SLIRP

Summary

SLIRP (SRA stem-loop interacting RNA binding protein, HGNC:20495) is a protein-coding gene on chromosome 14q24.3, encoding SRA stem-loop-interacting RNA-binding protein, mitochondrial (Q9GZT3). RNA-binding protein that acts as a nuclear receptor corepressor. It is a selective cancer dependency (DepMap: 10.7% of cell lines).

Steroid receptor RNA activator (SRA, or SRA1; MIM 603819) is a complex RNA molecule containing multiple stable stem-loop structures that functions in coactivation of nuclear receptors. SLIRP interacts with stem-loop structure-7 of SRA (STR7) and modulates nuclear receptor transactivation (Hatchell et al., 2006 [PubMed 16762838]).

Source: NCBI Gene 81892 — RefSeq curated summary.

At a glance

• Gene–disease (curated): inborn mitochondrial metabolism disorder (Limited, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 31 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 10.7% of screened cell lines
• MANE Select transcript: NM_031210

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20495
Approved symbol	SLIRP
Name	SRA stem-loop interacting RNA binding protein
Location	14q24.3
Locus type	gene with protein product
Status	Approved
Aliases	DC50
Ensembl gene	ENSG00000119705
Ensembl biotype	protein_coding
OMIM	610211
Entrez	81892

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 17 protein_coding, 2 retained_intron, 2 nonsense_mediated_decay

ENST00000238688, ENST00000553981, ENST00000554074, ENST00000555890, ENST00000556310, ENST00000556375, ENST00000556831, ENST00000556956, ENST00000557342, ENST00000557431, ENST00000557623, ENST00000613856, ENST00000853900, ENST00000923197, ENST00000923198, ENST00000923199, ENST00000923200, ENST00000923201, ENST00000923202, ENST00000923203, ENST00000923204

RefSeq mRNA: 3 — MANE Select: NM_031210 NM_001267863, NM_001267864, NM_031210

CCDS: CCDS58331, CCDS73668, CCDS9866

Canonical transcript exons

ENST00000557342 — 4 exons

Exon	Start	End
ENSE00002520182	77708103	77708208
ENSE00003463277	77710838	77710896
ENSE00003518878	77717496	77717598
ENSE00003598026	77715772	77715879

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 99.02.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 247.0510 / max 3004.1122, expressed in 1824 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
140787	244.1576	1824
140786	2.8934	1501

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	99.02	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.94	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.78	gold quality
apex of heart	UBERON:0002098	98.77	gold quality
heart left ventricle	UBERON:0002084	98.76	gold quality
right atrium auricular region	UBERON:0006631	98.75	gold quality
nucleus accumbens	UBERON:0001882	98.74	gold quality
muscle of leg	UBERON:0001383	98.73	gold quality
gastrocnemius	UBERON:0001388	98.72	gold quality
anterior cingulate cortex	UBERON:0009835	98.71	gold quality
cardiac ventricle	UBERON:0002082	98.70	gold quality
cingulate cortex	UBERON:0003027	98.70	gold quality
caudate nucleus	UBERON:0001873	98.67	gold quality
amygdala	UBERON:0001876	98.66	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.61	gold quality
heart	UBERON:0000948	98.58	gold quality
cardiac atrium	UBERON:0002081	98.56	gold quality
right frontal lobe	UBERON:0002810	98.56	gold quality
muscle organ	UBERON:0001630	98.50	gold quality
rectum	UBERON:0001052	98.46	gold quality
adenohypophysis	UBERON:0002196	98.45	gold quality
putamen	UBERON:0001874	98.43	gold quality
spinal cord	UBERON:0002240	98.43	gold quality
right testis	UBERON:0004534	98.43	gold quality
left testis	UBERON:0004533	98.42	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.38	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.38	gold quality
left coronary artery	UBERON:0001626	98.35	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.34	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	98.34	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-CURD-98	yes	1096.36
E-CURD-122	yes	19.70
E-MTAB-10042	yes	14.14
E-MTAB-10018	no	2185.92
E-MTAB-9435	no	2148.90
E-MTAB-9388	no	1851.89
E-MTAB-8271	no	11.47
E-GEOD-81547	no	9.87
E-GEOD-93593	no	8.03
E-MTAB-9801	no	2.53
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 10.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 13)

