PDSS1

Summary

PDSS1 (decaprenyl diphosphate synthase subunit 1, HGNC:17759) is a protein-coding gene on chromosome 10p12.1, encoding All trans-polyprenyl-diphosphate synthase PDSS1 (Q5T2R2). 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. It is a selective cancer dependency (DepMap: 17.6% of cell lines).

The protein encoded by this gene is an enzyme that elongates 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. The protein may be peripherally associated with the inner mitochondrial membrane, though no transit peptide has been definitively identified to date. Defects in this gene are a cause of coenzyme Q10 deficiency.

Source: NCBI Gene 23590 — RefSeq curated summary.

At a glance

• Gene–disease (curated): deafness-encephaloneuropathy-obesity-valvulopathy syndrome (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 428 total — 7 pathogenic, 9 likely-pathogenic
• Phenotypes (HPO): 17
• Cancer dependency (DepMap): dependent in 17.6% of screened cell lines
• MANE Select transcript: NM_014317

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17759
Approved symbol	PDSS1
Name	decaprenyl diphosphate synthase subunit 1
Location	10p12.1
Locus type	gene with protein product
Status	Approved
Aliases	TPT, COQ1, COQ1A
Ensembl gene	ENSG00000148459
Ensembl biotype	protein_coding
OMIM	607429
Entrez	23590

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 7 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000376215, ENST00000470978, ENST00000473224, ENST00000491711, ENST00000869578, ENST00000869579, ENST00000917008, ENST00000917009, ENST00000944249, ENST00000944250

RefSeq mRNA: 3 — MANE Select: NM_014317 NM_001321978, NM_001321979, NM_014317

CCDS: CCDS31168

Canonical transcript exons

ENST00000376215 — 12 exons

Exon	Start	End
ENSE00000993752	26724014	26724123
ENSE00001605478	26702162	26702194
ENSE00001629104	26705286	26705394
ENSE00001704490	26704677	26704741
ENSE00001727057	26697701	26697840
ENSE00001748927	26720218	26720359
ENSE00001916839	26746333	26746798
ENSE00003477402	26709638	26709768
ENSE00003508335	26735240	26735320
ENSE00003544636	26742497	26742577
ENSE00003579846	26723806	26723917
ENSE00003669372	26735466	26735579

Expression profiles

Bgee: expression breadth ubiquitous, 242 present calls, max score 90.82.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.1591 / max 612.0219, expressed in 1772 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
104432	12.0166	1769
104430	1.3907	325
104429	1.3825	97
104423	0.5013	107
104425	0.3890	103
104426	0.1319	48
104431	0.1135	56
104428	0.1075	39
104424	0.0658	29
104427	0.0604	22

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	90.82	gold quality
rectum	UBERON:0001052	89.65	gold quality
jejunal mucosa	UBERON:0000399	87.92	gold quality
duodenum	UBERON:0002114	87.45	gold quality
monocyte	CL:0000576	84.76	gold quality
transverse colon	UBERON:0001157	84.49	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.28	gold quality
mononuclear cell	CL:0000842	84.28	gold quality
lower esophagus mucosa	UBERON:0035834	83.87	gold quality
leukocyte	CL:0000738	83.81	gold quality
small intestine Peyer’s patch	UBERON:0003454	83.60	gold quality
small intestine	UBERON:0002108	83.02	gold quality
cerebellar hemisphere	UBERON:0002245	82.90	gold quality
colonic mucosa	UBERON:0000317	82.85	gold quality
cerebellar cortex	UBERON:0002129	82.79	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.73	gold quality
ileal mucosa	UBERON:0000331	82.70	gold quality
right hemisphere of cerebellum	UBERON:0014890	82.33	gold quality
mucosa of sigmoid colon	UBERON:0004993	82.23	gold quality
ganglionic eminence	UBERON:0004023	81.83	gold quality
hindlimb stylopod muscle	UBERON:0004252	81.73	gold quality
intestine	UBERON:0000160	81.40	gold quality
esophagus mucosa	UBERON:0002469	81.23	gold quality
cerebellum	UBERON:0002037	81.04	gold quality
large intestine	UBERON:0000059	80.76	gold quality
colon	UBERON:0001155	80.70	gold quality
muscle of leg	UBERON:0001383	80.46	gold quality
gastrocnemius	UBERON:0001388	80.32	gold quality
calcaneal tendon	UBERON:0003701	80.15	gold quality
esophagus squamous epithelium	UBERON:0006920	80.04	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.08

