FAU

Summary

FAU (FAU ubiquitin like and ribosomal protein S30 fusion, HGNC:3597) is a protein-coding gene on chromosome 11q13.1, encoding Ubiquitin-like FUBI-ribosomal protein eS30 fusion protein (P62861). May have pro-apoptotic activity. It is a common-essential gene (DepMap: required in 100.0% of cancer cell lines).

This gene is the cellular homolog of the fox sequence in the Finkel-Biskis-Reilly murine sarcoma virus (FBR-MuSV). It encodes a fusion protein consisting of the ubiquitin-like protein fubi at the N terminus and ribosomal protein S30 at the C terminus. It has been proposed that the fusion protein is post-translationally processed to generate free fubi and free ribosomal protein S30. Fubi is a member of the ubiquitin family, and ribosomal protein S30 belongs to the S30E family of ribosomal proteins. Whereas the function of fubi is currently unknown, ribosomal protein S30 is a component of the 40S subunit of the cytoplasmic ribosome and displays antimicrobial activity. Pseudogenes derived from this gene are present in the genome. Similar to ribosomal protein S30, ribosomal proteins S27a and L40 are synthesized as fusion proteins with ubiquitin.

Source: NCBI Gene 2197 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 19 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• MANE Select transcript: NM_001997

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3597
Approved symbol	FAU
Name	FAU ubiquitin like and ribosomal protein S30 fusion
Location	11q13.1
Locus type	gene with protein product
Status	Approved
Aliases	RPS30, FLJ22986, Fub1, Fubi, MNSFbeta, asr1, S30, eS30
Ensembl gene	ENSG00000149806
Ensembl biotype	protein_coding
OMIM	134690
Entrez	2197

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 14 protein_coding, 1 retained_intron

ENST00000279259, ENST00000434372, ENST00000525297, ENST00000526555, ENST00000527548, ENST00000529259, ENST00000529639, ENST00000531357, ENST00000531743, ENST00000852065, ENST00000916351, ENST00000916352, ENST00000916353, ENST00000916354, ENST00000953483

RefSeq mRNA: 1 — MANE Select: NM_001997 NM_001997

CCDS: CCDS8095

Canonical transcript exons

ENST00000529639 — 5 exons

Exon	Start	End
ENSE00000992586	65121739	65121821
ENSE00001641635	65120981	65121036
ENSE00001787146	65121500	65121644
ENSE00002159621	65122090	65122134
ENSE00002181772	65120630	65120806

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.76.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 738.2676 / max 6401.5963, expressed in 1828 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
120532	626.3559	1828
120533	109.5245	1823
120530	1.5586	857
120531	0.8285	513

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	99.76	gold quality
endocervix	UBERON:0000458	99.76	gold quality
monocyte	CL:0000576	99.75	gold quality
leukocyte	CL:0000738	99.75	gold quality
left ovary	UBERON:0002119	99.75	gold quality
bone marrow cell	CL:0002092	99.74	gold quality
ovary	UBERON:0000992	99.74	gold quality
right uterine tube	UBERON:0001302	99.74	gold quality
temporal lobe	UBERON:0001871	99.74	gold quality
amygdala	UBERON:0001876	99.74	gold quality
popliteal artery	UBERON:0002250	99.74	gold quality
tibial artery	UBERON:0007610	99.74	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.74	gold quality
putamen	UBERON:0001874	99.73	gold quality
right ovary	UBERON:0002118	99.73	gold quality
bone marrow	UBERON:0002371	99.73	gold quality
fallopian tube	UBERON:0003889	99.73	gold quality
body of uterus	UBERON:0009853	99.73	gold quality
uterine cervix	UBERON:0000002	99.72	gold quality
pituitary gland	UBERON:0000007	99.72	gold quality
lymph node	UBERON:0000029	99.72	gold quality
nucleus accumbens	UBERON:0001882	99.72	gold quality
substantia nigra	UBERON:0002038	99.72	gold quality
adenohypophysis	UBERON:0002196	99.72	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.72	gold quality
left uterine tube	UBERON:0001303	99.71	gold quality
caudate nucleus	UBERON:0001873	99.71	gold quality
Ammon’s horn	UBERON:0001954	99.71	gold quality
lower esophagus	UBERON:0013473	99.71	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.71	gold quality

Single-cell (SCXA)

Detected in 25 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	92.87
E-CURD-88	yes	72.60
E-MTAB-6678	yes	36.24
E-MTAB-9221	yes	20.85
E-MTAB-10042	yes	15.72
E-GEOD-135922	yes	11.49
E-HCAD-35	yes	8.60
E-GEOD-137537	yes	5.83
E-HCAD-25	yes	4.35
E-MTAB-8142	no	6265.32
E-MTAB-10485	no	6167.10
E-MTAB-10662	no	3662.39
E-MTAB-9435	no	3647.75
E-MTAB-10885	no	3570.34
E-MTAB-7606	no	2996.12

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 100.0% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 11)

• role in transforming osteogenic sarcoma cells to anchorage-independence (PMID:12660817)
• The C-terminal portion of the encoded protein displays antimicrobial activity against B. megaterium. (PMID:12860195)
• Overexpression of fau in the sense orientation induces cell death, which is inhibited both by Bcl-2 and by inhibition of caspases, in line with its proposed role in apoptosis (PMID:15543234)
• siRNA-mediated downregulation of either Fau or Bcl-G expression inhibited apoptosis, and the inhibition produced by combining the two siRNAs was consistent with control of Bcl-G by Fau. (PMID:19671159)
• data support a role for FAU in the regulation of platinum-resistance in ovarian cancer (PMID:19830698)
• In 293T/17 cells, Bcl-G knockdown also attenuates UV-induced apoptosis, so that Bcl-G may constitute a common factor in the pathways by which both FAU and UV-irradiation induce apoptosis (PMID:21550398)
• The FAU rs769440 G allele had higher frequencies in patients with recurrent pregnancy loss. (PMID:29084471)
• FAU knockdown increased the plasma membrane targeting and function of F508del-CFTR, but not of wild-type CFTR. Investigation into the mechanism of action revealed a preferential physical interaction of FAU with mutant CFTR, leading to its degradation. (PMID:29158263)
• MNSFbeta Promotes the Proliferation and Migration of Human Extravillous Trophoblast Cells and the Villus Expression Level of MNSFbeta Is Decreased in Recurrent Miscarriage Patients. (PMID:33326956)
• Processing of the ribosomal ubiquitin-like fusion protein FUBI-eS30/FAU is required for 40S maturation and depends on USP36. (PMID:34318747)
• MNSFbeta Regulates TNFalpha Production by Interacting with RC3H1 in Human Macrophages, and Dysfunction of MNSFbeta in Decidual Macrophages Is Associated With Recurrent Pregnancy Loss. (PMID:34589082)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	faub	ENSDARG00000043663
danio_rerio	faua	ENSDARG00000099022
mus_musculus	Fau	ENSMUSG00000038274
rattus_norvegicus	LOC102548890	ENSRNOG00000018083
rattus_norvegicus	Fau	ENSRNOG00000020982
rattus_norvegicus	AABR07005572.2	ENSRNOG00000062071
drosophila_melanogaster	RpS30	FBGN0038834
caenorhabditis_elegans		WBGENE00004499

Protein

Protein identifiers

Ubiquitin-like FUBI-ribosomal protein eS30 fusion protein — P62861 (reviewed: P62861)

Alternative names: FAU ubiquitin like and ribosomal protein S30 fusion

All UniProt accessions (5): P62861, E9PM49, E9PMS9, E9PR30, J3KN89

UniProt curated annotations — full annotation on UniProt →

Function. May have pro-apoptotic activity. Component of the 40S subunit of the ribosome. Contributes to the assembly and function of 40S ribosomal subunits.

Subunit / interactions. Component of the 40S subunit of the ribosome.

Subcellular location. Cytoplasm. Nucleus.

Post-translational modifications. FUBI is cleaved from ribosomal protein S30 by the deubiquitinase USP36 before the assembly of ribosomal protein S30 into pre-40S ribosomal particles. FUBI removal from ribosomal protein S30 is a crucial event for the final maturation of pre-40S particles.

Miscellaneous. FAU encodes a fusion protein consisting of the ubiquitin-like protein FUBI at the N terminus and ribosomal protein S30 at the C terminus. Lacks the typical lysine residues that participate in Ub’s polyubiquitination. However contains a C-terminal di-glycine signature after its proteolytic separation from ribosomal protein S30 and could theoretically be conjugated onto target proteins.

Similarity. In the N-terminal section; belongs to the ubiquitin family. In the C-terminal section; belongs to the eukaryotic ribosomal protein eS30 family.

RefSeq proteins (1): NP_001988* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000626	Ubiquitin-like_dom	Domain
IPR006846	Ribosomal_eS30	Family
IPR019954	Ubiquitin_CS	Conserved_site
IPR019956	Ubiquitin_dom	Domain
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR039415	FUBI	Domain

Pfam: PF00240, PF04758

UniProt features (22 total): helix 5, strand 4, chain 3, mutagenesis site 3, sequence variant 2, turn 1, domain 1, region of interest 1, compositionally biased region 1, modified residue 1

Structure

Experimental structures (PDB)

205 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
8GLP	ELECTRON MICROSCOPY	1.67
8QOI	ELECTRON MICROSCOPY	1.9
9O3W	ELECTRON MICROSCOPY	1.9
8YOO	ELECTRON MICROSCOPY	2
9C3H	ELECTRON MICROSCOPY	2
7R4X	ELECTRON MICROSCOPY	2.15
9I2D	ELECTRON MICROSCOPY	2.19
9PBE	ELECTRON MICROSCOPY	2.19
8BS3	X-RAY DIFFRACTION	2.2
8YOP	ELECTRON MICROSCOPY	2.2
9O3V	ELECTRON MICROSCOPY	2.2
9O3Y	ELECTRON MICROSCOPY	2.2
8JDK	ELECTRON MICROSCOPY	2.26
8G5Y	ELECTRON MICROSCOPY	2.29
9S3D	ELECTRON MICROSCOPY	2.32
9RPV	ELECTRON MICROSCOPY	2.35
9S3B	ELECTRON MICROSCOPY	2.38
8K2C	ELECTRON MICROSCOPY	2.4
8XSX	ELECTRON MICROSCOPY	2.4
9SPF	ELECTRON MICROSCOPY	2.4
9SPI	ELECTRON MICROSCOPY	2.4
8JDL	ELECTRON MICROSCOPY	2.42
9S3C	ELECTRON MICROSCOPY	2.42
9QLO	ELECTRON MICROSCOPY	2.47
9P8B	ELECTRON MICROSCOPY	2.48
7XNY	ELECTRON MICROSCOPY	2.5
8JDJ	ELECTRON MICROSCOPY	2.5
9RUC	ELECTRON MICROSCOPY	2.5
8G60	ELECTRON MICROSCOPY	2.54
8IFE	ELECTRON MICROSCOPY	2.57

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P62861-F1	91.30	0.79

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 (1): 125

Mutagenesis-validated functional residues (3):

Position	Phenotype
74	abolishes fubi-ribosomal protein s30 processing; when associated with a-73. impairs 40s ribosome biogenesis.
74	abolishes fubi-ribosomal protein s30 processing. impairs 40s ribosome biogenesis.
73	abolishes fubi-ribosomal protein s30 processing; when associated with a-74. impairs 40s ribosome biogenesis.

Function

Pathways and Gene Ontology

Reactome pathways

50 pathways

ID	Pathway
R-HSA-156827	L13a-mediated translational silencing of Ceruloplasmin expression
R-HSA-156902	Peptide chain elongation
R-HSA-1799339	SRP-dependent cotranslational protein targeting to membrane
R-HSA-192823	Viral mRNA Translation
R-HSA-2408557	Selenocysteine synthesis
R-HSA-6791226	Major pathway of rRNA processing in the nucleolus and cytosol
R-HSA-72649	Translation initiation complex formation
R-HSA-72689	Formation of a pool of free 40S subunits
R-HSA-72695	Formation of the ternary complex, and subsequently, the 43S complex
R-HSA-72702	Ribosomal scanning and start codon recognition
R-HSA-72706	GTP hydrolysis and joining of the 60S ribosomal subunit
R-HSA-72764	Eukaryotic Translation Termination
R-HSA-9010553	Regulation of expression of SLITs and ROBOs
R-HSA-9633012	Response of EIF2AK4 (GCN2) to amino acid deficiency
R-HSA-9735869	SARS-CoV-1 modulates host translation machinery
R-HSA-9754678	SARS-CoV-2 modulates host translation machinery
R-HSA-975956	Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)
R-HSA-975957	Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)
R-HSA-9954714	PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA
R-HSA-9954716	ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA
R-HSA-1266738	Developmental Biology
R-HSA-1430728	Metabolism
R-HSA-156842	Eukaryotic Translation Elongation
R-HSA-1643685	Disease
R-HSA-168255	Influenza Infection
R-HSA-168273	Influenza Viral RNA Transcription and Replication
R-HSA-2262752	Cellular responses to stress
R-HSA-2408522	Selenoamino acid metabolism
R-HSA-376176	Signaling by ROBO receptors
R-HSA-392499	Metabolism of proteins

MSigDB gene sets: 256 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, GOBP_RIBOSOME_BIOGENESIS, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, ENK_UV_RESPONSE_KERATINOCYTE_UP, MORF_UBE2I, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_RIBOSOME_ASSEMBLY, chr11q13, GOBP_ORGAN_OR_TISSUE_SPECIFIC_IMMUNE_RESPONSE, GOBP_TRANSLATION, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, MORF_CCNI, GOBP_INNATE_IMMUNE_RESPONSE_IN_MUCOSA, GOBP_RIBOSOMAL_SMALL_SUBUNIT_BIOGENESIS, GOMF_STRUCTURAL_CONSTITUENT_OF_RIBOSOME

GO Biological Process (8): cytoplasmic translation (GO:0002181), innate immune response in mucosa (GO:0002227), translation (GO:0006412), protein ubiquitination (GO:0016567), antibacterial humoral response (GO:0019731), modification-dependent protein catabolic process (GO:0019941), defense response to Gram-positive bacterium (GO:0050830), antimicrobial humoral immune response mediated by antimicrobial peptide (GO:0061844)

GO Molecular Function (5): RNA binding (GO:0003723), structural constituent of ribosome (GO:0003735), protein tag activity (GO:0031386), ubiquitin protein ligase binding (GO:0031625), protein binding (GO:0005515)

GO Cellular Component (10): obsolete extracellular space (GO:0005615), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), small ribosomal subunit (GO:0015935), cytosolic ribosome (GO:0022626), cytosolic small ribosomal subunit (GO:0022627), ribosome (GO:0005840), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Cap-dependent Translation Initiation	4
Translation	2
Nonsense-Mediated Decay (NMD)	2
Ribosome-associated quality control	2
Eukaryotic Translation Initiation	1
Eukaryotic Translation Elongation	1
Influenza Viral RNA Transcription and Replication	1
Selenoamino acid metabolism	1
rRNA processing in the nucleus and cytosol	1
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	1
Signaling by ROBO receptors	1
Cellular response to starvation	1
SARS-CoV-1-host interactions	1
SARS-CoV-2-host interactions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
antimicrobial humoral response	2
defense response to bacterium	2
ribosome	2
translation	1
mucosal immune response	1
innate immune response	1
peptidyltransferase activity	1
translational initiation	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
protein modification by small protein conjugation	1
protein catabolic process	1
protein modification process	1
modification-dependent macromolecule catabolic process	1
nucleic acid binding	1
structural molecule activity	1
molecular tag activity	1
ubiquitin-like protein ligase binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
ribosomal subunit	1
cytosol	1
small ribosomal subunit	1
cytosolic ribosome	1
intracellular membraneless organelle	1
protein-containing complex	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

129 interactions, top by confidence:

A	B	Type	Score
RIOK1	PRMT5	psi-mi:“MI:0914”(association)	0.710
RACK1	RPS17	psi-mi:“MI:0915”(physical association)	0.610
KLK6	FAU	psi-mi:“MI:0915”(physical association)	0.560
MAPT	KIF2A	psi-mi:“MI:0914”(association)	0.530
GRB2	SH3PXD2B	psi-mi:“MI:0914”(association)	0.530
H1-6	ZNF724	psi-mi:“MI:0914”(association)	0.530
DDX31	IGLL5	psi-mi:“MI:0914”(association)	0.530
RRP8	NVL	psi-mi:“MI:0914”(association)	0.530
PUM3	RRP8	psi-mi:“MI:0914”(association)	0.530
FAU	RET	psi-mi:“MI:0195”(covalent binding)	0.440
ANKRD18A	FAU	psi-mi:“MI:0915”(physical association)	0.400
RPS3	FAU	psi-mi:“MI:0915”(physical association)	0.400
FAU	H2AZ1	psi-mi:“MI:0915”(physical association)	0.400
GNL1	FAU	psi-mi:“MI:0915”(physical association)	0.400
Ctcf	RPL36A	psi-mi:“MI:0915”(physical association)	0.400
CHTOP	SAP18	psi-mi:“MI:0915”(physical association)	0.400
SDC1	ILVBL	psi-mi:“MI:0915”(physical association)	0.400
FAU	TAF7	psi-mi:“MI:0915”(physical association)	0.370
Rpl35	RPS6	psi-mi:“MI:0914”(association)	0.350
Eif3a	RPSA	psi-mi:“MI:0914”(association)	0.350
Srp72		psi-mi:“MI:0914”(association)	0.350
Rrbp1	PIPSL	psi-mi:“MI:0914”(association)	0.350
NPM1	RPSA	psi-mi:“MI:0914”(association)	0.350
Eif3e	RPSA	psi-mi:“MI:0914”(association)	0.350

ESM2 similar proteins: A0A2R8Y7D0, A1L020, A2ARS0, A6NDN8, G1T8A2, O70418, O75426, P29473, P29597, P49897, P49898, P52824, P55073, P62861, P62862, P70313, P79209, Q08097, Q08DF2, Q148R9, Q1LZC5, Q28969, Q39491, Q4R327, Q566C8, Q5SPX3, Q62600, Q6DN07, Q6H5L4, Q6N063, Q6NXT1, Q6QN11, Q6ZS82, Q758T2, Q7L9B9, Q86SG2, Q8C2K5, Q8MJG0, Q8N8A6, Q8TD08

Diamond homologs: A0A1D8PSK2, G1T8A2, O96269, P0C2F0, P0CT62, P0CT63, P0CX33, P0CX34, P49689, P62860, P62861, P62862, P62863, P62864, P62866, P62867, Q556Y1, Q9W6Y0, A6NDN8, P0C032, P0C2F1, P14794, P19848, P55812, P62865, P62868, P62975, P68197, P69310, P69313, P69317, P69326, Q05474, Q60435, Q865C5, B9DHA6, P0C030, P0C031, P0C073, P0C224

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
FAU	“form complex”	“40S cytosolic small ribosomal subunit”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 149 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
Eukaryotic Translation Initiation	7	21.4×	8e-07
Cap-dependent Translation Initiation	7	21.4×	8e-07
SARS-CoV-1 modulates host translation machinery	7	21.4×	8e-07
Eukaryotic Translation Elongation	7	19.3×	2e-06
Formation of the ternary complex, and subsequently, the 43S complex	9	19.2×	3e-08
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	7	18.8×	2e-06
Eukaryotic Translation Termination	15	17.9×	4e-13
Formation of a pool of free 40S subunits	16	17.7×	1e-13

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	17	24.8×	2e-16
ribosomal large subunit biogenesis	5	17.5×	2e-03
translational initiation	5	14.1×	4e-03
translation	17	13.8×	2e-12
ribosomal small subunit biogenesis	7	12.6×	3e-04
rRNA processing	10	11.2×	6e-06
negative regulation of translation	6	9.3×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	9
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

362 predictions. Top by Δscore:

Variant	Effect	Δscore
11:65120803:CCAC:C	acceptor_gain	1.0000
11:65120804:CAC:C	acceptor_gain	1.0000
11:65120804:CACC:C	acceptor_gain	1.0000
11:65120807:C:CC	acceptor_gain	1.0000
11:65121495:CTCA:C	donor_loss	1.0000
11:65121496:TCAC:T	donor_loss	1.0000
11:65121498:A:AC	donor_gain	1.0000
11:65121498:ACCT:A	donor_gain	1.0000
11:65121499:C:CC	donor_gain	1.0000
11:65121499:CCT:C	donor_gain	1.0000
11:65121499:CCTC:C	donor_gain	1.0000
11:65121523:T:TA	donor_gain	1.0000
11:65121640:TGAGC:T	acceptor_gain	1.0000
11:65121641:GAGC:G	acceptor_gain	1.0000
11:65121642:AGC:A	acceptor_gain	1.0000
11:65121643:GC:G	acceptor_gain	1.0000
11:65121644:CC:C	acceptor_gain	1.0000
11:65121645:C:CC	acceptor_gain	1.0000
11:65121648:C:CT	acceptor_gain	1.0000
11:65121649:A:T	acceptor_gain	1.0000
11:65121735:TTACC:T	donor_loss	1.0000
11:65121736:TA:T	donor_loss	1.0000
11:65121737:A:AC	donor_gain	1.0000
11:65121737:AC:A	donor_gain	1.0000
11:65121737:ACC:A	donor_loss	1.0000
11:65121738:C:CA	donor_gain	1.0000
11:65121738:CC:C	donor_gain	1.0000
11:65121817:GGCGA:G	acceptor_gain	1.0000
11:65121818:GCGA:G	acceptor_gain	1.0000
11:65121819:CGA:C	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000188824 (11:65122657 T>C), RS1001216092 (11:65122399 A>C), RS1001628612 (11:65123613 A>C), RS1002071969 (11:65123203 T>C), RS1003542760 (11:65123903 T>A), RS1005348183 (11:65122074 A>C), RS1005943218 (11:65123048 G>C), RS1007437925 (11:65123571 A>C), RS1007743492 (11:65122617 C>G,T), RS1007950154 (11:65120423 T>C), RS1008000581 (11:65123236 C>A,T), RS1009235893 (11:65123909 G>C,T), RS1009509982 (11:65123602 C>A,G,T), RS1009562096 (11:65123803 T>G), RS1009847715 (11:65122212 A>G,T)

Disease associations

OMIM: gene MIM:134690 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3987582 (PROTEIN NUCLEIC-ACID COMPLEX), CHEMBL6067544 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds).

Molecule	Name	Phase	Patents
CHEMBL6067484	GENTAMICIN SULFATE	4

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

ChEMBL bioactivities

48 potent at pChembl≥5 of 54 total, top 47 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.52	IC50	300	nM	CHEMBL4109308
6.42	IC50	380	nM	CHEMBL4109308
6.42	IC50	380	nM	CHEMBL4574496
6.41	IC50	390	nM	CHEMBL4126894
6.39	IC50	410	nM	CHEMBL4114159
6.35	IC50	450	nM	CHEMBL4126496
6.30	IC50	500	nM	CHEMBL4574496
6.30	IC50	500	nM	CHEMBL4560206
6.25	Kd	562.2	nM	CHEMBL3752910
6.25	ED50	562.2	nM	CHEMBL3752910
6.16	IC50	690	nM	CHEMBL4130157
6.15	IC50	710	nM	CHEMBL4108338
6.11	IC50	780	nM	CHEMBL4114159
6.09	IC50	820	nM	CHEMBL4109308
6.07	IC50	850	nM	CHEMBL4107559
6.07	IC50	850	nM	CHEMBL4533299
6.05	IC50	900	nM	CHEMBL4126894
6.05	IC50	900	nM	CHEMBL4126496
6.04	IC50	920	nM	CHEMBL4554909
5.97	IC50	1060	nM	CHEMBL4128388
5.89	IC50	1290	nM	CHEMBL4130157
5.86	IC50	1370	nM	CHEMBL4107559
5.84	IC50	1440	nM	CHEMBL4108338
5.81	IC50	1540	nM	CHEMBL4534859
5.76	IC50	1730	nM	CHEMBL4534859
5.69	IC50	2050	nM	CHEMBL4566239
5.68	IC50	2080	nM	CHEMBL4446635
5.66	IC50	2210	nM	CHEMBL4446635
5.66	EC50	2200	nM	CHEMBL4464929
5.64	IC50	2270	nM	CHEMBL4533299
5.63	IC50	2330	nM	CHEMBL4566239
5.62	IC50	2380	nM	CHEMBL4128388
5.58	IC50	2630	nM	CHEMBL4128250
5.55	IC50	2820	nM	CHEMBL4127458
5.53	IC50	2970	nM	CHEMBL4127311
5.51	IC50	3080	nM	CHEMBL4126072
5.46	IC50	3500	nM	CHEMBL4525277
5.44	IC50	3630	nM	CHEMBL4469712
5.39	IC50	4100	nM	CHEMBL4128560
5.37	IC50	4300	nM	CHEMBL4127016
5.36	IC50	4380	nM	CHEMBL4527910
5.16	IC50	7000	nM	CHEMBL4109308
5.13	IC50	7400	nM	CHLORAMPHENICOL SULFATE SALT
5.09	IC50	8040	nM	CHEMBL4128250
5.08	IC50	8370	nM	CHEMBL4128250
5.03	IC50	9320	nM	CHEMBL4127016
5.03	IC50	9240	nM	CHEMBL4128560

PubChem BioAssay actives

47 with measured affinity, of 209 total; 27 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
N-(3-chloro-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-4-(triazolo[4,5-b]pyridin-3-yl)benzamide	1585498: Binding affinity to 80S ribosome in human HuH7 cells expressing human C-terminal V5/6-His-tagged PCSK9 assessed as inhibition of PCSK9 secretion after 16 to 24 hrs by AlphaLISA method	ic50	0.3000	uM
N-(3-chloro-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-3-[4-(triazolo[4,5-b]pyridin-3-yl)phenyl]propanamide	1532845: Binding affinity to 80S ribosome in human HuH7 cells harboring human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.3800	uM
N-isoquinolin-1-yl-N-[(3R)-piperidin-3-yl]-4-(triazolo[4,5-b]pyridin-3-yl)benzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.3900	uM
N-(3-chloro-2-pyridinyl)-4-(6-methyltriazolo[4,5-b]pyridin-3-yl)-N-[(3R)-piperidin-3-yl]benzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.4100	uM
N-(3-chloro-2-pyridinyl)-4-(5-methyltriazolo[4,5-b]pyridin-3-yl)-N-[(3R)-piperidin-3-yl]benzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.4500	uM
N-(1-methylpyrrolo[2,3-c]pyridin-7-yl)-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	0.5000	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148376: Binding affinity to human FAU incubated for 45 mins by Kinobead based pull down assay	kd	0.5622	uM
N-isoquinolin-1-yl-N-[(3R)-piperidin-3-yl]-4-pyrazolo[1,5-a]pyrimidin-3-ylbenzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.6900	uM
N-(3-chloro-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-5-(triazolo[4,5-b]pyridin-3-yl)pyridine-2-carboxamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.7100	uM
N-(3-chloro-2-pyridinyl)-3-[5-(6-methyltriazolo[4,5-b]pyridin-3-yl)-2-pyridinyl]-N-[(3R)-piperidin-3-yl]propanamide	1532845: Binding affinity to 80S ribosome in human HuH7 cells harboring human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.8500	uM
N-(3-chloro-2-pyridinyl)-5-(6-methyltriazolo[4,5-b]pyridin-3-yl)-N-[(3R)-piperidin-3-yl]pyridine-2-carboxamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	0.8500	uM
N-(3-methyl-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-4-pyrazolo[1,5-a]pyrimidin-3-ylpiperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	0.9200	uM
N-isoquinolin-1-yl-4-(1-methylpyrazol-4-yl)-N-[(3R)-piperidin-3-yl]benzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	1.0600	uM
N-isoquinolin-1-yl-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	1.5400	uM
N-(3-methyl-2-pyridinyl)-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532845: Binding affinity to 80S ribosome in human HuH7 cells harboring human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	2.0500	uM
N-(3-chloro-2-pyridinyl)-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	2.0800	uM
N-(5,8-dihydroisoquinolin-1-yl)-3-(4-methoxyphenyl)-N-[(3R)-piperidin-3-yl]propanamide	1584424: Inhibition of human 80S ribosome-mediated PCSK9 translation expressed in CHO-K1 cells assessed as reduction in PCSK9 secretion	ec50	2.2000	uM
N-isoquinolin-1-yl-3-(4-methoxyphenyl)-N-[(3R)-piperidin-3-yl]propanamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	2.6300	uM
N-(3-chloro-2-pyridinyl)-4-(6-methylpyrazin-2-yl)-N-[(3R)-piperidin-3-yl]benzamide	1497963: Binding affinity to 80S ribosome in human HuH7 cells assessed as inhibition of PCSK9 mRNA translation after overnight incubation by ELISA	ic50	2.8200	uM
N-(3-chloro-2-pyridinyl)-4-[6-(dimethylamino)pyrazin-2-yl]-N-[(3R)-piperidin-3-yl]benzamide	1497963: Binding affinity to 80S ribosome in human HuH7 cells assessed as inhibition of PCSK9 mRNA translation after overnight incubation by ELISA	ic50	2.9700	uM
N-(3-chloro-2-pyridinyl)-4-[6-(methylamino)pyrazin-2-yl]-N-[(3R)-piperidin-3-yl]benzamide	1497963: Binding affinity to 80S ribosome in human HuH7 cells assessed as inhibition of PCSK9 mRNA translation after overnight incubation by ELISA	ic50	3.0800	uM
N-isoquinolin-1-yl-4-(6-methyl-1,2-benzoxazol-3-yl)-N-[(3R)-piperidin-3-yl]piperazine-1-carboxamide	1532845: Binding affinity to 80S ribosome in human HuH7 cells harboring human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	3.5000	uM
N-(3-methylpyrazin-2-yl)-4-phenyl-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	3.6300	uM
N-(3-chloro-2-pyridinyl)-N-[(3R)-piperidin-3-yl]-6-(triazolo[4,5-b]pyridin-3-yl)pyridine-3-carboxamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	4.1000	uM
N-isoquinolin-1-yl-N-[(3R)-piperidin-3-yl]-4-pyrazin-2-ylbenzamide	1497947: Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay	ic50	4.3000	uM
4-(2-fluorophenyl)-N-(3-methyl-2-pyridinyl)-N-[(3R)-piperidin-3-yl]piperidine-1-carboxamide	1532846: Binding affinity to 80S ribosome in human HeLa cells lysates using human full length PCSK9 encoding mRNAs assessed as inhibition of PCSK9 mRNA translation after 45 mins by Steady-Glo luciferase reporter gene assay	ic50	4.3800	uM
2,2-dichloro-N-[(1R,2R)-1,3-dihydroxy-1-(4-nitrophenyl)propan-2-yl]acetamide;sulfuric acid	717551: Inhibition of mitochondrial ribosome-mediated protein synthesis in human HeLa cells assessed as {35S]methionine incorporation by autoradiography	ic50	7.4000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation, increases expression	3
bisphenol A	affects expression, decreases expression	2
sodium arsenite	decreases expression, increases abundance, increases expression	2
Air Pollutants	affects expression, increases abundance, decreases expression	2
Cadmium	increases abundance, increases palmitoylation, increases expression, decreases reaction	2
Smoke	decreases expression, increases abundance	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
tris(2-butoxyethyl) phosphate	increases expression	1
arsenite	affects binding, increases reaction	1
methylparaben	decreases expression	1
3,3’-diindolylmethane	decreases expression, increases reaction	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
ochratoxin A	affects cotreatment, decreases expression	1
cyclic 3’,5’-uridine monophosphate	affects binding	1
epigallocatechin gallate	increases expression	1
CGP 52608	affects binding, increases reaction	1
chloropicrin	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Arsenic	increases abundance, increases expression	1
Vehicle Emissions	decreases expression, increases abundance	1
Caffeine	increases expression	1

ChEMBL screening assays

90 unique, capped per target: 90 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1920845	Binding	Induction of ribosome to readthrough in human A-T lymphoblastoid cells assessed as ATM ser1981 autophosphorylation at 30 uM after 4 days by PTT-ELISA assay	Synthesis and evaluation of compounds that induce readthrough of premature termination codons. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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