• Our data demonstrate that SLIRP modulates NR transactivation, suggest it may regulate mitochondrial function, and provide mechanistic insight into interactions between SRA, SLIRP, SRC-1, and NCoR. (PMID:16762838)
• SLIRP plays an essential role in maintaining mitochondrial-localized mRNA transcripts that encode OxPhos protein subunits. (PMID:19680543)
• LRPPRC exists in a high-molecular-weight complex, and it coimmunoprecipitates with SLIRP, a stem-loop RNA-binding protein. (PMID:20200222)
• The LRPPRC/SLIRP complex suppressed 3’ exonucleolytic mRNA degradation mediated by PNPase and SUV3. (PMID:22661577)
• Although SLIRP is not involved in mediating bcl-2 ability to protect from apoptosis and oxidative damage, bcl-2 binds and stabilizes SLIRP protein and regulates mitochondrial mRNA levels. The BH4 domain of bcl-2 has a role in maintaining this binding. (PMID:26866271)
• LRPPRC displays a broad and strong RNA binding capacity in vitro in contrast to SLIRP that associates only weakly with RNA. (PMID:27353330)
• assessed, by using CRISPR-Cas9-introduced affinity tag and ChIP-Seq analysis, the genome-wide occupancy of SLIRP, and showed that the protein binds preferentially to G-rich DNA sequences that can fold into G4 structures (PMID:28859475)
• 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)
• Interaction between androgen receptor and coregulator SLIRP is regulated by Ack1 tyrosine kinase and androgen. (PMID:31819114)
• Messenger RNA delivery to mitoribosomes - hints from a bacterial toxin. (PMID:32329962)
• Effects of SLIRP on Sperm Motility and Oxidative Stress. (PMID:33150185)
• Pathogenic SLIRP variants as a novel cause of autosomal recessive mitochondrial encephalomyopathy with complex I and IV deficiency. (PMID:34426662)
• Mitochondrial Protein SLIRP Affects Biosynthesis of Cytochrome c Oxidase Subunits in HEK293T Cells. (PMID:38203264)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	slirp	ENSDARG00000097753
mus_musculus	Slirp	ENSMUSG00000021040
rattus_norvegicus	LOC108352643	ENSRNOG00000068606

Protein

Protein identifiers

SRA stem-loop-interacting RNA-binding protein, mitochondrial — Q9GZT3 (reviewed: Q9GZT3)

All UniProt accessions (9): A0A087WUN7, Q9GZT3, G3V2S9, G3V4X6, H0YJ07, H0YJ40, H0YJI1, H0YJU7, H0YJW7

UniProt curated annotations — full annotation on UniProt →

Function. RNA-binding protein that acts as a nuclear receptor corepressor. Probably acts by binding the SRA RNA, and repressing the SRA-mediated nuclear receptor coactivation. Binds the STR7 loop of SRA RNA. Also able to repress glucocorticoid (GR), androgen (AR), thyroid (TR) and VDR-mediated transactivation.

Subcellular location. Mitochondrion. Nucleus.

Tissue specificity. Ubiquitously expressed, with highest level in heart, liver, skeletal muscle and testis.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9GZT3-1	1	yes
Q9GZT3-2	2

RefSeq proteins (3): NP_001254792, NP_001254793, NP_112487* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR034152	SLIRP_RRM	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR052462	SLIRP/GR-RBP-like	Family

Pfam: PF00076

UniProt features (12 total): mutagenesis site 4, modified residue 3, transit peptide 1, chain 1, sequence conflict 1, domain 1, splice variant 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-Q9GZT3-F1	81.54	0.59

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 (3): 15, 101, 102

Mutagenesis-validated functional residues (4):

Position	Phenotype
62	impairs sra-mediated repression; when associated with 24-a-a-25.
7	impairs corepressor activity; when associated with 13-a-a-14.
13–14	impairs corepressor activity; when associated with a-7.
24–25	impairs sra-mediated repression; when associated with a-62.

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: 164 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, GOBP_SINGLE_FERTILIZATION, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, PAL_PRMT5_TARGETS_UP, GOCC_SECRETORY_GRANULE, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_MALE_GAMETE_GENERATION, WEI_MYCN_TARGETS_WITH_E_BOX, chr14q24, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_CILIUM_MOVEMENT, GOBP_MITOCHONDRIAL_RNA_PROCESSING

GO Biological Process (7): mitochondrion organization (GO:0007005), spermatid development (GO:0007286), single fertilization (GO:0007338), flagellated sperm motility (GO:0030317), 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 (4): RNA binding (GO:0003723), mRNA binding (GO:0003729), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (8): acrosomal vesicle (GO:0001669), nucleus (GO:0005634), mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), sperm flagellum (GO:0036126), perinuclear region of cytoplasm (GO:0048471), 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
binding	2
intracellular membrane-bounded organelle	2
cytoplasm	2
cellular anatomical structure	2
organelle organization	1
germ cell development	1
spermatid differentiation	1
fertilization	1
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	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
nucleic acid binding	1
RNA binding	1
secretory granule	1
mitochondrion	1
intracellular organelle lumen	1
9+2 motile cilium	1
protein-containing complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2899 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLIRP	LRPPRC	P42704	997
SLIRP	SNW1	Q13573	798
SLIRP	MTPAP	Q9NVV4	742
SLIRP	PDE12	Q6L8Q7	697
SLIRP	NCOA1	Q15788	689
SLIRP	PUS1	Q9Y606	638
SLIRP	SRA1	Q9HD15	637
SLIRP	SUPV3L1	Q8IYB8	634
SLIRP	PNPT1	Q8TCS8	628
SLIRP	GRSF1	Q12849	627
SLIRP	POLRMT	O00411	617
SLIRP	TACO1	Q9BSH4	585
SLIRP	PTCD3	Q96EY7	526
SLIRP	MT-ND6	P03923	516
SLIRP	MTIF3	Q9H2K0	512

IntAct

159 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
NDUFAB1	SLIRP	psi-mi:“MI:0915”(physical association)	0.680
WTAP	SLIRP	psi-mi:“MI:0915”(physical association)	0.670
LRPPRC	SLIRP	psi-mi:“MI:0915”(physical association)	0.670
CFTR	HAX1	psi-mi:“MI:0914”(association)	0.610
SLIRP	CCDC102B	psi-mi:“MI:0915”(physical association)	0.560
SLIRP	MTUS2	psi-mi:“MI:0915”(physical association)	0.560
KRT40	SLIRP	psi-mi:“MI:0915”(physical association)	0.560
SLIRP	PNMA1	psi-mi:“MI:0915”(physical association)	0.560
CCDC102B	SLIRP	psi-mi:“MI:0915”(physical association)	0.560
MTUS2	SLIRP	psi-mi:“MI:0915”(physical association)	0.560
SLIRP	KRT40	psi-mi:“MI:0915”(physical association)	0.560
PNMA1	SLIRP	psi-mi:“MI:0915”(physical association)	0.560
KRT27	SLIRP	psi-mi:“MI:0915”(physical association)	0.560
SLIRP	PICK1	psi-mi:“MI:0915”(physical association)	0.560
GOLGA6L9	SLIRP	psi-mi:“MI:0915”(physical association)	0.560
STK40	SLIRP	psi-mi:“MI:0915”(physical association)	0.560
AMOT	SLIRP	psi-mi:“MI:0915”(physical association)	0.560
ERBB2	NDUFA4	psi-mi:“MI:0914”(association)	0.530
NDUFAB1	MIEF1	psi-mi:“MI:0915”(physical association)	0.490
vpu	SCAMP3	psi-mi:“MI:0914”(association)	0.460

BioGRID (397): SLIRP (Two-hybrid), SLIRP (Two-hybrid), SLIRP (Two-hybrid), KRT40 (Two-hybrid), SLIRP (Affinity Capture-MS), SLIRP (Affinity Capture-MS), SLIRP (Affinity Capture-MS), SLIRP (Affinity Capture-MS), SLIRP (Affinity Capture-MS), SLIRP (Affinity Capture-MS), SLIRP (Affinity Capture-MS), SLIRP (Affinity Capture-MS), SLIRP (Affinity Capture-MS), SLIRP (Affinity Capture-MS), SLIRP (Affinity Capture-Western)

ESM2 similar proteins: A6QPQ5, C0HFE5, F1QLR3, O70523, P35922, P51113, P51114, P82277, P86049, Q08BH5, Q12849, Q28ZX3, Q2KHP9, Q32KZ1, Q32P59, Q4R2Z0, Q4VXU2, Q5BJ56, Q5R8K3, Q5R9B4, Q5R9H4, Q5REG1, Q5SP50, Q5VRY0, Q5XI81, Q5YD48, Q6PBM8, Q6YWP9, Q80WE1, Q8BHN5, Q8C5Q4, Q8CFD1, Q8CGC6, Q8L440, Q8R3C6, Q8TBY0, Q8VYM4, Q8W4E1, Q923K9, Q99N96

Diamond homologs: A0A0D1DZT6, A3LXL0, A5A6M3, A5DM21, A6NDY0, O13620, O14327, P08199, P09405, P10979, P13383, P15771, P19338, P19682, P19683, P20397, P27476, P28644, P33240, P38159, P40561, P41891, P97855, Q03878, Q04836, Q05966, Q08473, Q08935, Q13283, Q1PEP5, Q23121, Q32LC7, Q32P59, Q39061, Q43349, Q43472, Q44554, Q44556, Q44560, Q4G338

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 133 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
Mitochondrial protein degradation	7	9.4×	3e-03
Mitochondrial ribosome-associated quality control	6	8.7×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	18
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2185 predictions. Top by Δscore:

Variant	Effect	Δscore
14:77708204:GTCGA:G	donor_gain	1.0000
14:77708207:GA:G	donor_gain	1.0000
14:77708209:G:GG	donor_gain	1.0000
14:77708227:G:GT	donor_gain	1.0000
14:77710892:CTTTT:C	donor_gain	1.0000
14:77710897:G:GG	donor_gain	1.0000
14:77715113:GCTT:G	donor_gain	1.0000
14:77715121:GCT:G	donor_gain	1.0000
14:77718282:CAAAT:C	acceptor_gain	1.0000
14:77718287:C:CC	acceptor_gain	1.0000
14:77718527:TACC:T	acceptor_gain	1.0000
14:77718529:CC:C	acceptor_gain	1.0000
14:77718530:CC:C	acceptor_gain	1.0000
14:77720706:TGTA:T	donor_loss	1.0000
14:77720708:TACCT:T	donor_loss	1.0000
14:77720709:A:C	donor_loss	1.0000
14:77720710:C:T	donor_loss	1.0000
14:77720745:A:C	donor_gain	1.0000
14:77720829:C:CC	acceptor_gain	1.0000
14:77720829:CT:C	acceptor_loss	1.0000
14:77720830:T:C	acceptor_loss	1.0000
14:77730982:TCATA:T	donor_loss	1.0000
14:77730983:CATA:C	donor_loss	1.0000
14:77730984:ATAC:A	donor_loss	1.0000
14:77730985:TA:T	donor_loss	1.0000
14:77730986:A:AC	donor_gain	1.0000
14:77730987:C:CC	donor_gain	1.0000
14:77731125:CGAGC:C	acceptor_gain	1.0000
14:77731126:GAGC:G	acceptor_gain	1.0000
14:77731127:AGC:A	acceptor_gain	1.0000

AlphaMissense

710 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:77715815:T:C	F67S	0.994
14:77710864:T:C	F42L	0.993
14:77710866:C:A	F42L	0.993
14:77710866:C:G	F42L	0.993
14:77715814:T:C	F67L	0.993
14:77715816:T:A	F67L	0.993
14:77715816:T:G	F67L	0.993
14:77715809:T:A	V65D	0.992
14:77715790:C:G	H59D	0.989
14:77710856:T:C	F39S	0.987
14:77715803:G:A	G63D	0.987
14:77710855:T:C	F39L	0.985
14:77710857:T:A	F39L	0.985
14:77710857:T:G	F39L	0.985
14:77715815:T:G	F67C	0.985
14:77710874:T:A	V45D	0.984
14:77710868:G:T	G43V	0.983
14:77710894:T:C	F52L	0.982
14:77710896:T:A	F52L	0.982
14:77710896:T:G	F52L	0.982
14:77715802:G:C	G63R	0.979
14:77717497:T:A	V89D	0.977
14:77710844:T:C	L35P	0.976
14:77715841:G:C	A76P	0.975
14:77708173:C:A	A21D	0.973
14:77708188:T:C	I26T	0.973
14:77708175:T:C	F22L	0.972
14:77708177:T:A	F22L	0.972
14:77708177:T:G	F22L	0.972
14:77708195:G:C	W28C	0.972

dbSNP variants (sampled 300 via entrez): RS1000391583 (14:77714760 AGAG>A), RS1000915167 (14:77716451 C>G), RS1001067737 (14:77708835 G>A), RS1001499283 (14:77710952 A>G,T), RS1002513221 (14:77716510 G>C), RS1002699671 (14:77711494 T>C), RS1002712466 (14:77716718 C>G), RS1002732174 (14:77711236 T>C), RS1002740115 (14:77711101 A>G), RS1002858249 (14:77717074 C>T), RS1003266266 (14:77712420 T>C,G), RS1003519928 (14:77717775 T>C), RS1003648976 (14:77706937 C>A,T), RS1003739033 (14:77712414 C>T), RS1003918722 (14:77711131 C>A)

Disease associations

OMIM: gene MIM:610211 | disease phenotypes: MIM:220111

GenCC curated gene-disease

Disease	Classification	Inheritance
inborn mitochondrial metabolism disorder	Limited	Autosomal recessive
mitochondrial encephalomyopathy	Limited	Autosomal recessive

Mondo (3): congenital lactic acidosis, Saguenay-Lac-Saint-Jean type (MONDO:0009069), inborn mitochondrial metabolism disorder (MONDO:0004069), mitochondrial encephalomyopathy (MONDO:0004675)

Orphanet (1): Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type (Orphanet:70472)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D028361	Mitochondrial Diseases	C18.452.660
D017237	Mitochondrial Encephalomyopathies	C05.651.460.620; C10.228.140.163.540; C10.668.491.500.500; C18.452.132.540; C18.452.660.560.620
C537004	Leigh syndrome , French Canadian type (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066420 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.67	Kd	0.214	nM	CHEMBL5653589
9.67	ED50	0.214	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 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-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149435: Binding affinity to human SLIRP incubated for 45 mins by Kinobead based pull down assay	kd	0.0002	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
bisphenol A	affects expression, decreases expression	2
Valproic Acid	affects cotreatment, increases expression	2
Particulate Matter	decreases reaction, increases expression	2
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
beta-lapachone	decreases expression, increases expression	1
arsenite	affects binding, increases reaction	1
cobaltous chloride	decreases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
cyclic 3’,5’-uridine monophosphate	affects binding	1
CD 437	decreases expression	1
chloropicrin	increases expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	increases expression, decreases reaction	1
LDN 193189	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Acetaminophen	affects expression	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Vehicle Emissions	decreases reaction, increases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Estradiol	decreases expression	1
Gold	decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Lead	affects expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652477	Binding	Binding affinity to human SLIRP incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03351998	PHASE4	COMPLETED	Impact of Statin Therapy on Muscle Mitochondrial Function and Aerobic Capacity
NCT00432744	PHASE3	COMPLETED	Phase III Trial of Coenzyme Q10 in Mitochondrial Disease
NCT05162768	PHASE3	COMPLETED	Study to Evaluate Efficacy and Safety of Elamipretide in Subjects With Primary Mitochondrial Disease From Nuclear DNA Mutations (nPMD)
NCT06451757	PHASE3	RECRUITING	KHENERFIN Study: A Trial to Evaluate the Efficacy and Safety of Sonlicromanol in Primary Mitochondrial Diseases
NCT02398201	PHASE2	COMPLETED	A Study of Bezafibrate in Mitochondrial Myopathy
NCT02473445	PHASE2	TERMINATED	A Long-term Extension of Study RP103-MITO-001 (NCT02023866) to Assess Cysteamine Bitartrate Delayed-release Capsules (RP103) in Children With Inherited Mitochondrial Disease
NCT02500628	PHASE2	COMPLETED	Heart Rate Variability in Response to Metformin Challenge
NCT02805790	PHASE2	COMPLETED	Safety, Tolerability, Efficacy of MTP-131 for Treatment of Mitochondrial Disease in Subjects From the MMPOWER Study
NCT02909400	PHASE2	COMPLETED	The KHENERGY Study
NCT02976038	PHASE2	TERMINATED	Open-Label Extension Trial to Characterize the Long-term Safety and Tolerability of Elamipretide in Subjects With Genetically Confirmed Primary Mitochondrial Myopathy (PMM)
NCT03177798	PHASE2	COMPLETED	Mitochondria and Chronic Kidney Disease
NCT03866954	PHASE2	WITHDRAWN	Trial of Erythrocyte Encapsulated Thymidine Phosphorylase In Mitochondrial Neurogastrointestinal Encephalomyopathy
NCT04165239	PHASE2	COMPLETED	The KHENERGYZE Study
NCT04604548	PHASE2	COMPLETED	The KHENEREXT Study
NCT04802707	PHASE2	RECRUITING	Deoxynucleosides Pyrimidines as Treatment for Mitochondrial Depletion Syndrome
NCT04846036	PHASE2	SUSPENDED	The KHENERGYC Study
NCT05650229	PHASE2	RECRUITING	Efficacy of KL1333 in Adult Patients With Primary Mitochondrial Disease
NCT05972954	PHASE2	COMPLETED	OMT-28 in Patients With Primary Mitochondrial Disease (PMD) (PMD-OPTION)
NCT06017869	PHASE2	RECRUITING	Evaluate the Safety and Therapeutic Effects of a Single Intravenous Infusion (IV) of Autologous CD34+ Cells Enriched With Allogenic Placenta-derived Mitochondria in Patients With a Diagnosis of Pearson Syndrome (PS)
NCT07514338	PHASE2	NOT_YET_RECRUITING	Open Label Extension to Assess Long Term Safety and Efficacy of KL1333 in Patients With Primary Mitochondrial Disease
NCT00060515	PHASE1	TERMINATED	RG2133 (2’,3’,5’-Tri-O-Acetyluridine) in Mitochondrial Disease
NCT02348125	PHASE1	UNKNOWN	Does Clinical Treatment of Mitochondrial Dysfunction Impact Autism Spectrum Disorder (ASD)?
NCT02544217	PHASE1	COMPLETED	A Dose-escalating Clinical Trial With KH176
NCT03888716	PHASE1	COMPLETED	A Phase Ia/Ib, SAD and MAD Study of of KL1333 in Healthy Subjects and Patients With Primary Mitochondrial Disease
NCT04086329	PHASE1	RECRUITING	Validation of Oxygen Nanosensor in Mitochondrial Myopathy
NCT04643249	PHASE1	COMPLETED	Drug-drug Interaction Study of KL1333 in Healthy Subjects
NCT05241262	PHASE1	RECRUITING	Study of N-acetylcysteine in the Treatment of Patients With the m.3243A>G Mutation and Low Brain Glutathione Levels
NCT05569122	PHASE1	RECRUITING	Applying pGz in Mitochondrial Disease
NCT06819683	PHASE1	RECRUITING	Validation of Nanosensor Oxygen Measurement
NCT07258667	PHASE1	NOT_YET_RECRUITING	Pilot Study of the Efficacy of Nicotinamide (Vitamin B3) in Leber’s Hereditary Optic Neuropathy
NCT04378075	PHASE2/PHASE3	TERMINATED	A Study to Evaluate Efficacy and Safety of Vatiquinone for Treating Mitochondrial Disease in Participants With Refractory Epilepsy
NCT01642056	PHASE1/PHASE2	COMPLETED	EPI-743 for Metabolism or Mitochondrial Disorders
NCT03384420	PHASE1/PHASE2	COMPLETED	A Study to Evaluate the Safety and Therapeutic Effects of Transplantation of MNV-BM-BLD in Pediatric Patients With Pearson Syndrome
NCT06051448	PHASE1/PHASE2	COMPLETED	Promoting Resilience in Stress Management (PRISM) and Clinical-focused Narrative (CFN) Pilot in Adults With Primary Mitochondrial Disease (PMD).
NCT01252979	EARLY_PHASE1	COMPLETED	Ketones & Mitochondrial Heteroplasmy
NCT00786539	Not specified	COMPLETED	Mitochondria Inborn Errors of Metabolism and ANT Defects in Mitochondria Diseases
NCT00829270	Not specified	COMPLETED	Economic and Medical Evaluation of the Whole Mitochondrial DNA Screening by Surveyor and Mitochips Techniques
NCT00831948	Not specified	UNKNOWN	Identification of Large-Scale Mutations of POLG Gene by QMPSF in Patients With Mitochondrial DNA Instability.
NCT01001585	Not specified	TERMINATED	Anesthetic Effects in Mitochondrial Disease
NCT01148550	Not specified	SUSPENDED	Longitudinal Study of Mitochondrial Hepatopathies