4	UNKNOWN	Reduction or Discontinuation of CNI’s With Conversion to Everolimus-Based Immunosuppresion
NCT00452478	PHASE4	TERMINATED	Conversion From Standard Phosphate Binder Therapy to Fosrenol® (Lanthanum Carbonate) in Chronic Kidney Disease Stage 5
NCT00492518	PHASE4	COMPLETED	Acetylcysteine, Theophylline, and a Combination of Both in the Prophylaxis of Contrast-Induced Nephropathy
NCT00505102	PHASE4	UNKNOWN	Safe Renal Function In Long Term Heart Transplanted Patients
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00688480	PHASE4	COMPLETED	Do Xanthine Oxidase Inhibitors Reduce Both Left Ventricular Hypertrophy and Endothelial Dysfunction in Cardiovascular Patients With Renal Dysfunction?
NCT00863707	PHASE4	COMPLETED	A Study of the Safety and Tolerance of Regadenoson in Subjects With Renal Impairment
NCT01101698	PHASE4	UNKNOWN	Vitamin K2 and Vessel Calcification in Chronic Kidney Disease Patients
NCT01150201	PHASE4	COMPLETED	Aliskiren Combined With Losartan in Proteinuric, Non-diabetic Chronic Kidney Disease
NCT01155141	PHASE4	COMPLETED	Idiopathic Focal Segmental Glomerulosclerosis (FSGS) and Treatment With ACTH
NCT01228279	PHASE4	COMPLETED	Sympathetic Activity in Patients With End-stage Renal Disease on Peritoneal Dialysis
NCT01334333	PHASE4	COMPLETED	Comparison of Medication Adherence Between Once and Twice Daily Tacrolimus in Stable Renal Transplant Recipients