LARP1

Summary

LARP1 (La ribonucleoprotein 1, translational regulator, HGNC:29531) is a protein-coding gene on chromosome 5q33.2, encoding La-related protein 1 (Q6PKG0). RNA-binding protein that regulates the translation of specific target mRNA species downstream of the mTORC1 complex, in function of growth signals and nutrient availability. It is a selective cancer dependency (DepMap: 15.8% of cell lines).

Enables several functions, including RNA binding activity; eukaryotic initiation factor 4E binding activity; and ribosomal small subunit binding activity. Involved in several processes, including TORC1 signaling; cellular response to rapamycin; and post-transcriptional regulation of gene expression. Located in TORC1 complex and cytoplasmic stress granule.

Source: NCBI Gene 23367 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Strong, GenCC)
• GWAS associations: 8
• Clinical variants (ClinVar): 144 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 15.8% of screened cell lines
• MANE Select transcript: NM_033551

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29531
Approved symbol	LARP1
Name	La ribonucleoprotein 1, translational regulator
Location	5q33.2
Locus type	gene with protein product
Status	Approved
Aliases	LARP, KIAA0731, MGC19556, Lar1, Lhp1
Ensembl gene	ENSG00000155506
Ensembl biotype	protein_coding
OMIM	612059
Entrez	23367

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 18 protein_coding, 5 retained_intron, 1 nonsense_mediated_decay

ENST00000336314, ENST00000517616, ENST00000518194, ENST00000518297, ENST00000518595, ENST00000518677, ENST00000518742, ENST00000518892, ENST00000519194, ENST00000519931, ENST00000521577, ENST00000522272, ENST00000523163, ENST00000524187, ENST00000524248, ENST00000685355, ENST00000685946, ENST00000687700, ENST00000688232, ENST00000690816, ENST00000913419, ENST00000913420, ENST00000913421, ENST00000955841

RefSeq mRNA: 9 — MANE Select: NM_033551 NM_001367713, NM_001367714, NM_001367715, NM_001367716, NM_001367717, NM_001367718, NM_001367719, NM_015315, NM_033551

CCDS: CCDS4328, CCDS93806, CCDS93807

Canonical transcript exons

ENST00000518297 — 19 exons

Exon	Start	End
ENSE00001127188	154811513	154811640
ENSE00001127197	154811247	154811356
ENSE00001220883	154805881	154806032
ENSE00001220897	154803540	154803745
ENSE00001220908	154803290	154803413
ENSE00001221032	154804201	154804307
ENSE00001221050	154802007	154802399
ENSE00001221074	154794100	154794262
ENSE00001859308	154813887	154817605
ENSE00002099281	154755377	154756193
ENSE00003504224	154790645	154790710
ENSE00003548035	154793800	154794000
ENSE00003566706	154799591	154799759
ENSE00003568394	154799873	154800042
ENSE00003570586	154795175	154795319
ENSE00003582483	154793595	154793723
ENSE00003611966	154808459	154808603
ENSE00003668223	154792622	154792796
ENSE00003671137	154790325	154790386

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 98.68.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 56.4289 / max 574.1446, expressed in 1824 samples.

FANTOM5 promoters (19 alternative TSS)

Promoter ID	TPM avg	Samples expressed
59739	34.6155	1816
59734	3.9761	1099
59733	3.0536	1381
59741	2.3125	1309
59749	2.2130	1339
59750	1.7036	1019
59745	1.0618	549
59751	0.9394	595
59738	0.9127	694
203760	0.8687	528

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
superior vestibular nucleus	UBERON:0007227	98.68	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.66	gold quality
dorsal root ganglion	UBERON:0000044	98.60	gold quality
substantia nigra pars compacta	UBERON:0001965	98.59	gold quality
middle temporal gyrus	UBERON:0002771	98.58	gold quality
lateral nuclear group of thalamus	UBERON:0002736	98.52	gold quality
adult organism	UBERON:0007023	98.51	gold quality
trigeminal ganglion	UBERON:0001675	98.45	gold quality
pylorus	UBERON:0001166	98.34	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.34	gold quality
renal medulla	UBERON:0000362	98.28	gold quality
pons	UBERON:0000988	98.16	gold quality
medulla oblongata	UBERON:0001896	98.14	gold quality
superior surface of tongue	UBERON:0007371	98.12	gold quality
nipple	UBERON:0002030	98.05	gold quality
cardia of stomach	UBERON:0001162	98.01	gold quality
ventral tegmental area	UBERON:0002691	97.90	gold quality
lateral globus pallidus	UBERON:0002476	97.88	gold quality
entorhinal cortex	UBERON:0002728	97.88	gold quality
penis	UBERON:0000989	97.86	gold quality
endometrium epithelium	UBERON:0004811	97.58	gold quality
inferior vagus X ganglion	UBERON:0005363	97.57	gold quality
pigmented layer of retina	UBERON:0001782	97.56	gold quality
tongue	UBERON:0001723	97.53	gold quality
caput epididymis	UBERON:0004358	97.53	gold quality
globus pallidus	UBERON:0001875	97.52	gold quality
dorsal plus ventral thalamus	UBERON:0001897	97.52	gold quality
saphenous vein	UBERON:0007318	97.52	gold quality
pharyngeal mucosa	UBERON:0000355	97.50	gold quality
medial globus pallidus	UBERON:0002477	97.45	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	12.78
E-MTAB-6524	no	141.77

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 15.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 33)

• Nuclear trafficking of La protein depends on a newly identified nucleolar localization signal and the ability to bind RNA (PMID:15060081)
• LARP1 may be involved in the post-transcriptional regulation of gene expression through the binding to 3’ terminus of the poly(A) tail. (PMID:23711370)
• LARP1 associates with actively translating ribosomes via PABP and that LARP1 stimulates the translation of mRNAs containing a 5’ terminal oligopyrimidine (TOP) motif (PMID:24532714)
• conclude that, through the post-transcriptional regulation of genes such as mTOR within cancer pathways, LARP1 contributes to cancer progression (PMID:25531318)
• LARP1 is a target of mTORC1 that associates with TOP mRNAs via their 5’TOP motif to repress their translation. (PMID:25940091)
• Data showed that LARP1 was upregulated in prostate cancer (PCa) and contributed to cancer cell invasion, indicating that it functioned as an oncogene. Its 3’UTR is the binding site for miR-26a and miR-26b. (PMID:26063484)
• The first evidence that the DM15 region of human LARP1 mediates its RNA binding activity. (PMID:26206669)
• Data indicate that RNA-binding protein LARP1 promotes ovarian cancer progression and chemotherapy resistance. (PMID:26717985)
• LARP1 plays an important role in the proliferation of colorectal cancer and represents a new prognostic indicator. (PMID:27614686)
• The authors show that LARP1 directly binds the cap and adjacent 5’TOP motif of TOP mRNAs, effectively impeding access of eIF4E to the cap and preventing eIF4F assembly. Thus, LARP1 is a specialized TOP mRNA cap-binding protein that controls ribosome biogenesis. (PMID:28379136)
• Thus, in response to cellular mTOR activity, LARP1 serves as a phosphorylation-sensitive molecular switch for turning off or on ribosomal protein mRNA translation and subsequent ribosome biogenesis. (PMID:28650797)
• A cytoplasmic isoform of La protein as well as LARPs 6, 4, and 1 function in mRNA metabolism and translation in distinct but similar ways, sometimes with the poly(A)-binding protein, and in some cases by direct binding to poly(A)-RNA. (PMID:28782243)
• we suggest that the dysfunction of the XIST/miR-374a/LARP1 axis contributes to non-small cell lung cancer (NSCLC)and may serve as a promising therapeutic strategy for treatment. (PMID:29039571)
• The results support a model whereby the translation of TOP mRNAs is controlled by a growth-regulated competition between eIF4F and LARP1 for their 5’ ends. (PMID:29244122)
• L-leucine increases translation of RPS14 and LARP1 in erythroblasts from del(5q) myelodysplastic syndrome patients. (PMID:29903759)
• circ-BANP promoted LARP1 expression through sponging miR-503 in lung cancer cells. (PMID:29969631)
• The LARP1 La-Module recognizes both ends of TOP mRNAs. (PMID:31601159)
• The molecular mechanism underlying TOP Rps6 mRNA binding to LARP1 has been deciphered. (PMID:31676287)
• These results establish the central role of LARP1 in TOP mRNA regulation on a transcriptome scale and show how it connects mTORC1 to a tunable and dynamic program of gene expression that is tailored to specific biological contexts. (PMID:32094190)
• LARP1 isoform expression in human cancer cell lines. (PMID:32286153)
• Knockdown of KCNQ1OT1 Inhibits Proliferation, Invasion, and Drug Resistance by Regulating miR-129-5p-Mediated LARP1 in Osteosarcoma. (PMID:32953888)
• The mTOR regulated RNA-binding protein LARP1 requires PABPC1 for guided mRNA interaction. (PMID:33332560)
• Hsa_circRNA_002144 promotes growth and metastasis of colorectal cancer through regulating miR-615-5p/LARP1/mTOR pathway. (PMID:33347535)
• mTORC1 promotes TOP mRNA translation through site-specific phosphorylation of LARP1. (PMID:33398329)
• The RNA-binding protein LARP1 is dispensable for pancreatic beta-cell function and mass. (PMID:33483593)
• The SARS-CoV-2 RNA interactome. (PMID:33989516)
• Global analysis of RNA-binding proteins identifies a positive feedback loop between LARP1 and MYC that promotes tumorigenesis. (PMID:35195778)
• O-GlcNAcylated LARP1 positively regulated by circCLNS1A facilitates hepatoblastoma progression through DKK4/beta-catenin signalling. (PMID:37070251)
• Proximity labeling of host factor ANXA3 in HCV infection reveals a novel LARP1 function in viral entry. (PMID:38636657)
• [1]H, [13]C, and [15]N resonance assignments of the La Motif of the human La-related protein 1. (PMID:38691336)
• Enhanced binding of guanylated poly(A) RNA by the LaM domain of LARP1. (PMID:39016322)
• LARP1, an RNA-binding protein, participates in ovarian cancer cell survival by regulating mitochondrial oxidative phosphorylation in response to the influence of the PI3K/mTOR pathway. (PMID:39111634)
• LARP1 haploinsufficiency is associated with an autosomal dominant neurodevelopmental disorder. (PMID:39182167)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	larp1	ENSDARG00000101722
mus_musculus	Larp1	ENSMUSG00000037331
rattus_norvegicus	Larp1	ENSRNOG00000031544
drosophila_melanogaster	Larp4B	FBGN0035424
caenorhabditis_elegans	larp-5	WBGENE00004147

Paralogs (6): LARP4B (ENSG00000107929), SSB (ENSG00000138385), LARP1B (ENSG00000138709), LARP4 (ENSG00000161813), LARP6 (ENSG00000166173), LARP7 (ENSG00000174720)

Protein

Protein identifiers

La-related protein 1 — Q6PKG0 (reviewed: Q6PKG0)

Alternative names: La ribonucleoprotein domain family member 1

All UniProt accessions (14): Q6PKG0, A0A0B4J210, A0A8I5KSP1, A0A8I5KWU3, E5RH50, E5RHK4, H0YAN4, H0YAX9, H0YBJ5, H0YBM7, H0YBR8, H0YBW1, H0YC33, H0YC73

