DIS3

Summary

DIS3 (DIS3 exosome endoribonuclease and 3’-5’ exoribonuclease, HGNC:20604) is a protein-coding gene on chromosome 13q21.33, encoding Exosome complex exonuclease RRP44 (Q9Y2L1). Putative catalytic component of the RNA exosome complex which has 3’->5’ exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events. It is a selective cancer dependency (DepMap: 85.4% of cell lines).

Enables 3’-5’-RNA exonuclease activity; endonuclease activity; and guanyl-nucleotide exchange factor activity. Involved in CUT catabolic process; RNA processing; and rRNA catabolic process. Located in cytosol and nucleoplasm. Part of nuclear exosome (RNase complex). Implicated in primary ovarian insufficiency.

Source: NCBI Gene 22894 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 159 total — 1 pathogenic, 2 likely-pathogenic
• Regional missense constraint (gnomAD): 1 of 3 regions constrained (≈2% of expected missense variation)
• GTEx eGene: eQTL in 17 tissues, sQTL in 0 (q < 0.05)
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types (inferred from mutation patterns)
• Cancer dependency (DepMap): dependent in 85.4% of screened cell lines
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.08 (unconstrained)
• MANE Select transcript: NM_014953
• Interaction hub: 2,642 STRING partners (top 4% of genes corpus-wide)
• Notable: 159 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20604
Approved symbol	DIS3
Name	DIS3 exosome endoribonuclease and 3’-5’ exoribonuclease
Location	13q21.33
Locus type	gene with protein product
Status	Approved
Aliases	dis3p, RRP44, EXOSC11
Ensembl gene	ENSG00000083520
Ensembl biotype	protein_coding
OMIM	607533
Entrez	22894

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 6 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000377767

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 4: 1, TSL 5: 1

ENST00000377767, ENST00000377780, ENST00000475871, ENST00000490646, ENST00000545453, ENST00000929767, ENST00000958787, ENST00001118951, ENST00001132058

RefSeq mRNA: 4 — MANE Select: NM_014953 NM_001128226, NM_001322348, NM_001322349, NM_014953

CCDS: CCDS45057, CCDS81772, CCDS9447

Canonical transcript exons

ENST00000377767 — 21 exons

Exon	Start	End
ENSE00000923650	72771081	72771145
ENSE00000923651	72771795	72771896
ENSE00000923654	72773684	72773821
ENSE00000923655	72773946	72774059
ENSE00000923659	72777420	72777493
ENSE00001121366	72770904	72770988
ENSE00001250231	72775211	72775375
ENSE00001355717	72752169	72759878
ENSE00001364184	72775925	72776092
ENSE00001927466	72781605	72781900
ENSE00003485310	72761363	72761521
ENSE00003521334	72772159	72772275
ENSE00003529866	72768785	72768912
ENSE00003551898	72760529	72760651
ENSE00003559660	72772693	72772839
ENSE00003583930	72778187	72778380
ENSE00003630761	72765972	72766058
ENSE00003631749	72763451	72763607
ENSE00003632437	72761923	72762137
ENSE00003671608	72761646	72761814
ENSE00003680822	72780846	72781003

Expression profiles

Bgee: expression breadth ubiquitous, 274 present calls, max score 94.14.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 34.3833 / max 321.5489, expressed in 1823 samples.

Highest expression (Bgee): sperm, calcaneal tendon, male germ cell, ventricular zone, male germ line stem cell (sensu Vertebrata) in testis.

Genetic regulation across tissues (GTEx eQTL / sQTL)

DIS3 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 17 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

17 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Thyroid	eqtl	1.0e-06	+0.15	13:72808153:T:TTTG
Brain Nucleus accumbens basal ganglia	eqtl	3.4e-06	+2.60	13:71898646:T:C
Brain Putamen basal ganglia	eqtl	2.4e-03	+2.32	13:71898646:T:C
Spleen	eqtl	4.9e-03	-0.86	13:71889387:C:T
Testis	eqtl	5.4e-03	+0.11	13:72894693:G:A
Brain Hypothalamus	eqtl	7.8e-03	+2.05	13:71898646:T:C
Brain Amygdala	eqtl	1.5e-02	+1.13	13:71865071:T:C
Skin Not Sun Exposed Suprapubic	eqtl	1.8e-02	+0.26	13:72949795:TA:T
Cells Cultured fibroblasts	eqtl	1.9e-02	+0.17	13:72996055:A:G
Brain Cortex	eqtl	2.3e-02	+1.01	13:71935999:A:G
Brain Frontal Cortex BA9	eqtl	2.7e-02	-0.53	13:72527294:C:A
Artery Aorta	eqtl	3.3e-02	+0.44	13:71865071:T:C
Artery Tibial	eqtl	3.7e-02	+0.16	13:72949795:TA:T
Esophagus Muscularis	eqtl	4.0e-02	-0.40	13:73523942:C:A
Heart Atrial Appendage	eqtl	4.0e-02	+0.44	13:71865071:T:C
Prostate	eqtl	4.2e-02	-0.78	13:72966126:A:G
Brain Substantia nigra	eqtl	4.4e-02	+1.26	13:71959614:A:G

FANTOM5 promoters

6 alternative TSS:

Promoter ID	TPM avg	Samples expressed
137582	30.0902	1821
137583	4.1108	1483
137581	0.1067	21
137584	0.0470	10
137585	0.0235	5
207058	0.0051	1

Top tissues by expression

showing 100 of 292 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	94.14	gold quality
calcaneal tendon	UBERON:0003701	93.87	gold quality
male germ cell	CL:0000015	91.29	gold quality
ventricular zone	UBERON:0003053	87.84	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.65	gold quality
cortical plate	UBERON:0005343	87.52	gold quality
stromal cell of endometrium	CL:0002255	86.66	gold quality
ganglionic eminence	UBERON:0004023	86.37	gold quality
adrenal tissue	UBERON:0018303	86.03	gold quality
rectum	UBERON:0001052	85.18	gold quality
islet of Langerhans	UBERON:0000006	84.99	gold quality
popliteal artery	UBERON:0002250	84.90	gold quality
tibial artery	UBERON:0007610	84.90	gold quality
right testis	UBERON:0004534	84.63	gold quality
cartilage tissue	UBERON:0002418	84.61	gold quality
gall bladder	UBERON:0002110	84.56	gold quality
testis	UBERON:0000473	84.45	gold quality
descending thoracic aorta	UBERON:0002345	84.43	gold quality
esophagus mucosa	UBERON:0002469	84.35	gold quality
lymph node	UBERON:0000029	84.28	gold quality
aorta	UBERON:0000947	84.27	gold quality
monocyte	CL:0000576	84.22	gold quality
left testis	UBERON:0004533	84.17	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.06	gold quality
left ovary	UBERON:0002119	84.02	gold quality
leukocyte	CL:0000738	83.92	gold quality
mononuclear cell	CL:0000842	83.90	gold quality
ectocervix	UBERON:0012249	83.89	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	83.62	gold quality
thoracic aorta	UBERON:0001515	83.61	gold quality
gastrocnemius	UBERON:0001388	83.52	gold quality
right ovary	UBERON:0002118	83.48	gold quality
ascending aorta	UBERON:0001496	83.47	gold quality
tendon	UBERON:0000043	83.45	gold quality
right coronary artery	UBERON:0001625	83.45	gold quality
right lung	UBERON:0002167	83.42	gold quality
skin of hip	UBERON:0001554	83.38	gold quality
tibial nerve	UBERON:0001323	83.30	gold quality
muscle of leg	UBERON:0001383	83.24	gold quality
ovary	UBERON:0000992	83.21	gold quality
adipose tissue	UBERON:0001013	83.21	gold quality
connective tissue	UBERON:0002384	83.17	gold quality
esophagus	UBERON:0001043	83.14	gold quality
adipose tissue of abdominal region	UBERON:0007808	83.14	gold quality
left uterine tube	UBERON:0001303	83.13	gold quality
mucosa of stomach	UBERON:0001199	83.11	gold quality
omental fat pad	UBERON:0010414	83.08	gold quality
oral cavity	UBERON:0000167	83.07	gold quality
peritoneum	UBERON:0002358	83.06	gold quality
left coronary artery	UBERON:0001626	82.98	gold quality
vagina	UBERON:0000996	82.90	gold quality
lower lobe of lung	UBERON:0008949	82.77	gold quality
tonsil	UBERON:0002372	82.63	gold quality
endometrium	UBERON:0001295	82.52	gold quality
subcutaneous adipose tissue	UBERON:0002190	82.49	gold quality
pancreas	UBERON:0001264	82.39	gold quality
body of uterus	UBERON:0009853	82.38	gold quality
vermiform appendix	UBERON:0001154	82.28	gold quality
coronary artery	UBERON:0001621	82.24	gold quality
endocervix	UBERON:0000458	82.15	gold quality
colonic epithelium	UBERON:0000397	82.07	gold quality
right lobe of thyroid gland	UBERON:0001119	82.03	gold quality
upper lobe of lung	UBERON:0008948	82.03	gold quality
upper lobe of left lung	UBERON:0008952	82.03	gold quality
hindlimb stylopod muscle	UBERON:0004252	81.95	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	81.93	gold quality
urinary bladder	UBERON:0001255	81.92	gold quality
minor salivary gland	UBERON:0001830	81.78	gold quality
left lobe of thyroid gland	UBERON:0001120	81.75	gold quality
skin of leg	UBERON:0001511	81.71	gold quality
lower esophagus	UBERON:0013473	81.63	gold quality
lower esophagus muscularis layer	UBERON:0035833	81.63	gold quality
thyroid gland	UBERON:0002046	81.58	gold quality
lower esophagus mucosa	UBERON:0035834	81.53	gold quality
skin of abdomen	UBERON:0001416	81.52	gold quality
right hemisphere of cerebellum	UBERON:0014890	81.42	gold quality
body of stomach	UBERON:0001161	81.37	gold quality
smooth muscle tissue	UBERON:0001135	81.23	gold quality
bone marrow	UBERON:0002371	81.23	gold quality
female reproductive system	UBERON:0000474	81.20	gold quality
corpus epididymis	UBERON:0004359	81.20	gold quality
body of pancreas	UBERON:0001150	81.19	gold quality
muscle layer of sigmoid colon	UBERON:0035805	81.18	gold quality
zone of skin	UBERON:0000014	81.14	gold quality
adrenal gland	UBERON:0002369	81.07	gold quality
mouth mucosa	UBERON:0003729	81.07	gold quality
right adrenal gland cortex	UBERON:0035827	81.05	gold quality
cerebellar hemisphere	UBERON:0002245	81.04	gold quality
cerebellar cortex	UBERON:0002129	80.98	gold quality
small intestine Peyer’s patch	UBERON:0003454	80.96	gold quality
transverse colon	UBERON:0001157	80.91	gold quality
left adrenal gland	UBERON:0001234	80.87	gold quality
right adrenal gland	UBERON:0001233	80.85	gold quality
stomach	UBERON:0000945	80.77	gold quality
sigmoid colon	UBERON:0001159	80.77	gold quality
intestine	UBERON:0000160	80.73	gold quality
right lobe of liver	UBERON:0001114	80.72	gold quality
heart left ventricle	UBERON:0002084	80.72	gold quality
mucosa of paranasal sinus	UBERON:0005030	80.72	gold quality
large intestine	UBERON:0000059	80.66	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.38
E-MTAB-10137	no	466.61

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Testis	tissue	19.9	medium
Bone marrow	tissue	19.3	medium
Choroid plexus	tissue	17.3
Lymph node	tissue	16.4	medium
Tonsil	tissue	16.2	medium
Liver	tissue	15.6	medium
Breast	tissue	14.8	medium
Postcentral gyrus	tissue	14.8
Thyroid gland	tissue	14.0	medium
Nucleus accumbens	tissue	13.5
Urinary bladder	tissue	13.2	high
Thymus	tissue	13.1
Adipose tissue	tissue	13.0	medium
Corpus callosum	tissue	12.9
Locus coeruleus	tissue	12.3
Kidney	tissue	11.9	medium
Appendix	tissue	11.7	medium
Spleen	tissue	11.5	medium
Prostate	tissue	11.5	medium
Placenta	tissue	11.3	high
Hippocampus	tissue	11.3	medium
Retina	tissue	11.2
Parathyroid gland	tissue	11.2	low
Esophagus	tissue	11.0	high
Heart muscle	tissue	10.9	low
Epididymis	tissue	10.9	medium
Lung	tissue	10.8	low
Ovary	tissue	10.7	low
Cervix	tissue	10.6	high
Midbrain	tissue	10.6
Skin 1	tissue	10.5	medium
Superior colliculi	tissue	10.5
Endometrium 1	tissue	10.4	low
Medulla oblongata	tissue	10.3
Vagina	tissue	10.2	medium
Rectum	tissue	10.2	high
Smooth muscle	tissue	10.2	medium
Thalamus	tissue	10.2
Putamen	tissue	10.1
Cerebellum	tissue	10.0	medium
Substantia nigra	tissue	10.0
Seminal vesicle	tissue	9.9	medium
Gallbladder	tissue	9.8	high
Spinal cord	tissue	9.8
Hippocampal formation	tissue	9.8
Pons	tissue	9.7
Tongue	tissue	9.7
Colon	tissue	9.4	medium
Stomach 1	tissue	9.3	high
Small intestine	tissue	9.3	high
Adrenal gland	tissue	9.3	medium
Hypothalamus	tissue	9.2
Periaqueductal gray	tissue	9.2
Ventral forebrain	tissue	9.1
Septum	tissue	9.0
Cerebral cortex	tissue	8.9	medium
Somatosensory cortex	tissue	8.9
Salivary gland	tissue	8.8	medium
Occipital cortex	tissue	8.8
Motor cortex	tissue	8.5

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Cerebellar cortex (21.3), Vermis (19.8), Flocculonodular lobe (18.8), Corpus callosum, splenium (white matter) (16.2), Corpus callosum, genu (white matter) (16.0).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting DIS3 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 156 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548N	99.98	71.94	4170
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-3065-5P	99.97	71.56	3281
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-605-3P	99.88	69.22	1833

Functional genomics

gnomAD constraint: pLI 3.62e-29, LOEUF 1.08, missense Z 0.692 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000377767 splits into 3 regions with different missense tolerance; 1 is missense-constrained (≈2% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
13:72,759,798–72,777,487	861 / 915.5	0.94	no
13:72,777,488–72,778,230	6 / 19.4	0.31	yes (p 2.3e-03)
13:72,778,231–72,781,832	254 / 232.2	1.09	no
DepMap (CRISPR cell-line fitness): dependent in 85.4% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): PSN1 (-1.967), PA-TU-8988T (-1.435), S-117 (-1.344), ACC-MESO-1 (-1.328), MHH-ES-1 (-1.301), OPM-2 (-1.283), SCC-9 (-1.272), RCC10RGB (-1.269), CH-157MN (-1.22), TYK-nu (-1.217), TF-1 (-1.171), KMS-26 (-1.153), SNU-626 (-1.15), SNU-886 (-1.142), HD-MY-Z (-1.136).

Literature-anchored findings (GeneRIF, showing 27)

• Protein-protein interactions between human exosome components support the assembly of RNase PH-type subunits into a six-membered PNPase-like ring. There appears to be no interaction between human dis3 and other exosome subunits, however. (PMID:12419256)
• Data show that hDIS3 and hDIS3L are active exonucleases, but only hDIS3 has retained endonucleolytic activity, and suggest that three different ribonucleases can serve as catalytic subunits for the exosome in human cells. (PMID:20531386)
• Multiple myeloma-associated hDIS3 mutations interfere with hDIS3 exonucleolytic activity. (PMID:24150935)
• Overexpression of DIS3 and LRCH1 associated with adenoma to carcinoma progression is linked to the colorectal cancer specific gain of 13q. (PMID:24478024)
• seven novel somatic DIS3 single nucleotide variants (SNVs) and defined three hot spot mutations within the RNB domain. (PMID:25521164)
• The study establishes that the ribonuclease DIS3, targeting LIN28B, sustains the maturation of let-7 miRNAs and suggests the increased translation of critical oncogenes as one of the biological outcomes of DIS3 inactivation. (PMID:25925570)
• structure and function of DIS3 (PMID:26193331)
• Results from a study on gene variability markers in early-stage human embryos shows that DIS3 is a putative variability marker for the 3-day, 8-cell embryo stage, identified by mixture models as well as standard ANOVA. (PMID:26288249)
• Data indicate the pathological relevance of exosome component 11 protein (DIS3) mutations in plasma cell dyscrasias and suggest that DIS3 may represent a potential tumor suppressor gene in such disorders. (PMID:26305418)
• Authors have identified a putative functional indel variant at chr13q22.1 that associates with decreased DIS3 expression in carriers of pancreatic cancer risk-increasing alleles, and could therefore affect nuclear RNA processing and/or decay. (PMID:28172817)
• DIS3 isoforms vary in their endoribonuclease activity and are differentially expressed within haematological cancers. (PMID:29802118)
• The 3.8 A resolution cryo-EM structure of the core complex bound to a single-stranded RNA reveals that the RNA channel path is formed by two distinct features of the hDIS3 exoribonuclease: an open conformation and a domain organization more similar to bacterial RNase II than to yeast Rrp44. (PMID:30047866)
• Here, we investigated the interplay of exosome-associated 3’-5’ exonucleases DIS3 and RRP6 in rRNA processing and by-product elimination in human cells (PMID:30266864)
• Authors engineered cells in which the 3’–>5’ exoribonucleases of the exosome complex, DIS3 and EXOSC10, can be rapidly eliminated to assess their immediate roles in nuclear RNA biology. The loss of DIS3 has the greatest impact, causing the substantial accumulation of thousands of transcripts within 60 min. (PMID:30840897)
• The germline variants in DIS3. (PMID:30967618)
• We further demonstrate that polyQ-expanded huntingtin delays Dis3 degradation during heat stress and thus hinders chaperone mRNA stabilization. Our findings not only reveal a post-transcriptional negative feedback loop for maintaining proteostasis, but also uncover a mechanism that contributes to the impaired heat stress response in Huntington’s disease (PMID:31428776)
• BRAF and DIS3 Mutations Associate with Adverse Outcome in a Long-term Follow-up of Patients with Multiple Myeloma. (PMID:31988198)
• DIS3 mutations in multiple myeloma impact the transcriptional signature and clinical outcome. (PMID:33951891)
• RNA-regulatory exosome complex confers cellular survival to promote erythropoiesis. (PMID:34059908)
• MicroRNA-125a/b-5p promotes malignant behavior in multiple myeloma cells and xenograft tumor growth by targeting DIS3. (PMID:35394705)
• MPP6 stimulates both RRP6 and DIS3 to degrade a specified subset of MTR4-sensitive substrates in the human nucleus. (PMID:35902094)
• Loss of ribonuclease DIS3 hampers genome integrity in myeloma by disrupting DNA:RNA hybrid metabolism. (PMID:36215697)
• DIS3: The Enigmatic Gene in Multiple Myeloma. (PMID:36835493)
• DIS3 Variants are Associated With Primary Ovarian Insufficiency: Importance of Transcription/Translation in Oogenesis. (PMID:36869713)
• DIS3 depletion in multiple myeloma causes extensive perturbation in cell cycle progression and centrosome amplification. (PMID:37439377)
• Dis3p is identical to Rrp44p, which comprises the exosome involved in ribosomal RNA processing. Similar to S. cerevisiae Dis3p, human Dis3p enhanced RCC1-stimulated nucleotide release from Ran, in a dose-dependent manner, and bound to GTP- or GDP-Ran. (PMID:9562621)
• S. cerevisiae Dis3p is identical to Rrp44p, which comprises the exosome involved in ribosomal RNA processing, S. cerevisiae Dis3p was found to be localized in the nucleolus. (PMID:9562621)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	dis3	ENSDARG00000060559
mus_musculus	Dis3	ENSMUSG00000033166
rattus_norvegicus	Dis3	ENSRNOG00000009125
drosophila_melanogaster	Dis3	FBGN0039183
caenorhabditis_elegans		WBGENE00001001

Paralogs (2): DIS3L2 (ENSG00000144535), DIS3L (ENSG00000166938)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1919912) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 13 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased body size	1
abnormal retina morphology	1
increased startle reflex	1
abnormal vitreous body morphology	1
chromosome breakage	1
abnormal class switch recombination	1
abnormal B cell morphology	1
impaired glucose tolerance	1
ascites	1
abnormal retina blood vessel morphology	1
increased plasmacytoma incidence	1
prenatal lethality, complete penetrance	1
preweaning lethality, complete penetrance	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5R5N8	99.0%	Diamond
Xenopus tropicalis	Q0P4R5	92.0%	Diamond
Xenopus laevis	Q6GN11	92.0%	Diamond
Bos taurus	A0JN80	91.8%	Diamond
Vibrio parahaemolyticus RIMD 2210633	P40611	83.5%	Diamond
Buchnera aphidicola str. Sg (Schizaphis graminum)	Q8K9Q5	77.8%	Diamond
Haemophilus influenzae Rd KW20	P44907	67.1%	Diamond
Schizosaccharomyces pombe 972h-	P37202	51.8%	Diamond
Saccharomyces cerevisiae S288C	Q08162	51.7%	Diamond
Acidithiobacillus ferrooxidans	P54084	51.2%	Diamond
Mycoplasmopsis pulmonis UAB CTIP	Q98QL0	49.7%	Diamond
Arabidopsis thaliana	Q9SHL7	48.0%	Diamond
Lactococcus lactis subsp. lactis Il1403	Q02146	46.1%	Diamond
Aquifex aeolicus VF5	O67834	39.8%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
PIBF1	protein-coding	10464
MZT1	protein-coding	440145
KLF5	protein-coding	688
BORA	protein-coding	79866

Protein

Protein identifiers

Exosome complex exonuclease RRP44 — Q9Y2L1 (reviewed: Q9Y2L1)

Alternative names: Protein DIS3 homolog, Ribosomal RNA-processing protein 44

All UniProt accessions (3): Q9Y2L1, F2Z2C0, G3V1J5

UniProt curated annotations — full annotation on UniProt →

Function. Putative catalytic component of the RNA exosome complex which has 3’->5’ exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events. In the nucleus, the RNA exosome complex is involved in proper maturation of stable RNA species such as rRNA, snRNA and snoRNA, in the elimination of RNA processing by-products and non-coding ‘pervasive’ transcripts, such as antisense RNA species and promoter-upstream transcripts (PROMPTs), and of mRNAs with processing defects, thereby limiting or excluding their export to the cytoplasm. The RNA exosome may be involved in Ig class switch recombination (CSR) and/or Ig variable region somatic hypermutation (SHM) by targeting AICDA deamination activity to transcribed dsDNA substrates. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover and specifically degrades inherently unstable mRNAs containing AU-rich elements (AREs) within their 3’ untranslated regions, and in RNA surveillance pathways, preventing translation of aberrant mRNAs. It seems to be involved in degradation of histone mRNA. DIS3 has both 3’-5’ exonuclease and endonuclease activities.

Subunit / interactions. Component of the RNA exosome complex; within the complex interacts with EXOSC4, EXOSC7 and EXOSC9 of the exosome core complex (Exo-9). The catalytically inactive RNA exosome core complex (Exo-9) associates with the catalytic subunit EXOSC10/RRP6. Exo-9 may associate with DIS3 to form the nucleolar exosome complex, or DIS3L to form the cytoplasmic exosome complex. Exo-9 is formed by a hexameric base ring consisting of the heterodimers EXOSC4-EXOSC9, EXOSC5-EXOSC8 and EXOSC6-EXOSC7, and a cap ring consisting of EXOSC1, EXOSC2 and EXOSC3; DIS3 associates with the base ring of Exo-9. The RNA exosome complex associates with cofactors C1D/RRP47, MPHOSPH6/MPP6 and MTREX/MTR4. Interacts with DHX34; the interaction is RNA-independent.

Subcellular location. Cytoplasm. Nucleus. Nucleolus. Nucleoplasm.

Tissue specificity. Widely expressed.

Miscellaneous. The association of DIS3 with the RNA exosome complex appears to be weak explaining its absence in some complex purifications.

Similarity. Belongs to the RNR ribonuclease family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y2L1-1	1	yes
Q9Y2L1-2	2

RefSeq proteins (4): NP_001121698, NP_001309277, NP_001309278, NP_055768* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001900	RNase_II/R	Domain
IPR002716	PIN_dom	Domain
IPR012340	NA-bd_OB-fold	Homologous_superfamily
IPR022966	RNase_II/R_CS	Conserved_site
IPR029060	PIN-like_dom_sf	Homologous_superfamily
IPR033770	RRP44_S1	Domain
IPR033771	Rrp44_CSD1	Domain
IPR041505	Dis3_CSD2	Domain
IPR050180	RNR_Ribonuclease	Family

Pfam: PF00773, PF13638, PF17215, PF17216, PF17849

UniProt features (88 total): strand 36, helix 28, turn 8, domain 4, modified residue 3, sequence variant 2, mutagenesis site 2, chain 1, splice variant 1, sequence conflict 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

3 structures by resolution:

PDB	Title	Method	Resolution (Å)
6D6Q	Human nuclear exosome-MTR4 RNA complex - overall reconstruction	ELECTRON MICROSCOPY	3.45
6D6R	Human nuclear exosome-MTR4 RNA complex - composite map after focused reconstruction	ELECTRON MICROSCOPY	3.45
6H25	Human nuclear RNA exosome EXO-10-MPP6 complex	ELECTRON MICROSCOPY	3.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y2L1-F1	86.12	0.52

Human Protein Atlas

Protein class: Predicted intracellular proteins, Plasma proteins, Cancer-related genes, Mutated cancer genes, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; cytosol

Antibody reliability (HPA): IH approved · IF supported

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 (3)

Type	Positions
N-acetylmethionine	1
N6-acetyllysine	18
Phosphoserine	215

Mutagenesis-validated functional residues (2)

Position	Phenotype
146	loss of endonuclease activity; when associated with n-487.
487	loss of exonuclease activity. loss of endonuclease activity; when associated with n-146.

Function

Pathways and Gene Ontology

Reactome pathways

7 curated (TAS) of 17; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

17 pathways:

ID	Pathway	Evidence
R-HSA-380994	ATF4 activates genes in response to endoplasmic reticulum stress	curated
R-HSA-450385	Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA	curated
R-HSA-450604	KSRP (KHSRP) binds and destabilizes mRNA	curated
R-HSA-6791226	Major pathway of rRNA processing in the nucleolus and cytosol	curated
R-HSA-9930044	Nuclear RNA decay	curated
R-HSA-450513	Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA	curated
R-HSA-429958	mRNA decay by 3’ to 5’ exoribonuclease	curated
R-HSA-8953897	Cellular responses to stimuli	—
R-HSA-2262752	Cellular responses to stress	—
R-HSA-429914	Deadenylation-dependent mRNA decay	—
R-HSA-8953854	Metabolism of RNA	—
R-HSA-381042	PERK regulates gene expression	—
R-HSA-450531	Regulation of mRNA stability by proteins that bind AU-rich elements	—
R-HSA-9938024	Somatic hypermutation of immunoglobulin genes	electronic
R-HSA-381119	Unfolded Protein Response (UPR)	—
R-HSA-72312	rRNA processing	—
R-HSA-8868773	rRNA processing in the nucleus and cytosol	—

MSigDB gene sets: 176 (showing top): chr13q21, GOBP_RIBOSOME_BIOGENESIS, GOMF_ENDONUCLEASE_ACTIVITY, REACTOME_UNFOLDED_PROTEIN_RESPONSE_UPR, GOMF_RNA_NUCLEASE_ACTIVITY, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOMF_NUCLEASE_ACTIVITY, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOBP_RNA_SURVEILLANCE, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CATABOLIC_PROCESS, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, SCHLOSSER_SERUM_RESPONSE_DN, GOBP_NUCLEAR_TRANSCRIBED_MRNA_CATABOLIC_PROCESS_DEADENYLATION_DEPENDENT_DECAY

GO Biological Process (9): nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay (GO:0000288), rRNA processing (GO:0006364), RNA processing (GO:0006396), RNA catabolic process (GO:0006401), rRNA catabolic process (GO:0016075), nuclear mRNA surveillance of mRNA 3’-end processing (GO:0071031), CUT catabolic process (GO:0071034), nuclear-transcribed mRNA catabolic process (GO:0000956), gene expression (GO:0010467)

GO Molecular Function (9): 3’-5’-RNA exonuclease activity (GO:0000175), RNA binding (GO:0003723), endonuclease activity (GO:0004519), guanyl-nucleotide exchange factor activity (GO:0005085), nuclease activity (GO:0004518), exonuclease activity (GO:0004527), RNA nuclease activity (GO:0004540), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (9): nuclear exosome (RNase complex) (GO:0000176), cytoplasmic exosome (RNase complex) (GO:0000177), exosome (RNase complex) (GO:0000178), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytosol (GO:0005829), membrane (GO:0016020), cytoplasm (GO:0005737)

Reactome top-level categories

10 top-level categories:

Category	Pathways
Metabolism of RNA	4
Regulation of mRNA stability by proteins that bind AU-rich elements	3
PERK regulates gene expression	1
Deadenylation-dependent mRNA decay	1
rRNA processing in the nucleus and cytosol	1
Affinity selection of immunoglobulins	1
Cellular responses to stimuli	1
Unfolded Protein Response (UPR)	1
Cellular responses to stress	1
rRNA processing	1

GO top-level categories

37 GO namespaces:

Category	Terms
cellular anatomical structure	4
nuclease activity	3
nuclear lumen	3
rRNA metabolic process	2
RNA catabolic process	2
exosome (RNase complex)	2
cytoplasm	2
intracellular anatomical structure	2
nuclear-transcribed mRNA catabolic process	1
mRNA destabilization	1
RNA processing	1
ribosome biogenesis	1
gene expression	1
RNA biosynthetic process	1
primary metabolic process	1
RNA metabolic process	1
nucleic acid catabolic process	1
nuclear mRNA surveillance	1
nuclear polyadenylation-dependent mRNA catabolic process	1
mRNA catabolic process	1
macromolecule biosynthetic process	1
3’-5’ exonuclease activity	1
RNA exonuclease activity, producing 5’-phosphomonoesters	1
nucleic acid binding	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1
catalytic activity, acting on a nucleic acid	1
hydrolase activity, acting on ester bonds	1
catalytic activity, acting on RNA	1
binding	1
catalytic activity	1
nucleus	1
nuclear protein-containing complex	1
exoribonuclease complex	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 12 of 27 annotations. The rest are phylogenetic / computational / electronic (IEA).

12 experimentally-supported GO terms:

GO term	NS	Evidence
CUT catabolic process	BP	mutant phenotype
RNA catabolic process	BP	direct assay
RNA processing	BP	direct assay
rRNA catabolic process	BP	mutant phenotype
cytosol	CC	direct assay
membrane	CC	high-throughput assay
nuclear exosome (RNase complex)	CC	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
3’-5’-RNA exonuclease activity	MF	mutant phenotype
endonuclease activity	MF	mutant phenotype
guanyl-nucleotide exchange factor activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 2,642 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DIS3	EXOSC10	Q01780	901
DIS3	EXOSC1	Q9Y3B2	841
DIS3	MTREX	P42285	821
DIS3	EXOSC3	Q9NQT5	819
DIS3	EXOSC4	Q9NPD3	809
DIS3	EXOSC9	Q06265	808
DIS3	EXOSC8	Q96B26	807
DIS3	EXOSC7	Q15024	806
DIS3	EXOSC6	Q5RKV6	796
DIS3	EXOSC5	Q9NQT4	793
DIS3	C1D	Q13901	774
DIS3	TENT5C	Q5VWP2	773
DIS3	EXOSC2	Q13868	741
DIS3	ZCCHC7	Q8N3Z6	733
DIS3	XRN1	Q8IZH2	730

IntAct

Human interaction partners of DIS3 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

27 partners by confidence:

Partner	Interaction type	MIscore	Records
EXOSC10	association	0.740	4
EXOSC3	physical association	0.740	1
EXOSC2	physical association	0.620	2
AHNAK	physical association	0.400	1
PLEC	physical association	0.400	1
DLX4	association	0.350	2
FBXW7	proximity	0.270	4
AKT1	proximity	0.270	1
BRAF	proximity	0.270	1
PTEN	proximity	0.270	1
TP53	proximity	0.270	1
CDK5	physical association	0.000	1
CHORDC1	physical association	0.000	1
COPZ1	physical association	0.000	1
DISC1	physical association	0.000	1
DRG1	physical association	0.000	1
EXOSC8	physical association	0.000	1
NME2	physical association	0.000	1
NTMT1	physical association	0.000	1
PRCC	physical association	0.000	1
SARNP	physical association	0.000	1
SCYL2	physical association	0.000	1
SEPTIN11	physical association	0.000	1
SEPTIN7	physical association	0.000	1
SH3GLB1	physical association	0.000	1
SUB1	physical association	0.000	1
ZBTB17	physical association	0.000	1

BioGRID (246 interactions; top human partners by supporting records): EXOSC10 (Co-fractionation; 4 records), DCX (Affinity Capture-MS; 3 records), EXOSC2 (Co-fractionation; 3 records), EXOSC7 (Co-fractionation; 3 records), EXOSC8 (Co-fractionation; 3 records), GAS2L1 (Affinity Capture-MS; 3 records), RBM23 (Affinity Capture-MS; 3 records), SSBP3 (Affinity Capture-MS; 3 records), C1D (Affinity Capture-MS; 2 records), CUL3 (Affinity Capture-MS; 2 records), CYP1A1 (Affinity Capture-MS; 2 records), DLX4 (Affinity Capture-MS; 2 records), EGFR (Affinity Capture-MS; 2 records), EXOSC3 (Affinity Capture-MS; 2 records), EXOSC4 (Co-fractionation; 2 records)

Protein complexes (CORUM) (2)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

2 complexes by size:

Complex	Subunits	Members
Exosome	11	EXOSC1, EXOSC2, EXOSC6, EXOSC7, EXOSC9, DIS3, EXOSC10, EXOSC3, EXOSC4, EXOSC5, EXOSC8
Exosome	10	EXOSC9, DIS3, EXOSC2, EXOSC3, EXOSC4, EXOSC5, EXOSC6, EXOSC7, EXOSC8, EXOSC1

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — PCM.

intOGen’s role is a computational inference from cohort mutation patterns and may diverge from the gene’s curated/literature role; read it alongside the evidence above.

Genetic variants

Variant evidence for DIS3: 159 ClinVar records (3 pathogenic / likely pathogenic); 1 GWAS association. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	2
Uncertain significance	121
Likely benign	6
Benign	4

Top pathogenic / likely-pathogenic (3)

Showing all 3 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
4759281	NM_014953.5(DIS3):c.1912C>T (p.Arg638Ter)	Likely pathogenic	criteria provided, single submitter	1
800341	NM_014953.5(DIS3):c.2335A>T (p.Ile779Phe)	Likely pathogenic	no assertion criteria provided	1
150124	GRCh38/hg38 13q21.31-22.1(chr13:64065900-73693578)x3	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore DIS3’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 38 predictions of 1,408):

Position(s)	Effect	Δscore	Sites
13:72760527–72760528	donor_loss	1.0000	5
13:72760652–72760653	acceptor_loss	1.0000	5
13:72761644–72761645	donor_loss	1.0000	5
13:72761815–72761816	acceptor_loss	1.0000	6
13:72761819	acceptor_gain	1.0000
13:72761823	acceptor_gain	1.0000
13:72762138–72762139	acceptor_loss	1.0000	4
13:72763449–72763450	donor_loss	1.0000	5
13:72763613	acceptor_gain	1.0000
13:72765970–72765971	donor_loss	1.0000	5

AlphaMissense

2,684 missense substitutions predicted likely pathogenic (of 6,351 scored), across 634 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M667	9	0.983	0.999
M539	9	0.968	0.995
M748	9	0.949	0.998
M823	9	0.781	0.964
D487	8	0.999	1.000
D488	8	0.998	0.999
H764	8	0.997	0.999
D784	8	0.997	0.999
D485	8	0.996	0.998
H691	8	0.996	0.999
D290	8	0.994	0.999
D479	8	0.994	0.998
D508	8	0.993	0.998
H774	8	0.992	0.999
H788	8	0.991	0.999
D69	8	0.989	0.997
D146	8	0.988	0.996
H415	8	0.987	0.999
N671	8	0.987	1.000
D28	8	0.984	0.994

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	1.15e-05

Disease associations

OMIM: gene MIM:607533 | disease phenotypes: MIM:254500

GenCC curated gene-disease

Mondo (1): plasma cell myeloma (MONDO:0009693)

Orphanet (2): Multiple myeloma (Orphanet:29073), AL amyloidosis (Orphanet:85443)

GWAS associations

1 associations:

Study	Trait	p-value
GCST005042_13	Restless legs syndrome	3e-9

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
D009101	Multiple Myeloma	C04.557.595.500; C14.907.454.460; C15.378.147.780.650; C15.378.463.515.460; C20.683.515.845; C20.683.780.650

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067309 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression	2
entinostat	decreases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	2
FR900359	increases phosphorylation	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression	1
decabromobiphenyl ether	decreases expression	1
trichostatin A	affects expression	1
di-n-butylphosphoric acid	affects expression	1
K 7174	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
jinfukang	decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
(+)-JQ1 compound	affects binding	1
Resveratrol	affects cotreatment, increases expression	1
Air Pollutants	increases abundance, decreases expression	1
Cadmium	increases expression	1
Cannabidiol	affects cotreatment, decreases expression	1
Cuprizone	affects cotreatment, decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ivermectin	decreases expression	1
Mitoxantrone	affects response to substance	1
Plant Extracts	increases expression, affects cotreatment	1
Ribonucleotides	affects binding	1
Rotenone	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651283	Binding	Binding affinity to human DIS3 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — *ChemMedChem*

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 300 trials:

NCT	Phase	Status	Title
NCT00029224	Phase 4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00104104	Phase 4	COMPLETED	A Multiple Myeloma Trial in Patients With Bone Metastases
NCT00211211	Phase 4	COMPLETED	FREE Study - Fracture Reduction Evaluation
NCT00242528	Phase 4	WITHDRAWN	Open-label Study, to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Bone Lesions Secondary to Multiple Myeloma.
NCT00257114	Phase 4	COMPLETED	Evaluation of VELCADE Given as Retreatment to Multiple Myeloma Patients for Efficacy, Safety and Tolerability
NCT00352703	Phase 4	COMPLETED	PROMPT - Palifermin in Reduction of Oral Mucositis in PBSC Transplantation
NCT00361140	Phase 4	COMPLETED	Busulfan Safety/Efficacy as Conditioning Prior to Hematopoietic Cell Transplantation (HCT)
NCT00622505	Phase 4	COMPLETED	Zoledronic Acid Treatment (Every 4 or 12 Weeks) to Prevent Skeletal Complications in Advanced Multiple Myeloma Participants
NCT00652041	Phase 4	COMPLETED	Bortezomib/Adriamycine/Melfalan/Prednisone (VAMP)/Thalidomide/Cyclophosphamide/Dexamethasone (TaCyDex) or Bortezomib/Melfalan/Prednisone (V-MP)/TaCyDex) in Refractary or Relapsed Multiple Myeloma
NCT00733538	Phase 4	COMPLETED	Stage I Multiple Myeloma Treatment
NCT01087008	Phase 4	COMPLETED	Zoledronic Acid in Patients With Multiple Myeloma and Asymptomatic Biochemical Relapse
NCT01249690	Phase 4	UNKNOWN	Efficacy Study of PAD and TAD in Newly Diagnosed Multiple Myeloma
NCT01410929	Phase 4	WITHDRAWN	Evaluation of Vertebral Compression Fracture Fixation With RF Kyphoplasty in Patients With Multiple Myeloma
NCT01731886	Phase 4	COMPLETED	Lenalidomide and Dexamethasone With/Without Stem Cell Transplant in Patients With Multiple Myeloma
NCT01868828	Phase 4	UNKNOWN	A Study of PAD Versus Velcade, Cyclophosphamide and Dexamethasone (VCD) Treatment in Subjects With Multiple Myeloma
NCT02268890	Phase 4	COMPLETED	A Pharmacokinetic Study of Bortezomib in Taiwanese Participants With Multiple Myeloma
NCT02286830	Phase 4	COMPLETED	Prolonged Protection From Bone Disease in Multiple Myeloma
NCT02559154	Phase 4	UNKNOWN	Modified Bortezomib-based Combination Therapy for Multiple Myeloma
NCT02577783	Phase 4	UNKNOWN	PDD vs PAD to Treat Initially Diagnosed MM
NCT02773550	Phase 4	TERMINATED	Treatment With a Scheme With Low Doses of Bortezomib / Melphalan / Prednisone (MPV) in Patients With Multiple Myeloma
NCT02958969	Phase 4	COMPLETED	Apixaban for Primary Prevention of Venous Thromboembolism in Patients With Multiple Myeloma
NCT03173092	Phase 4	TERMINATED	A Study of Ixazomib (NINLARO®) in Combination With Lenalidomide and Dexamethasone (IRD) for the Treatment of Participants With Multiple Myeloma (MM)
NCT03619252	Phase 4	COMPLETED	Pneumococcal Vaccination of Multiple Myeloma Patients on Novel Agents
NCT03768960	Phase 4	COMPLETED	A Study of DARZALEX (Daratumumab) In Indian Participants With Relapsed and Refractory Multiple Myeloma, Whose Prior Therapy Included a Proteasome Inhibitor and an Immunomodulatory Agent
NCT03829371	Phase 4	ACTIVE_NOT_RECRUITING	STUDY COMPARING TWO STANDARD TREATMENTS IN AUTOLOGOUS STEM CELL TRANSPLANTATION INELIGIBLE POPULATION AFFECTED BY MULTIPLE MYELOMA
NCT03908138	Phase 4	UNKNOWN	RDD Versus VDD in Newly Diagnosed Patients With Multiple Myeloma
NCT04217967	Phase 4	COMPLETED	Ixazomib, Lenalidomide, and Combination for Maintenance in NDMM Patients
NCT04952766	Phase 4	COMPLETED	Study Evaluating SARS-CoV-2 (COVID-19) Humoral Response After BNT162b2 Vaccine in Immunocompromised Adults Compared to Healthy Adults
NCT04989140	Phase 4	UNKNOWN	Study of Pomalidomide, Oral Dexamethasone and Ixazomib in Patients With Relapsed MM Who Have Received Lenalidomide
NCT05183139	Phase 4	WITHDRAWN	A Multicenter In-class Transition Study of Ixazomib Combined With Pomalidomide and Dexamethasone or With Lenalidomide and Dexamethasone in Adults With Relapsed/Refractory Multiple Myeloma
NCT05201781	Phase 4	RECRUITING	A Long-term Study for Participants Previously Treated With Ciltacabtagene Autoleucel
NCT05429515	Phase 4	NOT_YET_RECRUITING	Effect of HFR-SUPRA in the Treatment of Multiple Myeloma-related Acute Kidney Injury
NCT05511428	Phase 4	COMPLETED	Home Based Daratumumab Administration for Patients With Multiple Myeloma
NCT05545202	Phase 4	UNKNOWN	A Randomized, Comparative, Double-blind Trial of Pentaisomaltose and Dimethyl Sulphoxide for Cryoprotection of Hematopoietic Stem Cells in Subjects With Multiple Myeloma or Malignant Lymphoma With a Need for Autologous Transplantation
NCT05555329	Phase 4	COMPLETED	Alternative Dosing Scheme of Pomalidomide 4 mg Every Other Day Versus Pomalidomide 2 mg and 4 mg Every Day; the POMAlternative Study
NCT05722405	Phase 4	RECRUITING	Ixazomib Plus Low-dose Lenalidomide Versus Ixazomib Alone for Maintenance Treatment of High Risk Multiple Myeloma
NCT05855122	Phase 4	UNKNOWN	Safety and ASCT-related Symptom Burden Optimization of Tocilizumab in ASCT Following HD Melphalan Conditioning for Multiple Myeloma Patients
NCT05944783	Phase 4	NOT_YET_RECRUITING	Bioequivalence Studies of Dasatinib 100 Mg
NCT06057402	Phase 4	RECRUITING	Elranatamab Post Trial Access Study for Participants With Multiple Myeloma (MM)
NCT06251076	Phase 4	RECRUITING	Plan Development for Giving Teclistamab in the Outpatient Setting
NCT06409702	Phase 4	RECRUITING	Treatment of High-risk Newly Diagnosed Multiple Myeloma With Minimal Residual Disease Detection
NCT06425276	Phase 4	COMPLETED	Evaluate Safety and Efficacy of High-dose Melphalan HCL for Injection in MM Patients With Auto-HSC Transplantation
NCT07030517	Phase 4	ACTIVE_NOT_RECRUITING	A Study to Assess Safety of Teclistamab in Indian Participants With Relapsed and Refractory Multiple Myeloma
NCT07094048	Phase 4	RECRUITING	Immunoglobulins in Multiple Myeloma Patients Receiving a BCMA-Directed T Cell Engager
NCT07101445	Phase 4	RECRUITING	Evaluating Premedication Regimens (Methylprednisolone vs Dexamethasone-based) for the Prevention of Systemic and Injection Site Reactions to Motixafortide in Patients With Multiple Myeloma Undergoing Stem Cell Mobilization, PARADE Trial
NCT07154537	Phase 4	ACTIVE_NOT_RECRUITING	Pneumococcal Conjugated Vaccine 13 (PCV13) for Patients With Multiple Myeloma (MM)
NCT07334535	Phase 4	NOT_YET_RECRUITING	Isa-VRD in TIE HRMM
NCT07474961	Phase 4	NOT_YET_RECRUITING	BLOOD-dose: A Platform Trial Evaluating Dose Optimization in Hematological Diseases.
NCT00001561	Phase 3	COMPLETED	Active Immunization of Sibling Bone Marrow Transplant Donors Against Purified Myeloma Protein of the Recipient Undergoing Allogeneic Bone Marrow Transplantation
NCT00002548	Phase 3	COMPLETED	SWOG-9321 Melphalan, TBI, and Transplant vs Combo Chemo in Untreated Myeloma
NCT00002556	Phase 3	COMPLETED	Combination Chemotherapy With or Without High Dose Cyclophosphamide and Recombinant Interferon Alfa-2b in Treating Patients With Previously Untreated Stage I-III Multiple Myeloma
NCT00002850	Phase 3	COMPLETED	Antibiotic Therapy in Preventing Early Infection in Patients With Multiple Myeloma Who Are Receiving Chemotherapy
NCT00005834	Phase 3	TERMINATED	S9922 Combination Chemo Plus Filgrastim With or Without Thalidomide in Refractory Multiple Myeloma
NCT00037791	Phase 3	COMPLETED	Safety and Efficacy of (PN-152,243)/PN-196,444 in the Prevention of Thrombocytopenia
NCT00038233	Phase 3	COMPLETED	Thalidomide for Multiple Myeloma
NCT00048230	Phase 3	COMPLETED	PS-341 (VELCADE™) Versus High-Dose Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma
NCT00056160	Phase 3	COMPLETED	CC-5013 Plus Dexamethasone Versus Dexamethasone Alone in Previously Treated Subjects With Multiple Myeloma
NCT00057564	Phase 3	COMPLETED	A Study of Combination Thalidomide Plus Dexamethasone Therapy vs. Dexamethasone Therapy Alone in Previously Untreated Subjects With Multiple Myeloma
NCT00063726	Phase 3	COMPLETED	A Study of PS-341 Given to Patients With Multiple Myeloma Who Experienced Progressive Disease After Receiving Dexamethasone in M34101-039
NCT00064038	Phase 3	COMPLETED	S0232 Dexamethasone With or Without Lenalidomide in Treating Patients With Previously Untreated Stage I, Stage II, or Stage III Multiple Myeloma

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for DIS3 across ~30M SureChEMBL compounds — explore on Sugi Predict.