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

62 targeting PDSS1, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-561-3P	99.64	70.90	3647

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 17.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 8)

• murine and human solanesyl and decaprenyl diphosphate synthases are heterotetramers composed of newly characterized hDPS1 (mSPS1) and hDLP1 (mDLP1) (PMID:16262699)
• A deletirious mutation D308E that causes severe ubiquinone deficiency was identified in PDSS1. (PMID:17332895)
• low CoQ10 is another factor explaining the risk to cardiovascular disorder in depression (PMID:20010493)
• lowered levels of CoQ10 play a role in the pathophysiology of myalgic encephalomyelitis/ chronic fatigue and that symptoms, such as fatigue, and autonomic and neurocognitive symptoms may be caused by CoQ10 depletion (PMID:20010505)
• 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)
• Genetic variants in PDSS1 and SLC16A6 of the ketone body metabolic pathway predict cutaneous melanoma-specific survival. (PMID:32232919)
• Missense PDSS1 mutations in CoenzymeQ10 synthesis cause optic atrophy and sensorineural deafness. (PMID:33285023)
• PDSS1-Mediated Activation of CAMK2A-STAT3 Signaling Promotes Metastasis in Triple-Negative Breast Cancer. (PMID:34408002)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pdss1	ENSDARG00000017910
mus_musculus	Pdss1	ENSMUSG00000026784
rattus_norvegicus	Pdss1	ENSRNOG00000048849
drosophila_melanogaster	qless	FBGN0051005
caenorhabditis_elegans	coq-1	WBGENE00000761

Paralogs (2): GGPS1 (ENSG00000152904), PDSS2 (ENSG00000164494)

Protein

Protein identifiers

All trans-polyprenyl-diphosphate synthase PDSS1 — Q5T2R2 (reviewed: Q5T2R2)

Alternative names: All-trans-decaprenyl-diphosphate synthase subunit 1, Decaprenyl pyrophosphate synthase subunit 1, Decaprenyl-diphosphate synthase subunit 1, Solanesyl-diphosphate synthase subunit 1, Trans-prenyltransferase 1

All UniProt accessions (2): Q5T2R2, H0YEE6

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.

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

Subcellular location. Mitochondrion.

Disease relevance. Coenzyme Q10 deficiency, primary, 2 (COQ10D2) [MIM:614651] An autosomal recessive multisystem disorder characterized by early-onset deafness, optic atrophy, mild intellectual disability, peripheral neuropathy, obesity, livedo reticularis, and cardiac valvulopathy. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 2 Mg(2+) ions per subunit.

Pathway. Cofactor biosynthesis; ubiquinone biosynthesis.

Similarity. Belongs to the FPP/GGPP synthase family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q5T2R2-1	1	yes
Q5T2R2-2	2
Q5T2R2-3	3

RefSeq proteins (3): NP_001308907, NP_001308908, NP_055132* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000092	Polyprenyl_synt	Family
IPR008949	Isoprenoid_synthase_dom_sf	Homologous_superfamily
IPR033749	Polyprenyl_synt_CS	Conserved_site

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 (29 total): sequence conflict 16, binding site 8, splice variant 2, chain 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5T2R2-F1	78.45	0.63

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 (8): 134; 137; 173; 180; 180; 184; 184; 190

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-2142789	Ubiquinol biosynthesis

MSigDB gene sets: 214 (showing top): BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_KETONE_METABOLIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, FOSTER_TOLERANT_MACROPHAGE_UP, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, BLALOCK_ALZHEIMERS_DISEASE_UP, KEGG_TERPENOID_BACKBONE_BIOSYNTHESIS, GOCC_MITOCHONDRIAL_ENVELOPE, GOBP_LIPID_METABOLIC_PROCESS, GOBP_KETONE_BIOSYNTHETIC_PROCESS, DODD_NASOPHARYNGEAL_CARCINOMA_UP, GOBP_LIPID_BIOSYNTHETIC_PROCESS

GO Biological Process (4): ubiquinone biosynthetic process (GO:0006744), isoprenoid biosynthetic process (GO:0008299), lipid metabolic process (GO:0006629), quinone biosynthetic process (GO:1901663)