UniProt curated annotations — full annotation on UniProt →

Function. RNA-binding protein that regulates the translation of specific target mRNA species downstream of the mTORC1 complex, in function of growth signals and nutrient availability. Interacts on the one hand with the 3’ poly-A tails that are present in all mRNA molecules, and on the other hand with the 7-methylguanosine cap structure of mRNAs containing a 5’ terminal oligopyrimidine (5’TOP) motif, which is present in mRNAs encoding ribosomal proteins and several components of the translation machinery. The interaction with the 5’ end of mRNAs containing a 5’TOP motif leads to translational repression by preventing the binding of EIF4G1. When mTORC1 is activated, LARP1 is phosphorylated and dissociates from the 5’ untranslated region (UTR) of mRNA. Does not prevent binding of EIF4G1 to mRNAs that lack a 5’TOP motif. Interacts with the free 40S ribosome subunit and with ribosomes, both monosomes and polysomes. Under normal nutrient availability, interacts primarily with the 3’ untranslated region (UTR) of mRNAs encoding ribosomal proteins and increases protein synthesis. Associates with actively translating ribosomes and stimulates translation of mRNAs containing a 5’TOP motif, thereby regulating protein synthesis, and as a consequence, cell growth and proliferation. Stabilizes mRNAs species with a 5’TOP motif, which is required to prevent apoptosis. (Microbial infection) Positively regulates the replication of dengue virus (DENV).

Subunit / interactions. Interacts with PABPC1/PABP. Interacts with EIF4A1. Interacts with RPTOR. Recruited to the active mTORC1 complex via interaction with RPTOR. Inhibition of mTORC1 activity strongly reduces interaction with RPTOR and the mTORC1 complex. Identified in a complex with mRNA, PABPC1, EIF4E and EIF4G1. Found in a complex with PABPC1 and SHFL.

Subcellular location. Cytoplasm. Cytoplasmic granule.

Post-translational modifications. Phosphorylated on multiple Ser and Thr residues in response to active mTORC1. Phosphorylation is important for interaction with RPTOR and the mTORC1 complex. Phosphorylation promotes dissociation from the 5’UTR of mRNA molecules with a 5’TOP motif.

Domain organisation. The C-terminal region mediates interaction with the mRNA and polysomes. It is required for translational repression of mRNAs with a 5’TOP motif. The N-terminal region mediates interaction with PABPC1.

Induction. Up-regulated in a number of hepatocellular carcinoma cell lines and liver cancer lesions, as well as in patients with hepatocellular carcinoma with a lower survival rate (at protein level).

Similarity. Belongs to the LARP family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6PKG0-1	1	yes
Q6PKG0-3	2

RefSeq proteins (9): NP_001354642, NP_001354643, NP_001354644, NP_001354645, NP_001354646, NP_001354647, NP_001354648, NP_056130, NP_291029* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006607	DM15	Repeat
IPR006630	La_HTH	Domain
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR045180	La_dom_prot	Family

Pfam: PF05383, PF21071

UniProt features (110 total): modified residue 45, helix 16, compositionally biased region 14, mutagenesis site 12, region of interest 8, cross-link 4, turn 2, splice variant 2, sequence conflict 2, strand 2, initiator methionine 1, chain 1, domain 1

Structure

Experimental structures (PDB)

23 structures.

