CASC3

Summary

CASC3 (CASC3 exon junction complex subunit, HGNC:17040) is a protein-coding gene on chromosome 17q21.1, encoding Protein CASC3 (O15234). Required for pre-mRNA splicing as component of the spliceosome. It is a selective cancer dependency (DepMap: 34.4% of cell lines).

The product of this gene is a core component of the exon junction complex (EJC), a protein complex that is deposited on spliced mRNAs at exon-exon junctions and functions in nonsense-mediated mRNA decay (NMD). The encoded protein binds RNA and interacts with two other EJC core components. It is predominantly located in the cytoplasm, but shuttles into the nucleus where it localizes to nuclear speckles.

Source: NCBI Gene 22794 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 101 total
• Cancer dependency (DepMap): dependent in 34.4% of screened cell lines
• MANE Select transcript: NM_007359

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17040
Approved symbol	CASC3
Name	CASC3 exon junction complex subunit
Location	17q21.1
Locus type	gene with protein product
Status	Approved
Aliases	MLN51, BTZ
Ensembl gene	ENSG00000108349
Ensembl biotype	protein_coding
OMIM	606504
Entrez	22794

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 27 protein_coding, 6 retained_intron, 2 nonsense_mediated_decay

ENST00000264645, ENST00000394114, ENST00000418132, ENST00000474190, ENST00000577605, ENST00000579238, ENST00000581849, ENST00000583649, ENST00000583902, ENST00000584997, ENST00000850591, ENST00000853392, ENST00000853393, ENST00000853394, ENST00000853395, ENST00000853396, ENST00000853397, ENST00000853398, ENST00000853399, ENST00000853400, ENST00000853401, ENST00000853402, ENST00000853403, ENST00000853404, ENST00000853405, ENST00000853406, ENST00000932298, ENST00000932299, ENST00000932300, ENST00000971362, ENST00000971363, ENST00000971364, ENST00000971365, ENST00000971366, ENST00000971367

RefSeq mRNA: 1 — MANE Select: NM_007359 NM_007359

CCDS: CCDS11362

Canonical transcript exons

ENST00000264645 — 14 exons

Exon	Start	End
ENSE00000863358	40166797	40166861
ENSE00000900527	40168203	40168417
ENSE00000900529	40167498	40167612
ENSE00001306828	40140537	40140779
ENSE00001322421	40169324	40169446
ENSE00002719013	40170447	40172171
ENSE00003475183	40162725	40162901
ENSE00003475949	40163481	40164166
ENSE00003525096	40162002	40162153
ENSE00003548280	40141570	40141607
ENSE00003552971	40141207	40141234
ENSE00003554891	40167850	40167948
ENSE00003569311	40161753	40161911
ENSE00003662487	40169598	40169662

Expression profiles

Bgee: expression breadth ubiquitous, 299 present calls, max score 99.02.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 46.4254 / max 1248.3055, expressed in 1826 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
160687	41.0131	1824
160685	2.7655	956
160686	1.3329	664
160689	0.8726	566
160691	0.3116	149
160690	0.0587	14
160665	0.0389	18
160688	0.0320	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	99.02	gold quality
middle frontal gyrus	UBERON:0002702	98.88	gold quality
mucosa of stomach	UBERON:0001199	97.85	gold quality
ganglionic eminence	UBERON:0004023	97.84	gold quality
paraflocculus	UBERON:0005351	97.60	gold quality
body of uterus	UBERON:0009853	97.47	gold quality
Brodmann (1909) area 10	UBERON:0013541	97.46	gold quality
tibial nerve	UBERON:0001323	97.41	gold quality
popliteal artery	UBERON:0002250	97.40	gold quality
tibial artery	UBERON:0007610	97.40	gold quality
ventricular zone	UBERON:0003053	97.34	gold quality
endocervix	UBERON:0000458	97.30	gold quality
lateral globus pallidus	UBERON:0002476	97.25	gold quality
right lung	UBERON:0002167	97.18	gold quality
left ovary	UBERON:0002119	97.04	gold quality
right ovary	UBERON:0002118	97.03	gold quality
calcaneal tendon	UBERON:0003701	97.02	gold quality
left uterine tube	UBERON:0001303	97.00	gold quality
aorta	UBERON:0000947	96.99	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.97	gold quality
descending thoracic aorta	UBERON:0002345	96.90	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.90	gold quality
lower esophagus	UBERON:0013473	96.89	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.89	gold quality
right coronary artery	UBERON:0001625	96.88	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.86	gold quality
right testis	UBERON:0004534	96.84	gold quality
left testis	UBERON:0004533	96.81	gold quality
spinal cord	UBERON:0002240	96.76	gold quality
ectocervix	UBERON:0012249	96.76	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.47
E-GEOD-100618	no	349.94

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

113 targeting CASC3, 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-4533	100.00	69.48	2758
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-3919	99.87	69.45	2489

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 34.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 7)

• data demonstrate that metastatic lymph node(MLN)51 protein associates with exon junction complex in the nucleus and remains stably associated with messenger RNA in the cytoplasm (PMID:15166247)
• crystal structure of a tetrameric exon junction core complex containing the DEAD-box adenosine triphosphatase eukaryotic initiation factor 4AIII bound to an ATP analog, MAGOH, Y14, a fragment of MLN51, and a polyuracil mRNA mimic (PMID:16931718)
• MLN51 is recruited into cytoplasmic aggregates known as stress granules (SGs) together with the SG-resident proteins. (PMID:17652158)
• MLN51 is a key factor in fibroblast-like synoviocyte hyperplasia of rheumatoid arthritis patients. (PMID:21327427)
• MLN51, alone or as part of the EJC, interacts directly with the pivotal eukaryotic translation initiation factor eIF3 (PMID:23530232)
• High CASC3 expression is associated with hepatocellular carcinoma. (PMID:27029030)
• CASC3 promotes transcriptome-wide activation of nonsense-mediated decay by the exon junction complex. (PMID:32621609)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	casc3	ENSDARG00000029911
mus_musculus	Casc3	ENSMUSG00000078676
rattus_norvegicus	Casc3	ENSRNOG00000009716
drosophila_melanogaster	btz	FBGN0045862
caenorhabditis_elegans	casc-3	WBGENE00012343

Protein

Protein identifiers

Protein CASC3 — O15234 (reviewed: O15234)

Alternative names: Cancer susceptibility candidate gene 3 protein, Metastatic lymph node gene 51 protein, Protein barentsz

All UniProt accessions (4): O15234, J3KSY7, J3QSC4, K7EQ38

UniProt curated annotations — full annotation on UniProt →

Function. Required for pre-mRNA splicing as component of the spliceosome. Core component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junctions on mRNAs. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. The EJC marks the position of the exon-exon junction in the mature mRNA for the gene expression machinery and the core components remain bound to spliced mRNAs throughout all stages of mRNA metabolism thereby influencing downstream processes including nuclear mRNA export, subcellular mRNA localization, translation efficiency and nonsense-mediated mRNA decay (NMD). Stimulates the ATPase and RNA-helicase activities of EIF4A3. Plays a role in the stress response by participating in cytoplasmic stress granules assembly and by favoring cell recovery following stress. Component of the dendritic ribonucleoprotein particles (RNPs) in hippocampal neurons. May play a role in mRNA transport. Binds spliced mRNA in sequence-independent manner, 20-24 nucleotides upstream of mRNA exon-exon junctions. Binds poly(G) and poly(U) RNA homomer.

Subunit / interactions. Identified in the spliceosome C complex. Component of the mRNA splicing-dependent exon junction complex (EJC), which contains at least CASC3, EIF4A3, MAGOH, NXF1 and RBM8A/Y14. Identified in a complex composed of the EJC core, UPF3B and UPF2. The EJC core can also interact with UPF3A (in vitro). Forms homooligomers. Interacts with STAU in an RNA-dependent manner. Interacts with DHX34; the interaction is RNA-independent.

Subcellular location. Cytoplasm. Perinuclear region. Nucleus. Nucleus speckle. Stress granule. Cytoplasmic ribonucleoprotein granule. Cell projection. Dendrite.

Tissue specificity. Widely expressed. Overexpressed in breast cancers and metastasis, as well as in gastric cancers.

Post-translational modifications. ADP-ribosylated by tankyrase TNKS and TNKS2. Poly-ADP-ribosylated protein is recognized by RNF146, followed by ubiquitination. Ubiquitinated by RNF146 when poly-ADP-ribosylated, leading to its degradation.

Domain organisation. The coiled coil domain may be involved in oligomerization.

Similarity. Belongs to the CASC3 family.

RefSeq proteins (1): NP_031385* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018545	Btz_dom	Domain
IPR028544	CASC3	Family

Pfam: PF09405

UniProt features (44 total): compositionally biased region 15, modified residue 8, region of interest 6, mutagenesis site 6, short sequence motif 3, helix 3, chain 1, turn 1, coiled-coil region 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
2J0S	X-RAY DIFFRACTION	2.21
2HYI	X-RAY DIFFRACTION	2.3
3EX7	X-RAY DIFFRACTION	2.3
2J0U	X-RAY DIFFRACTION	3
6ICZ	ELECTRON MICROSCOPY	3
2J0Q	X-RAY DIFFRACTION	3.2
2XB2	X-RAY DIFFRACTION	3.4
8I0W	ELECTRON MICROSCOPY	3.4
5XJC	ELECTRON MICROSCOPY	3.6
7W59	ELECTRON MICROSCOPY	3.6
7W5A	ELECTRON MICROSCOPY	3.6
5YZG	ELECTRON MICROSCOPY	4.1
7W5B	ELECTRON MICROSCOPY	4.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15234-F1	54.18	0.08

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 (8): 35, 117, 148, 265, 357, 363, 373, 477

Mutagenesis-validated functional residues (6):

Position	Phenotype
181	does not affect ejc formation.
184–185	does not affect ejc formation.
188	does not affect ejc formation.
218	abolishes interaction with eif4a3, ejc formation and localization in nucleus speckles.
220–221	abolishes interaction with eif4a3, ejc formation and localization in nucleus speckles.
240–241	abolishes interaction with eif4a3, ejc formation and localization in nucleus speckles.

Function

Pathways and Gene Ontology

Reactome pathways

17 pathways

ID	Pathway
R-HSA-159236	Transport of Mature mRNA derived from an Intron-Containing Transcript
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-72187	mRNA 3’-end processing
R-HSA-9010553	Regulation of expression of SLITs and ROBOs
R-HSA-975957	Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)
R-HSA-73856	RNA Polymerase II Transcription Termination
R-HSA-1266738	Developmental Biology
R-HSA-376176	Signaling by ROBO receptors
R-HSA-422475	Axon guidance
R-HSA-72172	mRNA Splicing
R-HSA-72202	Transport of Mature Transcript to Cytoplasm
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8953854	Metabolism of RNA
R-HSA-927802	Nonsense-Mediated Decay (NMD)
R-HSA-9675108	Nervous system development

MSigDB gene sets: 199 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, HSIAO_HOUSEKEEPING_GENES, YY1_Q6, GOBP_TRANSLATION, GOBP_NUCLEAR_TRANSPORT, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, WANG_LMO4_TARGETS_DN, GOBP_REGULATION_OF_CATABOLIC_PROCESS, BLALOCK_ALZHEIMERS_DISEASE_UP, REACTOME_MRNA_3_END_PROCESSING, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA

GO Biological Process (9): nuclear-transcribed mRNA catabolic process, nonsense-mediated decay (GO:0000184), mRNA splicing, via spliceosome (GO:0000398), mRNA export from nucleus (GO:0006406), regulation of translation (GO:0006417), intracellular mRNA localization (GO:0008298), regulation of nuclear-transcribed mRNA catabolic process, nonsense-mediated decay (GO:2000622), mRNA processing (GO:0006397), RNA splicing (GO:0008380), mRNA transport (GO:0051028)

GO Molecular Function (6): RNA binding (GO:0003723), mRNA binding (GO:0003729), enzyme binding (GO:0019899), ubiquitin protein ligase binding (GO:0031625), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (15): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), cytoplasmic stress granule (GO:0010494), nuclear speck (GO:0016607), dendrite (GO:0030425), nuclear membrane (GO:0031965), exon-exon junction complex (GO:0035145), perinuclear region of cytoplasm (GO:0048471), U2-type catalytic step 1 spliceosome (GO:0071006), spliceosomal complex (GO:0005681), cytoplasm (GO:0005737), cytoplasmic ribonucleoprotein granule (GO:0036464), cell projection (GO:0042995), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
Processing of Capped Intron-Containing Pre-mRNA	3
Metabolism of RNA	2
Transport of Mature Transcript to Cytoplasm	1
mRNA Splicing	1
Signaling by ROBO receptors	1
Nonsense-Mediated Decay (NMD)	1
RNA Polymerase II Transcription	1
Axon guidance	1
Nervous system development	1
Gene expression (Transcription)	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cytoplasm	3
RNA processing	2
protein binding	2
nuclear protein-containing complex	2
nuclear-transcribed mRNA catabolic process	1
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
RNA export from nucleus	1
gene expression	1
mRNA transport	1
translation	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
RNA localization	1
nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	1
regulation of mRNA catabolic process	1
mRNA metabolic process	1
RNA transport	1
nucleic acid binding	1
RNA binding	1
ubiquitin-like protein ligase binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasmic ribonucleoprotein granule	1
nuclear ribonucleoprotein granule	1
neuron projection	1
dendritic tree	1
nucleus	1
nuclear envelope	1
organelle membrane	1
U2-type spliceosomal complex	1
U2 snRNP	1
U6 snRNP	1
catalytic step 1 spliceosome	1
ribonucleoprotein complex	1
intracellular anatomical structure	1
ribonucleoprotein granule	1
protein-containing complex	1

Protein interactions and networks

STRING

1428 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CASC3	EIF4A3	P38919	999
CASC3	MAGOH	P50606	999
CASC3	MAGOHB	Q96A72	999
CASC3	RBM8A	Q9Y5S9	998
CASC3	UPF3A	Q9H1J1	851
CASC3	RNPS1	Q15287	843
CASC3	UPF2	Q9HAU5	820
CASC3	UPF1	Q92900	818
CASC3	UPF3B	Q9BZI7	798
CASC3	NCBP1	Q09161	733
CASC3	SMG9	Q9H0W8	655
CASC3	SMG1	Q96Q15	646
CASC3	SMG5	Q9UPR3	642
CASC3	SMG6	Q86US8	638
CASC3	SMG8	Q8ND04	637

IntAct

213 interactions, top by confidence:

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

BioGRID (198): CASC3 (Affinity Capture-RNA), CASC3 (Affinity Capture-MS), CASC3 (Affinity Capture-MS), CASC3 (Affinity Capture-MS), CASC3 (Affinity Capture-MS), CASC3 (Affinity Capture-MS), CASC3 (Affinity Capture-MS), CASC3 (Affinity Capture-MS), CASC3 (Affinity Capture-MS), CASC3 (Affinity Capture-Western), CASC3 (Reconstituted Complex), CASC3 (Two-hybrid), CASC3 (Two-hybrid), CASC3 (Two-hybrid), CASC3 (Two-hybrid)

ESM2 similar proteins: A0A8M2, A0JMU8, A1L1K8, A5D7H5, B9DFV2, E1BUG7, F4JP52, G1SW77, G3X9Z4, O08719, O15234, O94913, Q0V898, Q1LVV0, Q2T9I5, Q32NW2, Q3MHF8, Q498K9, Q566L7, Q5CZI8, Q5JVS0, Q5R4R4, Q5T8P6, Q5TYQ8, Q659C4, Q68FI1, Q6AXS5, Q6NVR8, Q6NZN0, Q6PKG0, Q8AVJ2, Q8CGC4, Q8K2F8, Q8K3W3, Q8K3X0, Q8NC51, Q8ND56, Q91W18, Q91W39, Q96D71

Diamond homologs: A0JMU8, A5D7H5, O15234, Q1ECZ4, Q5CZI8, Q8K3W3, Q8K3X0

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
RNF146	“down-regulates quantity by destabilization”	CASC3	ubiquitination
TNKS2	“down-regulates quantity by destabilization”	CASC3	ADP-ribosylation
TNKS	“down-regulates quantity by destabilization”	CASC3	ADP-ribosylation
CASC3	“form complex”	“Exon junction complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 134 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 3’-end processing	12	28.5×	1e-12
Transport of Mature Transcript to Cytoplasm	6	27.5×	3e-06
Transport of Mature mRNA derived from an Intron-Containing Transcript	14	25.7×	7e-14
RNA Polymerase II Transcription Termination	6	15.9×	8e-05
mRNA Splicing	10	13.2×	3e-07
Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)	11	12.9×	8e-08
SARS-CoV-1-host interactions	6	12.7×	3e-04
mRNA Splicing - Major Pathway	18	11.8×	1e-12

GO biological processes:

GO term	Partners	Fold	FDR
mRNA splice site recognition	6	40.5×	8e-07
negative regulation of mRNA splicing, via spliceosome	6	38.6×	8e-07
nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	9	35.4×	8e-10
regulation of alternative mRNA splicing, via spliceosome	12	24.6×	4e-11
mRNA export from nucleus	8	19.9×	8e-07
mRNA transport	6	13.3×	4e-04
positive regulation of translation	6	11.5×	8e-04
mRNA splicing, via spliceosome	13	10.0×	1e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	82
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2183 predictions. Top by Δscore:

Variant	Effect	Δscore
17:40140776:GTGT:G	donor_gain	1.0000
17:40140778:GT:G	donor_gain	1.0000
17:40140780:G:GG	donor_gain	1.0000
17:40141232:ATGGT:A	donor_loss	1.0000
17:40141235:GT:G	donor_loss	1.0000
17:40141236:T:A	donor_loss	1.0000
17:40141608:G:GG	donor_gain	1.0000
17:40161750:CAGG:C	acceptor_loss	1.0000
17:40161751:A:AG	acceptor_gain	1.0000
17:40161751:AG:A	acceptor_gain	1.0000
17:40161751:AGG:A	acceptor_gain	1.0000
17:40161751:AGGGT:A	acceptor_gain	1.0000
17:40161752:G:GA	acceptor_gain	1.0000
17:40161752:GG:G	acceptor_gain	1.0000
17:40161752:GGG:G	acceptor_gain	1.0000
17:40161752:GGGT:G	acceptor_gain	1.0000
17:40161752:GGGTG:G	acceptor_gain	1.0000
17:40161907:GACAG:G	donor_gain	1.0000
17:40161912:G:A	donor_loss	1.0000
17:40161912:G:GG	donor_gain	1.0000
17:40161913:T:A	donor_loss	1.0000
17:40161996:CTCTA:C	acceptor_loss	1.0000
17:40161999:TAG:T	acceptor_loss	1.0000
17:40162000:A:AG	acceptor_gain	1.0000
17:40162000:A:AT	acceptor_loss	1.0000
17:40162000:AG:A	acceptor_gain	1.0000
17:40162001:G:GA	acceptor_gain	1.0000
17:40162001:GG:G	acceptor_gain	1.0000
17:40162001:GGA:G	acceptor_gain	1.0000
17:40162001:GGAGA:G	acceptor_gain	1.0000

AlphaMissense

4529 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:40162086:T:C	Y181H	1.000
17:40162086:T:G	Y181D	1.000
17:40162090:T:A	I182K	1.000
17:40162092:C:A	P183T	1.000
17:40162092:C:T	P183S	1.000
17:40162093:C:A	P183H	1.000
17:40162101:G:A	G186R	1.000
17:40162101:G:C	G186R	1.000
17:40162101:G:T	G186W	1.000
17:40162102:G:A	G186E	1.000
17:40162107:T:A	F188I	1.000
17:40162107:T:C	F188L	1.000
17:40162108:T:C	F188S	1.000
17:40162108:T:G	F188C	1.000
17:40162109:C:A	F188L	1.000
17:40162109:C:G	F188L	1.000
17:40162110:T:A	F189I	1.000
17:40162110:T:C	F189L	1.000
17:40162111:T:C	F189S	1.000
17:40162111:T:G	F189C	1.000
17:40162112:T:A	F189L	1.000
17:40162112:T:G	F189L	1.000
17:40162116:C:G	H191D	1.000
17:40162118:T:A	H191Q	1.000
17:40162118:T:G	H191Q	1.000
17:40162119:G:C	D192H	1.000
17:40162120:A:C	D192A	1.000
17:40162120:A:G	D192G	1.000
17:40162120:A:T	D192V	1.000
17:40162744:A:G	K210E	1.000

dbSNP variants (sampled 300 via entrez): RS1000068613 (17:40160514 A>C,G), RS1000085802 (17:40155908 T>A,C), RS1000230553 (17:40168956 T>C), RS1000262927 (17:40150312 C>G), RS1000286190 (17:40161184 T>C), RS1000301616 (17:40144322 C>T), RS1000371923 (17:40155247 G>A), RS1000438550 (17:40144503 C>T), RS1000596000 (17:40156885 G>A,T), RS1000663854 (17:40155480 C>G,T), RS1000708521 (17:40156586 G>A), RS1000719070 (17:40139137 T>C), RS1000847023 (17:40139309 A>G), RS1000859670 (17:40168125 A>G), RS1000917846 (17:40140092 G>A)

Disease associations

OMIM: gene MIM:606504 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST008916_85	Asthma	2.000000e-12
GCST009523_56	Household income	6.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009695	household income

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects expression	2
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, decreases methylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	decreases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
coumarin	affects phosphorylation	1
epigallocatechin gallate	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	increases expression	1
pyrachlostrobin	increases expression	1
picoxystrobin	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Fulvestrant	decreases methylation, affects cotreatment	1
Vorinostat	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Benzene	increases expression	1
Caffeine	decreases phosphorylation	1
Methyl Methanesulfonate	increases expression	1
Mitoxantrone	affects response to substance	1
Ozone	affects expression, increases abundance	1
Ribonucleotides	affects binding	1
Vanadates	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Metribolone	increases expression	1
Cyclosporine	increases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SG85	HAP1 CASC3 (-) 1	Cancer cell line	Male
CVCL_SG86	HAP1 CASC3 (-) 2	Cancer cell line	Male
CVCL_SG87	HAP1 CASC3 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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