PARS2

Summary

PARS2 (prolyl-tRNA synthetase 2, mitochondrial, HGNC:30563) is a protein-coding gene on chromosome 1p32.3, encoding Probable proline–tRNA ligase, mitochondrial (Q7L3T8). Mitochondrial aminoacyl-tRNA synthetase that catalyzes the specific attachment of the proline amino acid (aa) to the homologous transfer RNA (tRNA), further participating in protein synthesis. It is a selective cancer dependency (DepMap: 53.1% of cell lines).

This gene encodes a putative member of the class II family of aminoacyl-tRNA synthetases. These enzymes play a critical role in protein biosynthesis by charging tRNAs with their cognate amino acids. This protein is encoded by the nuclear genome but is likely to be imported to the mitochondrion where it is thought to catalyze the ligation of proline to tRNA molecules. Mutations have been found in this gene in some patients with Alpers syndrome.

Source: NCBI Gene 25973 — RefSeq curated summary.

At a glance

• Gene–disease (curated): developmental and epileptic encephalopathy, 75 (Strong, GenCC) — +2 more curated relationships
• Clinical variants (ClinVar): 216 total — 1 pathogenic, 7 likely-pathogenic
• Phenotypes (HPO): 76
• Cancer dependency (DepMap): dependent in 53.1% of screened cell lines
• MANE Select transcript: NM_152268

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30563
Approved symbol	PARS2
Name	prolyl-tRNA synthetase 2, mitochondrial
Location	1p32.3
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp727A071
Ensembl gene	ENSG00000162396
Ensembl biotype	protein_coding
OMIM	612036
Entrez	25973

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000371279, ENST00000887740

RefSeq mRNA: 1 — MANE Select: NM_152268 NM_152268

CCDS: CCDS597

Canonical transcript exons

ENST00000371279 — 2 exons

Exon	Start	End
ENSE00001217294	54764461	54764523
ENSE00001454836	54756898	54759190

Expression profiles

Bgee: expression breadth ubiquitous, 193 present calls, max score 89.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.5342 / max 25.0981, expressed in 1562 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
12473	3.5342	1562

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	89.61	gold quality
oocyte	CL:0000023	89.59	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.19	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.13	gold quality
epithelial cell of pancreas	CL:0000083	82.87	gold quality
sperm	CL:0000019	80.35	silver quality
left ventricle myocardium	UBERON:0006566	80.32	gold quality
cardiac muscle of right atrium	UBERON:0003379	80.20	gold quality
kidney epithelium	UBERON:0004819	78.85	gold quality
buccal mucosa cell	CL:0002336	78.08	silver quality
myocardium	UBERON:0002349	76.85	gold quality
biceps brachii	UBERON:0001507	76.64	silver quality
mucosa of transverse colon	UBERON:0004991	76.34	gold quality
stromal cell of endometrium	CL:0002255	76.26	gold quality
ileal mucosa	UBERON:0000331	76.03	silver quality
Brodmann (1909) area 23	UBERON:0013554	75.98	silver quality
palpebral conjunctiva	UBERON:0001812	74.56	gold quality
nasal cavity epithelium	UBERON:0005384	74.55	gold quality
islet of Langerhans	UBERON:0000006	74.10	gold quality
gingival epithelium	UBERON:0001949	73.82	silver quality
gingiva	UBERON:0001828	73.04	silver quality
colonic mucosa	UBERON:0000317	72.66	gold quality
muscle tissue	UBERON:0002385	72.52	gold quality
hindlimb stylopod muscle	UBERON:0004252	72.25	gold quality
adrenal tissue	UBERON:0018303	72.24	gold quality
germinal epithelium of ovary	UBERON:0001304	71.91	silver quality
gastrocnemius	UBERON:0001388	71.85	gold quality
muscle of leg	UBERON:0001383	71.81	gold quality
bronchial epithelial cell	CL:0002328	71.76	gold quality
skeletal muscle tissue	UBERON:0001134	71.65	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.67

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

47 targeting PARS2, 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-4500	99.99	72.72	2367
HSA-MIR-4531	99.99	69.70	3181
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-513C-5P	99.50	68.42	1730
HSA-MIR-514B-5P	99.50	68.19	1766
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-8065	99.19	70.38	1289
HSA-MIR-3152-3P	99.10	66.35	678
HSA-MIR-3168	99.08	67.75	1384

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 53.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 6)

• unusual 2.0 A structure showing that ATP directly locks onto and orients two parts of halofuginone (HF) onto human ProRS, so that one part of HF mimics bound proline and the other mimics the 3’ end of bound tRNA. (PMID:23263184)
• The PARS2 gene produced a significant association signal in a recent replication study of all known CRS-associations and is now the first human gene to be re-sequenced within CRS research. PARS2 showed an accumulation of low-frequency variants in CRS patients compared to background populations. (PMID:27348859)
• The individuals with PARS2 and NARS2 mutations demonstrate similar neurological features as those previously reported, with diversity in clinical presentation such as hearing loss and seizure type. (PMID:28077841)
• Depending on available data of six patients from three families, we describe a phenotype linked to PARS2 pathological variants. This phenotype includes: early epileptic encephalopathy, infantile spasms, and Alpers-like brain MRI changes with predominance of frontal cerebral volume loss (FCVL-AS). (PMID:29410512)
• study provides further evidence for validating the role of PARS2 in the pathology of related infantile-onset encephalopathy, contributing to the phenotypic features of this condition, and providing clinical and molecular insight for the diagnosis of this disease entity. (PMID:29915213)
• Novel mutation in PARS2 revealed highly variable phenotype of developmental and epileptic encephalopathy-75. (PMID:37956963)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pars2	ENSDARG00000044404
mus_musculus	Pars2	ENSMUSG00000043572
rattus_norvegicus	Pars2	ENSRNOG00000007327
drosophila_melanogaster	ProRS-m	FBGN0027082
caenorhabditis_elegans	pars-2	WBGENE00004190

Paralogs (4): TARS1 (ENSG00000113407), TARS2 (ENSG00000143374), MRPL39 (ENSG00000154719), TARS3 (ENSG00000185418)

Protein

Protein identifiers

Probable proline–tRNA ligase, mitochondrial — Q7L3T8 (reviewed: Q7L3T8)

Alternative names: Prolyl-tRNA synthetase, Prolyl-tRNA synthetase 2, mitochondrial

All UniProt accessions (1): Q7L3T8

UniProt curated annotations — full annotation on UniProt →

Function. Mitochondrial aminoacyl-tRNA synthetase that catalyzes the specific attachment of the proline amino acid (aa) to the homologous transfer RNA (tRNA), further participating in protein synthesis. The reaction occurs in a two steps: proline is first activated by ATP to form Pro-AMP and then transferred to the acceptor end of tRNA(Pro).

Subcellular location. Mitochondrion matrix.

Disease relevance. Developmental and epileptic encephalopathy 75 (DEE75) [MIM:618437] A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE75 is an autosomal recessive form characterized by onset of severe refractory seizures in the first months of life. The disease may be caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the class-II aminoacyl-tRNA synthetase family.

RefSeq proteins (1): NP_689481* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002314	aa-tRNA-synt_IIb	Domain
IPR002316	Pro-tRNA-ligase_IIa	Family
IPR004154	Anticodon-bd	Domain
IPR006195	aa-tRNA-synth_II	Domain
IPR033730	ProRS_core_prok	Domain
IPR036621	Anticodon-bd_dom_sf	Homologous_superfamily
IPR045864	aa-tRNA-synth_II/BPL/LPL	Homologous_superfamily
IPR050062	Pro-tRNA_synthetase	Family

Pfam: PF00587, PF03129

Catalyzed reactions (Rhea), 1 shown:

• tRNA(Pro) + L-proline + ATP = L-prolyl-tRNA(Pro) + AMP + diphosphate (RHEA:14305)

UniProt features (11 total): sequence variant 9, transit peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7L3T8-F1	88.30	0.79

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-379726	Mitochondrial tRNA aminoacylation
R-HSA-379724	tRNA Aminoacylation
R-HSA-392499	Metabolism of proteins
R-HSA-72766	Translation

MSigDB gene sets: 215 (showing top): GOBP_AMINO_ACID_ACTIVATION, MODULE_255, GOBP_TRNA_METABOLIC_PROCESS, MODULE_317, GOBP_TRANSLATION, KEGG_AMINOACYL_TRNA_BIOSYNTHESIS, REACTOME_MITOCHONDRIAL_TRNA_AMINOACYLATION, CETS1P54_01, GOCC_MITOCHONDRIAL_MATRIX, MARSON_BOUND_BY_E2F4_UNSTIMULATED, MODULE_69, SCGGAAGY_ELK1_02, GOMF_LIGASE_ACTIVITY_FORMING_CARBON_OXYGEN_BONDS, GOMF_ADENYL_NUCLEOTIDE_BINDING, MODULE_37

GO Biological Process (3): prolyl-tRNA aminoacylation (GO:0006433), translation (GO:0006412), tRNA aminoacylation for protein translation (GO:0006418)

GO Molecular Function (5): proline-tRNA ligase activity (GO:0004827), ATP binding (GO:0005524), nucleotide binding (GO:0000166), aminoacyl-tRNA ligase activity (GO:0004812), ligase activity (GO:0016874)

GO Cellular Component (3): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
tRNA Aminoacylation	1
Translation	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
tRNA aminoacylation for protein translation	1
peptidyltransferase activity	1
translational initiation	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
translation	1
tRNA aminoacylation	1
aminoacyl-tRNA ligase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
ligase activity, forming carbon-oxygen bonds	1
catalytic activity, acting on a tRNA	1
catalytic activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

2194 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PARS2	EPRS1	P07814	993
PARS2	IARS1	P41252	973
PARS2	QARS1	P47897	965
PARS2	LARS2	Q15031	963
PARS2	LARS1	Q9P2J5	961
PARS2	IARS2	Q9NSE4	956
PARS2	KARS1	Q15046	928
PARS2	MARS2	Q96GW9	896
PARS2	CARS2	Q9HA77	888
PARS2	YARS2	Q9Y2Z4	887
PARS2	CARS1	P49589	883
PARS2	WARS2	Q9UGM6	882
PARS2	YARS1	P54577	881
PARS2	EARS2	Q5JPH6	881
PARS2	MARS1	P56192	880

IntAct

36 interactions, top by confidence:

A	B	Type	Score
PRKAA1	PRKAB2	psi-mi:“MI:0914”(association)	0.950
DLD	PDHX	psi-mi:“MI:0914”(association)	0.880
PRKAB2	GYS1	psi-mi:“MI:0914”(association)	0.730
STIM2	PRKAB2	psi-mi:“MI:0914”(association)	0.640
HSPB9	USP12	psi-mi:“MI:0914”(association)	0.530
EMILIN1	METTL15	psi-mi:“MI:0914”(association)	0.530
LPCAT1	SLC27A2	psi-mi:“MI:0914”(association)	0.530
FOXM1	PES1	psi-mi:“MI:0914”(association)	0.500
JUN		psi-mi:“MI:0914”(association)	0.350
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
LMX1B	POTEF	psi-mi:“MI:0914”(association)	0.350
SH2D3C	TMEM14DP	psi-mi:“MI:0914”(association)	0.350
SQSTM1	CHEK1	psi-mi:“MI:0914”(association)	0.350
PRKAA2	DFFA	psi-mi:“MI:0914”(association)	0.350
CAPZB	ENAH	psi-mi:“MI:0914”(association)	0.350
LAMP1	DST	psi-mi:“MI:0914”(association)	0.350
PIN4	SEC22B	psi-mi:“MI:0914”(association)	0.350
IGKV1D-13	HNRNPA1L2	psi-mi:“MI:0914”(association)	0.350
DSE	GNPTAB	psi-mi:“MI:0914”(association)	0.350
YARS2	VWA8	psi-mi:“MI:0914”(association)	0.350
MRPS24	VWA8	psi-mi:“MI:0914”(association)	0.350
AK4	VWA8	psi-mi:“MI:0914”(association)	0.350
IL25	POTEF	psi-mi:“MI:0914”(association)	0.350
NDUFS7	NUDT19	psi-mi:“MI:0914”(association)	0.350
NQO2	NSF	psi-mi:“MI:0914”(association)	0.350
DNAJB11	CDC42EP1	psi-mi:“MI:0914”(association)	0.350
ZC4H2	VAMP3	psi-mi:“MI:0914”(association)	0.350

BioGRID (65): PARS2 (Affinity Capture-MS), PARS2 (Affinity Capture-MS), PARS2 (Affinity Capture-MS), EPRS (Co-fractionation), PARS2 (Affinity Capture-MS), PARS2 (Affinity Capture-MS), PARS2 (Affinity Capture-MS), PARS2 (Affinity Capture-MS), PARS2 (Affinity Capture-MS), PARS2 (Affinity Capture-MS), PARS2 (Co-fractionation), PARS2 (Co-fractionation), PARS2 (Co-fractionation), PARS2 (Co-fractionation), PARS2 (Co-fractionation)

ESM2 similar proteins: A2ADA5, A4PCD4, A6H611, D3ZDM7, F6PHZ6, O75344, P04053, P09838, P17256, P36195, P47823, P55345, Q01992, Q03426, Q08602, Q0V8R7, Q13144, Q1L8I0, Q3MIT2, Q4KM92, Q4QQT0, Q5CZL1, Q5E9Z1, Q5I0L3, Q5M7T9, Q5M934, Q5RFE6, Q5XGM5, Q64350, Q6GQ53, Q7L3T8, Q80W22, Q86YJ6, Q8BYL4, Q8C0D0, Q8CHW4, Q8N0Z8, Q8WWH5, Q91XW8, Q92089

Diamond homologs: A0L8I2, A1APU5, A1USY3, A1VE74, A4J5Y2, A5FX26, A5V8U0, A5VQ02, A6U7Z3, A6X1L5, A7GRE9, A7INT8, A8EZ51, A8GN90, A8GRW1, A8GU77, A8I438, A9BGA8, A9MAJ9, A9W1L5, B0BXB9, B0CLE9, B0SDM9, B0SM58, B0THP0, B0ULM2, B1HQZ9, B1LUL8, B1ZA28, B2S561, B2V6W5, B3PW17, B4RBZ9, B4U8B2, B5EIT9, B5ZYN2, B7KPK1, B8DNM5, B8FR28, B8GWT1

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 56 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.

GO biological processes:

GO term	Partners	Fold	FDR
regulation of cell population proliferation	5	11.3×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	7
Uncertain significance	126
Likely benign	57
Benign	11

Top pathogenic / likely-pathogenic (8)

Variant ID	HGVS	Classification
183148	NM_152268.4(PARS2):c.1130dup (p.Pro377_Lys378insTer)	Pathogenic
3067934	NM_152268.4(PARS2):c.886C>T (p.Gln296Ter)	Likely pathogenic
3340626	NM_152268.4(PARS2):c.401G>A (p.Trp134Ter)	Likely pathogenic
3767223	NM_152268.4(PARS2):c.877C>G (p.Pro293Ala)	Likely pathogenic
4086062	NM_152268.4(PARS2):c.1271A>T (p.Asp424Val)	Likely pathogenic
4823010	NM_152268.4(PARS2):c.661dup (p.Gln221fs)	Likely pathogenic
489035	NM_152268.4(PARS2):c.383G>A (p.Trp128Ter)	Likely pathogenic
520548	NM_152268.4(PARS2):c.865C>T (p.Gln289Ter)	Likely pathogenic

SpliceAI

268 predictions. Top by Δscore:

Variant	Effect	Δscore
1:54764118:A:AC	donor_gain	0.9800
1:54764119:C:CC	donor_gain	0.9800
1:54764490:C:CT	donor_gain	0.9700
1:54759190:CCTGA:C	acceptor_loss	0.9600
1:54759192:T:C	acceptor_loss	0.9600
1:54764133:T:TA	donor_gain	0.9400
1:54764459:A:AC	donor_gain	0.9400
1:54764460:C:CC	donor_gain	0.9400
1:54759191:C:CC	acceptor_gain	0.9300
1:54764455:ACCT:A	donor_loss	0.9300
1:54764456:CCTA:C	donor_loss	0.9300
1:54764457:CT:C	donor_loss	0.9300
1:54764458:TA:T	donor_loss	0.9300
1:54764459:ACC:A	donor_loss	0.9300
1:54764460:C:A	donor_loss	0.9300
1:54764453:TCAC:T	donor_loss	0.9200
1:54764454:CACC:C	donor_loss	0.9200
1:54764491:C:CT	donor_gain	0.9200
1:54764452:TTCAC:T	donor_loss	0.8900
1:54759188:CAC:C	acceptor_gain	0.8800
1:54764061:AGG:A	donor_gain	0.8800
1:54764360:GGA:G	donor_gain	0.8800
1:54764460:CCG:C	donor_gain	0.8800
1:54764450:CGT:C	donor_gain	0.8700
1:54764194:T:A	donor_gain	0.8500
1:54764334:CAAGG:C	donor_gain	0.8300
1:54764335:AAGGA:A	donor_gain	0.8300
1:54764129:G:T	donor_gain	0.8200
1:54764452:TTC:T	donor_gain	0.8100
1:54764480:T:TA	donor_gain	0.7900

AlphaMissense

3088 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:54758075:A:G	W363R	0.997
1:54758075:A:T	W363R	0.997
1:54758550:A:C	F204L	0.997
1:54758550:A:T	F204L	0.997
1:54758552:A:G	F204L	0.997
1:54758540:C:G	D208H	0.993
1:54757899:T:A	R421S	0.992
1:54757899:T:G	R421S	0.992
1:54758229:A:C	F311L	0.992
1:54758229:A:T	F311L	0.992
1:54758231:A:G	F311L	0.992
1:54758539:T:G	D208A	0.991
1:54758598:A:C	F188L	0.991
1:54758598:A:T	F188L	0.991
1:54758600:A:G	F188L	0.991
1:54758618:A:C	Y182D	0.989
1:54758685:C:A	E159D	0.989
1:54758685:C:G	E159D	0.989
1:54758764:C:G	R133P	0.989
1:54758952:G:C	S70R	0.989
1:54758952:G:T	S70R	0.989
1:54758954:T:G	S70R	0.989
1:54757900:C:G	R421T	0.988
1:54758073:C:A	W363C	0.988
1:54758073:C:G	W363C	0.988
1:54758539:T:A	D208V	0.987
1:54758596:C:G	R189P	0.987
1:54758780:A:G	W128R	0.987
1:54758780:A:T	W128R	0.987
1:54758145:G:C	C339W	0.986

dbSNP variants (sampled 300 via entrez): RS1000079823 (1:54757460 C>T), RS1000386459 (1:54762804 T>C), RS1000778013 (1:54762028 T>C), RS1000886583 (1:54758779 C>T), RS1001339305 (1:54765831 T>C), RS1001830457 (1:54760907 T>C), RS1001840356 (1:54760388 T>C), RS1003208554 (1:54759457 G>A), RS1003276475 (1:54763967 A>G,T), RS1003327380 (1:54763604 C>A,T), RS1003914371 (1:54760050 T>C), RS1004352075 (1:54765043 C>A), RS1004506558 (1:54764804 C>T), RS1005295352 (1:54758068 C>T), RS1005352188 (1:54764028 G>A)

Disease associations

OMIM: gene MIM:612036 | disease phenotypes: MIM:618437

GenCC curated gene-disease

Disease	Classification	Inheritance
developmental and epileptic encephalopathy, 75	Strong	Autosomal recessive
undetermined early-onset epileptic encephalopathy	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
mitochondrial disease	Moderate	AR

Mondo (3): developmental and epileptic encephalopathy, 75 (MONDO:0032752), myoepithelial tumor (MONDO:0002380), undetermined early-onset epileptic encephalopathy (MONDO:0018614)

Orphanet (0):

HPO phenotypes

76 total (30 of 76 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000194	Open mouth
HP:0000252	Microcephaly
HP:0000316	Hypertelorism
HP:0000322	Short philtrum
HP:0000331	Short chin
HP:0000340	Sloping forehead
HP:0000348	High forehead
HP:0000431	Wide nasal bridge
HP:0000463	Anteverted nares
HP:0000494	Downslanted palpebral fissures
HP:0000504	Abnormality of vision
HP:0000508	Ptosis
HP:0000520	Proptosis
HP:0000543	Optic disc pallor
HP:0000546	Retinal degeneration
HP:0000582	Upslanted palpebral fissure
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000668	Hypodontia
HP:0000708	Atypical behavior
HP:0000717	Autism
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001265	Hyporeflexia
HP:0001268	Mental deterioration

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D009208	Myoepithelioma	C04.557.435.585

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
dicrotophos	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
ferrous chloride	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	increases reaction, affects binding	1
2-palmitoylglycerol	increases expression	1
jinfukang	increases expression	1
Acetaminophen	increases expression	1
Arsenic	increases abundance, increases expression	1
Benzo(a)pyrene	decreases expression	1
Cisplatin	increases expression	1
Doxorubicin	decreases expression	1
Formaldehyde	decreases expression	1
Lead	decreases expression	1
Potassium Chloride	decreases expression, decreases response to substance	1
Dronabinol	decreases response to substance, decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	decreases expression	1
Cadmium Chloride	decreases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03600649	PHASE1	UNKNOWN	Clinical Trial of SP-2577 (Seclidemstat) in Patients With Relapsed or Refractory Ewing or Ewing-related Sarcomas
NCT05266196	PHASE1/PHASE2	UNKNOWN	A Rollover Protocol to Allow for Continued Access to the LSD1 Inhibitor Seclidemstat (SP-2577)
NCT06239272	PHASE1/PHASE2	RECRUITING	NRSTS2021, A Risk Adapted Study Evaluating Maintenance Pazopanib, Limited Margin, Dose-Escalated Radiation Therapy and Selinexor in Non-Rhabdomyosarcoma Soft Tissue Sarcoma (NRSTS)
NCT06625190	PHASE1/PHASE2	RECRUITING	Alpha/Beta T and B Cell Depletion With Zoledronic Acid for Solid Tumors
NCT06244420	Not specified	COMPLETED	Malignant Myoepithelioma of Bone and Soft Tissues: Diagnostic Imaging and Histology in Relation to Prognosis