PDB	Method	Resolution (Å)
7SOQ	X-RAY DIFFRACTION	1.15
8G90	X-RAY DIFFRACTION	1.2
8G91	X-RAY DIFFRACTION	1.2
7SOS	X-RAY DIFFRACTION	1.25
7SOW	X-RAY DIFFRACTION	1.3
8EY8	X-RAY DIFFRACTION	1.3
7SOR	X-RAY DIFFRACTION	1.35
8EY7	X-RAY DIFFRACTION	1.35
7SOU	X-RAY DIFFRACTION	1.45
7SOV	X-RAY DIFFRACTION	1.45
7SOT	X-RAY DIFFRACTION	1.52
7SOP	X-RAY DIFFRACTION	1.55
8EY6	X-RAY DIFFRACTION	1.63
7SOO	X-RAY DIFFRACTION	1.65
5V87	X-RAY DIFFRACTION	1.69
5V4R	X-RAY DIFFRACTION	1.77
4ZC4	X-RAY DIFFRACTION	1.86
5C0V	X-RAY DIFFRACTION	2.2
6PW3	X-RAY DIFFRACTION	2.34
5V7C	X-RAY DIFFRACTION	2.59
9ED0	ELECTRON MICROSCOPY	2.8
8XP2	ELECTRON MICROSCOPY	3.2
8XP3	ELECTRON MICROSCOPY	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6PKG0-F1	54.16	0.16

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 (49): 2, 75, 90, 143, 165, 215, 220, 223, 225, 228, 240, 324, 327, 376, 517, 521, 526, 548, 591, 627 …

Mutagenesis-validated functional residues (12):

Position	Phenotype
497–507	strongly reduced interaction with pabpc1.
505	strongly reduced interaction with pabpc1.
766	loss of phosphorylation by mtor; when associated with a-769. decreased interaction with rptor and impaired dissociation
769	loss of phosphorylation by mtor; when associated with a-766. decreased interaction with rptor and impaired dissociation
847	strongly reduced phosphorylation mediated by akt and rps6kb1. decreased interaction with rptor and impaired dissociation
917	abolishes rna binding. abolishes inhibition of eif4g1 binding to mrna molecules with a 5’top motif; when associated with
960	abolishes rna binding. abolishes translational repression of mrnas with a 5’top motif. abolishes inhibition of eif4g1 bi
963	strongly decreased rna binding.
966–970	loss of interaction with rptor.
966	no effect on interaction with rptor.
999	strongly decreased rna binding.
1058	strongly reduced phosphorylation mediated by akt and rps6kb1. decreased interaction with rptor and impaired dissociation

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-9705671	SARS-CoV-2 activates/modulates innate and adaptive immune responses
R-HSA-1643685	Disease
R-HSA-5663205	Infectious disease
R-HSA-9679506	SARS-CoV Infections
R-HSA-9694516	SARS-CoV-2 Infection
R-HSA-9705683	SARS-CoV-2-host interactions
R-HSA-9824446	Viral Infection Pathways

MSigDB gene sets: 370 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, MODULE_255, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_VIRAL_GENOME_REPLICATION, MODULE_317, TATTATA_MIR374, GOBP_TRANSLATIONAL_INITIATION, CTATGCA_MIR153, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_TRANSLATION, GOBP_MACROAUTOPHAGY, GOBP_NEGATIVE_REGULATION_OF_TRANSLATIONAL_INITIATION, PATIL_LIVER_CANCER

GO Biological Process (16): translational initiation (GO:0006413), cell population proliferation (GO:0008283), post-transcriptional regulation of gene expression (GO:0010608), positive regulation of macroautophagy (GO:0016239), negative regulation of translation (GO:0017148), TOR signaling (GO:0031929), TORC1 signaling (GO:0038202), positive regulation of viral genome replication (GO:0045070), positive regulation of translation (GO:0045727), negative regulation of translational initiation (GO:0045947), positive regulation of translational initiation (GO:0045948), mRNA stabilization (GO:0048255), cellular response to rapamycin (GO:0072752), response to amino acid starvation (GO:1990928), translation (GO:0006412), regulation of translation (GO:0006417)

GO Molecular Function (11): RNA cap binding (GO:0000339), RNA 7-methylguanosine cap binding (GO:0000340), RNA binding (GO:0003723), mRNA 3’-UTR binding (GO:0003730), eukaryotic initiation factor 4E binding (GO:0008190), translation activator activity (GO:0008494), translation initiation factor binding (GO:0031369), ribosomal small subunit binding (GO:0043024), cadherin binding (GO:0045296), mRNA 5’-UTR binding (GO:0048027), protein binding (GO:0005515)

