ASXL1

Summary

ASXL1 (ASXL transcriptional regulator 1, HGNC:18318) is a protein-coding gene on chromosome 20q11.21, encoding Polycomb group protein ASXL1 (Q8IXJ9). Probable Polycomb group (PcG) protein involved in transcriptional regulation mediated by ligand-bound nuclear hormone receptors, such as retinoic acid receptors (RARs) and peroxisome proliferator-activated receptor gamma (PPARG). It is haploinsufficient (ClinGen: sufficient evidence).

This gene is similar to the Drosophila additional sex combs gene, which encodes a chromatin-binding protein required for normal determination of segment identity in the developing embryo. The protein is a member of the Polycomb group of proteins, which are necessary for the maintenance of stable repression of homeotic and other loci. The protein is thought to disrupt chromatin in localized areas, enhancing transcription of certain genes while repressing the transcription of other genes. The protein encoded by this gene functions as a ligand-dependent co-activator for retinoic acid receptor in cooperation with nuclear receptor coactivator 1. Mutations in this gene are associated with myelodysplastic syndromes and chronic myelomonocytic leukemia. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 171023 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Bohring-Opitz syndrome (Definitive, ClinGen)
• GWAS associations: 3
• Clinical variants (ClinVar): 2,625 total — 106 pathogenic, 38 likely-pathogenic
• Phenotypes (HPO): 184
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 14 cancer types
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_015338

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18318
Approved symbol	ASXL1
Name	ASXL transcriptional regulator 1
Location	20q11.21
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0978
Ensembl gene	ENSG00000171456
Ensembl biotype	protein_coding
OMIM	612990
Entrez	171023

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 11 protein_coding, 8 retained_intron, 6 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000306058, ENST00000375687, ENST00000375689, ENST00000470145, ENST00000497249, ENST00000553345, ENST00000555343, ENST00000555564, ENST00000619344, ENST00000642676, ENST00000643168, ENST00000644060, ENST00000644168, ENST00000644587, ENST00000644615, ENST00000645035, ENST00000645337, ENST00000645514, ENST00000645688, ENST00000646367, ENST00000646985, ENST00000647223, ENST00000649901, ENST00000651418, ENST00000905973, ENST00000915088

RefSeq mRNA: 3 — MANE Select: NM_015338 NM_001164603, NM_001363734, NM_015338

CCDS: CCDS13201, CCDS86944, CCDS86945

Canonical transcript exons

ENST00000375687 — 13 exons

Exon	Start	End
ENSE00001154526	32433284	32433917
ENSE00001154553	32429901	32430053
ENSE00001154561	32429338	32429431
ENSE00001154566	32428325	32428422
ENSE00001914317	32434432	32439319
ENSE00003562781	32431583	32431679
ENSE00003610854	32428128	32428248
ENSE00003651720	32367727	32367729
ENSE00003656905	32366384	32366466
ENSE00003675353	32369015	32369123
ENSE00003716413	32431321	32431484
ENSE00003718315	32432880	32432985
ENSE00003897215	32358331	32358832

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 98.01.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 64.3820 / max 545.4387, expressed in 1825 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
184035	45.6690	1817
184038	11.4616	1792
184039	2.6509	1404
184040	2.2266	1334
184041	0.6360	305
184042	0.3694	152
184037	0.3194	146
184046	0.2794	101
184036	0.2707	111
184034	0.2541	105

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	98.01	gold quality
sperm	CL:0000019	95.20	gold quality
adrenal tissue	UBERON:0018303	95.16	gold quality
mucosa of stomach	UBERON:0001199	94.86	gold quality
left testis	UBERON:0004533	93.45	gold quality
male germ cell	CL:0000015	93.33	gold quality
ventricular zone	UBERON:0003053	93.33	gold quality
body of pancreas	UBERON:0001150	93.28	gold quality
nerve	UBERON:0001021	93.27	gold quality
tibial nerve	UBERON:0001323	93.27	gold quality
right testis	UBERON:0004534	93.01	gold quality
oocyte	CL:0000023	92.94	gold quality
colonic epithelium	UBERON:0000397	92.93	gold quality
left lobe of thyroid gland	UBERON:0001120	92.89	gold quality
left ovary	UBERON:0002119	92.89	gold quality
metanephros cortex	UBERON:0010533	92.88	gold quality
right ovary	UBERON:0002118	92.87	gold quality
nipple	UBERON:0002030	92.84	gold quality
right lung	UBERON:0002167	92.78	gold quality
thyroid gland	UBERON:0002046	92.57	gold quality
body of uterus	UBERON:0009853	92.50	gold quality
right lobe of thyroid gland	UBERON:0001119	92.48	gold quality
upper lobe of left lung	UBERON:0008952	92.46	gold quality
omental fat pad	UBERON:0010414	92.42	gold quality
muscle layer of sigmoid colon	UBERON:0035805	92.42	gold quality
peritoneum	UBERON:0002358	92.40	gold quality
ovary	UBERON:0000992	92.15	gold quality
testis	UBERON:0000473	92.06	gold quality
endocervix	UBERON:0000458	91.98	gold quality
lower esophagus muscularis layer	UBERON:0035833	91.96	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	20.03
E-MTAB-7249	yes	11.04
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

5 targets.

Target	Regulation
CDKN2A	Activation
CDKN2B	Activation
FABP4	Unknown
HOXA9	Repression
RARA	Activation

Upstream regulators (CollecTRI, top): KMT2A, SOX2, TFAP2A, ZNF263

miRNA regulators (miRDB)

139 targeting ASXL1, 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-8485	100.00	77.57	4731
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3163	100.00	77.23	8605
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4514	99.99	67.10	1870
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Data show that sequences 3’ of PAX5 disrupting ASXL1, and ZCCHC7 disrupted by sequences 3’ of FRG1B and LOC1499503. (PMID:19586940)
• ASXL1 haploinsufficiency plays a role in leukemogenesis (PMID:19609284)
• ASXL1 mutations were mutually exclusive with NPM1 alterations in acute myeloid leukemias. (PMID:19865112)
• Mutations of the polycomb-associated gene ASXL1 is associated with myelodysplastic syndromes and acute myeloid leukemia. (PMID:20182461)
• ASXL1 mutations are associated with refractory anemia with ring sideroblasts and thrombocytosis. (PMID:20334914)
• 2 novel heterozygous (nonsense and frameshift) mutations in exon 12 of ASLX1 in 49 juvenile myelomonocytic leukaemia patients (PMID:20408841)
• ASXL1 gene mutation is associated with chronic myeloid leukemia. (PMID:20410925)
• the 8 mononucleotide guanine repeat sequence in the reference sequence for ASXL1 in this region may confound delimitation of the true repeat number in this region (PMID:20596031)
• Mutations in ASXL1 were frequent in refractory anemia with excess of blasts. (PMID:20678218)
• Acute myeloid leukemia bearing ASXL1 mutations showed distinct clinical and biological features. (PMID:20693432)
• Studies indicate that additional mutations in genes which appear to affect the epigenome of MPN patients have been discovered including mutations in TET2, IDH1/ 2, EZH2, and ASXL1. (PMID:21307773)
• ASXL1 mutation is asssociated with chronic myelogenous leukemia. (PMID:21346257)
• 9 new missense mutations were found in myelofibrosis, chronic myelomonocytic leukemia and blast-phase myeloproliferative disorders. (PMID:21455215)
• results suggest that ASXL1 mutations are frequent molecular aberrations in myelodysplastic syndrome that predict an adverse prognostic outcome (PMID:21576631)
• Nonsense mutations in ASXL1 cause Bohring-Opitz syndrome. (PMID:21706002)
• ASXL1 haploinsufficiency is associated with a myelofibrosis phenotype in the context of other known and unknown lesions, and disruption of ASXL1 function may contribute to the disease pathogenesis of myelofibrosis. (PMID:21712540)
• Data show that TET2 and ASXL1 pathogenic mutations are found in 8% of myeloproliferative neoplasms lacking JAK2 and MPL mutations, whereas IDH1, IDH2, and c-CBL mutations are not detected in this subset of patients. (PMID:21904853)
• ASXL1 mutations were already seen at diagnosis in most patients with primary or secondary myelofibrosis. They were associated with progression from the chronic phase of a previous polycythemia vera or essential thrombocythemia. (PMID:21923651)
• Results indicate that demonstrates that ASXL1-mutated older patients have unfavorable outcomes and may be candidates for experimental treatment approaches. (PMID:22031865)
• ASXL1 mutations are common mutations in acute myeloid leukemia and indicate a poor therapy outcome. (PMID:22058207)
• Germline GATA2 mutations predispose to familial myelodysplastic syndrome/acute myeloid leukemia; monosomy 7 and ASXL1 mutations may be recurrent secondary genetic abnormalities triggering overt malignancy. (PMID:22271902)
• study reports on 2 novel cases of Bohring-Opitz syndrome (BOS) carrying two previously undescribed ASXL1 mutations (c.2407_2411del5 [p.Q803TfsX17] and c.2893C>T [p.R965X]); these new data further support ASXL1 as cause of BOS (PMID:22419483)
• A systematic determination of ASXL1 mutational status in myeloid malignancies should help in prognosis assessment. (PMID:22436456)
• We found a high incidence of ASXL1 mutation in myelofibrosis patients (20%) and a low incidence in polycythemia vera (7%) and essential thrombocythemia (4%) patients. (PMID:22489043)
• genetic association studies in a French population: Data suggest that acute myeloid leukemia with myelodysplasia-related changes is associated with higher frequency of ASXL1 mutations in intergenic DNA regions. (PMID:22535592)
• ASXL1 may be a direct target of SOX2 and may play a role in maintaining the pluripotency of stem cells. (PMID:22542624)
• ASXL1 associates with the PRC2 and loss of ASXL1 in vivo collaborates with NRASG12D to promote myeloid leukemogenesis. (PMID:22897849)
• TET2, DNMT3A, CBL and ASXL1 mutations are present in mastocytosis and these mutations may affect prognosis, as demonstrated by worse OS in mutated patients (PMID:22905207)
• Mutations in ASXL1 is associated with worse response to therapy in acute myeloid leukemia. (PMID:22915647)
• Patients with ASXL1 mutations did not harbor IDH1, FLT3, or CEBPA mutations, and a combination of ASXL1 and IDH2 mutations was found only in one patient with acute myeloid leukemia. (PMID:22929312)
• ASXL1 mutations are associated with the pathogenesis of myeloproliferative neoplasms. (PMID:23009937)
• ASXL1 exon 12 mutations are frequent in acute myeloid leukemia. (PMID:23018865)
• Data show that myelodysplastic chronic myelomonocytic leukemias are characterized by mutations in transcription/epigenetic regulators ASXL1, RUNX1, TET2 and SRSF2. (PMID:23065512)
• ASXL1 mutations might results in dominance of the mutant clone in Chinese with myelodysplastic syndromes. (PMID:23099237)
• ASXL1 knockdown perturbs human granulomonocytic differentiation. (PMID:23294243)
• Data indicate there were two patients carried ASXL1 mutations, both with t(8;21), 2 had DNMT3A mutations, 2 had IDH1 mutations, 1 had IDH2 mutation, and 3 had TET2 mutations. (PMID:23365461)
• We evaluated the prognostic relevance of several clinical and laboratory parameters in 226 Mayo Clinic patients with chronic myelomonocytic leukemia and spliceosome component (P=0.4) and ASXL1 mutations (P=0.37) had no impact survival. (PMID:23531518)
• A new prognostic score including ASXL1 status, age, hemoglobin, WBC, and platelet counts defines three groups of CMML patients with distinct outcomes. This score appears more discriminative than those based solely on clinical parameters. (PMID:23690417)
• duplication of ASXL1 contributes to the metopic ridging/trigonocephaly phenotype in patients with 20q11.2 duplication syndrome (PMID:23704076)
• The low incidence of mutations in younger patients with primary disease and the lack of significance indicate that there is a limited role for screening at diagnosis for ASXL1 mutations for the purpose of prognostic stratification. (PMID:23952244)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	asxl1	ENSDARG00000036956
mus_musculus	Asxl1	ENSMUSG00000042548
rattus_norvegicus	Asxl1	ENSRNOG00000061603
drosophila_melanogaster	Asx	FBGN0261823

Paralogs (2): ASXL3 (ENSG00000141431), ASXL2 (ENSG00000143970)

Protein

Protein identifiers

Polycomb group protein ASXL1 — Q8IXJ9 (reviewed: Q8IXJ9)

Alternative names: Additional sex combs-like protein 1

All UniProt accessions (13): A0A087WWN0, A0A2R8Y4U9, A0A2R8Y5U1, A0A2R8Y627, A0A2R8Y6F0, A0A2R8Y6V0, A0A494C1R1, Q8IXJ9, H0YJC9, Q498B9, Q5JWS8, Q6P1M8, Q76L82

UniProt curated annotations — full annotation on UniProt →

Function. Probable Polycomb group (PcG) protein involved in transcriptional regulation mediated by ligand-bound nuclear hormone receptors, such as retinoic acid receptors (RARs) and peroxisome proliferator-activated receptor gamma (PPARG). Acts as a coactivator of RARA and RXRA through association with NCOA1. Acts as a corepressor for PPARG and suppresses its adipocyte differentiation-inducing activity. Non-catalytic component of the PR-DUB complex, a complex that specifically mediates deubiquitination of histone H2A monoubiquitinated at ‘Lys-119’ (H2AK119ub1). Acts as a sensor of N(6)-methyladenine methylation on DNA (6mA): recognizes and binds 6mA DNA, leading to its ubiquitination and degradation by TRIP12, thereby inactivating the PR-DUB complex and regulating Polycomb silencing. The PR-DUB complex is an epigenetic regulator of gene expression and acts as a transcriptional coactivator, affecting genes involved in development, cell communication, signaling, cell proliferation and cell viability. ASXL1, ASXL2 and ASXL3 function redundantly in the PR-DUB complex. The ASXL proteins are essential for chromatin recruitment and transcriptional activation of associated genes. ASXL1 and ASXL2 are important for BAP1 protein stability. Together with BAP1, negatively regulates epithelial-mesenchymal transition (EMT) of trophoblast stem cells during placental development by regulating genes involved in epithelial cell integrity, cell adhesion and cytoskeletal organization.

Subunit / interactions. Core component of the polycomb repressive deubiquitinase (PR-DUB) complex, at least composed of BAP1, one of ASXL1, ASXL2 or (probably) ASXL3, and one of MBD5 or MBD6. Distinct combinations of ASXL and MBD proteins may preferentially bind specific histone modification marks. The PR-DUB core associates with a number of accessory proteins, including FOXK1, FOXK2, KDM1B, HCFC1 and OGT; KDM1B specifically associates with ASXL2 PR-DUB complexes. Interacts (via DEUBAD domain) with BAP1 (via ULD domain); the interaction is direct and forms a ubiquitin binding cleft. The interaction with BAP1 is important for maintaining BAP1 stability. Together with BAP1, associates (via DEUBAD domain) with nucleosomes; interacts with nucleosomal DNA and stabilizes the orientation of the nucleosome to line up the PR-DUB complex active site with its H2AK118ub1 substrate. Interacts (via PHD domain) with MBD5 and MBD6 (via MBD domain); the interaction is probably direct and mediates association of MBD proteins with the PR-DUB core. Interacts with RARA, RXRA and NCOA1. Interacts with PPARA and PPARG.

Subcellular location. Nucleus.

Tissue specificity. Widely expressed at low level. Expressed in heart, brain, skeletal muscle, placenta, pancreas, spleen, prostate, small intestine, colon, peripheral blood, leukocytes, bone marrow and fetal liver. Highly expressed in testes.

Post-translational modifications. Ubiquitinated by TRIP12, leading to its subsequent degradation following binding of N(6)-methyladenine methylated DNA (6mA).

Disease relevance. Bohring-Opitz syndrome (BOPS) [MIM:605039] A syndrome characterized by severe intrauterine growth retardation, poor feeding, profound intellectual disability, trigonocephaly, prominent metopic suture, exophthalmos, nevus flammeus of the face, upslanting palpebral fissures, hirsutism, and flexion of the elbows and wrists with deviation of the wrists and metacarpophalangeal joints. The disease is caused by variants affecting the gene represented in this entry. Myelodysplastic syndrome (MDS) [MIM:614286] A heterogeneous group of closely related clonal hematopoietic disorders. All are characterized by a hypercellular or hypocellular bone marrow with impaired morphology and maturation, dysplasia of the myeloid, megakaryocytic and/or erythroid lineages, and peripheral blood cytopenias resulting from ineffective blood cell production. Included diseases are: refractory anemia (RA), refractory anemia with ringed sideroblasts (RARS), refractory anemia with excess blasts (RAEB), refractory cytopenia with multilineage dysplasia and ringed sideroblasts (RCMD-RS); chronic myelomonocytic leukemia (CMML) is a myelodysplastic/myeloproliferative disease. MDS is considered a premalignant condition in a subgroup of patients that often progresses to acute myeloid leukemia (AML). The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The HARE HTH-type domain recognizes and binds N(6)-methyladenine methylated DNA (6mA). Contains one Leu-Xaa-Xaa-Leu-Leu (LXXLL) motif, which may be required for an association with nuclear receptors. The deubiquitinase adapter domain (DEUBAD), together with the BAP1 UCH domain, forms the ubiquitin binding cleft of the PR-DUB complex. The Asn-Glu-Phe (NEF) motif stabilizes the interaction of BAP1 and UBB/ubiquitin.

Similarity. Belongs to the Asx family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8IXJ9-1	1	yes
Q8IXJ9-2	2

RefSeq proteins (3): NP_001158075, NP_001350663, NP_056153* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007759	Asxl_HARE-HTH	Domain
IPR024811	ASX/ASX-like	Family
IPR026905	ASX-like_PHD	Domain
IPR028020	ASX_DEUBAD_dom	Domain
IPR044867	DEUBAD_dom	Domain

Pfam: PF05066, PF13919, PF13922

UniProt features (63 total): region of interest 13, compositionally biased region 12, mutagenesis site 6, sequence conflict 5, helix 5, sequence variant 4, turn 4, short sequence motif 3, strand 3, domain 2, modified residue 2, splice variant 2, chain 1, zinc finger region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
8H1T	ELECTRON MICROSCOPY	3
9U5U	ELECTRON MICROSCOPY	3.12
8SVF	ELECTRON MICROSCOPY	3.2
9VQ1	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IXJ9-F1	42.74	0.04

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 501, 503

Mutagenesis-validated functional residues (6):

Position	Phenotype
243–246	reduced pr-dub complex deubiquitination activity towards h2ak119ub1 substrates in the context of the nucleosome, but no
262	reduced pr-dub complex deubiquitination activity towards h2ak119ub1 substrates in the context of the nucleosome, but no
267	reduced pr-dub complex deubiquitination activity towards h2ak119ub1 substrates in the context of the nucleosome, but no
336–346	reduced pr-dub complex deubiquitination activity towards h2ak119ub1 substrates in the context of the nucleosome, but no
1108	abolishes interaction with rara.
1111	abolishes interaction with rara.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-5689603	UCH proteinases
R-HSA-392499	Metabolism of proteins
R-HSA-5688426	Deubiquitination
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 717 (showing top): GOBP_EPITHELIUM_DEVELOPMENT, YAATNRNNNYNATT_UNKNOWN, GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, DACOSTA_UV_RESPONSE_VIA_ERCC3_XPCS_DN, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_EPITHELIAL_CELL_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_FAT_CELL_DIFFERENTIATION, AAGTCCA_MIR422B_MIR422A, LFA1_Q6, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GOBP_REGULATION_OF_RETINOIC_ACID_RECEPTOR_SIGNALING_PATHWAY, GOBP_THYMUS_DEVELOPMENT, GTTAAAG_MIR302B, TGACCTY_ERR1_Q2, FOXO4_01

GO Biological Process (19): cell morphogenesis (GO:0000902), heart morphogenesis (GO:0003007), chromatin organization (GO:0006325), animal organ morphogenesis (GO:0009887), hemopoiesis (GO:0030097), response to retinoic acid (GO:0032526), negative regulation of peroxisome proliferator activated receptor signaling pathway (GO:0035359), regulation of kidney size (GO:0035564), negative regulation of fat cell differentiation (GO:0045599), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of retinoic acid receptor signaling pathway (GO:0048386), thymus development (GO:0048538), bone marrow development (GO:0048539), homeostasis of number of cells (GO:0048872), lung saccule development (GO:0060430), podocyte development (GO:0072015), regulation of DNA-templated transcription (GO:0006355), hematopoietic or lymphoid organ development (GO:0048534), bone development (GO:0060348)

GO Molecular Function (8): DNA binding (GO:0003677), chromatin binding (GO:0003682), transcription coactivator activity (GO:0003713), zinc ion binding (GO:0008270), nuclear retinoic acid receptor binding (GO:0042974), peroxisome proliferator activated receptor binding (GO:0042975), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (3): nucleoplasm (GO:0005654), PR-DUB complex (GO:0035517), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Deubiquitination	1
Post-translational protein modification	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
animal organ development	3
anatomical structure morphogenesis	2
positive regulation of DNA-templated transcription	2
hematopoietic or lymphoid organ development	2
binding	2
heart development	1
animal organ morphogenesis	1
cellular component organization	1
cell development	1
response to lipid	1
response to oxygen-containing compound	1
peroxisome proliferator activated receptor signaling pathway	1
regulation of peroxisome proliferator activated receptor signaling pathway	1
negative regulation of intracellular signal transduction	1
kidney morphogenesis	1
regulation of anatomical structure size	1
fat cell differentiation	1
negative regulation of cell differentiation	1
regulation of fat cell differentiation	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
retinoic acid receptor signaling pathway	1
regulation of retinoic acid receptor signaling pathway	1
positive regulation of intracellular signal transduction	1
gland development	1
tissue development	1
bone development	1
multicellular organismal-level homeostasis	1
lung alveolus development	1
anatomical structure development	1
podocyte differentiation	1
glomerular epithelial cell development	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
immune system development	1
skeletal system development	1
nucleic acid binding	1
transcription coregulator activity	1
transition metal ion binding	1

Protein interactions and networks

STRING

2336 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ASXL1	BAP1	Q92560	990
ASXL1	EZH2	Q15910	981
ASXL1	TET2	Q6N021	976
ASXL1	DNMT3A	Q9Y6K1	936
ASXL1	SUZ12	Q15022	936
ASXL1	OGT	O15294	919
ASXL1	FOXK1	P85037	918
ASXL1	IDH1	O75874	899
ASXL1	SRSF2	Q01130	888
ASXL1	SH2B3	Q9UQQ2	885
ASXL1	U2AF1	Q01081	881
ASXL1	SETBP1	Q9Y6X0	876
ASXL1	RUNX1	Q01196	874
ASXL1	JAK2	O60674	873
ASXL1	FLT3	P36888	861

IntAct

78 interactions, top by confidence:

A	B	Type	Score
EZH2	EED	psi-mi:“MI:0914”(association)	0.930
BAP1	ASXL1	psi-mi:“MI:0915”(physical association)	0.830
ASXL1	BAP1	psi-mi:“MI:0915”(physical association)	0.830
ASXL1	BAP1	psi-mi:“MI:0914”(association)	0.830
BAP1	OGT	psi-mi:“MI:0914”(association)	0.730
FOXK2	DVL2	psi-mi:“MI:0914”(association)	0.640
ASXL1	AKT1	psi-mi:“MI:0915”(physical association)	0.620
AKT1	ASXL1	psi-mi:“MI:2364”(proximity)	0.620
AR	KMT2D	psi-mi:“MI:0914”(association)	0.600
GOLGA6L9	ASXL1	psi-mi:“MI:0915”(physical association)	0.560
ASXL1	EZH2	psi-mi:“MI:0915”(physical association)	0.560
EZH2	ASXL1	psi-mi:“MI:0915”(physical association)	0.560
ASXL1	Rxra	psi-mi:“MI:0915”(physical association)	0.530
ASXL1	ESR1	psi-mi:“MI:0915”(physical association)	0.530
ASXL1	THRB	psi-mi:“MI:0915”(physical association)	0.530
Rxra	ASXL1	psi-mi:“MI:0407”(direct interaction)	0.530
ASXL1	THRB	psi-mi:“MI:0407”(direct interaction)	0.530
ASXL1	ESR1	psi-mi:“MI:0407”(direct interaction)	0.530
EED	ASXL1	psi-mi:“MI:0915”(physical association)	0.500
ASXL1	EED	psi-mi:“MI:0915”(physical association)	0.500
ASXL1	EED	psi-mi:“MI:0914”(association)	0.500
RARB	ASXL1	psi-mi:“MI:0407”(direct interaction)	0.440
ASXL1	SRPK1	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
GRB2	ASXL1	psi-mi:“MI:0915”(physical association)	0.400
ASXL1	NCK1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (402): ASXL1 (Affinity Capture-MS), ASXL1 (Affinity Capture-MS), ASXL1 (Affinity Capture-MS), ASXL1 (Affinity Capture-Western), ASXL1 (Reconstituted Complex), OGT (Affinity Capture-Western), HCFC1 (Affinity Capture-Western), FOXK1 (Affinity Capture-Western), FOXK2 (Affinity Capture-Western), ASXL1 (Reconstituted Complex), ASXL1 (Reconstituted Complex), ASXL1 (Affinity Capture-Western), ASXL1 (Affinity Capture-Western), BAP1 (Affinity Capture-MS), FOXK1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0A6YY25, A6NGG8, A6X8Z5, B2RQL2, B2RXH4, D3ZMK9, D3ZUE1, E9Q7F2, O08696, O14513, P59598, P97691, Q05860, Q05AH6, Q08050, Q0GGX2, Q0VET5, Q13029, Q2M1Z3, Q3U0P1, Q571I4, Q5PSV9, Q5SSG4, Q5U2M8, Q5VV67, Q63755, Q66H04, Q68DA7, Q69ZL1, Q6DIA7, Q6JPI3, Q6P1D7, Q6PAC4, Q6PG16, Q71F56, Q76N32, Q811R2, Q86YN6, Q86YV5, Q8BJS7

Diamond homologs: P59598, Q5ZM88, Q76L83, Q8BZ32, Q8C4A5, Q8IXJ9, Q9C0F0, Q9V727

SIGNOR signaling

11 interactions.

A	Effect	B	Mechanism
ASXL1	“up-regulates activity”	RARA	binding
ASXL1	“up-regulates activity”	RXRA	binding
ASXL1	“up-regulates activity”	“Polycomb repressive complex 2”	binding
NCOA1	“up-regulates activity”	ASXL1	binding
ASXL1	“up-regulates activity”	NCOA1	binding
ASXL1	“up-regulates quantity by expression”	RARA	“transcriptional regulation”
ASXL1	“down-regulates quantity by repression”	HOXA9	“transcriptional regulation”
ASXL1	“down-regulates activity”	PPARG	binding
ASXL1	down-regulates	Proliferation
ASXL1	“up-regulates quantity by expression”	CDKN2B	“transcriptional regulation”
ASXL1	“up-regulates quantity by expression”	CDKN2A	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 42 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
SUMOylation of intracellular receptors	5	49.4×	1e-05
Formation of WDR5-containing histone-modifying complexes	5	39.1×	2e-05
Nuclear Receptor transcription pathway	6	35.4×	7e-06
PKMTs methylate histone lysines	5	23.6×	2e-04
UCH proteinases	6	21.9×	3e-05
Activation of anterior HOX genes in hindbrain development during early embryogenesis	7	18.8×	1e-05
PIP3 activates AKT signaling	5	9.8×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
response to estradiol	5	26.8×	2e-04
chromatin organization	5	13.4×	1e-03
positive regulation of gene expression	7	7.3×	1e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 14 cancer types — AML, BLCA, BRCA, CCRCC, CHOL, CLLSLL, COAD, ESCA, HGGNOS, HNSC, MBL, PAST…(+2 more).

Clinical variants and AI predictions

ClinVar

2625 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	106
Likely pathogenic	38
Uncertain significance	1304
Likely benign	912
Benign	49

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1031902	NM_015338.6(ASXL1):c.3437C>A (p.Ser1146Ter)	Pathogenic
1075418	NM_015338.6(ASXL1):c.1720-2A>G	Pathogenic
1076637	NM_015338.6(ASXL1):c.1770_1773dup (p.Gln592fs)	Pathogenic
1174493	NM_015338.6(ASXL1):c.1719+1G>A	Pathogenic
1188832	NM_015338.6(ASXL1):c.2759_2762dup (p.Val922fs)	Pathogenic
1204208	NM_015338.6(ASXL1):c.1569dup (p.Arg524fs)	Pathogenic
1223850	NM_015338.6(ASXL1):c.4118_4134del (p.Thr1372_Phe1373insTer)	Pathogenic
1354428	NM_015338.6(ASXL1):c.2145_2154del (p.Ala716fs)	Pathogenic
1381947	NM_015338.6(ASXL1):c.3194G>A (p.Trp1065Ter)	Pathogenic
145102	GRCh38/hg38 20q11.21(chr20:31254983-32575288)x3	Pathogenic
1451498	NM_015338.6(ASXL1):c.203del (p.Glu68fs)	Pathogenic
1453118	NM_015338.6(ASXL1):c.2141_2142del (p.Met713_Ser714insTer)	Pathogenic
146032	GRCh38/hg38 20q11.21(chr20:31254983-33473080)x3	Pathogenic
1701085	NM_015338.6(ASXL1):c.1720A>G (p.Ile574Val)	Pathogenic
1727002	NM_015338.6(ASXL1):c.1436_1437del (p.Pro479fs)	Pathogenic
1803980	NM_015338.6(ASXL1):c.3942_3957del (p.Gln1315fs)	Pathogenic
1923411	NM_015338.6(ASXL1):c.3583C>T (p.Gln1195Ter)	Pathogenic
2014043	NM_015338.6(ASXL1):c.4002del (p.Ser1335fs)	Pathogenic
2014166	NM_015338.6(ASXL1):c.2987del (p.Gly996fs)	Pathogenic
2016278	NM_015338.6(ASXL1):c.2788dup (p.Trp930fs)	Pathogenic
2020014	NM_015338.6(ASXL1):c.1925_1926insC (p.Gly643fs)	Pathogenic
2100886	NM_015338.6(ASXL1):c.3550dup (p.Thr1184fs)	Pathogenic
2107834	NM_015338.6(ASXL1):c.1114C>T (p.Gln372Ter)	Pathogenic
2426140	NC_000020.10:g.(?31019104)(31019307_?)del	Pathogenic
2426141	NC_000020.10:g.(?31015911)(31025141_?)del	Pathogenic
2499575	NM_015338.6(ASXL1):c.1368_1371del (p.Asp457fs)	Pathogenic
2500280	NM_015338.6(ASXL1):c.4254_4260delinsCTCAC (p.Lys1419fs)	Pathogenic
2504109	NM_015338.6(ASXL1):c.1892_1938del (p.His631fs)	Pathogenic
2584479	NM_015338.6(ASXL1):c.2324T>G (p.Leu775Ter)	Pathogenic
2609056	NM_015338.6(ASXL1):c.3595_3596dup (p.Pro1200fs)	Pathogenic

SpliceAI

2877 predictions. Top by Δscore:

Variant	Effect	Δscore
20:32366380:TCA:T	acceptor_loss	1.0000
20:32366381:CAG:C	acceptor_loss	1.0000
20:32366382:A:AG	acceptor_gain	1.0000
20:32366382:A:T	acceptor_loss	1.0000
20:32366383:G:GC	acceptor_loss	1.0000
20:32366383:G:GG	acceptor_gain	1.0000
20:32366383:GGT:G	acceptor_gain	1.0000
20:32366459:GAAA:G	donor_gain	1.0000
20:32366463:TGAGG:T	donor_loss	1.0000
20:32366464:GAGGT:G	donor_loss	1.0000
20:32366465:AGG:A	donor_loss	1.0000
20:32366467:GTTT:G	donor_loss	1.0000
20:32367669:A:AG	acceptor_gain	1.0000
20:32367669:AT:A	acceptor_gain	1.0000
20:32367669:ATGG:A	acceptor_gain	1.0000
20:32367670:T:A	acceptor_gain	1.0000
20:32367670:T:G	acceptor_gain	1.0000
20:32369004:T:TA	acceptor_gain	1.0000
20:32369005:G:A	acceptor_gain	1.0000
20:32369009:TTACA:T	acceptor_loss	1.0000
20:32369010:TACAG:T	acceptor_loss	1.0000
20:32369011:A:AG	acceptor_gain	1.0000
20:32369011:ACAGT:A	acceptor_gain	1.0000
20:32369012:CA:C	acceptor_loss	1.0000
20:32369013:A:AG	acceptor_gain	1.0000
20:32369013:AGT:A	acceptor_gain	1.0000
20:32369013:AGTG:A	acceptor_gain	1.0000
20:32369013:AGTGG:A	acceptor_gain	1.0000
20:32369014:G:GA	acceptor_gain	1.0000
20:32369014:GT:G	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000053033 (20:32419266 G>A), RS1000059778 (20:32409027 G>A), RS1000106715 (20:32357804 T>G), RS1000114030 (20:32373868 GA>G,GAA), RS1000131055 (20:32371307 A>G), RS1000215205 (20:32411981 T>G), RS1000221433 (20:32367665 T>A,G), RS1000273798 (20:32367941 A>G), RS1000278342 (20:32408859 G>C,T), RS1000293441 (20:32422248 G>A), RS1000300183 (20:32416472 G>T), RS1000392780 (20:32370926 G>T), RS1000402188 (20:32374233 A>G), RS1000430430 (20:32422603 T>A), RS1000464491 (20:32369725 T>A)

Disease associations

OMIM: gene MIM:612990 | disease phenotypes: MIM:605039, MIM:614286, MIM:213000, MIM:180850, MIM:607785

GenCC curated gene-disease

Disease	Classification	Inheritance
Bohring-Opitz syndrome	Definitive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Bohring-Opitz syndrome	Definitive	AD

Mondo (10): Bohring-Opitz syndrome (MONDO:0011510), myelodysplastic syndrome (MONDO:0018881), intellectual disability (MONDO:0001071), autism spectrum disorder (MONDO:0005258), atypical chronic myeloid leukemia, BCR-ABL1 negative (MONDO:0004653), hypertrichosis (MONDO:0019280), isolated cerebellar hypoplasia/agenesis (MONDO:0008939), Rubinstein Taybi like syndrome (MONDO:0043195), juvenile myelomonocytic leukemia (MONDO:0011908), microcephaly (MONDO:0001149)

Orphanet (9): Bohring-Opitz syndrome (Orphanet:97297), Myelodysplastic syndrome (Orphanet:52688), Atypical chronic myeloid leukemia (Orphanet:98824), Rare disorder with hypertrichosis (Orphanet:79365), Isolated cerebellar agenesis (Orphanet:1398), Cerebellar hypoplasia-tapetoretinal degeneration syndrome (Orphanet:2246), Juvenile myelomonocytic leukemia (Orphanet:86834), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

184 total (30 of 184 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000016	Urinary retention
HP:0000076	Vesicoureteral reflux
HP:0000160	Narrow mouth
HP:0000175	Cleft palate
HP:0000187	Broad alveolar ridges
HP:0000189	Narrow palate
HP:0000204	Cleft upper lip
HP:0000243	Trigonocephaly
HP:0000252	Microcephaly
HP:0000276	Long face
HP:0000278	Retrognathia
HP:0000286	Epicanthus
HP:0000293	Full cheeks
HP:0000294	Low anterior hairline
HP:0000297	Facial hypotonia
HP:0000316	Hypertelorism
HP:0000329	Facial hemangioma
HP:0000341	Narrow forehead
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000431	Wide nasal bridge
HP:0000463	Anteverted nares
HP:0000486	Strabismus
HP:0000520	Proptosis
HP:0000545	Myopia
HP:0000582	Upslanted palpebral fissure
HP:0000587	Abnormal optic nerve morphology
HP:0000589	Coloboma

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST004131_132	Inflammatory bowel disease	6.000000e-06
GCST007611_4	Chronic obstructive pulmonary disease or high blood pressure (pleiotropy)	4.000000e-08
GCST90002404_548	Red cell distribution width	2.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009188	Red cell distribution width

MeSH disease descriptors (7)

Descriptor	Name	Tree numbers
D006983	Hypertrichosis	C17.800.329.875
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D054429	Leukemia, Myelomonocytic, Juvenile	C04.557.337.539.525; C15.378.190.615.520; C15.378.508.539.525
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
C537419	Bohring syndrome (supp.)
C562568	Cerebellar Hypoplasia (supp.)
C535877	Rubinstein Taybi like syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases expression, affects expression	5
methylmercuric chloride	increases expression, affects cotreatment	4
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression, increases expression	3
sodium arsenite	increases abundance, increases expression, affects cotreatment, decreases expression	2
Acetaminophen	decreases expression, increases expression	2
FR900359	affects phosphorylation	1
TAK-243	increases sumoylation	1
trichostatin A	increases expression	1
arsenite	increases methylation	1
perfluorooctanoic acid	decreases expression	1
ochratoxin A	decreases acetylation, decreases expression	1
coumarin	decreases phosphorylation	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
perfluorohexanesulfonic acid	decreases expression	1
ICG 001	increases expression	1
14-deoxy-11,12-didehydroandrographolide	decreases expression	1
abrine	increases expression	1
ON 01910	increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	decreases expression	1
qinghuang	affects response to substance	1
Arsenic	affects cotreatment, decreases expression, increases abundance, increases expression	1
Vehicle Emissions	decreases methylation	1
Benzene	increases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	increases abundance, increases expression	1

Cellosaurus cell lines

12 cell lines: 11 cancer cell line, 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_0098	SKM-1	Cancer cell line	Male
CVCL_0373	KBM-5	Cancer cell line	Female
CVCL_0425	MEG-01	Cancer cell line	Male
CVCL_3022	MEG-01s	Cancer cell line	Male
CVCL_3023	MEG-01SSF	Cancer cell line	Male
CVCL_A691	TS9;22	Cancer cell line	Male
CVCL_B1K7	Abcam HeLa ASXL1 KO	Cancer cell line	Female
CVCL_E2Q6	HyCyte MEG-01 hJAK2_p.V617F_c.1849G>T	Cancer cell line	Male
CVCL_LK61	INCABRi001-A	Induced pluripotent stem cell	Female
CVCL_SD72	HAP1 ASXL1 (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00003398	PHASE4	COMPLETED	Bone Marrow Transplantation in Treating Patients With Hematologic Cancer
NCT00117507	PHASE4	COMPLETED	Study for the Treatment of Transfusional Iron Overload in Myelodysplastic Patients
NCT00202371	PHASE4	WITHDRAWN	Transfusion Effects in Myelodysplastic Patients: Limiting Exposure
NCT00361140	PHASE4	COMPLETED	Busulfan Safety/Efficacy as Conditioning Prior to Hematopoietic Cell Transplantation (HCT)
NCT00452660	PHASE4	COMPLETED	Evaluation the Effect of Exjade on Oxidative Stress in Low Risk Myelodysplastic Syndrome Patients With Iron Over Load
NCT00481143	PHASE4	COMPLETED	Efficacy and Safety of Deferasirox in Patients With Myelodysplastic Syndrome and Transfusion-dependent Iron Overload
NCT00487448	PHASE4	COMPLETED	SMD_FLAG-IDA_98: FLAG-IDA in Induction Treatment of High Risk Myelodysplastic Syndromes or Secondary Acute Myeloblastic Leukemia
NCT00488436	PHASE4	COMPLETED	Antithymocyte Globulin and Cyclosporine in Treating Low Risk Patients With Myelodysplastic Syndrome
NCT00564941	PHASE4	COMPLETED	Evaluating the Efficacy of Deferasirox in Transfusion Dependent Chronic Anaemias (Myelodysplastic Syndrome, Beta-thalassaemia Patients) With Chronic Iron Overload
NCT00673608	PHASE4	COMPLETED	Magnetic Resonance Imaging (MRI) Assessments of the Heart and Liver Iron Load in Patients With Transfusion Induced Iron Overload
NCT01011283	PHASE4	TERMINATED	To Demonstrate Superiority of Decitabine Over Azacitidine in Subjects With Intermediate- or High-risk MDS.
NCT01200355	PHASE4	COMPLETED	Posaconazole Versus Micafungin for Prophylaxis Against Invasive Fungal Infections During Neutropenia in Patients Undergoing Chemotherapy for Acute Myelogenous Leukemia, Acute Lymphocytic Leukemia or Myelodysplastic Syndrome
NCT01201811	PHASE4	COMPLETED	Study of Azacitidine in Adult Taiwanese Subjects With Higher-Risk Myelodysplastic Syndromes (MDS)
NCT01250951	PHASE4	COMPLETED	This Study Will Evaluate Efficacy and Safety of Deferasirox in Patients With Myelodysplastic Syndromes (MDS), Thalassemia and Rare Anemia Types Having Transfusion-induced Iron Overload.
NCT01326845	PHASE4	TERMINATED	Myelodysplastic Syndrome (MDS) Gastrointestinal (GI) Tolerability Study
NCT01339988	PHASE4	UNKNOWN	Busulfan and Cyclophosphamide Instead of Total Boby Irradiation (TBI) and Cyclophosphamide for Hematological Malignancies Hematocrit (HCT)
NCT02013102	PHASE4	UNKNOWN	A Phase Ⅳ Study of Decitabine in Myelodysplastic Syndrome
NCT02145026	PHASE4	COMPLETED	A Study of Epoetin Beta Treatment in Anemic Participants With Myelodysplastic Syndrome (MDS)
NCT02875743	PHASE4	COMPLETED	King’s Invasive Aspergillosis Study II
NCT03176849	PHASE4	COMPLETED	A Randomized Phase IV Control Trial of Single High Dose Oral Vitamin D3 in Pediatric Patients Undergoing HSCT
NCT03335943	PHASE4	UNKNOWN	Myelodysplastic Syndrome–CDA-2 Hematological Improvement National Affirmation Study
NCT03598582	PHASE4	COMPLETED	Biological Predictive Factors of Response to ESA in Low Risk MDS Patients
NCT06004765	PHASE4	UNKNOWN	Efficacy and Safety of Lenalidomide Combined With Azacitidine vs Azacitidine in the Treatment of MDS-RS
NCT06006949	PHASE4	UNKNOWN	Roxadustat Combined With Luspatercept Versus Luspatercept Monotherapy in the Treatment of Refractory MDS-RS
NCT00000591	PHASE3	COMPLETED	T-Cell Depletion in Unrelated Donor Marrow Transplantation
NCT00002517	PHASE3	COMPLETED	Combination Chemotherapy in Treating Children With Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndrome
NCT00002742	PHASE3	COMPLETED	Antifungal Therapy for Fever and Neutropenia in Patients Receiving Treatment for Hematologic Cancer
NCT00002798	PHASE3	COMPLETED	Combination Chemotherapy With or Without Bone Marrow Transplantation in Treating Children With Acute Myelogenous Leukemia or Myelodysplastic Syndrome
NCT00002926	PHASE3	UNKNOWN	Combination Chemotherapy With or Without Peripheral Stem Cell Transplantation in Treating Patients With Myelodysplastic Syndrome or Acute Myelogenous Leukemia
NCT00002989	PHASE3	UNKNOWN	Combination Chemotherapy With or Without Idarubicin and Peripheral Stem Cell Transplantation in Treating Patients With Leukemia or Myelodysplastic Syndrome
NCT00003138	PHASE3	COMPLETED	Erythropoietin (EPO)+/- Filgrastim (G-CSF) vs. Supportive Therapy Alone for Patients With Myelodysplastic Syndromes
NCT00003436	PHASE3	COMPLETED	Combination Chemotherapy With or Without Bone Marrow Transplantation in Treating Children With Acute Myeloid Leukemia
NCT00003593	PHASE3	COMPLETED	Chemotherapy in Treating Children With Down Syndrome and Myeloproliferative Disorder, Acute Myelogenous Leukemia, or Myelodysplastic Syndrome
NCT00003602	PHASE3	UNKNOWN	Combination Chemotherapy in Treating Older Patients With Acute Myeloid Leukemia
NCT00003687	PHASE3	COMPLETED	Treatment for Chronic Pain in Patients With Advanced Cancer
NCT00003805	PHASE3	COMPLETED	Prevention of Infection in Patients With Hematologic Cancer and Persistent Fever Caused by a Low White Blood Cell Count
NCT00004208	PHASE3	COMPLETED	Antithymocyte Globulin and Cyclosporine in Treating Patients With Myelodysplastic Syndrome
NCT00005805	PHASE3	COMPLETED	St. John’s Wort in Relieving Fatigue in Patients Undergoing Chemotherapy or Hormone Therapy for Cancer
NCT00005823	PHASE3	COMPLETED	Intensive Compared With Nonintensive Chemotherapy in Treating Older Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome
NCT00005863	PHASE3	COMPLETED	Combination Chemotherapy With or Without Filgrastim and/or Tretinoin in Treating Patients With Acute Myeloid Leukemia