LRPPRC

Summary

LRPPRC (leucine rich pentatricopeptide repeat containing, HGNC:15714) is a protein-coding gene on chromosome 2p21, encoding Leucine-rich PPR motif-containing protein, mitochondrial (P42704). May play a role in RNA metabolism in both nuclei and mitochondria. It is a selective cancer dependency (DepMap: 64.4% of cell lines).

This gene encodes a leucine-rich protein that has multiple pentatricopeptide repeats (PPR). The precise role of this protein is unknown but studies suggest it may play a role in cytoskeletal organization, vesicular transport, or in transcriptional regulation of both nuclear and mitochondrial genes. The protein localizes primarily to mitochondria and is predicted to have an N-terminal mitochondrial targeting sequence. Mutations in this gene are associated with the French-Canadian type of Leigh syndrome.

Source: NCBI Gene 10128 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mitochondrial disease (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 15
• Clinical variants (ClinVar): 2,363 total — 81 pathogenic, 225 likely-pathogenic
• Phenotypes (HPO): 108
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 64.4% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_133259

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15714
Approved symbol	LRPPRC
Name	leucine rich pentatricopeptide repeat containing
Location	2p21
Locus type	gene with protein product
Status	Approved
Aliases	GP130, LRP130
Ensembl gene	ENSG00000138095
Ensembl biotype	protein_coding
OMIM	607544
Entrez	10128

Gene structure

Transcript identifiers

Ensembl transcripts: 83 — 31 retained_intron, 29 protein_coding, 20 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined

ENST00000260665, ENST00000409659, ENST00000409946, ENST00000419884, ENST00000447246, ENST00000463456, ENST00000467058, ENST00000472420, ENST00000483489, ENST00000681959, ENST00000681961, ENST00000681993, ENST00000682104, ENST00000682154, ENST00000682295, ENST00000682303, ENST00000682308, ENST00000682353, ENST00000682434, ENST00000682480, ENST00000682496, ENST00000682546, ENST00000682585, ENST00000682595, ENST00000682607, ENST00000682612, ENST00000682637, ENST00000682696, ENST00000682779, ENST00000682845, ENST00000682885, ENST00000682933, ENST00000682999, ENST00000683002, ENST00000683072, ENST00000683080, ENST00000683082, ENST00000683096, ENST00000683125, ENST00000683213, ENST00000683220, ENST00000683236, ENST00000683329, ENST00000683346, ENST00000683409, ENST00000683459, ENST00000683528, ENST00000683590, ENST00000683623, ENST00000683645, ENST00000683694, ENST00000683796, ENST00000683802, ENST00000683833, ENST00000683934, ENST00000683989, ENST00000683994, ENST00000684290, ENST00000684306, ENST00000684329, ENST00000684341, ENST00000684383, ENST00000684397, ENST00000684418, ENST00000684433, ENST00000684454, ENST00000684482, ENST00000684619, ENST00000684691, ENST00000684705, ENST00000684743, ENST00000903378, ENST00000903379, ENST00000903380, ENST00000918906, ENST00000918907, ENST00000918908, ENST00000918909, ENST00000918910, ENST00000958035, ENST00000958036, ENST00000958037, ENST00000958038

RefSeq mRNA: 1 — MANE Select: NM_133259 NM_133259

CCDS: CCDS33189

Canonical transcript exons

ENST00000260665 — 38 exons

Exon	Start	End
ENSE00000932579	43945332	43945417
ENSE00000932580	43946113	43946243
ENSE00000932581	43947257	43947370
ENSE00000932582	43947731	43947775
ENSE00000932590	43973607	43973714
ENSE00000932591	43973795	43973900
ENSE00000932596	43976994	43977052
ENSE00000932597	43977155	43977276
ENSE00000962626	43976143	43976229
ENSE00000962627	43975091	43975217
ENSE00000962631	43943687	43943894
ENSE00000962632	43934754	43934878
ENSE00000962633	43934190	43934296
ENSE00000962634	43925893	43925961
ENSE00000962635	43925067	43925157
ENSE00000962636	43918256	43918398
ENSE00000962638	43912432	43912558
ENSE00000962639	43905692	43905780
ENSE00001069565	43886224	43888656
ENSE00001069586	43979826	43979948
ENSE00001159309	43948122	43948199
ENSE00001159316	43948412	43948518
ENSE00001159345	43963588	43963706
ENSE00001284066	43974614	43974758
ENSE00001303077	43982238	43982434
ENSE00001505996	43918025	43918133
ENSE00001582235	43995799	43995989
ENSE00002695342	43901320	43901524
ENSE00003533354	43896634	43896708
ENSE00003562345	43899466	43899605
ENSE00003563677	43960541	43960634
ENSE00003568798	43957385	43957451
ENSE00003608189	43950573	43950600
ENSE00003634191	43949602	43949659
ENSE00003649877	43899219	43899334
ENSE00003679152	43894545	43894629
ENSE00003682490	43889734	43889876
ENSE00003790517	43974150	43974295

Expression profiles

Bgee: expression breadth ubiquitous, 303 present calls, max score 97.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 95.5486 / max 700.3871, expressed in 1826 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
28114	83.0929	1826
28115	12.4556	1768