GO Cellular Component (6): cytoplasm (GO:0005737), cytosol (GO:0005829), cytoplasmic stress granule (GO:0010494), membrane (GO:0016020), TORC1 complex (GO:0031931), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
SARS-CoV-2-host interactions	1
Disease	1
Viral Infection Pathways	1
SARS-CoV Infections	1
SARS-CoV-2 Infection	1
Infectious disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
translation	4
translational initiation	3
cellular anatomical structure	3
regulation of translation	2
regulation of translational initiation	2
positive regulation of translation	2
mRNA binding	2
formation of translation initiation ternary complex	1
metabolic process	1
cellular process	1
regulation of gene expression	1
positive regulation of autophagy	1
macroautophagy	1
regulation of macroautophagy	1
negative regulation of gene expression	1
negative regulation of protein metabolic process	1
intracellular signal transduction	1
TOR signaling	1
viral genome replication	1
regulation of viral genome replication	1
positive regulation of viral process	1
positive regulation of gene expression	1
positive regulation of protein metabolic process	1
negative regulation of translation	1
regulation of mRNA stability	1
RNA stabilization	1
negative regulation of mRNA catabolic process	1
cellular response to ether	1
cellular response to alcohol	1
response to rapamycin	1
cellular response to ketone	1
cellular response to nitrogen compound	1
response to starvation	1
peptidyltransferase activity	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
post-transcriptional regulation of gene expression	1

Protein interactions and networks

STRING

2450 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LARP1	PABPC1	P11940	845
LARP1	COL7A1	Q02388	813
LARP1	MSI1	O43347	765
LARP1	EIF4E	P06730	724
LARP1	RPTOR	Q8N122	700
LARP1	ATXN2	Q99700	624
LARP1	MTOR	P42345	615
LARP1	EIF4B	P23588	591
LARP1	FXR1	P51114	591
LARP1	FLNB	O75369	557
LARP1	HNRNPC	P07910	553
LARP1	RPL32	P02433	550
LARP1	YBX1	P16990	549
LARP1	UPF1	Q92900	547
LARP1	UBB	P02248	543

IntAct

425 interactions, top by confidence:

A	B	Type	Score
YWHAH	ABLIM1	psi-mi:“MI:0914”(association)	0.800
FBL	NOP56	psi-mi:“MI:0914”(association)	0.800
YWHAB	PIK3C2A	psi-mi:“MI:0914”(association)	0.800
NS	PIK3R2	psi-mi:“MI:0914”(association)	0.750
CNOT2	CNOT1	psi-mi:“MI:0914”(association)	0.740
N	HNRNPR	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
H1-1	RRP8	psi-mi:“MI:0914”(association)	0.640
NOL12	RRP8	psi-mi:“MI:0914”(association)	0.640
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
NCBP1	KPNA3	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
YWHAE	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
YWHAZ	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
KASH5	LARP1	psi-mi:“MI:0915”(physical association)	0.560
YWHAG	SHTN1	psi-mi:“MI:0914”(association)	0.560
NP	KPNA6	psi-mi:“MI:0914”(association)	0.550
H1-4	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
ILF2	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
GSPT2	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
PRR11	NVL	psi-mi:“MI:0914”(association)	0.530
RPL6	MRPS14	psi-mi:“MI:0914”(association)	0.530
ZCRB1	DKC1	psi-mi:“MI:0914”(association)	0.530
BHLHA15	RPLP0	psi-mi:“MI:0914”(association)	0.530
N	RRP9	psi-mi:“MI:0914”(association)	0.530

BioGRID (646): CCDC155 (Two-hybrid), LARP1 (Affinity Capture-MS), LARP1 (Affinity Capture-MS), LARP1 (Affinity Capture-MS), LARP1 (Affinity Capture-MS), LARP1 (Affinity Capture-MS), LARP1 (Affinity Capture-MS), LARP1 (Affinity Capture-MS), LARP1 (Affinity Capture-MS), LARP1 (Affinity Capture-MS), LARP1 (Affinity Capture-MS), LARP1 (Affinity Capture-MS), LARP1 (Affinity Capture-MS), LARP1 (Affinity Capture-MS), LARP1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IZ84, A0A1L8H8C0, A0A1L8HFX9, A2RUV4, F1LP90, F5HSE3, O43310, O60237, O75167, O88453, P41110, P61406, Q12830, Q1LVF3, Q2HJG4, Q2PFD7, Q3TLH4, Q5RAK6, Q5ZMS6, Q66HC1, Q6A0A2, Q6NRP6, Q6NZL0, Q6P1U3, Q6PKG0, Q75N33, Q7TN02, Q7TPM1, Q7YZA2, Q7Z6E9, Q80TN7, Q80XI3, Q86UR5, Q86US8, Q8IVL0, Q8IVL1, Q8K0V4, Q8N4C8, Q90YL3, Q90YY5

Diamond homologs: D5MCN2, J9VT60, O80567, P05455, P10881, P25567, P28048, P28049, P32067, P33399, P38656, P40796, Q05CL8, Q12034, Q26457, Q28G87, Q4G0J3, Q4R627, Q5XI01, Q659C4, Q6PKG0, Q6ZQ58, Q71RC2, Q7ZWE3, Q8BN59, Q8BWW4, Q8RWR2, Q94A38, Q94K80, Q9BRS8, Q9I7T7, Q9LHL3, Q9P6K0, Q9VAW5, Q940X9, P87058, Q04504, A8NS61, A8WLV5, B4NB54

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
AKT1	“down-regulates activity”	LARP1	phosphorylation
LARP1	“up-regulates activity”	mTORC1	binding
CDK2	“up-regulates activity”	LARP1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 210 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
Activation of BAD and translocation to mitochondria	7	39.2×	6e-08
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	34.6×	7e-08
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	34.6×	7e-08
Activation of BH3-only proteins	7	25.6×	7e-07
RHO GTPases activate PKNs	7	16.3×	1e-05
Intrinsic Pathway for Apoptosis	7	15.1×	2e-05
FOXO-mediated transcription	6	14.8×	1e-04
SARS-CoV-1-host interactions	11	14.2×	6e-08

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	7	14.1×	3e-04
mRNA stabilization	6	12.1×	2e-03
RNA processing	7	8.4×	2e-03
regulation of RNA splicing	7	8.4×	2e-03
intracellular protein localization	11	6.3×	4e-04
rRNA processing	8	6.2×	4e-03
mRNA splicing, via spliceosome	12	6.0×	3e-04
translation	10	5.7×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	111
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

3798 predictions. Top by Δscore:

Variant	Effect	Δscore
5:154790320:CACA:C	acceptor_loss	1.0000
5:154790322:CAG:C	acceptor_loss	1.0000
5:154790323:A:AG	acceptor_gain	1.0000
5:154790324:G:GC	acceptor_gain	1.0000
5:154790324:GA:G	acceptor_gain	1.0000
5:154790324:GAA:G	acceptor_gain	1.0000
5:154790324:GAAC:G	acceptor_gain	1.0000
5:154790324:GAACA:G	acceptor_gain	1.0000
5:154790383:CAAG:C	donor_loss	1.0000
5:154790384:AAGGT:A	donor_loss	1.0000
5:154790385:AGGT:A	donor_loss	1.0000
5:154790386:GGT:G	donor_loss	1.0000
5:154790387:GT:G	donor_loss	1.0000
5:154790388:T:A	donor_loss	1.0000
5:154792792:GAAAG:G	donor_gain	1.0000
5:154793798:AG:A	acceptor_gain	1.0000
5:154793799:GG:G	acceptor_gain	1.0000
5:154793889:G:GT	donor_gain	1.0000
5:154793998:GAA:G	donor_gain	1.0000
5:154794001:G:GG	donor_gain	1.0000
5:154794098:A:AG	acceptor_gain	1.0000
5:154794099:G:GG	acceptor_gain	1.0000
5:154794099:GCC:G	acceptor_gain	1.0000
5:154794099:GCCC:G	acceptor_gain	1.0000
5:154794099:GCCCA:G	acceptor_gain	1.0000
5:154794259:AGAT:A	donor_gain	1.0000
5:154794260:GAT:G	donor_gain	1.0000
5:154794260:GATG:G	donor_gain	1.0000
5:154794261:AT:A	donor_gain	1.0000
5:154794263:G:GG	donor_gain	1.0000

AlphaMissense

5307 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000014446 (5:154735642 C>T), RS1000037353 (5:154812377 A>C,G), RS1000057443 (5:154726508 T>A,C), RS1000059239 (5:154771795 A>C,G), RS1000071129 (5:154694034 CACAAAGAAGCAATCAG>C), RS1000074791 (5:154722285 C>T), RS1000080574 (5:154681649 G>A), RS1000145033 (5:154777597 C>G,T), RS1000145322 (5:154815051 G>A,C), RS1000161213 (5:154698502 C>A,G), RS1000174348 (5:154789315 G>A), RS1000259013 (5:154702916 A>C,G), RS1000261698 (5:154705919 C>T), RS1000293757 (5:154746968 C>T), RS1000294224 (5:154684681 C>A)

Disease associations

OMIM: gene MIM:612059 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Strong	Autosomal dominant

Mondo (1): neurodevelopmental disorder (MONDO:0700092)

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST003989_46	Chin dimples	1.000000e-08
GCST003996_34	Monobrow	2.000000e-20
GCST90002386_43	High light scatter reticulocyte percentage of red cells	5.000000e-12
GCST90002390_143	Mean corpuscular hemoglobin	3.000000e-20
GCST90002390_144	Mean corpuscular hemoglobin	3.000000e-19
GCST90002392_640	Mean corpuscular volume	5.000000e-14
GCST90002405_158	Reticulocyte count	6.000000e-11
GCST90002406_185	Reticulocyte fraction of red cells	1.000000e-14

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007906	synophrys measurement
EFO:0004527	mean corpuscular hemoglobin
EFO:0007986	reticulocyte count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067151 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.77	Kd	1686	nM	CHEMBL5653589
5.77	ED50	1686	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 4 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	2148638: Binding affinity to human LARP1 incubated for 45 mins by Kinobead based pull down assay	kd	1.6856	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, decreases expression	3
Estradiol	increases expression, increases phosphorylation	3
bisphenol F	increases expression, affects cotreatment, decreases expression	2
methylmercuric chloride	increases expression, affects cotreatment	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	affects sumoylation	1
dicrotophos	increases expression	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression, affects localization, increases expression	1
salinomycin	decreases expression	1
decabromobiphenyl ether	increases expression	1
trichostatin A	affects expression	1
cobaltous chloride	increases expression	1
coumarin	affects phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
1-(4-(6-bromobenzo(1,3)dioxol-5-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta(c)quinolin-8-yl)ethanone	increases phosphorylation	1
bisphenol S	increases expression	1
1-(4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenyl)-9-(quinolin-3-yl)benzo(h)(1,6)naphthyridin-2(1H)-one	decreases expression, increases response to substance, affects binding, decreases reaction, increases reaction	1
bisphenol AF	increases expression	1
Acetaminophen	decreases 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
CHEMBL5651680	Binding	Binding affinity to human LARP1 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

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3A2	Abcam HEK293T LARP1 KO	Transformed cell line	Female
CVCL_E2AW	HAP1 LARP1 (-) 2	Cancer cell line	Male
CVCL_XQ06	HAP1 LARP1 (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice