LARP4

Summary

LARP4 (La ribonucleoprotein 4, HGNC:24320) is a protein-coding gene on chromosome 12q13.12, encoding La-related protein 4 (Q71RC2). RNA binding protein that binds to the poly-A tract of mRNA molecules. It is a selective cancer dependency (DepMap: 13.9% of cell lines).

Enables mRNA 3’-UTR binding activity and poly(A) binding activity. Involved in cytoskeleton organization; positive regulation of translation; and regulation of cell morphogenesis. Located in cytoplasmic stress granule and cytosolic small ribosomal subunit.

Source: NCBI Gene 113251 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 111 total
• Cancer dependency (DepMap): dependent in 13.9% of screened cell lines
• MANE Select transcript: NM_052879

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24320
Approved symbol	LARP4
Name	La ribonucleoprotein 4
Location	12q13.12
Locus type	gene with protein product
Status	Approved
Aliases	PP13296
Ensembl gene	ENSG00000161813
Ensembl biotype	protein_coding
OMIM	618657
Entrez	113251

Gene structure

Transcript identifiers

Ensembl transcripts: 38 — 37 protein_coding, 1 retained_intron

ENST00000293618, ENST00000347328, ENST00000398473, ENST00000429001, ENST00000517559, ENST00000518444, ENST00000518561, ENST00000520064, ENST00000521120, ENST00000522085, ENST00000523389, ENST00000548174, ENST00000548697, ENST00000548993, ENST00000550260, ENST00000550522, ENST00000551886, ENST00000552445, ENST00000903011, ENST00000903012, ENST00000903013, ENST00000903014, ENST00000903015, ENST00000903016, ENST00000903017, ENST00000903018, ENST00000903019, ENST00000938275, ENST00000938276, ENST00000938277, ENST00000938278, ENST00000938279, ENST00000938280, ENST00000938281, ENST00000938282, ENST00000938283, ENST00000938284, ENST00000958867

RefSeq mRNA: 30 — MANE Select: NM_052879 NM_001170803, NM_001170804, NM_001170808, NM_001330415, NM_001352304, NM_001352305, NM_001352306, NM_001352307, NM_001352308, NM_001352309, NM_001352310, NM_001352311, NM_001352312, NM_001352313, NM_001352314, NM_001352315, NM_001352316, NM_001352317, NM_001352318, NM_001352319, NM_001352320, NM_001352321, NM_001352322, NM_001352323, NM_001352324, NM_001352325, NM_001352326, NM_052879, NM_199188, NM_199190

CCDS: CCDS41782, CCDS44879, CCDS44880, CCDS53789, CCDS53790, CCDS81690, CCDS86300

Canonical transcript exons

ENST00000398473 — 16 exons

Exon	Start	End
ENSE00001230497	50473999	50474167
ENSE00001631570	50461135	50461347
ENSE00001655473	50430495	50430570
ENSE00001681874	50462582	50462630
ENSE00001707001	50454314	50454417
ENSE00001714506	50473415	50473536
ENSE00001722264	50437735	50437838
ENSE00001745658	50466959	50467120
ENSE00001768656	50440439	50440549
ENSE00001778960	50435488	50435624
ENSE00002105635	50475526	50480004
ENSE00002135853	50400885	50401028
ENSE00003544435	50428935	50429090
ENSE00003573747	50453460	50453672
ENSE00003626284	50441590	50441643
ENSE00003643095	50427762	50427909

Expression profiles

Bgee: expression breadth ubiquitous, 296 present calls, max score 96.49.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.7320 / max 300.1042, expressed in 1811 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
125427	20.6111	1807
125428	4.4252	1523
125429	0.5378	295
125430	0.1580	48