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.94	gold quality
biceps brachii	UBERON:0001507	97.34	gold quality
adrenal tissue	UBERON:0018303	97.33	gold quality
mucosa of sigmoid colon	UBERON:0004993	97.10	gold quality
colonic mucosa	UBERON:0000317	97.09	gold quality
body of tongue	UBERON:0011876	96.75	gold quality
nephron tubule	UBERON:0001231	96.74	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	96.64	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	96.62	gold quality
jejunum	UBERON:0002115	96.58	gold quality
mucosa of transverse colon	UBERON:0004991	96.50	gold quality
cortical plate	UBERON:0005343	96.46	gold quality
upper leg skin	UBERON:0004262	96.43	gold quality
buccal mucosa cell	CL:0002336	96.41	gold quality
heart right ventricle	UBERON:0002080	96.38	gold quality
calcaneal tendon	UBERON:0003701	96.37	gold quality
tongue	UBERON:0001723	96.30	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.30	gold quality
gastrocnemius	UBERON:0001388	96.28	gold quality
muscle of leg	UBERON:0001383	96.23	gold quality
skeletal muscle tissue	UBERON:0001134	96.22	gold quality
vastus lateralis	UBERON:0001379	96.15	gold quality
middle temporal gyrus	UBERON:0002771	96.15	gold quality
muscle organ	UBERON:0001630	96.11	gold quality
skeletal muscle organ	UBERON:0014892	96.11	gold quality
skin of hip	UBERON:0001554	96.07	gold quality
superior surface of tongue	UBERON:0007371	95.99	gold quality
diaphragm	UBERON:0001103	95.97	gold quality
jejunal mucosa	UBERON:0000399	95.96	gold quality
gluteal muscle	UBERON:0002000	95.96	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.33
E-CURD-112	yes	7.09
E-GEOD-98556	no	708.37

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

98 targeting LRPPRC, 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-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-4271	99.88	68.32	2244

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 64.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• regulatory role of LRPPRC in integration of cytoskeletal networks with vesicular trafficking, nucleocytosolic shuttling, transcription, chromosome remodeling, and cytokinesis (PMID:11827465)
• using an integrative genomics approach, a single candidate gene, LRPPRC, was identified and shown to be the causative gene underlying Leigh syndrome, French-Canadian type (LSFC) (PMID:12529507)
• The LRP130 protein has a role in transcription of the MDR1 and MVP genes. (PMID:15272088)
• LRPPRC exists in a high-molecular-weight complex, and it coimmunoprecipitates with SLIRP, a stem-loop RNA-binding protein. (PMID:20200222)
• Mitochondrial and nuclear genomic responses to loss of LRPPRC expression. (PMID:20220140)
• LRPPRC protein is imported to the mitochondrial matrix and its mitochondrial targeting sequence is cleaved upon entry. (PMID:20633537)
• LRP130 did not affect the capacity of hepatocarcinoma cells to extrude drugs since LRP130 down-regulation was insufficient to significantly reduce P-glycoprotein. (PMID:21109938)
• Acute acidotic crises in a child with suspected mitochondrial disease may be suggestive of LRPPRC related COX deficiency. (PMID:21266382)
• LRP130 protein remodels mitochondria and stimulates fatty acid oxidation. (PMID:21971050)
• The LRPPRC/SLIRP complex suppressed 3’ exonucleolytic mRNA degradation mediated by PNPase and SUV3. (PMID:22661577)
• These data identify LRPPRC as a HIV-1 factor that is involved in HIV-1 replication through more than one mechanism. (PMID:22808186)
• found that the tubulin-binding domain of NF1 is a binding partner of LRPPRC. Our findings provide clues to how loss or mutation of NF1 and LRPPRC may contribute to the manifestations of neurofibromatosis 1 and Leigh Syndrome, French Canadian variant. (PMID:23361976)
• LRPPRC does not directly regulate mtDNA transcription but rather acts as a post-transcriptional regulator of mammalian mtDNA expression. (PMID:23599432)
• LRPPRC therefore acts to suppress the initiation of basal levels of autophagy to clean up dysfunctional mitochondria and other cellular debris during the normal cell cycle. (PMID:23822101)
• Data indicate that C14C10.4/MMA-1 Is the Structural and functional homolog of mammalian LRPPRC. (PMID:23878239)
• LRPPRC overexpression is associated with gastric cancer. (PMID:24375316)
• LRPPRC functions as a checkpoint protein that prevents mitochondria from autophagy degradation and impact tumorigenesis. (PMID:24722279)
• LRPPRC is a transcription factor related to ABCB1 expression and highlight the importance of epigenetic regulation in CML resistance. (PMID:25089713)
• LRPPRC levels were reduced in muscle cells and undetectable in liver from French Canadian Leigh Syndrome patients. (PMID:25214534)
• Downregulation of LRPPRC expression resulted in the reduced expression of Bcl-2, upregulation of Bax, and cleaved caspase-9 and caspase-3. This induces apoptosis through the mitochondria-mediated pathway in PCa cells. (PMID:25379610)
• Tetherin binds with the mitochondrion-associated autophagy suppressor LRPPRC and prohibits its association with the autophagy initiation complex. (PMID:25631043)
• LRPPRC knock-down in mammalian cells leads to an imbalance between mitochondria-encoded and nuclear-encoded subunits of complex IV (PMID:26412102)
• study identifies LRPPRC as an important disease-causing gene in an early-onset, multisystem and neurological mitochondrial disease. (PMID:26510951)
• LRPPRC displays a broad and strong RNA binding capacity in vitro in contrast to SLIRP that associates only weakly with RNA. (PMID:27353330)
• There were no significant correlations between LRP130, SIRT3, or PGC-1alpha mRNA expression in response to acute sprint-interval training. Changes in protein expression of LRP130, SIRT3, and PGC-1alpha were positively correlated at several time points with large effect sizes, which suggest that the regulation of these proteins may be coordinated in human skeletal muscle. (PMID:27604398)
• High expression of ULK1 concomitant with high expression of LRPPRC may serve as useful markers for shorter biochemical progression (BCP)-free survival and overall survival in patients with metastatic prostate cancer (PCa) after androgen deprivation therapy (ADT). (PMID:27679555)
• This is the first study to report hypermethylation of LRPPRC, RAB6C, and ZNF471 in squamous cell carcinoma of the tongue (PMID:28255813)
• To investigate the impact of the OXPHOS defect in the liver, aothors analyzed the mitochondrial phenotype in mice harboring an hepatocyte-specific inactivation of Lrpprc. Loss of LRPPRC in the liver caused a generalized growth delay, and typical histological features of mitochondrial hepatopathy. (PMID:28575497)
• Study demonstrated that the LRPPRC-SLIRP complex is a global RNA chaperone that stabilizes RNA structures to expose the required sites for translation, stabilization, and polyadenylation. (PMID:29146908)
• Data demonstrate the importance of mTORC1, independent of the HIF-1alpha/PDHK1 axis, in maintaining LRPPRC and COX expression dermal fibroblasts from Leigh syndrome French Canadian type patients. (PMID:30995105)
• Knock-down of LRPPRC promotes apoptosis of hormone resistant prostate cancer cells. (PMID:31223111)
• Fiber-specific and whole-muscle LRP130 expression in rested, exercised, and fasted human skeletal muscle. (PMID:32065259)
• LRPPRC sustains Yap-P27-mediated cell ploidy and P62-HDAC6-mediated autophagy maturation and suppresses genome instability and hepatocellular carcinomas. (PMID:32203162)
• Messenger RNA delivery to mitoribosomes - hints from a bacterial toxin. (PMID:32329962)
• Alzheimer’s and Parkinson’s brain tissues have reduced expression of genes for mtDNA OXPHOS Proteins, mitobiogenesis regulator PGC-1alpha protein and mtRNA stabilizing protein LRPPRC (LRP130). (PMID:32497722)
• LRPPRC contributes to the cisplatin resistance of lung cancer cells by regulating MDR1 expression. (PMID:33649818)
• LncRNA SNHG17 interacts with LRPPRC to stabilize c-Myc protein and promote G1/S transition and cell proliferation. (PMID:34671012)
• Deubiquitylase PSMD14 inhibits autophagy to promote ovarian cancer progression via stabilization of LRPPRC. (PMID:36328147)
• LRPPRC facilitates tumor progression and immune evasion through upregulation of m[6]A modification of PD-L1 mRNA in hepatocellular carcinoma. (PMID:37063837)
• GREM1, LRPPRC and SLC39A4 as potential biomarkers of intervertebral disc degeneration: a bioinformatics analysis based on multiple microarray and single-cell sequencing data. (PMID:37700277)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	lrpprc	ENSDARG00000043970
mus_musculus	Lrpprc	ENSMUSG00000024120
rattus_norvegicus	Lrpprc	ENSRNOG00000005877
drosophila_melanogaster	Lrpprc2	FBGN0027794
drosophila_melanogaster	bsf	FBGN0284256

Protein

Protein identifiers

Leucine-rich PPR motif-containing protein, mitochondrial — P42704 (reviewed: P42704)

Alternative names: 130 kDa leucine-rich protein, GP130

All UniProt accessions (35): P42704, A0A0C4DG06, A0A804HHY9, A0A804HI14, A0A804HI23, A0A804HI40, A0A804HI44, A0A804HIG4, A0A804HIN4, A0A804HIQ7, A0A804HIV5, A0A804HJA1, A0A804HJD8, A0A804HJG8, A0A804HJH8, A0A804HJI0, A0A804HJZ1, A0A804HK02, A0A804HK30, A0A804HKI2, A0A804HKJ0, A0A804HKK7, A0A804HKR3, A0A804HKR5, A0A804HKX0, A0A804HKX6, A0A804HL40, A0A804HLG8, A0A804HLJ6, A0A804HLK8, A0A804HLL8, B8ZZ38, C9JCA9, E5KNY5, H7C3W8

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in RNA metabolism in both nuclei and mitochondria. In the nucleus binds to HNRPA1-associated poly(A) mRNAs and is part of nmRNP complexes at late stages of mRNA maturation which are possibly associated with nuclear mRNA export. Positively modulates nuclear export of mRNAs containing the EIF4E sensitivity element (4ESE) by binding simultaneously to both EIF4E and the 4ESE and acting as a platform for assembly for the RNA export complex. Also binds to exportin XPO1/CRM1 to engage the nuclear pore and traffic the bound mRNAs to the cytoplasm. May bind mature mRNA in the nucleus outer membrane. In mitochondria binds to poly(A) mRNA. Plays a role in translation or stability of mitochondrially encoded cytochrome c oxidase (COX) subunits. May be involved in transcription regulation. Cooperates with PPARGC1A to regulate certain mitochondrially encoded genes and gluconeogenic genes and may regulate docking of PPARGC1A to transcription factors. Seems to be involved in the transcription regulation of the multidrug-related genes MDR1 and MVP. Part of a nuclear factor that binds to the invMED1 element of MDR1 and MVP gene promoters. Binds single-stranded DNA. Required for maintaining mitochondrial potential. Suppresses the initiation of basal levels of autophagy and mitophagy by sustaining BCL2 levels.

Subunit / interactions. Component of mRNP complexes associated with HNRPA1. Component of the complex, at least composed of LRPPRC, BECN1 and BCL2; the interactions prevent BECN1 from forming an autophagy-inducing complex with PIK3C3. Interacts with CECR2, HEBP2, MAP1S and UXT. Interacts with PPARGC1A. Interacts with FOXO1. Interacts (via N-terminus) with EIF4E; the interaction promotes association of EIF4E with 4ESE-containing mRNAs. Interacts with exportin XPO1/CRM1; interacts both alone and in complex with EIF4E and 4ESE-containing mRNAs to form an EIF4E-dependent mRNA export complex. Interacts with importin IPO8; the interaction occurs when LRPPRC is in its RNA-free form and returns LRPPRC to the nucleus for further export rounds. Interacts with BECN1. Interacts with Aedes aegypti venom allergen-1; the interaction interrupts BECN1 and LRPPRC association.

Subcellular location. Mitochondrion. Nucleus. Nucleoplasm. Nucleus inner membrane. Nucleus outer membrane.

Tissue specificity. Expressed ubiquitously. Expression is highest in heart, skeletal muscle, kidney and liver, intermediate in brain, non-mucosal colon, spleen and placenta, and lowest in small intestine, thymus, lung and peripheral blood leukocytes.

Disease relevance. Mitochondrial complex IV deficiency, nuclear type 5 (MC4DN5) [MIM:220111] An autosomal recessive, severe mitochondrial disease with multisystemic manifestations and early onset. Clinical features include delayed psychomotor development, impaired intellectual development with speech delay, mild dysmorphic facial features, hypotonia, ataxia, and seizures. Brain imaging shows bilaterally symmetrical necrotic lesions in subcortical brain regions. Mortality is high, due to episodes of severe metabolic acidosis and coma. The disease is caused by variants affecting the gene represented in this entry.

RefSeq proteins (1): NP_573566* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002885	PPR_rpt	Repeat
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR033443	PROP1-like_PPR_dom	Domain
IPR033490	LRP130	Family

Pfam: PF01535, PF13812, PF17177

UniProt features (54 total): repeat 20, modified residue 13, sequence conflict 11, sequence variant 4, region of interest 2, mutagenesis site 2, transit peptide 1, chain 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
9OLF	ELECTRON MICROSCOPY	2.46
8ANY	ELECTRON MICROSCOPY	2.85

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P42704-F1	77.35	0.02

Functional residue map

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

Post-translational modifications (13): 155, 187, 226, 292, 463, 613, 726, 750, 1026, 1027, 1029, 1136, 1138

Mutagenesis-validated functional residues (2):

Position	Phenotype
441	reduces binding to eif4e.
583	reduces binding to eif4e.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-9836573	Mitochondrial RNA degradation
R-HSA-9937008	Mitochondrial mRNA modification
R-HSA-8953854	Metabolism of RNA

MSigDB gene sets: 521 (showing top): MORF_DNMT1, GNF2_MSH2, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, MODULE_151, MORF_RRM1, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_MITOCHONDRIAL_TRANSLATION, MORF_CDK2, TGACCTY_ERR1_Q2, MORF_HDAC2, GOBP_ORGANELLE_TRANSPORT_ALONG_MICROTUBULE, SHIPP_DLBCL_CURED_VS_FATAL_DN, RODWELL_AGING_KIDNEY_NO_BLOOD_DN, GOBP_TRANSLATION

GO Biological Process (8): mitochondrial RNA catabolic process (GO:0000957), autophagy (GO:0006914), mitochondrion transport along microtubule (GO:0047497), mRNA transport (GO:0051028), regulation of mitochondrial translation (GO:0070129), mitochondrial mRNA polyadenylation (GO:0097222), negative regulation of mitochondrial mRNA catabolic process (GO:1905638), negative regulation of mitochondrial RNA catabolic process (GO:0000961)

GO Molecular Function (9): single-stranded DNA binding (GO:0003697), RNA binding (GO:0003723), mRNA binding (GO:0003729), mRNA 3’-UTR binding (GO:0003730), microtubule binding (GO:0008017), ubiquitin protein ligase binding (GO:0031625), beta-tubulin binding (GO:0048487), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (17): condensed nuclear chromosome (GO:0000794), acrosomal vesicle (GO:0001669), nucleus (GO:0005634), nuclear inner membrane (GO:0005637), nuclear outer membrane (GO:0005640), nucleoplasm (GO:0005654), mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), cytoskeleton (GO:0005856), microtubule (GO:0005874), membrane (GO:0016020), mitochondrial nucleoid (GO:0042645), perinuclear region of cytoplasm (GO:0048471), sperm midpiece (GO:0097225), sperm end piece (GO:0097229), ribonucleoprotein complex (GO:1990904), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Metabolism of RNA	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
mitochondrion	3
nucleic acid binding	2
tubulin binding	2
intracellular membrane-bounded organelle	2
nuclear membrane	2
cytoplasm	2
intracellular membraneless organelle	2
sperm flagellum	2
mitochondrial RNA metabolic process	1
RNA catabolic process	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
establishment of mitochondrion localization, microtubule-mediated	1
organelle transport along microtubule	1
RNA transport	1
regulation of translation	1
mitochondrial translation	1
regulation of mitochondrial gene expression	1
mitochondrial RNA processing	1
mitochondrial mRNA catabolic process	1
negative regulation of mitochondrial RNA catabolic process	1
negative regulation of mRNA catabolic process	1
regulation of mitochondrial mRNA catabolic process	1
mitochondrial RNA catabolic process	1
regulation of mitochondrial RNA catabolic process	1
negative regulation of RNA catabolic process	1
DNA binding	1
RNA binding	1
mRNA binding	1
ubiquitin-like protein ligase binding	1
binding	1
nuclear chromosome	1
condensed chromosome	1
nucleus	1
secretory granule	1
organelle inner membrane	1
organelle outer membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1

Protein interactions and networks

STRING

2262 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LRPPRC	SLIRP	Q9GZT3	997
LRPPRC	MAP1S	Q66K74	959
LRPPRC	XPO1	O14980	921
LRPPRC	TACO1	Q9BSH4	887
LRPPRC	HEBP2	Q9Y5Z4	849
LRPPRC	COX10	Q12887	802
LRPPRC	COX15	Q7KZN9	800
LRPPRC	SURF1	Q15526	800
LRPPRC	YTHDF1	Q9BYJ9	800
LRPPRC	CECR2	Q9BXF3	799
LRPPRC	ALKBH5	Q6P6C2	789
LRPPRC	ETHE1	O95571	775
LRPPRC	HNRNPA2B1	P22626	769
LRPPRC	MT-CO3	P00414	748
LRPPRC	UXT	Q9UBK9	727

IntAct

273 interactions, top by confidence:

A	B	Type	Score
CDH1	CTNND1	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
RAC1	COX6C	psi-mi:“MI:0914”(association)	0.640
IGF2BP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
NCBP1	KPNA3	psi-mi:“MI:0914”(association)	0.640
CFTR	HAX1	psi-mi:“MI:0914”(association)	0.610
LRPPRC	APP	psi-mi:“MI:0915”(physical association)	0.580
LRPPRC	APP	psi-mi:“MI:2364”(proximity)	0.580
APP	LRPPRC	psi-mi:“MI:0914”(association)	0.580
YWHAZ	SHTN1	psi-mi:“MI:0914”(association)	0.530
PPARGC1A	LRPPRC	psi-mi:“MI:0915”(physical association)	0.520
NDUFAB1	MIEF1	psi-mi:“MI:0915”(physical association)	0.490
Ppargc1a	LRPPRC	psi-mi:“MI:0915”(physical association)	0.400
LRPPRC	APP	psi-mi:“MI:0915”(physical association)	0.400
ACTB	DDX3X	psi-mi:“MI:0915”(physical association)	0.400
SIRT4	VWA8	psi-mi:“MI:0914”(association)	0.350
Bub1	PEX10	psi-mi:“MI:0914”(association)	0.350
Kctd5		psi-mi:“MI:0914”(association)	0.350
Cdh1	ARVCF	psi-mi:“MI:0914”(association)	0.350

BioGRID (1032): LRPPRC (Affinity Capture-RNA), LRPPRC (Affinity Capture-RNA), LRPPRC (Affinity Capture-RNA), LRPPRC (Affinity Capture-MS), LRPPRC (Affinity Capture-MS), LRPPRC (Affinity Capture-MS), LRPPRC (Affinity Capture-MS), LRPPRC (Affinity Capture-MS), LRPPRC (Affinity Capture-MS), LRPPRC (Affinity Capture-MS), LRPPRC (Affinity Capture-MS), LRPPRC (Affinity Capture-MS), LMAN1 (Co-fractionation), LRPPRC (Co-fractionation), LRPPRC (Co-fractionation)

ESM2 similar proteins: A1A5P5, A1L2L5, A1Z9A8, B5DF07, O15091, P42704, Q07DV3, Q08CK1, Q0IHP3, Q14C51, Q14CX7, Q14CZ7, Q28C74, Q28DE0, Q2KI62, Q32LU7, Q32N55, Q32PI8, Q3SZ55, Q4R366, Q4R6I5, Q53R41, Q566X6, Q58CX2, Q5R503, Q5R8W8, Q5RFI6, Q5SGE0, Q5XIR8, Q5ZKK3, Q5ZLS8, Q68FN9, Q6AYP3, Q6DI86, Q6GQ66, Q6PB66, Q6QI44, Q7L8L6, Q7TMV3, Q7Z3E5

Diamond homologs: P42704, Q28C74, Q5SGE0, Q6PB66

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 201 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
VEGFR2 mediated vascular permeability	6	17.6×	4e-04
TRAF6 mediated NF-kB activation	5	16.4×	1e-03
Oncogenic MAPK signaling	7	12.5×	4e-04
RHO GTPases Activate WASPs and WAVEs	5	11.4×	4e-03
TAK1-dependent IKK and NF-kappa-B activation	5	10.8×	4e-03
FCGR3A-mediated phagocytosis	7	9.4×	1e-03
Regulation of actin dynamics for phagocytic cup formation	7	9.3×	1e-03
Signaling by BRAF and RAF1 fusions	7	8.6×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
cellular response to nerve growth factor stimulus	5	13.0×	8e-03
ERK1 and ERK2 cascade	6	10.6×	6e-03
mRNA splicing, via spliceosome	11	5.6×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

2363 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	81
Likely pathogenic	225
Uncertain significance	579
Likely benign	1192
Benign	116

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1071132	NM_133259.4(LRPPRC):c.3626_3627del (p.Lys1209fs)	Pathogenic
1076186	NM_133259.4(LRPPRC):c.277_278insTTTTTTTTTTTTTTTTTTTTNNNNNNNNNNCCACCGACCCCAGCCCGCGGCGCCTTCGAGCCTTCTCTTGACGTTGTTTTCAAATAATCATAGTTGCCAGGAAAGAAGCCACTACCCGAGACTAGATCTTT (p.Ser93delinsPhePhePhePhePhePhePheXaaXaaXaaXaaThrAspProSerProArgArgLeuArgAlaPheSerTer)	Pathogenic
1355066	NM_133259.4(LRPPRC):c.3022_3023del (p.Pro1008fs)	Pathogenic
1356002	NM_133259.4(LRPPRC):c.1051G>T (p.Glu351Ter)	Pathogenic
1359952	NM_133259.4(LRPPRC):c.960T>A (p.Tyr320Ter)	Pathogenic
1389688	NM_133259.4(LRPPRC):c.2166T>A (p.Cys722Ter)	Pathogenic
1395779	NM_133259.4(LRPPRC):c.2058_2059del (p.Leu687fs)	Pathogenic
1443686	NM_133259.4(LRPPRC):c.4050dup (p.Leu1351fs)	Pathogenic
1447712	NM_133259.4(LRPPRC):c.3758del (p.Pro1253fs)	Pathogenic
1451370	NM_133259.4(LRPPRC):c.551del (p.Phe184fs)	Pathogenic
1451599	NM_133259.4(LRPPRC):c.3597del (p.Asn1199fs)	Pathogenic
1454185	NM_133259.4(LRPPRC):c.3682G>T (p.Glu1228Ter)	Pathogenic
1455749	NM_133259.4(LRPPRC):c.1431_1432del (p.Thr478fs)	Pathogenic
1457003	NC_000002.11:g.(?44200736)(44209583_?)del	Pathogenic
1457256	NM_133259.4(LRPPRC):c.2325_2326delinsGT (p.Glu776Ter)	Pathogenic
1459192	NC_000002.11:g.(?44200736)(44223096_?)del	Pathogenic
1460230	NM_133259.4(LRPPRC):c.2830G>T (p.Glu944Ter)	Pathogenic
1460406	NM_133259.4(LRPPRC):c.2247dup (p.Lys750fs)	Pathogenic
1925538	NM_133259.4(LRPPRC):c.3989C>G (p.Ser1330Ter)	Pathogenic
1956664	NM_133259.4(LRPPRC):c.3253C>T (p.Gln1085Ter)	Pathogenic
1999239	NM_133259.4(LRPPRC):c.2839_2840dup (p.Gln947fs)	Pathogenic
2003159	NM_133259.4(LRPPRC):c.2944C>T (p.Gln982Ter)	Pathogenic
2005776	NM_133259.4(LRPPRC):c.2912_2913insAT (p.Trp971Ter)	Pathogenic
2016441	NM_133259.4(LRPPRC):c.46dup (p.Ala16fs)	Pathogenic
2022058	NM_133259.4(LRPPRC):c.30G>A (p.Trp10Ter)	Pathogenic
2026351	NM_133259.4(LRPPRC):c.2046_2047insGGGCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGCGGATCACGAGGTCANNNNNNNNNNAAAAAAAAAAAAAAAAAAAAAAGAGATGTCCTA (p.Lys683fs)	Pathogenic
2031215	NM_133259.4(LRPPRC):c.3340C>T (p.Gln1114Ter)	Pathogenic
2040293	NM_133259.4(LRPPRC):c.2464_2465del (p.Thr822fs)	Pathogenic
2064915	NM_133259.4(LRPPRC):c.1659_1663dup (p.Asn555delinsIleTer)	Pathogenic
2084629	NM_133259.4(LRPPRC):c.3844G>T (p.Glu1282Ter)	Pathogenic

SpliceAI

5250 predictions. Top by Δscore:

Variant	Effect	Δscore
2:43889726:ATACT:A	donor_loss	1.0000
2:43889728:ACTC:A	donor_loss	1.0000
2:43889730:TCACA:T	donor_loss	1.0000
2:43889731:CA:C	donor_loss	1.0000
2:43889732:A:AC	donor_gain	1.0000
2:43889733:C:CC	donor_gain	1.0000
2:43889733:C:T	donor_loss	1.0000
2:43889733:CAGG:C	donor_gain	1.0000
2:43889733:CAGGG:C	donor_gain	1.0000
2:43889872:TGAGA:T	acceptor_gain	1.0000
2:43889874:AGA:A	acceptor_gain	1.0000
2:43889875:GA:G	acceptor_gain	1.0000
2:43889877:C:CC	acceptor_gain	1.0000
2:43889881:C:CT	acceptor_gain	1.0000
2:43894549:G:C	donor_gain	1.0000
2:43899331:CTTA:C	acceptor_gain	1.0000
2:43899333:TA:T	acceptor_gain	1.0000
2:43899335:C:CC	acceptor_gain	1.0000
2:43899464:ACT:A	donor_gain	1.0000
2:43899465:CT:C	donor_gain	1.0000
2:43899465:CTC:C	donor_gain	1.0000
2:43899465:CTCT:C	donor_gain	1.0000
2:43899465:CTCTT:C	donor_gain	1.0000
2:43899601:TATTA:T	acceptor_gain	1.0000
2:43899602:ATTA:A	acceptor_gain	1.0000
2:43899603:TTA:T	acceptor_gain	1.0000
2:43899603:TTAC:T	acceptor_loss	1.0000
2:43899604:TA:T	acceptor_gain	1.0000
2:43899606:C:A	acceptor_loss	1.0000
2:43899606:C:CC	acceptor_gain	1.0000

AlphaMissense

9178 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:43977048:G:T	T199K	0.997
2:43977247:C:G	A167P	0.997
2:43934207:C:G	A907P	0.996
2:43925081:A:G	L961P	0.995
2:43934206:G:T	A907D	0.995
2:43934230:A:G	L899P	0.995
2:43976167:A:G	L238P	0.995
2:43977048:G:C	T199R	0.995
2:43977240:A:G	L169P	0.995
2:43925078:A:G	L962P	0.994
2:43977248:A:C	N166K	0.994
2:43977248:A:T	N166K	0.994
2:43979908:A:C	S129R	0.994
2:43979908:A:T	S129R	0.994
2:43979910:T:G	S129R	0.994
2:43918363:A:G	W978R	0.993
2:43918363:A:T	W978R	0.993
2:43977240:A:T	L169H	0.993
2:43918268:A:C	F1009L	0.992
2:43918268:A:T	F1009L	0.992
2:43918270:A:G	F1009L	0.992
2:43918306:C:G	A997P	0.992
2:43976997:G:T	A216D	0.992
2:43905756:G:C	F1100L	0.991
2:43905756:G:T	F1100L	0.991
2:43905758:A:G	F1100L	0.991
2:43918374:G:T	A974D	0.991
2:43976158:C:T	G241E	0.991
2:43977020:A:C	C208W	0.991
2:43977036:A:G	L203S	0.991

dbSNP variants (sampled 300 via entrez): RS1000064397 (2:43948931 T>C), RS1000098485 (2:43993329 C>G), RS1000102458 (2:43982011 G>A,T), RS1000146411 (2:43961015 G>T), RS1000160592 (2:43927805 T>C), RS1000189010 (2:43891548 T>A), RS1000191464 (2:43927499 A>G), RS1000194583 (2:43900970 C>A), RS1000211933 (2:43996660 T>C), RS1000239321 (2:43897000 A>C), RS1000258812 (2:43966148 T>C), RS1000290192 (2:43896697 T>C), RS1000298826 (2:43932868 T>C), RS1000333098 (2:43996729 G>C,T), RS1000353306 (2:43943499 T>C)

Disease associations

OMIM: gene MIM:607544 | disease phenotypes: MIM:220111, MIM:256000

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital lactic acidosis, Saguenay-Lac-Saint-Jean type	Definitive	Autosomal recessive
cytochrome-c oxidase deficiency disease	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
mitochondrial disease	Definitive	AR
Leigh syndrome	Definitive	AR

Mondo (4): congenital lactic acidosis, Saguenay-Lac-Saint-Jean type (MONDO:0009069), Leigh syndrome (MONDO:0009723), intellectual disability (MONDO:0001071), (MONDO:0009068)

Orphanet (3): Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type (Orphanet:70472), Leigh syndrome (Orphanet:506), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

108 total (30 of 108 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000047	Hypospadias
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000272	Malar flattening
HP:0000294	Low anterior hairline
HP:0000316	Hypertelorism
HP:0000347	Micrognathia
HP:0000369	Low-set ears
HP:0000431	Wide nasal bridge
HP:0000463	Anteverted nares
HP:0000474	Thickened nuchal skin fold
HP:0000486	Strabismus
HP:0000565	Esotropia
HP:0000639	Nystagmus
HP:0000750	Delayed speech and language development
HP:0000822	Hypertension
HP:0001007	Hirsutism
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001290	Generalized hypotonia
HP:0001298	Encephalopathy
HP:0001310	Dysmetria
HP:0001320	Cerebellar vermis hypoplasia
HP:0001324	Muscle weakness
HP:0001332	Dystonia

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST005235_8	Hand grip strength	1.000000e-10
GCST005830_44	Hand grip strength	4.000000e-08
GCST007327_94	Smoking status (ever vs never smokers)	1.000000e-09
GCST007565_100	Morning person	7.000000e-17
GCST007576_298	Chronotype	7.000000e-17
GCST007929_86	Medication use (calcium channel blockers)	1.000000e-08
GCST007931_69	Medication use (HMG CoA reductase inhibitors)	5.000000e-08
GCST008522_5	Bitter alcoholic beverage consumption	3.000000e-08
GCST008811_44	Alcohol consumption (drinks per week)	6.000000e-09
GCST010002_389	Refractive error	3.000000e-26
GCST011065_11	Levodopa-induced dyskinesia in levodopa treated Parkinson’s disease	7.000000e-06
GCST011065_4	Levodopa-induced dyskinesia in levodopa treated Parkinson’s disease	6.000000e-07
GCST011065_9	Levodopa-induced dyskinesia in levodopa treated Parkinson’s disease	5.000000e-06
GCST012336_3	Alcohol use disorder (consumption score)	2.000000e-08
GCST90020053_2	Frailty index	1.000000e-08

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0006941	grip strength measurement
EFO:0004318	smoking behavior
EFO:0008328	chronotype measurement
EFO:0009930	Calcium channel blocker use measurement
EFO:0009932	HMG CoA reductase inhibitor use measurement
EFO:0010092	bitter alcoholic beverage consumption measurement
EFO:0010747	response to levodopa
EFO:0007645	longitudinal alcohol consumption measurement
EFO:0009458	alcohol use disorder measurement
EFO:0009885	frailty measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D007888	Leigh Disease	C10.228.140.163.100.412; C16.320.565.189.412; C16.320.565.202.810.444; C18.452.132.100.412; C18.452.648.189.412; C18.452.648.202.810.444; C18.452.660.520
C537004	Leigh syndrome , French Canadian type (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295762 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.95	Kd	111.8	nM	CHEMBL3752910
6.95	ED50	111.8	nM	CHEMBL3752910
5.49	Kd	3277	nM	CHEMBL5653589
5.49	ED50	3277	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 9 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148665: Binding affinity to human LRPPRC incubated for 45 mins by Kinobead based pull down assay	kd	0.1118	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148665: Binding affinity to human LRPPRC incubated for 45 mins by Kinobead based pull down assay	kd	3.2771	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, decreases methylation, affects cotreatment	6
sodium arsenite	decreases expression	3
bisphenol F	increases expression, affects cotreatment, decreases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	2
Formaldehyde	decreases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
bisphenol A	decreases expression	1
pyrogallol 1,3-dimethyl ether	increases expression, decreases expression, affects cotreatment, affects localization	1
trichostatin A	increases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	decreases expression	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
cyclic 3’,5’-uridine monophosphate	affects binding	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
CGP 52608	affects binding, increases reaction	1
tanespimycin	affects cotreatment, increases expression	1
corosolic acid	decreases expression	1
nutlin 3	affects cotreatment, increases secretion	1
bisphenol B	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	increases expression	1
jinfukang	decreases expression	1
VER 155008	increases expression, affects cotreatment	1
LDN 193189	affects cotreatment, decreases expression	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4119050	Binding	Binding affinity to LRPPRC in human NCI-H358 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT01721733	PHASE2	COMPLETED	Safety and Efficacy Study of EPI-743 in Children With Leigh Syndrome
NCT02352896	PHASE2	COMPLETED	Long-Term Safety and Efficacy Evaluation of EPI-743 in Children With Leigh Syndrome
NCT03747328	PHASE2	WITHDRAWN	ABI-009 (Nab-sirolimus) in Patients With Genetically-confirmed Leigh or Leigh-like Syndrome
NCT06843811	PHASE2	ENROLLING_BY_INVITATION	Sirolimus for Leigh Syndrome
NCT06990984	PHASE2	NOT_YET_RECRUITING	A Dose-ranging Study of TTI-0102 in Adults and Children With Leigh Syndrome Spectrum (LSS)
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT02544217	PHASE1	COMPLETED	A Dose-escalating Clinical Trial With KH176
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT04378075	PHASE2/PHASE3	TERMINATED	A Study to Evaluate Efficacy and Safety of Vatiquinone for Treating Mitochondrial Disease in Participants With Refractory Epilepsy
NCT01780168	Not specified	RECRUITING	The NIH MINI Study: Metabolism, Infection, and Immunity in Inborn Errors of Metabolism
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT01803906	Not specified	ENROLLING_BY_INVITATION	Tissue Sample Study for Mitochondrial Disorders
NCT03137355	Not specified	RECRUITING	The International Registry for Leigh Syndrome
NCT05277363	Not specified	WITHDRAWN	A Study of the Natural Course of SURF1 Deficiency
NCT05554835	Not specified	RECRUITING	Global Registry and Natural History Study for Mitochondrial Disorders
NCT06967831	Not specified	RECRUITING	Drug Repurposing for Mitochondrial Disorders Using iPSCs Derived Neural Cells
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic