XRN1

Summary

XRN1 (5’-3’ exoribonuclease 1, HGNC:30654) is a protein-coding gene on chromosome 3q23, encoding 5’-3’ exoribonuclease 1 (Q8IZH2). Major 5’-3’ exoribonuclease involved in mRNA decay. It is a selective cancer dependency (DepMap: 63.0% of cell lines).

This gene encodes a member of the 5’-3’ exonuclease family. The encoded protein may be involved in replication-dependent histone mRNA degradation, and interacts directly with the enhancer of mRNA-decapping protein 4. In addition to mRNA metabolism, a similar protein in yeast has been implicated in a variety of nuclear and cytoplasmic functions, including homologous recombination, meiosis, telomere maintenance, and microtubule assembly. Mutations in this gene are associated with osteosarcoma, suggesting that the encoded protein may also play a role in bone formation. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 54464 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 215 total
• Cancer dependency (DepMap): dependent in 63.0% of screened cell lines
• MANE Select transcript: NM_001282857

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30654
Approved symbol	XRN1
Name	5’-3’ exoribonuclease 1
Location	3q23
Locus type	gene with protein product
Status	Approved
Aliases	SEP1
Ensembl gene	ENSG00000114127
Ensembl biotype	protein_coding
OMIM	607994
Entrez	54464

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 10 protein_coding, 5 retained_intron, 2 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000264951, ENST00000392981, ENST00000463916, ENST00000465074, ENST00000465507, ENST00000467077, ENST00000468894, ENST00000470537, ENST00000472625, ENST00000472697, ENST00000477237, ENST00000486211, ENST00000489241, ENST00000498077, ENST00000863186, ENST00000863187, ENST00000863188, ENST00000941074, ENST00000941075

RefSeq mRNA: 3 — MANE Select: NM_001282857 NM_001282857, NM_001282859, NM_019001

CCDS: CCDS3123, CCDS63801, CCDS75028

Canonical transcript exons

ENST00000392981 — 41 exons

Exon	Start	End
ENSE00000779137	142376479	142376594
ENSE00000779138	142375798	142375944
ENSE00000779144	142356912	142357119
ENSE00000779145	142355401	142355496
ENSE00000779147	142347234	142347342
ENSE00000779149	142335448	142335509
ENSE00000779151	142332967	142333089
ENSE00000779155	142329434	142329615
ENSE00000779159	142318592	142318694
ENSE00000779161	142312598	142312758
ENSE00001838732	142447870	142448037
ENSE00001863580	142306610	142311813
ENSE00003460305	142422582	142422750
ENSE00003463731	142432661	142432893
ENSE00003470919	142318790	142318903
ENSE00003478269	142425429	142425538
ENSE00003495513	142417140	142417229
ENSE00003507043	142414135	142414291
ENSE00003507215	142426744	142426841
ENSE00003511523	142365310	142365366
ENSE00003529112	142421016	142421153
ENSE00003543337	142403674	142403772
ENSE00003546864	142365047	142365179
ENSE00003548602	142380082	142380180
ENSE00003549961	142397329	142397460
ENSE00003549988	142400444	142400547
ENSE00003570821	142383300	142383413
ENSE00003587853	142423560	142423642
ENSE00003590093	142359862	142359931
ENSE00003595261	142422835	142422922
ENSE00003597827	142332375	142332534
ENSE00003602023	142403869	142403989
ENSE00003606029	142371239	142371328
ENSE00003619440	142404907	142405076
ENSE00003636427	142370485	142370620
ENSE00003646731	142384523	142384685
ENSE00003649860	142425222	142425332
ENSE00003659154	142412544	142412663
ENSE00003661869	142418815	142418881
ENSE00003667665	142421476	142421543
ENSE00003678051	142418504	142418609

Expression profiles

Bgee: expression breadth ubiquitous, 259 present calls, max score 98.64.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.2853 / max 690.9302, expressed in 1781 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
44846	8.5882	1707
44844	6.3533	1338
44845	5.8827	1547
44847	0.9714	455
202953	0.3283	128
44843	0.1539	76
44841	0.0074	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
epithelial cell of pancreas	CL:0000083	98.64	gold quality
oviduct epithelium	UBERON:0004804	98.39	gold quality
calcaneal tendon	UBERON:0003701	98.09	gold quality
germinal epithelium of ovary	UBERON:0001304	97.84	gold quality
visceral pleura	UBERON:0002401	97.49	gold quality
parietal pleura	UBERON:0002400	97.46	gold quality
tibia	UBERON:0000979	97.26	gold quality
bone marrow cell	CL:0002092	96.56	gold quality
esophagus squamous epithelium	UBERON:0006920	96.27	gold quality
gingival epithelium	UBERON:0001949	96.03	gold quality
endothelial cell	CL:0000115	96.00	gold quality
palpebral conjunctiva	UBERON:0001812	95.95	gold quality
tibialis anterior	UBERON:0001385	95.84	gold quality
jejunal mucosa	UBERON:0000399	95.75	gold quality
deltoid	UBERON:0001476	95.74	gold quality
upper arm skin	UBERON:0004263	95.57	gold quality
tendon	UBERON:0000043	95.26	gold quality
trabecular bone tissue	UBERON:0002483	95.00	gold quality
epithelium of nasopharynx	UBERON:0001951	94.98	gold quality
nasopharynx	UBERON:0001728	94.96	gold quality
gingiva	UBERON:0001828	94.71	gold quality
sural nerve	UBERON:0015488	94.64	gold quality
amniotic fluid	UBERON:0000173	94.58	gold quality
ileal mucosa	UBERON:0000331	94.51	gold quality
eye	UBERON:0000970	94.39	gold quality
adrenal tissue	UBERON:0018303	94.20	gold quality
buccal mucosa cell	CL:0002336	94.07	gold quality
Brodmann (1909) area 23	UBERON:0013554	94.07	gold quality
pancreatic ductal cell	CL:0002079	93.96	gold quality
colonic epithelium	UBERON:0000397	93.71	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.38
E-MTAB-7303	no	227.29

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): DMBX1

miRNA regulators (miRDB)

285 targeting XRN1, 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-4668-3P	100.00	68.74	2635
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-12136	99.98	72.81	5713

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 63.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 18)

• LSm1-7 proteins colocalize with DCP1,DCP2 and Xrn1 in cytoplasmic foci (PMID:12515382)
• findings reveal a role for XRN1 in decapping and provide a molecular basis for the coupling of decapping to 5’–>3’ mRNA degrada (PMID:23142987)
• Data show that 5’ exonuclease Xrn1 knockdown and miR-122 supplementation have equal, redundant, and nonadditive effects on the rate of viral RNA decay, indicating that miR-122 protects HCV RNA from 5’ decay. (PMID:23248316)
• Authors conclude that Xrn1 is the dominant 5’ exoribonuclease mediating decay of hepatitis C virus RNA and that miR-122 provides protection against it (PMID:25673723)
• Thus, Xrn1 is a cellular factor regulating dsRNA accumulation and dsRNA-responsive innate immune effectors. (PMID:25766294)
• Data show that the AR-miR-204-XRN1-miR-34a positive feedback loop and a dual function of miR-204/XRN1 axis in prostate cancer. (PMID:25797256)
• Occupation of each miR-122 binding site on 5’ untranslated region of the hepatitis C virus genome contributes equally and cooperatively to virus replication via protecting from Xrn1 exoribonuclease degradation. (PMID:25855736)
• Insertion of 5’-3’ exoribonuclease 1 (XRN1)-resistant sequences (xrRNAs) into different reporter mRNAs allowed to monitor RNA decay activity by the nonsense-mediated mRNA decay pathway (NMD). (PMID:27917860)
• These findings suggest that sequestration of the exoribonucleases DIS3L2 and XRN1 to nuclear inclusions may be related to the pathogenesis of intranuclear inclusion body disease (PMID:29100804)
• Authors use a series of assays to demonstrate that the 3’-terminal portion of the nucleocapsid (N) mRNA of Rift Valley fever virus can effectively stall and repress XRN1. The region responsible for impeding XRN1 includes a G-rich portion that likely forms a G-quadruplex structure. The 3’-terminal portions of ambisense-derived transcripts of multiple arenaviruses also stalled XRN1. (PMID:29118186)
• This work provides insight into the role of the RNA decay factor Xrn1/XRN1 as a post-transcriptional regulator of autophagy. (PMID:29465287)
• We show that knockdown of human XRN1, CNOT6 and ETF1 genes in HepG2 cells led to significant alteration in stability of specific mRNAs, alterations in half-life were inversely associated with transcription rates, mostly not resulting in changes in abundance (PMID:31116665)
• Another decapping activator PatL1 directly interacts with CIR and alleviates the CIR-mediated inhibition of CCR4-NOT activity in vitro. Ribosome profiling revealed that XRN1 loss impacts not only on mRNA levels but also on the translational efficiency of many cellular transcripts likely as a consequence of incomplete decay (PMID:31340047)
• Genome-wide analyses of XRN1-sensitive targets in osteosarcoma cells identify disease-relevant transcripts containing G-rich motifs. (PMID:34266995)
• Cellular 5’-3’ mRNA Exoribonuclease XRN1 Inhibits Interferon Beta Activation and Facilitates Influenza A Virus Replication. (PMID:34311580)
• Dysregulated non-coding telomerase RNA component and associated exonuclease XRN1 in leucocytes from women developing preeclampsia-possible link to enhanced senescence. (PMID:34611223)
• Host 5’-3’ Exoribonuclease XRN1 Acts as a Proviral Factor for Measles Virus Replication by Downregulating the dsRNA-Activated Kinase PKR. (PMID:36300942)
• Mouse Xrn1 plays a role in RNA turnover. (PMID:9049243)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	xrn1	ENSDARG00000091652
mus_musculus	Xrn1	ENSMUSG00000032410
rattus_norvegicus	Xrn1	ENSRNOG00000042951
drosophila_melanogaster	pcm	FBGN0020261
caenorhabditis_elegans		WBGENE00012730

Paralogs (1): XRN2 (ENSG00000088930)

Protein

Protein identifiers

5’-3’ exoribonuclease 1 — Q8IZH2 (reviewed: Q8IZH2)

Alternative names: Strand-exchange protein 1 homolog

All UniProt accessions (5): C9JCZ8, F8WDA0, Q8IZH2, H7C583, H7C5E4

UniProt curated annotations — full annotation on UniProt →

Function. Major 5’-3’ exoribonuclease involved in mRNA decay. Required for the 5’-3’-processing of the G4 tetraplex-containing DNA and RNA substrates. The kinetic of hydrolysis is faster for G4 RNA tetraplex than for G4 DNA tetraplex and monomeric RNA tetraplex. Plays a role in replication-dependent histone mRNA degradation. May act as a tumor suppressor protein in osteogenic sarcoma (OGS).

Subunit / interactions. Found in a mRNP complex with UPF1, UPF2, UPF3B and XRN1. Associates with alpha and beta tubulins. Interacts with DIS3L2. Interacts with ZC3HAV1 in an RNA-dependent manner. Interacts with ZFP36L1. Interacts with TRIM71 (via NHL repeats) in an RNA-dependent manner. Interacts with YTHDC2 (via ANK repeats). Interacts with DHX34; the interaction is RNA-independent.

Subcellular location. Cytoplasm.

Tissue specificity. Expressed in heart, brain, pancreas, spleen, testis, osteogenic sarcoma (OGS) biopsy and primary cell lines.

Induction. By GDNF/glial cell line-derived neurotrophic factor.

Miscellaneous. Down-regulated in OGS biopsy.

Similarity. Belongs to the 5’-3’ exonuclease family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8IZH2-1	1	yes
Q8IZH2-2	2
Q8IZH2-3	3

RefSeq proteins (3): NP_001269786, NP_001269788, NP_061874 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004859	Xrn1_N	Domain
IPR016494	5_3_exoribonuclease_1	Family
IPR027073	5_3_exoribonuclease	Family
IPR040992	XRN1_D1	Domain
IPR041106	XRN1_D2_D3	Domain
IPR041385	SH3_12	Domain
IPR041412	Xrn1_helical	Domain
IPR047007	XRN1_D1_sf	Homologous_superfamily
IPR047008	XRN1_SH3_sf	Homologous_superfamily

Pfam: PF03159, PF17846, PF18129, PF18332, PF18334

UniProt features (25 total): sequence conflict 11, splice variant 4, compositionally biased region 4, sequence variant 2, modified residue 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
9E70	X-RAY DIFFRACTION	2.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IZH2-F1	70.35	0.28

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 (2): 1348, 1645

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-430039	mRNA decay by 5’ to 3’ exoribonuclease
R-HSA-450385	Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA
R-HSA-450513	Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA
R-HSA-9918487	Dengue Virus Genome Translation and Replication

MSigDB gene sets: 291 (showing top): GOBP_RNA_TEMPLATED_DNA_BIOSYNTHETIC_PROCESS, GOBP_CHROMOSOME_ORGANIZATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOMF_RNA_NUCLEASE_ACTIVITY, GOBP_NEGATIVE_REGULATION_OF_TELOMERE_MAINTENANCE_VIA_TELOMERASE, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOMF_NUCLEASE_ACTIVITY, ATACCTC_MIR202, REACTOME_MRNA_DECAY_BY_5_TO_3_EXORIBONUCLEASE, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_TELOMERE_MAINTENANCE_VIA_TELOMERE_LENGTHENING, GOBP_TELOMERE_ORGANIZATION, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_1, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND

GO Biological Process (10): nuclear-transcribed mRNA catabolic process (GO:0000956), rRNA catabolic process (GO:0016075), negative regulation of translation (GO:0017148), negative regulation of telomere maintenance via telomerase (GO:0032211), response to testosterone (GO:0033574), nuclear mRNA surveillance (GO:0071028), histone mRNA catabolic process (GO:0071044), cellular response to cycloheximide (GO:0071409), cellular response to puromycin (GO:1905795), RNA metabolic process (GO:0016070)

GO Molecular Function (12): G-quadruplex RNA binding (GO:0002151), RNA binding (GO:0003723), 5’-3’ RNA exonuclease activity (GO:0004534), G-quadruplex DNA binding (GO:0051880), telomerase RNA binding (GO:0070034), nucleic acid binding (GO:0003676), DNA binding (GO:0003677), nuclease activity (GO:0004518), exonuclease activity (GO:0004527), protein binding (GO:0005515), 5’-3’ exonuclease activity (GO:0008409), hydrolase activity (GO:0016787)

GO Cellular Component (8): P-body (GO:0000932), nucleus (GO:0005634), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), dendrite (GO:0030425), neuronal cell body (GO:0043025), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Regulation of mRNA stability by proteins that bind AU-rich elements	2
Deadenylation-dependent mRNA decay	1
Dengue Virus Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
nuclear-transcribed mRNA catabolic process	2
cellular response to nitrogen compound	2
RNA binding	2
nucleic acid binding	2
binding	2
mRNA catabolic process	1
RNA catabolic process	1
rRNA metabolic process	1
translation	1
regulation of translation	1
negative regulation of gene expression	1
negative regulation of protein metabolic process	1
telomere maintenance via telomerase	1
regulation of telomere maintenance via telomerase	1
negative regulation of telomere maintenance via telomere lengthening	1
negative regulation of DNA biosynthetic process	1
response to lipid	1
response to ketone	1
nuclear RNA surveillance	1
histone mRNA metabolic process	1
response to cycloheximide	1
cellular response to alcohol	1
cellular response to ketone	1
cellular response to oxygen-containing compound	1
response to puromycin	1
nucleic acid metabolic process	1
5’-3’ exonuclease activity	1
RNA exonuclease activity, producing 5’-phosphomonoesters	1
DNA binding	1
catalytic activity, acting on a nucleic acid	1
nuclease activity	1
hydrolase activity, acting on ester bonds	1
exonuclease activity	1
catalytic activity	1
cytoplasmic ribonucleoprotein granule	1
intracellular membrane-bounded organelle	1
cytoplasm	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

3298 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
XRN1	LSM1	O15116	999
XRN1	DCP2	Q8IU60	999
XRN1	EDC3	Q96F86	999
XRN1	DDX6	P26196	991
XRN1	YTHDC2	Q9H6S0	984
XRN1	DCP1A	Q9NPI6	984
XRN1	EDC4	Q6P2E9	978
XRN1	TNRC6A	Q8NDV7	973
XRN1	PATL1	Q86TB9	965
XRN1	LSM7	Q9UK45	962
XRN1	EIF4E	P06730	961
XRN1	LSM6	P62312	951
XRN1	UPF1	Q92900	950
XRN1	LSM4	Q9Y4Z0	940
XRN1	LSM2	Q9Y333	936

IntAct

137 interactions, top by confidence:

A	B	Type	Score
CEP97	CCP110	psi-mi:“MI:2364”(proximity)	0.950
LSM3	LSM1	psi-mi:“MI:0914”(association)	0.950
MED4	MED19	psi-mi:“MI:2364”(proximity)	0.900
DCP1A	EDC4	psi-mi:“MI:0403”(colocalization)	0.880
PATL1	LSM1	psi-mi:“MI:0914”(association)	0.770
EDC4	XRN1	psi-mi:“MI:0915”(physical association)	0.750
XRN1	EDC4	psi-mi:“MI:0914”(association)	0.750
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
CEP104	CCDC66	psi-mi:“MI:2364”(proximity)	0.540
TUBB3	POTEF	psi-mi:“MI:0914”(association)	0.530
FGF3	GTPBP10	psi-mi:“MI:0914”(association)	0.530
MAGEB2	POLRMT	psi-mi:“MI:0914”(association)	0.530
POLR3H	POLR3A	psi-mi:“MI:0914”(association)	0.530
RBM4	NVL	psi-mi:“MI:0914”(association)	0.530
NAGK	ZBTB43	psi-mi:“MI:0914”(association)	0.530
MAGEB2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
LIN28B	ELAVL2	psi-mi:“MI:0914”(association)	0.530
LSM4	PRMT5	psi-mi:“MI:0914”(association)	0.530
KIAA0753	OFD1	psi-mi:“MI:2364”(proximity)	0.480
CC2D2A	OFD1	psi-mi:“MI:2364”(proximity)	0.420
ZC3HAV1	XRN1	psi-mi:“MI:0915”(physical association)	0.400
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
Meioc	XRN1	psi-mi:“MI:0914”(association)	0.350
MYC	ILVBL	psi-mi:“MI:0914”(association)	0.350
UPF1	GSPT1	psi-mi:“MI:0914”(association)	0.350

BioGRID (317): XRN1 (Two-hybrid), XRN1 (Affinity Capture-MS), XRN1 (Affinity Capture-MS), XRN1 (Affinity Capture-MS), RPS4X (Co-fractionation), RPS7 (Co-fractionation), SYNCRIP (Co-fractionation), XRN1 (Co-fractionation), XRN1 (Co-fractionation), XRN1 (Co-fractionation), XRN1 (Affinity Capture-MS), XRN1 (Proximity Label-MS), XRN1 (Proximity Label-MS), XRN1 (Proximity Label-MS), XRN1 (Proximity Label-MS)

ESM2 similar proteins: A0A3L7I2I8, A0FKG7, A1Z3X3, A4GWN3, A5PK39, E9Q4Z2, O00763, O55236, O60733, O60942, P10687, P10894, P29144, P49754, P82922, P97570, P97789, P97819, Q15147, Q2KJA6, Q32PW3, Q5IH13, Q5KU39, Q5R8R4, Q5ZKK2, Q640G7, Q641K1, Q64514, Q64560, Q69YN2, Q6NY98, Q6NYU2, Q7ZVK4, Q80YV4, Q8BPM2, Q8CI33, Q8IVH8, Q8IZH2, Q8K114, Q8QFR2

Diamond homologs: P0CL88, P0CL89, P40383, P40848, P97789, Q02792, Q2GNZ6, Q2UCP5, Q4HWE2, Q4P149, Q5AMG5, Q5BFH3, Q5R4L5, Q5ZIP4, Q60SG7, Q6BNU7, Q6C961, Q6CKX0, Q6FKN6, Q74ZA0, Q8IZH2, Q8TFZ1, Q8WZX5, Q9DBR1, Q9FQ02, Q9FQ03, Q9FQ04, Q9H0D6, Q9U299, Q9VM71, P22147, Q197A1, Q5UQ94, P23252

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 161 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
mRNA decay by 5’ to 3’ exoribonuclease	7	49.4×	4e-09
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	15	16.4×	4e-12
Eukaryotic Translation Termination	13	14.5×	9e-10
Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)	16	14.5×	4e-12
SARS-CoV-1 modulates host translation machinery	5	14.3×	6e-04
Peptide chain elongation	12	14.1×	4e-09
Viral mRNA Translation	12	14.1×	4e-09
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	12	13.9×	4e-09

GO biological processes:

GO term	Partners	Fold	FDR
P-body assembly	5	36.8×	3e-05
centriole replication	6	30.7×	9e-06
cytoplasmic translation	13	16.8×	7e-10
nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	5	16.4×	1e-03
negative regulation of translation	9	12.3×	1e-05
non-motile cilium assembly	5	10.2×	9e-03
translation	14	10.1×	5e-08
cilium assembly	10	5.2×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	172
Likely benign	7
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

6332 predictions. Top by Δscore:

Variant	Effect	Δscore
3:142311815:T:A	acceptor_loss	1.0000
3:142312592:TCTTA:T	donor_loss	1.0000
3:142312593:CTTAC:C	donor_loss	1.0000
3:142312594:TTA:T	donor_loss	1.0000
3:142312595:TA:T	donor_loss	1.0000
3:142312596:A:AT	donor_loss	1.0000
3:142312597:C:A	donor_loss	1.0000
3:142312726:C:CT	acceptor_gain	1.0000
3:142312727:A:T	acceptor_gain	1.0000
3:142312754:ATTAG:A	acceptor_gain	1.0000
3:142312755:TTAG:T	acceptor_gain	1.0000
3:142312755:TTAGC:T	acceptor_loss	1.0000
3:142312756:TAG:T	acceptor_gain	1.0000
3:142312756:TAGC:T	acceptor_loss	1.0000
3:142312757:AG:A	acceptor_gain	1.0000
3:142312757:AGC:A	acceptor_loss	1.0000
3:142312758:GCTG:G	acceptor_loss	1.0000
3:142312759:C:CA	acceptor_loss	1.0000
3:142312759:C:CC	acceptor_gain	1.0000
3:142312760:T:A	acceptor_loss	1.0000
3:142312762:T:C	acceptor_gain	1.0000
3:142312762:T:TC	acceptor_gain	1.0000
3:142318659:T:C	acceptor_gain	1.0000
3:142318789:CCAA:C	donor_gain	1.0000
3:142318900:TTGT:T	acceptor_gain	1.0000
3:142318901:TGT:T	acceptor_gain	1.0000
3:142318904:C:CC	acceptor_gain	1.0000
3:142332370:CTTA:C	donor_loss	1.0000
3:142332371:TTACC:T	donor_loss	1.0000
3:142332372:TACCT:T	donor_loss	1.0000

AlphaMissense

11218 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:142375845:C:A	W977C	1.000
3:142375845:C:G	W977C	1.000
3:142375847:A:G	W977R	1.000
3:142375847:A:T	W977R	1.000
3:142375902:T:A	K958N	1.000
3:142375902:T:G	K958N	1.000
3:142375904:T:C	K958E	1.000
3:142375906:A:G	L957P	1.000
3:142375915:C:T	G954D	1.000
3:142376512:C:T	G933E	1.000
3:142376527:A:T	V928D	1.000
3:142400496:A:G	W719R	1.000
3:142400496:A:T	W719R	1.000
3:142403740:G:C	F679L	1.000
3:142403740:G:T	F679L	1.000
3:142403741:A:G	F679S	1.000
3:142403742:A:C	F679V	1.000
3:142403742:A:G	F679L	1.000
3:142403742:A:T	F679I	1.000
3:142412573:C:G	A562P	1.000
3:142412577:C:A	W560C	1.000
3:142412577:C:G	W560C	1.000
3:142412578:C:G	W560S	1.000
3:142412579:A:G	W560R	1.000
3:142412579:A:T	W560R	1.000
3:142412589:T:A	K556N	1.000
3:142412589:T:G	K556N	1.000
3:142414172:G:T	P519Q	1.000
3:142414175:A:G	L518P	1.000
3:142414187:A:G	L514P	1.000

dbSNP variants (sampled 300 via entrez): RS1000015755 (3:142378697 T>C), RS1000042089 (3:142364300 C>G,T), RS1000080013 (3:142376316 CAT>C), RS1000122209 (3:142371222 T>A,C), RS1000124885 (3:142326043 A>G,T), RS1000139036 (3:142416215 T>C), RS1000147960 (3:142405651 C>T), RS1000173821 (3:142307043 A>G), RS1000210598 (3:142446444 T>C), RS1000215949 (3:142352941 G>A), RS1000216755 (3:142307676 T>G), RS1000243839 (3:142396200 A>G), RS1000264031 (3:142307368 GAA>G,GA,GAAA), RS1000268542 (3:142353179 C>T), RS1000287366 (3:142351832 C>A)

Disease associations

OMIM: gene MIM:607994 | disease phenotypes:

GenCC curated gene-disease

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
GCST004863_127	Mosquito bite size	1.000000e-06
GCST006979_303	Heel bone mineral density	2.000000e-12
GCST008155_2	Waist-hip ratio	2.000000e-06
GCST008362_210	Birth weight	2.000000e-09
GCST010566_3	Benign childhood epilepsy with centro-temporal spikes	5.000000e-06
GCST011126_6	Caffeine consumption from coffee or tea	1.000000e-10
GCST90000015_30	Parkinson’s disease motor subtype (tremor to postural instability/gait difficulty score ratio)	1.000000e-05
GCST90002397_79	Mean spheric corpuscular volume	3.000000e-12

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0008378	mosquito bite reaction size measurement
EFO:0009270	heel bone mineral density
EFO:0004343	waist-hip ratio
EFO:0004344	birth weight
EFO:0006781	coffee consumption measurement
EFO:0010091	tea consumption measurement
EFO:0600011	Parkinson’s disease symptom measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	2
aristolochic acid I	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
arsenite	decreases reaction, affects binding	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
coumarin	decreases phosphorylation	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
pentabromodiphenyl ether	increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Acetaminophen	affects expression	1
Benzo(a)pyrene	decreases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Nickel	increases expression	1
Polychlorinated Biphenyls	affects expression	1
Ribonucleotides	affects binding	1
Tretinoin	increases expression	1
Vanadates	decreases expression	1
Metribolone	increases expression, decreases reaction	1
Cyclosporine	affects expression	1
Asbestos, Crocidolite	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_A5EI	HEK293T-XRN1-null	Transformed cell line	Female

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