GO Molecular Function (7): prenyltransferase activity (GO:0004659), metal ion binding (GO:0046872), 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 (6): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), 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
catalytic complex	2
ubiquinone metabolic process	1
quinone biosynthetic process	1
isoprenoid metabolic process	1
lipid biosynthetic process	1
primary metabolic process	1
ketone biosynthetic process	1
quinone metabolic process	1
transferase activity, transferring alkyl or aryl (other than methyl) groups	1
cation binding	1
protein dimerization activity	1
binding	1
catalytic activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1
transferase complex	1
polyprenyl diphosphate synthase complex	1
inner mitochondrial membrane protein complex	1

Protein interactions and networks

STRING

1754 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PDSS1	COQ8A	Q8NI60	988
PDSS1	COQ9	O75208	985
PDSS1	COQ2	Q96H96	984
PDSS1	COQ8B	Q96D53	935
PDSS1	COQ4	Q9Y3A0	916
PDSS1	COQ6	Q9Y2Z9	898
PDSS1	COQ5	Q5HYK3	874
PDSS1	COQ7	Q99807	869
PDSS1	COQ3	Q9NZJ6	864
PDSS1	APTX	Q7Z2E3	836
PDSS1	PDSS2	Q86YH6	800
PDSS1	ETFDH	Q16134	716
PDSS1	COQ10A	Q96MF6	636
PDSS1	COQ10B	Q9H8M1	626
PDSS1	GGPS1	O95749	584

IntAct

19 interactions, top by confidence:

A	B	Type	Score
SDHA	SDHB	psi-mi:“MI:0914”(association)	0.820
FCGRT	GOLIM4	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
FDPS	ZMPSTE24	psi-mi:“MI:0914”(association)	0.530
NECTIN4	EIF2B2	psi-mi:“MI:0914”(association)	0.530
ACAD9	NDUFS2	psi-mi:“MI:0914”(association)	0.350
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
GYPA	HYKK	psi-mi:“MI:0914”(association)	0.350
SEMA4C	ARVCF	psi-mi:“MI:0914”(association)	0.350
TNFSF13B	TNPO2	psi-mi:“MI:0914”(association)	0.350
THEM4	PRORP	psi-mi:“MI:0914”(association)	0.350
LINC02872	NMT2	psi-mi:“MI:0914”(association)	0.350
PCSK1N	CLTCL1	psi-mi:“MI:0914”(association)	0.350
PDSS1	PCBP3	psi-mi:“MI:0914”(association)	0.350
MCCD1	USP4	psi-mi:“MI:0914”(association)	0.350
NECTIN4	EIF2B5	psi-mi:“MI:0914”(association)	0.350
SLC27A1	RIMOC1	psi-mi:“MI:0914”(association)	0.350

BioGRID (38): PDSS1 (Affinity Capture-MS), PDSS1 (Affinity Capture-MS), PDSS1 (Affinity Capture-MS), PDSS1 (Affinity Capture-MS), PDSS1 (Affinity Capture-MS), PDSS1 (Affinity Capture-MS), PDSS1 (Affinity Capture-MS), PDSS1 (Affinity Capture-MS), PDSS1 (Affinity Capture-MS), PDSS1 (Affinity Capture-MS), PDSS1 (Affinity Capture-MS), PDSS1 (Affinity Capture-MS), PDSS1 (Proximity Label-MS), PDSS1 (Proximity Label-MS), PDSS1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0E3D8M9, A0A0E3D8P4, A0A0P0ZD79, A0A140JWS2, A0A1L9UKS1, A0A1U8QLG8, A0A1V0QSA8, A0A2I6PJ05, A0A2Z6AQX6, A0A3Q9FFM1, A0A3S5XFG0, A0A7D0AGU9, A0A858E6N7, A0A858E7G0, A0A858E7J4, A0A8D5M3Y5, B2DBE8, B2DBE9, D3U715, E9F5E9, F9WWF1, F9WZD2, F9XLC1, H1VQB1, I1RL14, J7FIX8, O00763, P0DL13, P24322, P9WEQ2, P9WEW2, P9WEW8, P9WEX3, P9WEX9, Q09152, Q33DR2, Q4WBI4, Q4WP25, Q56RZ3, Q56RZ7