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	96.49	gold quality
adrenal tissue	UBERON:0018303	94.62	gold quality
choroid plexus epithelium	UBERON:0003911	93.94	gold quality
biceps brachii	UBERON:0001507	93.63	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	93.56	gold quality
calcaneal tendon	UBERON:0003701	93.01	gold quality
liver	UBERON:0002107	92.90	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	92.49	gold quality
buccal mucosa cell	CL:0002336	92.13	gold quality
decidua	UBERON:0002450	92.09	gold quality
tibia	UBERON:0000979	91.75	gold quality
visceral pleura	UBERON:0002401	91.48	gold quality
pigmented layer of retina	UBERON:0001782	91.31	gold quality
pleura	UBERON:0000977	91.22	gold quality
upper leg skin	UBERON:0004262	91.13	gold quality
nephron tubule	UBERON:0001231	91.08	gold quality
renal medulla	UBERON:0000362	91.07	gold quality
parietal pleura	UBERON:0002400	90.96	gold quality
islet of Langerhans	UBERON:0000006	90.71	gold quality
eye	UBERON:0000970	90.66	gold quality
palpebral conjunctiva	UBERON:0001812	90.46	gold quality
right lobe of liver	UBERON:0001114	90.45	gold quality
blood vessel layer	UBERON:0004797	90.42	gold quality
colonic epithelium	UBERON:0000397	90.32	gold quality
skeletal muscle tissue	UBERON:0001134	90.12	gold quality
mucosa of urinary bladder	UBERON:0001259	90.01	gold quality
tonsil	UBERON:0002372	90.00	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.97	gold quality
cardia of stomach	UBERON:0001162	89.92	gold quality
diaphragm	UBERON:0001103	89.71	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-7303	no	381.37
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

318 targeting LARP4, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-181A-5P	99.99	72.96	2995

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 13.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 22)

• The c-MPL protein altered expression provide an opportunity to diagnose and identify subpopulations of MPD patients. (PMID:15572213)
• FISH study showed no cytogenetic abnormalities in any of the analyzed cases. (PMID:16682284)
• LARP4 activity is integrated with other PAM2 protein activities by PABP as part of mRNA homeostasis. (PMID:21098120)
• The results demonstrate that the La modules of the human LARP4 is also active in tRNA-mediated suppression, even in the absence of stable UUU-3’OH trailer protection. (PMID:23887937)
• Involvement of LARP4 as a target of TNF-alpha-TTP regulation provides a clue as to how its functional activity may be used in a physiologic pathway. (PMID:26644407)
• LARP4 inhibits migration and invasion of cancer cells, and that some cancer-associated mutations stimulate these effects of LARP4. (PMID:27615744)
• 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)
• The expression of circLARP4 was downregulated in GC tissues and represented an independent prognostic factor for overall survival of GC patients. (PMID:28893265)
• The results indicate that LARP4 is a posttranscriptional regulator of ribosomal protein production in mammalian cells and suggest that this activity can be controlled by tRNA levels. (PMID:28895529)
• These results indicated that circLARP4 expression was lower and highlighted that circLARP4 was identified as a potential biomarker of ovarian cancer prognosis. (PMID:30468459)
• The role of circLARP4/miR-761/RUNX3/p53/p21 signaling in HCC progression, providing a potential survival predictor and therapeutic candidate for HCC. (PMID:30520539)
• LARP4 could suppress motility and metastatic potential of ovarian cancer cells. (PMID:30686809)
• LARP4A recognizes polyA RNA via a novel binding mechanism mediated by disordered regions and involving the PAM2w motif, revealing interplay between PABP, LARP4A and mRNA. (PMID:30820564)
• Circular RNA LARP4 correlates with decreased Enneking stage, better histological response, and prolonged survival profiles, and it elevates chemosensitivity to cisplatin and doxorubicin via sponging microRNA-424 in osteosarcoma. (PMID:31642110)
• Circular RNA_LARP4 Sponges miR-1323 and Hampers Progression of Esophageal Squamous Cell Carcinoma Through Modulating PTEN/PI3K/AKT Pathway. (PMID:31897898)
• Circular RNA_LARP4 inhibits the progression of non-small-cell lung cancer by regulating the expression of SMAD7. (PMID:32141555)
• Circular RNA La-related RNA-binding protein 4 correlates with reduced tumor stage, as well as better prognosis, and promotes chemosensitivity to doxorubicin in breast cancer. (PMID:32187743)
• Circular RNA_LARP4 inhibits cell migration and invasion of prostate cancer by targeting FOXO3A. (PMID:32495863)
• Single molecule poly(A) tail-seq shows LARP4 opposes deadenylation throughout mRNA lifespan with most impact on short tails. (PMID:32744499)
• CircBNC2 affects epithelial ovarian cancer progression through the miR-223-3p/ LARP4 axis. (PMID:36730544)
• LARP4 is an RNA-binding protein that binds nuclear-encoded mitochondrial mRNAs to promote mitochondrial function. (PMID:38164626)
• Biological functions of Circular RNA_LARP4/ Upstream frameshift 1 in development of gastric cancer. (PMID:38678610)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	larp4ab	ENSDARG00000074979
danio_rerio	larp4aa	ENSDARG00000078401
mus_musculus	Larp4	ENSMUSG00000023025
rattus_norvegicus	Larp4	ENSRNOG00000068079
drosophila_melanogaster	Larp4B	FBGN0035424
caenorhabditis_elegans	larp-5	WBGENE00004147

Paralogs (6): LARP4B (ENSG00000107929), SSB (ENSG00000138385), LARP1B (ENSG00000138709), LARP1 (ENSG00000155506), LARP6 (ENSG00000166173), LARP7 (ENSG00000174720)

Protein

Protein identifiers

La-related protein 4 — Q71RC2 (reviewed: Q71RC2)

Alternative names: La ribonucleoprotein domain family member 4

All UniProt accessions (12): E5RHZ8, E5RJH8, Q71RC2, F8VNV1, F8VSA9, F8VXL0, F8VY40, F8VZ60, F8W1I4, F8W1Z5, Q96J85, X6RLN4

UniProt curated annotations — full annotation on UniProt →

Function. RNA binding protein that binds to the poly-A tract of mRNA molecules. Associates with the 40S ribosomal subunit and with polysomes. Plays a role in the regulation of mRNA translation. Plays a role in the regulation of cell morphology and cytoskeletal organization.

Subunit / interactions. Interacts (via N-terminal region) with PABPC1. Interacts with RACK1.

Subcellular location. Cytoplasm. Stress granule. Cytosol.

Miscellaneous. May be due to competing acceptor splice site.

Isoforms (7)

UniProt ID	Names	Canonical?
Q71RC2-1	1	yes
Q71RC2-2	2
Q71RC2-3	3
Q71RC2-4	4
Q71RC2-5	5
Q71RC2-6	6
Q71RC2-7	7

RefSeq proteins (30): NP_001164274, NP_001164275, NP_001164279, NP_001317344, NP_001339233, NP_001339234, NP_001339235, NP_001339236, NP_001339237, NP_001339238, NP_001339239, NP_001339240, NP_001339241, NP_001339242, NP_001339243, NP_001339244, NP_001339245, NP_001339246, NP_001339247, NP_001339248, NP_001339249, NP_001339250, NP_001339251, NP_001339252, NP_001339253, NP_001339254, NP_001339255, NP_443111, NP_954658, NP_954660 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006630	La_HTH	Domain
IPR034903	LARP4_RRM	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR045180	La_dom_prot	Family
IPR058699	RRM_LARP4/4B	Domain

Pfam: PF05383, PF26088

UniProt features (56 total): modified residue 12, helix 8, strand 8, splice variant 7, compositionally biased region 5, region of interest 5, sequence conflict 3, domain 2, sequence variant 2, mutagenesis site 2, chain 1, turn 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
3PKN	X-RAY DIFFRACTION	1.8
2CQK	SOLUTION NMR
6I9B	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q71RC2-F1	55.00	0.20

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 (12): 1, 368, 392, 505, 578, 579, 583, 597, 647, 649, 686, 722

Mutagenesis-validated functional residues (2):

Position	Phenotype
15	nearly abolishes interaction with pabpc1; when associated with a-22.
22	nearly abolishes interaction with pabpc1; when associated with a-15.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 297 (showing top): RNGTGGGC_UNKNOWN, ELVIDGE_HYPOXIA_DN, ACTACCT_MIR196A_MIR196B, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, PAX4_01, TGCACTT_MIR519C_MIR519B_MIR519A, AREB6_03, TGACCTY_ERR1_Q2, CAGCTG_AP4_Q5, PUJANA_CHEK2_PCC_NETWORK, GOBP_TRANSLATION, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, SOX9_B1, BLALOCK_ALZHEIMERS_DISEASE_UP

GO Biological Process (5): translation (GO:0006412), cytoskeleton organization (GO:0007010), post-transcriptional regulation of gene expression (GO:0010608), regulation of cell morphogenesis (GO:0022604), positive regulation of translation (GO:0045727)

GO Molecular Function (5): RNA binding (GO:0003723), mRNA 3’-UTR binding (GO:0003730), poly(A) binding (GO:0008143), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (5): cytosol (GO:0005829), cytoplasmic stress granule (GO:0010494), membrane (GO:0016020), cytoplasm (GO:0005737), cytosolic small ribosomal subunit (GO:0022627)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
binding	2
peptidyltransferase activity	1
translational initiation	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
organelle organization	1
regulation of gene expression	1
cell morphogenesis	1
regulation of anatomical structure morphogenesis	1
translation	1
regulation of translation	1
positive regulation of gene expression	1
positive regulation of protein metabolic process	1
nucleic acid binding	1
mRNA binding	1
poly-purine tract binding	1
cytoplasm	1
cytoplasmic ribonucleoprotein granule	1
intracellular anatomical structure	1
small ribosomal subunit	1
cytosolic ribosome	1

Protein interactions and networks

STRING

1544 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LARP4	PABPC1	P11940	903
LARP4	RACK1	P25388	845
LARP4	LARP6	Q9BRS8	725
LARP4	LATS1	O95835	643
LARP4	RBM41	Q96IZ5	519
LARP4	DDX6	P26196	519
LARP4	NABP1	Q96AH0	518
LARP4	PABPC4	Q13310	509
LARP4	COX14	Q96I36	500
LARP4	DDX55	Q8NHQ9	493
LARP4	RPUSD4	Q96CM3	488
LARP4	NOL6	Q9H6R4	486
LARP4	EIF4E	P06730	470
LARP4	DDX18	Q9NVP1	454
LARP4	CDC40	O60508	440

IntAct

108 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
LARP4	NPM1	psi-mi:“MI:0915”(physical association)	0.670
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
RACK1	RIOK3	psi-mi:“MI:0914”(association)	0.640
LARP4	LRRK2	psi-mi:“MI:0407”(direct interaction)	0.590
PFDN1	ARHGAP32	psi-mi:“MI:0914”(association)	0.530
GSPT2	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
DDX6	MCRIP1	psi-mi:“MI:0914”(association)	0.510
	LARP4	psi-mi:“MI:0407”(direct interaction)	0.440
CRX	LARP4	psi-mi:“MI:0915”(physical association)	0.370
Eif3a	RPSA	psi-mi:“MI:0914”(association)	0.350
MYO1C	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
RPL10	RPS6	psi-mi:“MI:0914”(association)	0.350
Srp72		psi-mi:“MI:0914”(association)	0.350
AKAP1	TNNI3	psi-mi:“MI:0914”(association)	0.350
Ccdc77	TBC1D31	psi-mi:“MI:0914”(association)	0.350
Kif2a	GMDS	psi-mi:“MI:0914”(association)	0.350
NPM1	RPSA	psi-mi:“MI:0914”(association)	0.350
Pabpc1	ZC3HAV1	psi-mi:“MI:0914”(association)	0.350
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
E4	MCRIP1	psi-mi:“MI:0914”(association)	0.350
KSR1		psi-mi:“MI:0914”(association)	0.350
NBEAL2	HAX1	psi-mi:“MI:0914”(association)	0.350
COPS6	DDX3X	psi-mi:“MI:0914”(association)	0.350
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
SRC	ACTN4	psi-mi:“MI:0914”(association)	0.350

BioGRID (271): LARP4 (Two-hybrid), LARP4 (Two-hybrid), LARP4 (Affinity Capture-MS), LARP4 (Affinity Capture-MS), LARP4 (Affinity Capture-MS), LARP4 (Affinity Capture-MS), LARP4 (Affinity Capture-MS), LARP4 (Affinity Capture-MS), LARP4 (Affinity Capture-MS), LARP4 (Affinity Capture-MS), LARP4 (Affinity Capture-MS), LARP4 (Affinity Capture-MS), LARP4 (Affinity Capture-MS), LARP4 (Affinity Capture-MS), LARP4 (Affinity Capture-MS)

ESM2 similar proteins: A0A1S3C4H6, A2X0Q6, A3A2Z8, A6NCI8, B4FXN6, B6TCE8, B8ANX9, B8B5N8, B9FXV5, C7IW64, F4J7T2, F4J7T3, F4JP43, F4KDH9, G5CEW6, O14029, O43303, O82804, O94378, P0C945, P23226, P48415, Q10LZ1, Q38796, Q53HY2, Q5PNS0, Q5QNA6, Q5Z8V7, Q6AT41, Q6CM10, Q6EVK6, Q6FRV6, Q6YXY2, Q6YYC0, Q6Z156, Q71RC2, Q74ZJ8, Q76E23, Q8L7I1, Q8LL04

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, P87058, Q0V7U7, Q93ZV7, Q940X9, Q6A0A2, Q92615

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 129 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
Nonsense-Mediated Decay (NMD)	7	17.9×	1e-05
Eukaryotic Translation Initiation	5	17.0×	3e-04
Cap-dependent Translation Initiation	5	17.0×	3e-04
SARS-CoV-1 modulates host translation machinery	5	17.0×	3e-04
Formation of the ternary complex, and subsequently, the 43S complex	7	16.6×	2e-05
Eukaryotic Translation Elongation	5	15.3×	4e-04
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	5	14.9×	4e-04
Translation initiation complex formation	7	14.6×	2e-05

GO biological processes:

GO term	Partners	Fold	FDR
nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	5	20.5×	8e-04
translational initiation	6	18.9×	2e-04
cytoplasmic translation	9	14.6×	1e-05
negative regulation of translation	8	13.8×	6e-05
mRNA export from nucleus	5	13.0×	7e-03
translation	9	8.1×	4e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	82
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3178 predictions. Top by Δscore:

Variant	Effect	Δscore
12:50396289:CTAC:C	donor_loss	1.0000
12:50396290:TACCT:T	donor_loss	1.0000
12:50396291:ACCTC:A	donor_loss	1.0000
12:50396292:C:T	donor_loss	1.0000
12:50396292:CCTCT:C	donor_gain	1.0000
12:50402067:G:T	donor_gain	1.0000
12:50412403:A:AG	acceptor_gain	1.0000
12:50412404:G:GG	acceptor_gain	1.0000
12:50412404:GC:G	acceptor_gain	1.0000
12:50427906:GAGG:G	donor_gain	1.0000
12:50427908:GG:G	donor_gain	1.0000
12:50427909:GG:G	donor_gain	1.0000
12:50427910:G:GA	donor_loss	1.0000
12:50427910:G:GG	donor_gain	1.0000
12:50427911:T:TC	donor_loss	1.0000
12:50428930:TACA:T	acceptor_loss	1.0000
12:50428932:CAG:C	acceptor_loss	1.0000
12:50429060:GATC:G	donor_gain	1.0000
12:50429063:C:G	donor_gain	1.0000
12:50429068:T:G	donor_gain	1.0000
12:50429088:CCG:C	donor_loss	1.0000
12:50429090:GGTA:G	donor_loss	1.0000
12:50429091:GTAA:G	donor_loss	1.0000
12:50429092:T:A	donor_loss	1.0000
12:50430487:A:AG	acceptor_gain	1.0000
12:50430488:C:G	acceptor_gain	1.0000
12:50430494:GGA:G	acceptor_gain	1.0000
12:50430538:TCTG:T	donor_gain	1.0000
12:50435486:A:AG	acceptor_gain	1.0000
12:50435487:G:GG	acceptor_gain	1.0000

AlphaMissense

4740 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:50430540:T:C	L123P	1.000
12:50435523:A:C	Q145P	1.000
12:50435559:T:A	V157D	1.000
12:50437807:T:A	L203H	1.000
12:50437807:T:C	L203P	1.000
12:50437810:G:C	R204T	1.000
12:50437810:G:T	R204I	1.000
12:50437811:A:C	R204S	1.000
12:50437811:A:T	R204S	1.000
12:50440455:T:C	F219S	1.000
12:50440511:T:A	W238R	1.000
12:50440511:T:C	W238R	1.000
12:50440523:T:C	F242L	1.000
12:50440524:T:C	F242S	1.000
12:50440525:C:A	F242L	1.000
12:50440525:C:G	F242L	1.000
12:50441603:T:C	L255S	1.000
12:50441607:A:C	R256S	1.000
12:50441607:A:T	R256S	1.000
12:50441623:T:C	F262L	1.000
12:50441624:T:C	F262S	1.000
12:50441625:T:A	F262L	1.000
12:50441625:T:G	F262L	1.000
12:50453464:G:C	R270T	1.000
12:50453464:G:T	R270M	1.000
12:50453465:G:C	R270S	1.000
12:50453465:G:T	R270S	1.000
12:50453469:A:G	K272E	1.000
12:50453471:A:C	K272N	1.000
12:50453471:A:T	K272N	1.000

dbSNP variants (sampled 300 via entrez): RS1000003071 (12:50416217 G>T), RS1000018827 (12:50469459 C>A,T), RS1000048544 (12:50469754 G>C,T), RS1000051031 (12:50439508 T>C), RS1000074919 (12:50423332 A>C), RS1000086129 (12:50463374 A>G), RS1000104920 (12:50480223 A>G), RS1000106993 (12:50423360 A>C,G), RS1000187283 (12:50405355 T>G), RS1000215869 (12:50470726 G>A,C,T), RS1000234049 (12:50446623 T>G), RS1000269484 (12:50463472 C>T), RS1000286291 (12:50446760 C>T), RS1000305283 (12:50462425 C>T), RS1000316483 (12:50415687 C>T)

Disease associations

OMIM: gene MIM:618657 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST007269_315	Pulse pressure	1.000000e-08
GCST007293_76	Body fat distribution (arm fat ratio)	4.000000e-07
GCST007294_123	Body fat distribution (trunk fat ratio)	2.000000e-09
GCST007294_2	Body fat distribution (trunk fat ratio)	1.000000e-18
GCST007295_152	Body fat distribution (leg fat ratio)	4.000000e-13
GCST010703_176	Brain morphology (MOSTest)	5.000000e-11
GCST90025872_12	Chronic widespread musculoskeletal pain	2.000000e-07

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0005763	pulse pressure measurement
EFO:0004341	body fat distribution
EFO:0004346	neuroimaging measurement
EFO:0010099	chronic widespread pain

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
Estradiol	affects expression, increases expression	3
entinostat	increases expression, affects cotreatment	2
Tobacco Smoke Pollution	increases expression	2
Valproic Acid	decreases expression, increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	increases expression	1
FR900359	affects phosphorylation	1
TAK-243	increases sumoylation	1
geldanamycin	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
deoxynivalenol	increases expression	1
trichostatin A	decreases expression	1
beta-lapachone	decreases expression	1
cobaltous chloride	increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
coumarin	increases phosphorylation	1
cupric oxide	increases expression	1
nivalenol	increases expression	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
beta-methylcholine	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	decreases expression	1
Vorinostat	increases expression	1
Acetaminophen	decreases expression	1
Acrolein	affects cotreatment, increases expression, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D9ID	Ubigene HEK293 LARP4 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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