UPF2

Summary

UPF2 (UPF2 regulator of nonsense mediated mRNA decay, HGNC:17854) is a protein-coding gene on chromosome 10p14, encoding Regulator of nonsense transcripts 2 (Q9HAU5). Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons by associating with the nuclear exon junction complex (EJC). It is a common-essential gene (DepMap: required in 98.8% of cancer cell lines).

This gene encodes a protein that is part of a post-splicing multiprotein complex involved in both mRNA nuclear export and mRNA surveillance. mRNA surveillance detects exported mRNAs with truncated open reading frames and initiates nonsense-mediated mRNA decay (NMD). When translation ends upstream from the last exon-exon junction, this triggers NMD to degrade mRNAs containing premature stop codons. This protein is located in the perinuclear area. It interacts with translation release factors and the proteins that are functional homologs of yeast Upf1p and Upf3p. Two splice variants have been found for this gene; both variants encode the same protein.

Source: NCBI Gene 26019 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 172 total — 1 pathogenic
• Cancer dependency (DepMap): dependent in 98.8% of screened cell lines (common-essential)
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_015542

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17854
Approved symbol	UPF2
Name	UPF2 regulator of nonsense mediated mRNA decay
Location	10p14
Locus type	gene with protein product
Status	Approved
Aliases	RENT2, DKFZP434D222, KIAA1408, smg-3
Ensembl gene	ENSG00000151461
Ensembl biotype	protein_coding
OMIM	605529
Entrez	26019

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 13 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000356352, ENST00000357604, ENST00000397053, ENST00000460569, ENST00000879617, ENST00000879618, ENST00000879619, ENST00000879620, ENST00000879621, ENST00000911435, ENST00000911436, ENST00000911437, ENST00000969826, ENST00000969827

RefSeq mRNA: 2 — MANE Select: NM_015542 NM_015542, NM_080599

CCDS: CCDS7086

Canonical transcript exons

ENST00000357604 — 22 exons

Exon	Start	End
ENSE00000999707	12028745	12029524
ENSE00001094595	11929865	11929985
ENSE00001094602	11931641	11931782
ENSE00001094605	11936545	11936712
ENSE00001213463	11999906	12000009
ENSE00001213468	12001676	12001825
ENSE00001213473	12004530	12004727
ENSE00001349465	12014024	12014184
ENSE00001410454	12042755	12042809
ENSE00001479914	11920022	11921307
ENSE00001595330	11955232	11955507
ENSE00001617394	11959171	11959356
ENSE00001647744	11952066	11952249
ENSE00001649100	11967341	11967454
ENSE00001649308	11979057	11979165
ENSE00001662463	11948369	11948508
ENSE00001724518	11956320	11956523
ENSE00001742008	11964009	11964125
ENSE00001754391	11997672	11997757
ENSE00001754512	11943064	11943168
ENSE00001760455	11942665	11942763
ENSE00003529100	12035059	12035441

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 99.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.7000 / max 814.1123, expressed in 1656 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
108266	8.4290	1581
108265	1.7986	711
108267	1.4724	857

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	99.06	gold quality
calcaneal tendon	UBERON:0003701	94.85	gold quality
tendon	UBERON:0000043	94.81	gold quality
tendon of biceps brachii	UBERON:0008188	93.76	gold quality
medial globus pallidus	UBERON:0002477	90.79	gold quality
sperm	CL:0000019	90.62	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.18	gold quality
male germ cell	CL:0000015	89.71	gold quality
biceps brachii	UBERON:0001507	89.48	gold quality
globus pallidus	UBERON:0001875	89.28	gold quality
ventricular zone	UBERON:0003053	89.26	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	89.22	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	89.17	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	89.05	gold quality
gluteal muscle	UBERON:0002000	88.80	gold quality
esophagus squamous epithelium	UBERON:0006920	88.49	gold quality
tibia	UBERON:0000979	88.34	gold quality
deltoid	UBERON:0001476	88.32	gold quality
postcentral gyrus	UBERON:0002581	88.30	gold quality
amniotic fluid	UBERON:0000173	88.18	gold quality
blood vessel layer	UBERON:0004797	88.06	gold quality
gastrocnemius	UBERON:0001388	88.05	gold quality
seminal vesicle	UBERON:0000998	88.01	gold quality
superficial temporal artery	UBERON:0001614	87.70	gold quality
muscle of leg	UBERON:0001383	87.68	gold quality
trabecular bone tissue	UBERON:0002483	87.60	gold quality
inferior olivary complex	UBERON:0002127	87.56	gold quality
monocyte	CL:0000576	87.38	gold quality
buccal mucosa cell	CL:0002336	87.36	gold quality
mononuclear cell	CL:0000842	87.32	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.95

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
UPF1	Unknown

miRNA regulators (miRDB)

92 targeting UPF2, 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-3613-3P	100.00	76.36	7965
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-7978	99.86	66.90	856
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-199A-3P	99.75	70.48	929
HSA-MIR-199B-3P	99.75	70.48	929
HSA-MIR-3129-5P	99.75	70.46	914
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-1296-3P	99.72	64.04	636
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-4756-3P	99.62	66.30	1319
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-885-5P	99.59	68.59	879
HSA-MIR-425-5P	99.59	67.67	900
HSA-MIR-762	99.58	66.61	1994

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 98.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 17)

• The complex between the interacting domains of human UPF2 and UPF3b at a 1.95 A resolution. (PMID:15004547)
• During nonsense-mediated mRNA decay, CBP80 interacts with Upf1 and promotes the interaction of Upf1 with Upf2 but not with Stau1. (PMID:16186820)
• UPF2-silenced HeLa cells were impaired in their ability to recognize ectopically expressed aberrant premature termination codon transcripts (PMID:16449641)
• The Upf complex communicates with the exon-junction complex and triggers nonsense-mediated decay in the cytoplasm. (PMID:17803942)
• UPF2 and UPF3b cooperatively stimulate both ATPase and RNA helicase activities of UPF1. (PMID:18066079)
• The authors propose that the bipartite mode of UPF2 binding to UPF1 brings the ribosome and the exon junction complex in close proximity by forming a tight complex after an initial weak encounter with either element. (PMID:19556969)
• Data show that upon binding to Upf2, the regulatory CH domain of Upf1 undergoes a large conformational change, causing the catalytic helicase domain to bind RNA less extensively and triggering its helicase activity. (PMID:21419344)
• This study demonstrated the quantitative regulation of Upf1 and Upf2 proteins by ubiquitin-proteasome system and SMG1. (PMID:24173962)
• UPF2 MIF4G-1 and MIF4G-2 domains appear to have a crucial scaffolding role, while the MIF4G-3 domain is the key module required for triggering nonsense-mediated decay. (PMID:24271394)
• UPF2 binds the FRB domain of SMG1, a region that regulates the related mTOR kinase. (PMID:25002321)
• we find that the interaction of UPF2 with UPF3b interferes with the assembly of the UPF2-eRF3 complex, and that UPF2 binds UPF3b more strongly than eRF3 (PMID:26740584)
• our findings indicate that impaired UPF2-dependent nonsense-mediated decay leads to neurodevelopmental dysfunction (PMID:31585809)
• UPF2 acts as an adaptor between Stau1 and UPF1, stimulates the catalytic activity of UPF1 and plays a central role in the formation of an Staufen-mediated mRNA decay-competent mRNP. (PMID:31699982)
• Structures of nonsense-mediated mRNA decay factors UPF3B and UPF3A in complex with UPF2 reveal molecular basis for competitive binding and for neurodevelopmental disorder-causing mutation. (PMID:35640974)
• Modulation of RNA-binding properties of the RNA helicase UPF1 by its activator UPF2. (PMID:36456182)
• An alternative spliced UPF2 transcript in pancreatic inflammatory myofibroblastic tumors. (PMID:38056247)
• UPF1 helicase orchestrates mutually exclusive interactions with the SMG6 endonuclease and UPF2. (PMID:38709891)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000111388
mus_musculus	Upf2	ENSMUSG00000043241
rattus_norvegicus	Upf2	ENSRNOG00000023593
drosophila_melanogaster	Upf2	FBGN0029992
caenorhabditis_elegans		WBGENE00004881

Protein

Protein identifiers

Regulator of nonsense transcripts 2 — Q9HAU5 (reviewed: Q9HAU5)

Alternative names: Up-frameshift suppressor 2 homolog

All UniProt accessions (1): Q9HAU5

UniProt curated annotations — full annotation on UniProt →

Function. Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons by associating with the nuclear exon junction complex (EJC). Recruited by UPF3B associated with the EJC core at the cytoplasmic side of the nuclear envelope and the subsequent formation of an UPF1-UPF2-UPF3 surveillance complex (including UPF1 bound to release factors at the stalled ribosome) is believed to activate NMD. In cooperation with UPF3B stimulates both ATPase and RNA helicase activities of UPF1. Binds spliced mRNA.

Subunit / interactions. Found in a post-splicing messenger ribonucleoprotein (mRNP) complex. Associates with the exon junction complex (EJC). Interacts with SMG1, EST1A, UPF1, UPF3A, UPF3B, EIF4A1 and EIF1.

Subcellular location. Cytoplasm. Perinuclear region.

Tissue specificity. Ubiquitous.

RefSeq proteins (2): NP_056357, NP_542166 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003890	MIF4G-like_typ-3	Domain
IPR007193	Upf2/Nmd2_C	Domain
IPR016024	ARM-type_fold	Homologous_superfamily
IPR039762	Nmd2/UPF2	Family

Pfam: PF02854, PF04050

UniProt features (111 total): helix 51, mutagenesis site 19, region of interest 14, strand 6, turn 5, compositionally biased region 4, sequence conflict 4, domain 3, coiled-coil region 2, chain 1, modified residue 1, sequence variant 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
1UW4	X-RAY DIFFRACTION	1.95
4CEK	X-RAY DIFFRACTION	2.35
4CEM	X-RAY DIFFRACTION	2.6
7NWU	X-RAY DIFFRACTION	2.6
2WJV	X-RAY DIFFRACTION	2.85
7QG6	X-RAY DIFFRACTION	2.95

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HAU5-F1	77.40	0.51

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): 1088

Mutagenesis-validated functional residues (19):

Position	Phenotype
796–797	strongly impairs rna-binding.
847	does not abolish interaction with upf3b.
851–852	does not abolish interaction with upf3b. does not abolish interaction with upf3b; when associated with d-854.
854	does not abolish interaction with upf3b; when associated with k-851 and r-852.
858	abolishes interaction with upf3b and association with smg1 and rbm8a; reduces phosphorylation of upf1.
894	does not impair rna-binding; when associated with a-932.
932	does not impair rna-binding; when associated with a-894.
1113	abolishes interaction with upf1.
1120	decreases interaction with upf1; does not reduce nmd efficiency.
1121	decreases interaction with upf1; does not reduce nmd efficiency.
1123	decreases interaction with upf1.
1169	decreases interaction with upf1.
1171	abolishes interaction with upf1; reduces nmd efficiency.
1171	greatly reduces nmd efficiency; when associated with e-1173 and e-1174.
1173	abolishes interaction with upf1.
1173	greatly reduces nmd efficiency; when associated with e-1171 and e-1174.
1174	abolishes interaction with upf1; reduces nmd efficiency.
1174	greatly reduces nmd efficiency; when associated with e-1171 and e-1173.
1176	decreases interaction with upf1.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-9010553	Regulation of expression of SLITs and ROBOs
R-HSA-975957	Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)

MSigDB gene sets: 181 (showing top): CREL_01, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, TGCGCANK_UNKNOWN, LFA1_Q6, MAZ_Q6, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_REGENERATION, SP1_Q2_01, GOBP_NUCLEAR_TRANSPORT, WEI_MYCN_TARGETS_WITH_E_BOX, IRF7_01, WTGAAAT_UNKNOWN, GOBP_NUCLEOBASE_CONTAINING_COMPOUND_TRANSPORT, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_DN, GGGNNTTTCC_NFKB_Q6_01

GO Biological Process (4): nuclear-transcribed mRNA catabolic process, nonsense-mediated decay (GO:0000184), liver development (GO:0001889), mRNA export from nucleus (GO:0006406), animal organ regeneration (GO:0031100)

GO Molecular Function (3): RNA binding (GO:0003723), telomeric repeat DNA binding (GO:0042162), protein binding (GO:0005515)

GO Cellular Component (6): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), exon-exon junction complex (GO:0035145), cytoplasmic ribonucleoprotein granule (GO:0036464), perinuclear region of cytoplasm (GO:0048471)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Signaling by ROBO receptors	1
Nonsense-Mediated Decay (NMD)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cytoplasm	3
nuclear-transcribed mRNA catabolic process	1
gland development	1
hepaticobiliary system development	1
RNA export from nucleus	1
gene expression	1
mRNA transport	1
regeneration	1
animal organ development	1
nucleic acid binding	1
sequence-specific DNA binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
nuclear protein-containing complex	1
ribonucleoprotein granule	1

Protein interactions and networks

STRING

1698 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UPF2	UPF3B	Q9BZI7	999
UPF2	UPF1	Q92900	999
UPF2	SMG1	Q96Q15	999
UPF2	UPF3A	Q9H1J1	999
UPF2	SMG8	Q8ND04	982
UPF2	SMG9	Q9H0W8	979
UPF2	SMG5	Q9UPR3	978
UPF2	SMG7	Q92540	969
UPF2	SMG6	Q86US8	945
UPF2	NCBP1	Q09161	929
UPF2	HBS1L	Q9Y450	906
UPF2	EIF4A3	P38919	892
UPF2	RBM8A	Q9Y5S9	885
UPF2	STAU1	O95793	883
UPF2	RNPS1	Q15287	881

IntAct

149 interactions, top by confidence:

A	B	Type	Score
CASC3	EIF4A3	psi-mi:“MI:0915”(physical association)	0.980
EIF4A3	CASC3	psi-mi:“MI:0914”(association)	0.980
UPF2	UPF1	psi-mi:“MI:0914”(association)	0.960
UPF2	UPF1	psi-mi:“MI:0915”(physical association)	0.960
UPF1	UPF2	psi-mi:“MI:0407”(direct interaction)	0.960
UPF2	UPF1	psi-mi:“MI:0407”(direct interaction)	0.960
UPF1	UPF2	psi-mi:“MI:0915”(physical association)	0.960

BioGRID (248): UPF2 (Two-hybrid), UPF2 (Dosage Rescue), UPF2 (Co-fractionation), UPF2 (Co-fractionation), UPF2 (Co-fractionation), UPF2 (Co-fractionation), UPF3B (Co-fractionation), UPF2 (Affinity Capture-MS), UPF2 (Affinity Capture-MS), RPS25 (Two-hybrid), UPF2 (Affinity Capture-MS), UPF2 (Affinity Capture-MS), UPF2 (Affinity Capture-MS), UPF2 (Two-hybrid), EIF4A1 (Two-hybrid)

ESM2 similar proteins: A0A3Q1LSX9, A2APV2, A2AT37, A2VD00, A4II09, B0KWH8, B1AZI6, B1MTK1, B2KI97, B3MS75, B3NU52, B4GW22, B4I0W6, B4JM29, B4L2J8, B4NC41, B4Q034, C0H906, C1FXW9, F4IUX6, Q09161, Q16UN6, Q1LUC1, Q1LXC9, Q29G82, Q2L4X1, Q3UYV9, Q4R6R4, Q56A27, Q5R7L4, Q5ZJZ6, Q5ZL42, Q5ZLT7, Q5ZMW3, Q6DDM4, Q6DIE2, Q6GQ80, Q6GQD0, Q6P2Z0, Q6P7P5

Diamond homologs: A2AT37, F4IUX6, Q9HAU5

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
UPF2	up-regulates	Synaptic_plasticity
UPF2	“form complex”	Upf-EJC	binding
UPF2	“up-regulates activity”	UPF1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 106 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)	9	27.6×	3e-09
Transport of Mature Transcript to Cytoplasm	5	25.0×	4e-05
Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)	19	24.4×	4e-19
Nuclear RNA decay	6	24.4×	6e-06
Dengue Virus Genome Translation and Replication	5	20.9×	9e-05
mRNA 3’-end processing	7	18.1×	5e-06
Translation initiation complex formation	6	15.0×	7e-05
RNA Polymerase II Transcription Termination	5	14.4×	5e-04

GO biological processes:

GO term	Partners	Fold	FDR
nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	14	68.3×	3e-20
RNA catabolic process	6	28.5×	5e-06
mRNA export from nucleus	6	18.5×	6e-05
rRNA processing	11	16.2×	2e-08
mRNA transport	5	13.7×	2e-03
regulation of alternative mRNA splicing, via spliceosome	5	12.7×	2e-03
positive regulation of translation	5	11.9×	3e-03
cytoplasmic translation	6	11.6×	8e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	126
Likely benign	9
Benign	7

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1407764	NM_015542.4(UPF2):c.2021_2024del (p.Thr674fs)	Pathogenic

SpliceAI

4104 predictions. Top by Δscore:

Variant	Effect	Δscore
10:11929866:TCCC:T	donor_gain	1.0000
10:11929904:C:CA	donor_gain	1.0000
10:11929992:T:TC	acceptor_gain	1.0000
10:11931635:TTATA:T	donor_loss	1.0000
10:11931636:TATAC:T	donor_loss	1.0000
10:11931637:ATACC:A	donor_loss	1.0000
10:11931638:TACC:T	donor_loss	1.0000
10:11931640:CCTT:C	donor_loss	1.0000
10:11931778:TTAAA:T	acceptor_gain	1.0000
10:11931781:AA:A	acceptor_gain	1.0000
10:11931783:C:CC	acceptor_gain	1.0000
10:11931784:T:C	acceptor_loss	1.0000
10:11936539:TCTTA:T	donor_loss	1.0000
10:11936540:CTTA:C	donor_loss	1.0000
10:11936541:TTA:T	donor_loss	1.0000
10:11936543:A:AT	donor_loss	1.0000
10:11936544:CCTG:C	donor_gain	1.0000
10:11936711:TG:T	acceptor_gain	1.0000
10:11936713:C:CC	acceptor_gain	1.0000
10:11942765:T:C	acceptor_gain	1.0000
10:11943058:A:AC	donor_gain	1.0000
10:11943059:C:CC	donor_gain	1.0000
10:11943060:GTACA:G	donor_loss	1.0000
10:11943061:TACAG:T	donor_loss	1.0000
10:11943062:A:AC	donor_gain	1.0000
10:11943062:ACAGT:A	donor_loss	1.0000
10:11943063:C:CC	donor_gain	1.0000
10:11943063:CA:C	donor_gain	1.0000
10:11943063:CAG:C	donor_gain	1.0000
10:11943063:CAGT:C	donor_gain	1.0000

AlphaMissense

8565 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:11929879:A:C	F1265L	1.000
10:11929879:A:T	F1265L	1.000
10:11929880:A:C	F1265C	1.000
10:11929880:A:G	F1265S	1.000
10:11929881:A:C	F1265V	1.000
10:11929881:A:G	F1265L	1.000
10:11929881:A:T	F1265I	1.000
10:11929883:A:C	I1264S	1.000
10:11929883:A:G	I1264T	1.000
10:11929883:A:T	I1264N	1.000
10:11929886:A:G	L1263P	1.000
10:11929898:G:T	P1259H	1.000
10:11929899:G:A	P1259S	1.000
10:11929899:G:T	P1259T	1.000
10:11929904:C:T	G1257E	1.000
10:11929905:C:G	G1257R	1.000
10:11929905:C:T	G1257R	1.000
10:11929914:G:C	H1254D	1.000
10:11931664:C:G	R1222P	1.000
10:11931679:A:G	L1217P	1.000
10:11931679:A:T	L1217Q	1.000
10:11931685:A:G	L1215P	1.000
10:11931690:T:A	K1213N	1.000
10:11931690:T:G	K1213N	1.000
10:11931745:G:T	A1195D	1.000
10:11931748:A:G	L1194P	1.000
10:11931772:A:G	L1186P	1.000
10:11936563:T:A	R1176S	1.000
10:11936563:T:G	R1176S	1.000
10:11936564:C:G	R1176T	1.000

dbSNP variants (sampled 300 via entrez): RS1000033476 (10:11966528 G>A,C), RS1000036979 (10:11955971 G>A), RS1000041471 (10:11922462 G>A,T), RS1000071076 (10:11922158 C>A), RS1000104765 (10:11998595 G>A), RS1000105613 (10:11960831 C>A), RS1000143421 (10:11961868 G>C), RS1000152657 (10:11920603 TAAA>T), RS1000196683 (10:12012227 T>C), RS1000197539 (10:11975767 T>C), RS1000214643 (10:12043588 C>A), RS1000226745 (10:12006548 A>T), RS1000233311 (10:11982605 TC>T), RS1000236782 (10:11995077 C>T), RS1000253974 (10:11967628 C>T)

Disease associations

OMIM: gene MIM:605529 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): autism spectrum disorder (MONDO:0005258)

Orphanet (1): NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006479_4	Diverticular disease	6.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009959	diverticular disease

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression, increases methylation	2
Tobacco Smoke Pollution	increases expression	2
Particulate Matter	increases reaction, affects cotreatment, decreases expression, increases abundance, affects expression	2
FR900359	increases phosphorylation	1
dicrotophos	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
deoxynivalenol	increases expression	1
beta-lapachone	decreases expression	1
sodium arsenite	increases expression	1
tetrabromobisphenol A	decreases expression	1
benzo(e)pyrene	decreases methylation	1
beta-methylcholine	affects expression	1
jasplakinolide	affects binding, decreases reaction	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine	increases reaction, affects expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	affects cotreatment, decreases methylation	1
PCI 5002	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Leflunomide	decreases expression	1
Vehicle Emissions	affects expression, increases reaction	1
Benzo(a)pyrene	affects methylation	1
Doxorubicin	decreases expression	1
Endosulfan	decreases expression	1
Estradiol	affects expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	PHASE3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	PHASE3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	PHASE3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	PHASE3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	PHASE3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	PHASE3	COMPLETED	Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder
NCT04623398	PHASE3	COMPLETED	Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency)
NCT04725383	PHASE3	TERMINATED	Amitriptyline for Repetitive Behaviors in Autism Spectrum Disorders
NCT05212493	PHASE3	COMPLETED	The Effects of Medical Cannabis in Children With Autistic Spectrum Disorder
NCT05361707	PHASE3	UNKNOWN	Evaluating the Effects of Tasimelteon in Individuals With Autism Spectrum Disorder (ASD) and Sleep Disturbances
NCT05439616	PHASE3	COMPLETED	Study of Cariprazine Oral Capsules or Solution to Assess Adverse Events and Change in Irritability Due to Autism Spectrum Disorder (ASD) in Participants Aged 5-17 Years With ASD
NCT06229210	PHASE3	RECRUITING	Safety and Tolerability Trial of Lumateperone in Pediatric Patients With Schizophrenia, Bipolar Disorder or Autism Spectrum Disorder