Diamond homologs: A0A0A7GEY4, A0A0U3BRC5, A0A8K1AY78, B1XJV9, O04046, O06428, O22043, O24743, O26156, O43091, O50410, O66126, O66952, P0A5H9, P0AD57, P0AD58, P17060, P21684, P22873, P22939, P31171, P34802, P39464, P44916, P45204, P48368, P54383, P54976, P55539, P55785, P57537, P72580, P80042, P95999, P9WKH0, P9WKH1, Q08291, Q0INZ4, Q33DR2, Q39108

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 33 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	24.8×	8e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	9
Uncertain significance	172
Likely benign	133
Benign	62

Top pathogenic / likely-pathogenic (16)

Variant ID	HGVS	Classification
1033282	NM_014317.5(PDSS1):c.1164_1165del (p.Ile388fs)	Pathogenic
214985	NM_014317.5(PDSS1):c.968del (p.Thr323fs)	Pathogenic
2499453	NM_014317.5(PDSS1):c.735G>T (p.Gln245His)	Pathogenic
2499454	NM_014317.5(PDSS1):c.716T>G (p.Val239Gly)	Pathogenic
3237	NM_014317.5(PDSS1):c.924T>G (p.Asp308Glu)	Pathogenic
375348	NM_014317.5(PDSS1):c.1108A>C (p.Ser370Arg)	Pathogenic
687975	GRCh37/hg19 10p12.1(chr10:27005348-27022507)x1	Pathogenic
1878854	NM_014317.5(PDSS1):c.18G>A (p.Trp6Ter)	Likely pathogenic
214984	NM_014317.5(PDSS1):c.336+5G>T	Likely pathogenic
2499451	NM_014317.5(PDSS1):c.661C>T (p.Arg221Ter)	Likely pathogenic
2500794	NM_014317.5(PDSS1):c.173_174insA (p.Ile58_Asn59insTer)	Likely pathogenic
3338756	NM_014317.5(PDSS1):c.622G>T (p.Gly208Ter)	Likely pathogenic
3594203	NM_014317.5(PDSS1):c.52dup (p.Ala18fs)	Likely pathogenic
3594270	NM_014317.5(PDSS1):c.436C>T (p.Arg146Ter)	Likely pathogenic
3767224	NM_014317.5(PDSS1):c.668G>T (p.Gly223Val)	Likely pathogenic
4081585	NM_014317.5(PDSS1):c.709_710insCA (p.Asp237fs)	Likely pathogenic

SpliceAI

1553 predictions. Top by Δscore:

Variant	Effect	Δscore
10:26697838:CAG:C	donor_loss	1.0000
10:26697839:AG:A	donor_loss	1.0000
10:26697840:GG:G	donor_loss	1.0000
10:26697842:T:A	donor_loss	1.0000
10:26702195:G:GC	donor_loss	1.0000
10:26702196:T:G	donor_loss	1.0000
10:26705278:T:G	acceptor_gain	1.0000
10:26705282:CCA:C	acceptor_loss	1.0000
10:26705283:CA:C	acceptor_loss	1.0000
10:26705284:A:AC	acceptor_loss	1.0000
10:26705285:G:GT	acceptor_loss	1.0000
10:26724009:TATA:T	acceptor_loss	1.0000
10:26724011:TA:T	acceptor_loss	1.0000
10:26724012:A:AG	acceptor_gain	1.0000
10:26724012:A:C	acceptor_loss	1.0000
10:26724013:G:GG	acceptor_gain	1.0000
10:26724013:GGT:G	acceptor_gain	1.0000
10:26724013:GGTGA:G	acceptor_gain	1.0000
10:26724113:GTT:G	donor_gain	1.0000
10:26724118:AAAGC:A	donor_gain	1.0000
10:26724119:AAGCA:A	donor_gain	1.0000
10:26724120:AGCA:A	donor_gain	1.0000
10:26724121:GCA:G	donor_gain	1.0000
10:26724121:GCAG:G	donor_gain	1.0000
10:26724124:G:GG	donor_gain	1.0000
10:26724128:G:GG	donor_gain	1.0000
10:26735237:CA:C	acceptor_loss	1.0000
10:26735239:GGT:G	acceptor_gain	1.0000
10:26735239:GGTCT:G	acceptor_gain	1.0000
10:26735317:TCAG:T	donor_loss	1.0000

AlphaMissense

2698 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:26720289:A:T	D180V	1.000
10:26720273:G:C	A175P	0.999
10:26720276:A:C	S176R	0.999
10:26720278:T:A	S176R	0.999
10:26720278:T:G	S176R	0.999
10:26720280:T:C	L177P	0.999
10:26720288:G:C	D180H	0.999
10:26720289:A:C	D180A	0.999
10:26720290:T:A	D180E	0.999
10:26720290:T:G	D180E	0.999
10:26720291:G:C	D181H	0.999
10:26720292:A:T	D181V	0.999
10:26720300:G:C	D184H	0.999
10:26720301:A:T	D184V	0.999
10:26720302:C:A	D184E	0.999
10:26720302:C:G	D184E	0.999
10:26720319:G:C	R190T	0.999
10:26723917:G:C	G241R	0.999
10:26724092:C:T	T267I	0.999
10:26724095:C:A	A268D	0.999
10:26724107:C:A	A272D	0.999
10:26735295:G:A	G296E	0.999
10:26735295:G:T	G296V	0.999
10:26735306:G:A	G300R	0.999
10:26735306:G:C	G300R	0.999
10:26735307:G:A	G300E	0.999
10:26735315:T:C	F303L	0.999
10:26735317:T:A	F303L	0.999
10:26735317:T:G	F303L	0.999
10:26735467:T:C	L305P	0.999

dbSNP variants (sampled 300 via entrez): RS1000013311 (10:26744367 A>T), RS1000231837 (10:26698616 G>C), RS1000250712 (10:26738769 CCT>C), RS1000253396 (10:26706411 G>C), RS1000292163 (10:26695779 C>T), RS1000308277 (10:26716431 C>T), RS1000360477 (10:26700987 C>T), RS1000414359 (10:26700673 G>GT), RS1000448027 (10:26744066 C>T), RS1000581775 (10:26740142 A>C), RS1000599096 (10:26696606 T>C,G), RS1000613178 (10:26709166 G>A), RS1000643829 (10:26715188 G>T), RS1000699179 (10:26702153 A>G), RS1000855921 (10:26722190 G>T)

Disease associations

OMIM: gene MIM:607429 | disease phenotypes: MIM:614651, MIM:181500

GenCC curated gene-disease

Disease	Classification	Inheritance
deafness-encephaloneuropathy-obesity-valvulopathy syndrome	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
mitochondrial disease	Moderate	AR

Mondo (2): deafness-encephaloneuropathy-obesity-valvulopathy syndrome (MONDO:0013837), schizophrenia (MONDO:0005090)

Orphanet (2): Deafness-encephaloneuropathy-obesity-valvulopathy syndrome (Orphanet:254898), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

17 total (18 of 17 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000256	Macrocephaly
HP:0000365	Hearing impairment
HP:0000648	Optic atrophy
HP:0001256	Mild intellectual disability
HP:0001284	Areflexia
HP:0001513	Obesity
HP:0001653	Mitral regurgitation
HP:0001659	Aortic regurgitation
HP:0002092	Pulmonary arterial hypertension
HP:0002151	Increased circulating lactate concentration
HP:0009830	Peripheral neuropathy
HP:0011463	Childhood onset
HP:0025502	Overweight
HP:0032653	Elevated lactate:pyruvate ratio
HP:0033505	Livedo reticularis
HP:0100739	Bulimia
HP:0100753	Schizophrenia

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST004896_1	Overall survival in serous epithelial ovarian cancer treated with paclitaxel and cisplatin	9.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0000638	overall survival

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	3
Valproic Acid	increases expression, affects expression, decreases expression	3
Acetaminophen	decreases expression	2
Cisplatin	affects cotreatment, decreases expression, increases reaction	2
Estradiol	increases expression	2
Hydrogen Peroxide	affects expression, increases expression	2
Cyclosporine	decreases expression	2
afuresertib	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	decreases expression	1
trichostatin A	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
GW 4064	decreases expression, affects cotreatment	1
6-(4-chlorophenyl)imidazo(2,1-b)(1,3)thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime	increases expression, affects cotreatment	1
ICG 001	decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
NSC 689534	affects binding, decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Atrazine	decreases expression	1
Calcitriol	decreases expression, affects cotreatment	1
Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone	decreases expression	1
Copper	affects binding, decreases expression	1
Coumestrol	affects cotreatment, increases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Doxorubicin	decreases expression	1
Farnesol	increases expression	1
Lipopolysaccharides	increases expression, affects response to substance	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E2GK	HAP1 PDSS1 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	PHASE4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008	PHASE4	COMPLETED	Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety