MLLT10

Summary

MLLT10 (MLLT10 histone lysine methyltransferase DOT1L cofactor, HGNC:16063) is a protein-coding gene on chromosome 10p12.31, encoding Protein AF-10 (P55197). Probably involved in transcriptional regulation.

This gene encodes a transcription factor and has been identified as a partner gene involved in several chromosomal rearrangements resulting in various leukemias. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 8028 — RefSeq curated summary.

At a glance

• GWAS associations: 29
• Clinical variants (ClinVar): 140 total
• Phenotypes (HPO): 3
• MANE Select transcript: NM_001195626

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16063
Approved symbol	MLLT10
Name	MLLT10 histone lysine methyltransferase DOT1L cofactor
Location	10p12.31
Locus type	gene with protein product
Status	Approved
Aliases	AF10
Ensembl gene	ENSG00000078403
Ensembl biotype	protein_coding
OMIM	602409
Entrez	8028

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 16 protein_coding, 6 nonsense_mediated_decay, 5 protein_coding_CDS_not_defined, 3 retained_intron

ENST00000307729, ENST00000377059, ENST00000377072, ENST00000377091, ENST00000377100, ENST00000420525, ENST00000430455, ENST00000438473, ENST00000462999, ENST00000468309, ENST00000471315, ENST00000476557, ENST00000479634, ENST00000480415, ENST00000495130, ENST00000621220, ENST00000631589, ENST00000650772, ENST00000650893, ENST00000650921, ENST00000651097, ENST00000651298, ENST00000651382, ENST00000651405, ENST00000652258, ENST00000652497, ENST00000858156, ENST00000937604, ENST00000942647, ENST00000942648

RefSeq mRNA: 7 — MANE Select: NM_001195626 NM_001195626, NM_001195627, NM_001195628, NM_001195630, NM_001324296, NM_001324297, NM_004641

CCDS: CCDS55706, CCDS55707, CCDS55708, CCDS7135

Canonical transcript exons

ENST00000307729 — 23 exons

Exon	Start	End
ENSE00000693489	21614831	21614924
ENSE00000693494	21617112	21617207
ENSE00000693508	21651673	21651768
ENSE00000693513	21670449	21670704
ENSE00000693542	21673350	21673919
ENSE00000816097	21681332	21681376
ENSE00000996535	21682225	21682257
ENSE00001472758	21534232	21534520
ENSE00001612483	21726244	21726355
ENSE00001619074	21740030	21740236
ENSE00001707021	21733504	21733592
ENSE00001739181	21733768	21734129
ENSE00001750689	21732899	21733087
ENSE00001793039	21735139	21735235
ENSE00001803822	21727856	21727928
ENSE00002239963	21713772	21713950
ENSE00002719058	21730900	21731054
ENSE00003480818	21741939	21743630
ENSE00003500808	21538833	21538912
ENSE00003515646	21586294	21586348
ENSE00003608001	21612348	21612451
ENSE00003613907	21595331	21595440
ENSE00003756250	21534645	21534804

Expression profiles

Bgee: expression breadth ubiquitous, 275 present calls, max score 97.18.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.9300 / max 422.9215, expressed in 1808 samples.

FANTOM5 promoters (15 alternative TSS)

Promoter ID	TPM avg	Samples expressed
104208	8.5981	1727
104210	3.9289	1483
104212	0.9755	620
104209	0.9006	550
104198	0.6711	201
104197	0.6146	244
104205	0.4707	234
104217	0.4701	207
104222	0.4627	236
104211	0.3159	159

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	97.18	gold quality
adult organism	UBERON:0007023	95.39	gold quality
colonic epithelium	UBERON:0000397	94.07	gold quality
calcaneal tendon	UBERON:0003701	93.57	gold quality
right testis	UBERON:0004534	93.22	gold quality
left testis	UBERON:0004533	93.14	gold quality
secondary oocyte	CL:0000655	92.89	gold quality
sperm	CL:0000019	92.78	gold quality
testis	UBERON:0000473	92.76	gold quality
adrenal tissue	UBERON:0018303	92.05	gold quality
tibia	UBERON:0000979	91.60	gold quality
tendon	UBERON:0000043	91.51	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.33	gold quality
upper leg skin	UBERON:0004262	91.07	gold quality
ventricular zone	UBERON:0003053	90.80	gold quality
superficial temporal artery	UBERON:0001614	90.76	gold quality
oocyte	CL:0000023	90.51	gold quality
male germ cell	CL:0000015	90.46	gold quality
skin of hip	UBERON:0001554	90.23	gold quality
sural nerve	UBERON:0015488	90.15	gold quality
cortical plate	UBERON:0005343	89.90	gold quality
muscle layer of sigmoid colon	UBERON:0035805	89.71	gold quality
skin of abdomen	UBERON:0001416	89.54	gold quality
left ovary	UBERON:0002119	89.28	gold quality
right ovary	UBERON:0002118	89.22	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.03	gold quality
mucosa of stomach	UBERON:0001199	89.03	gold quality
body of uterus	UBERON:0009853	89.01	gold quality
ganglionic eminence	UBERON:0004023	88.99	gold quality
skin of leg	UBERON:0001511	88.97	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.24

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
BAX	Repression
CDKN1A	Repression
MDM2	Repression

Upstream regulators (CollecTRI, top): CTNNB1, KMT2A, LEF1

miRNA regulators (miRDB)

139 targeting MLLT10, 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-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-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
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-196A-1-3P	99.99	72.15	2772
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-12136	99.98	72.81	5713
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784

Literature-anchored findings (GeneRIF, showing 23)

• FISH analysis in infant AML-M5 showed a complex rearrangement between chromosomes 10 and 11, disrupting the MLL gene, a paracentric inversion of the 11q13-q23 fragment translocated to 10p12. AF10 was the fusion partner gene of MLL in this rearrangement. (PMID:12127405)
• ALL1 is involved in remodeling, acetylating, deacetylating, and methylating nucleosomes and/or free histones (PMID:12453419)
• data reveal new properties for the leucine zipper domain and thus might provide new clues to understanding the mechanisms by which AF10 fusion proteins in which the PHD domain is lost might trigger leukemias in humans (PMID:12482966)
• The patients with immunophenotype of Pre-B-acute lymphoblastic leukemia were found to carry: MLL/AF10. (PMID:16215946)
• Data show that the nuclear isoform of FLRG lacks an intrinsic transactivation domain, but enhances AF10-mediated transcription, probably through promoting the homo-oligomerization of AF10, thus facilitating the recruitment of co-activators. (PMID:17868029)
• CALM(PICALM)/AF10 fusion protein might interfere with normal Ikaros (IKZF1)function, and thereby block lymphoid differentiation in CALM/AF10 positive leukemias. (PMID:18037964)
• the CALM-AF10 fusion protein can also greatly reduce global H3K79 methylation in both human and murine leukemic cells by disrupting the AF10-mediated association of hDOT1L with chromatin (PMID:19443658)
• In leukemia cells, full-length CALM-AF10 localized to the nucleus with no consistent effect on growth factor endocyctosis, and suppressed histone H3 lysine 79 methylation regardless of the presence of clathrin (PMID:21706055)
• a new susceptibility locus for meningioma at 10p12.31 (MLLT10, rs11012732, odds ratio = 1.46, P(combined) = 1.88 x 10(-14)) was identified. (PMID:21804547)
• results strongly indicate that the differential regulation of these three genes is not due to the break point effect but as a consequence of the CALM/AF10 fusion gene expression, though the mechanism of regulation is not well understood (PMID:22064352)
• detection of PICALM-MLLT10 fusion transcript occurs in 7% of children with T-lineage ALL and is not associated with a poorer outcome for patients treated with contemporary, intensive chemotherapy (PMID:23670296)
• In pediatric T-acute lymphoblastic leukemia, we have identified 2 RNA processing genes, that is, HNRNPH1/5q35 and DDX3X/Xp11.3 as new MLLT10 fusion partners. (PMID:23673860)
• we report that variants at the MLLT10 locus are unlikely to alter risk of glioma, and they have no prognostic value among patients with high-grade tumors (glioblastoma). (PMID:24755950)
• Results provide evidence that transformation driven by MLL fusions as well as the recurrent AML-associated NUP98-NSD1 fusion oncogene is critically dependent on the ability of AF10 to stimulate DOT1L activity. (PMID:25464900)
• The PZP domain of AF10 senses unmodified H3K27 to regulate DOT1L-mediated methylation of H3K79. (PMID:26439302)
• Our results provide evidence for new loci influencing abdominal visceral (BBS9, ADCY8, KCNK9) and subcutaneous (MLLT10/DNAJC1/EBLN1) fat, and confirmed a locus (THNSL2) previously reported to be associated with abdominal fat in women (PMID:26480920)
• In a retroviral transduction/transplantation mouse model, mice transplanted with MLL/AF10(OM-LZ) cells harboring PTPN11(wt) developed myelomonocytic leukemia. Those transplanted with cells harboring PTPN11(G503A) -induced monocytic leukemia in a shorter latency. Adding PTPN11(G503A) to MLL/AF10 affected cell proliferation, chemo-resistance, differentiation, in vivo BM recruitment/clonal expansion and faster progression. (PMID:27859216)
• In vitro, the overexpression of MLLT10 promoted colorectal cancer (CRC) cell migration and invasion, while after MLLT10 was knocked down, the opposite results were observed. In lung metastasis sites, the knockdown of MLLT10 in SW620 cells significantly inhibited Vimentin expression, whereas the E-Cadherin was increased. These results indicate that MLLT10 regulates the metastasis of CRC cells via EMT. (PMID:30102091)
• the oligomerization ability of the DOT1L-AF10 complex is essential for MLL1-AF10’s leukemogenic function (PMID:31527241)
• MLLT10 in benign and malignant hematopoiesis. (PMID:32569758)
• A JAK/STAT-mediated inflammatory signaling cascade drives oncogenesis in AF10-rearranged AML. (PMID:33690798)
• AF10 (MLLT10) prevents somatic cell reprogramming through regulation of DOT1L-mediated H3K79 methylation. (PMID:34215314)
• The role of the PZP domain of AF10 in acute leukemia driven by AF10 translocations. (PMID:34226546)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	mllt10	ENSDARG00000045401
mus_musculus	Mllt10	ENSMUSG00000026743
rattus_norvegicus	Mllt10	ENSRNOG00000022249
drosophila_melanogaster	Br140	FBGN0033155
caenorhabditis_elegans		WBGENE00003034
caenorhabditis_elegans		WBGENE00021810

Paralogs (8): JADE2 (ENSG00000043143), JADE1 (ENSG00000077684), BRPF3 (ENSG00000096070), BRD1 (ENSG00000100425), JADE3 (ENSG00000102221), PHF14 (ENSG00000106443), BRPF1 (ENSG00000156983), MLLT6 (ENSG00000275023)

Protein

Protein identifiers

Protein AF-10 — P55197 (reviewed: P55197)

Alternative names: ALL1-fused gene from chromosome 10 protein

All UniProt accessions (8): P55197, A0A494C038, A0A494C093, A0A494C0R2, A0A494C1P9, H0Y5C4, H0Y5P4, Q5JT35

UniProt curated annotations — full annotation on UniProt →

Function. Probably involved in transcriptional regulation. In vitro or as fusion protein with KMT2A/MLL1 has transactivation activity. Binds to cruciform DNA. In cells, binding to unmodified histone H3 regulates DOT1L functions including histone H3 ‘Lys-79’ dimethylation (H3K79me2) and gene activation.

Subunit / interactions. Self-associates. Interacts with FSTL3 isoform 2; the interaction enhances MLLT10 in vitro transcriptional activity and self-association. Interacts with YEATS4. Interacts with SS18. Interacts with DOT1L; this interaction also occurs with the KMT2A/MLL1 fusion protein. Interacts with histone H3; interaction is necessary for MLLT10 binding to nucleosomes; interaction is inhibited by histone H3 ‘Lys-27’ methylations (H3K27me1, H3K27me2 and H3K27me3) amd acetylation; interaction stabilizes association of MLLT10 at chromatin; interaction is essential for histone H3 ‘Lys-79’ dimethylation (H3K79me2).

Subcellular location. Nucleus.

Tissue specificity. Expressed abundantly in testis.

Disease relevance. A chromosomal aberration involving MLLT10 is associated with acute leukemias. Translocation t(10;11)(p12;q23) with KMT2A/MLL1. The result is a rogue activator protein. A chromosomal aberration involving MLLT10 is associated with diffuse histiocytic lymphomas. Translocation t(10;11)(p13;q14) with PICALM.

Isoforms (4)

UniProt ID	Names	Canonical?
P55197-4	4	yes
P55197-1	1
P55197-2	2
P55197-3	3

RefSeq proteins (7): NP_001182555, NP_001182556, NP_001182557, NP_001182559, NP_001311225, NP_001311226, NP_004632 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001965	Znf_PHD	Domain
IPR011011	Znf_FYVE_PHD	Homologous_superfamily
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR019786	Zinc_finger_PHD-type_CS	Conserved_site
IPR019787	Znf_PHD-finger	Domain
IPR034732	EPHD	Domain
IPR049773	AF10-like_CC	Domain
IPR049775	AF10_ePHD	Domain
IPR049781	AF10/AF17_PHD	Domain
IPR050701	Histone_Mod_Regulator	Family

Pfam: PF13831, PF13832

UniProt features (83 total): compositionally biased region 16, strand 13, region of interest 11, helix 10, mutagenesis site 9, modified residue 7, splice variant 7, zinc finger region 3, site 3, turn 2, chain 1, cross-link 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
5DAG	X-RAY DIFFRACTION	1.6
6CKO	X-RAY DIFFRACTION	2
7MJU	X-RAY DIFFRACTION	2.1
6CKN	X-RAY DIFFRACTION	2.49
5DAH	X-RAY DIFFRACTION	2.61
6JN2	X-RAY DIFFRACTION	3.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P55197-F1	50.98	0.18

Functional residue map

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

Catalytic / active sites (3): 266 (kmt2a/mll1 fusion point (in acute myeloid leukemia patient b)); 627 (kmt2a/mll1 fusion point (in acute myeloid leukemia patient c)); 664 (kmt2a/mll1 fusion point (in acute myeloid leukemia patient a))

Post-translational modifications (8): 217, 252, 436, 532, 684, 686, 689, 280

Mutagenesis-validated functional residues (9):

Position	Phenotype
22	does not affect interaction with histone h3.
80	does not affect interaction with histone h3.
106	impairs interaction with histone h3.
107	impairs interaction with histone h3. reduces association to chromatin. does not rescued histone h3 ’lys-79’ dimethylatio
109	impairs interaction with histone h3.
114	impairs interaction with histone h3.
120	impairs interaction with histone h3.
179	impairs interaction with histone h3.
190	impairs interaction with histone h3.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 258 (showing top): MULLIGHAN_NPM1_SIGNATURE_3_UP, MORF_MSH3, HOFMANN_CELL_LYMPHOMA_UP, CMYB_01, TTTGTAG_MIR520D, MORF_BRCA1, MAZ_Q6, CHEOK_RESPONSE_TO_MERCAPTOPURINE_AND_LD_MTX_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, CHX10_01, GGGTGGRR_PAX4_03, CHANDRAN_METASTASIS_DN, MORF_RAD51L3

GO Biological Process (3): regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (7): DNA binding (GO:0003677), chromatin binding (GO:0003682), zinc ion binding (GO:0008270), nucleosome binding (GO:0031491), histone binding (GO:0042393), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), protein-containing complex (GO:0032991), cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase II	2
binding	2
cellular anatomical structure	2
regulation of DNA-templated transcription	1
regulation of transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
nucleic acid binding	1
transition metal ion binding	1
chromatin binding	1
protein-containing complex binding	1
protein binding	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular_component	1
cytoplasm	1

Protein interactions and networks

STRING

1164 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MLLT10	DOT1L	Q8TEK3	994
MLLT10	MLLT3	P42568	993
MLLT10	AFF1	P51825	979
MLLT10	MLLT1	Q03111	966
MLLT10	MLLT6	P55198	936
MLLT10	PICALM	Q13492	920
MLLT10	ELL	P55199	916
MLLT10	AFDN	P55196	898
MLLT10	KMT2A	Q03164	845
MLLT10	YEATS4	O95619	816
MLLT10	CLP1	Q92989	778
MLLT10	HOXA9	P31269	768
MLLT10	NUP98	P52948	759
MLLT10	ARIH2	O95376	723
MLLT10	SEPTIN6	Q14141	709

IntAct

51 interactions, top by confidence:

A	B	Type	Score
TCF4	CTNNB1	psi-mi:“MI:0914”(association)	0.940
DOT1L	MLLT3	psi-mi:“MI:0914”(association)	0.820
DOT1L	MLLT10	psi-mi:“MI:0915”(physical association)	0.770
MLLT10	CTNNB1	psi-mi:“MI:0407”(direct interaction)	0.660
CTNNB1	MLLT10	psi-mi:“MI:0914”(association)	0.660
MLLT10	CTNNB1	psi-mi:“MI:0915”(physical association)	0.660
PFDN1	PFDN6	psi-mi:“MI:0914”(association)	0.640
MLLT6	RGPD8	psi-mi:“MI:0914”(association)	0.530
DAXX	TNRC18	psi-mi:“MI:0914”(association)	0.530
PFDN1	ARHGAP32	psi-mi:“MI:0914”(association)	0.530
EPS15	MLLT10	psi-mi:“MI:0407”(direct interaction)	0.440
MLLT10	H1-5	psi-mi:“MI:0915”(physical association)	0.400
Naa50	WDR46	psi-mi:“MI:0914”(association)	0.350
ZNF526	VAMP4	psi-mi:“MI:0914”(association)	0.350
Ube2i	POM121C	psi-mi:“MI:0914”(association)	0.350
DOT1L	IBTK	psi-mi:“MI:0914”(association)	0.350
TMPO		psi-mi:“MI:0914”(association)	0.350
Mllt1	ELL2	psi-mi:“MI:0914”(association)	0.350
Scai	BCR	psi-mi:“MI:0914”(association)	0.350
Mta1	MTA3	psi-mi:“MI:0914”(association)	0.350
MLLT10	TCF4	psi-mi:“MI:0914”(association)	0.350
TCF4	MLLT10	psi-mi:“MI:0914”(association)	0.350
DOT1L	TCF4	psi-mi:“MI:0914”(association)	0.350
TCP10L	RNF40	psi-mi:“MI:0914”(association)	0.350
PMF1	RGPD8	psi-mi:“MI:0914”(association)	0.350
KIF6	ACADS	psi-mi:“MI:0914”(association)	0.350
MLLT10	SOD1	psi-mi:“MI:0914”(association)	0.350

BioGRID (78): MLLT10 (Proximity Label-MS), MLLT10 (Affinity Capture-MS), MLLT10 (Affinity Capture-MS), MLLT10 (Affinity Capture-MS), MLLT10 (Affinity Capture-MS), MLLT10 (Affinity Capture-MS), MLLT10 (Affinity Capture-MS), MLLT10 (Affinity Capture-MS), MLLT10 (Affinity Capture-MS), MLLT10 (Affinity Capture-MS), MLLT10 (Affinity Capture-MS), MLLT10 (Affinity Capture-MS), MLLT10 (Affinity Capture-MS), Tuba1a (Affinity Capture-MS), YEATS4 (Reconstituted Complex)

ESM2 similar proteins: A0A096MJY4, A0A486WWJ9, A2ICN5, A2VDZ3, A4UTP7, A8WL06, B7ZR65, H2LBU8, O89038, P10071, P40791, P55197, P55879, Q02078, Q03413, Q03414, Q06413, Q0VGT2, Q14814, Q2KIA0, Q2MJT0, Q32NP8, Q4VYR7, Q5IS56, Q5R444, Q5REW7, Q5U4X3, Q60929, Q61602, Q63943, Q6DFF5, Q6DIF3, Q6F2E7, Q7ZY13, Q8BUR3, Q8CFN5, Q91660, Q91661, Q9DE25, Q9EPK5

Diamond homologs: A0A286Y9D1, A1YVX4, A7E320, B2KF05, B2RRD7, B6CHA3, F4KBP5, F6UA42, G5E8P1, G5EBZ4, O54826, O75164, O94880, O94953, P0CB22, P29375, P34447, P41229, P41230, P47156, P55197, P55198, P55201, Q0P4S5, Q12311, Q20318, Q22516, Q29EQ3, Q30DN6, Q38JA7, Q3UXZ9, Q5E9T7, Q5RD88, Q5TKR9, Q62240, Q6GQJ2, Q6IE81, Q6IE82, Q6IQX0, Q6K431

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MLLT10	“form complex”	SS18/MLLT10	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	93
Likely benign	16
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

6058 predictions. Top by Δscore:

Variant	Effect	Δscore
10:21534259:G:GT	donor_gain	1.0000
10:21538827:CAACA:C	acceptor_loss	1.0000
10:21538828:A:AG	acceptor_gain	1.0000
10:21538828:AACAG:A	acceptor_loss	1.0000
10:21538829:A:G	acceptor_gain	1.0000
10:21538829:ACAGC:A	acceptor_loss	1.0000
10:21538830:CAG:C	acceptor_loss	1.0000
10:21538831:A:AG	acceptor_gain	1.0000
10:21538831:AGC:A	acceptor_loss	1.0000
10:21538831:AGCTT:A	acceptor_gain	1.0000
10:21538832:G:GG	acceptor_gain	1.0000
10:21538832:GC:G	acceptor_gain	1.0000
10:21538832:GCT:G	acceptor_gain	1.0000
10:21538832:GCTT:G	acceptor_gain	1.0000
10:21538832:GCTTG:G	acceptor_gain	1.0000
10:21538908:GAGTG:G	donor_gain	1.0000
10:21538910:GTG:G	donor_gain	1.0000
10:21538912:GGTAA:G	donor_loss	1.0000
10:21538913:G:A	donor_loss	1.0000
10:21538913:G:GG	donor_gain	1.0000
10:21538914:T:G	donor_loss	1.0000
10:21586290:ATAG:A	acceptor_loss	1.0000
10:21586292:A:AC	acceptor_loss	1.0000
10:21586292:A:AG	acceptor_gain	1.0000
10:21586293:G:GG	acceptor_gain	1.0000
10:21586293:GA:G	acceptor_gain	1.0000
10:21586293:GAGAT:G	acceptor_gain	1.0000
10:21586345:GGGG:G	donor_gain	1.0000
10:21586346:GGG:G	donor_gain	1.0000
10:21586346:GGGG:G	donor_gain	1.0000

AlphaMissense

6932 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:21534706:T:C	M21T	1.000
10:21534707:G:A	M21I	1.000
10:21534707:G:C	M21I	1.000
10:21534707:G:T	M21I	1.000
10:21534711:G:A	G23R	1.000
10:21534711:G:C	G23R	1.000
10:21534712:G:A	G23E	1.000
10:21534714:G:C	G24R	1.000
10:21534715:G:A	G24D	1.000
10:21534717:T:A	C25S	1.000
10:21534717:T:C	C25R	1.000
10:21534717:T:G	C25G	1.000
10:21534718:G:A	C25Y	1.000
10:21534718:G:C	C25S	1.000
10:21534718:G:T	C25F	1.000
10:21534719:T:G	C25W	1.000
10:21534720:T:C	C26R	1.000
10:21534721:G:A	C26Y	1.000
10:21534722:C:G	C26W	1.000
10:21534724:T:A	V27D	1.000
10:21534724:T:C	V27A	1.000
10:21534726:T:A	C28S	1.000
10:21534726:T:C	C28R	1.000
10:21534726:T:G	C28G	1.000
10:21534727:G:A	C28Y	1.000
10:21534727:G:C	C28S	1.000
10:21534727:G:T	C28F	1.000
10:21534728:C:G	C28W	1.000
10:21534732:G:C	D30H	1.000
10:21534732:G:T	D30Y	1.000

dbSNP variants (sampled 300 via entrez): RS1000002550 (10:21570749 C>T), RS1000005617 (10:21736567 C>T), RS1000027362 (10:21575516 A>G), RS1000027739 (10:21704251 T>A), RS1000043127 (10:21651034 G>A), RS1000053263 (10:21649801 T>G), RS1000069679 (10:21616941 G>A), RS1000104660 (10:21685662 G>A,C), RS1000110038 (10:21552253 C>T), RS1000116839 (10:21571110 A>G,T), RS1000125466 (10:21643622 T>A), RS1000133979 (10:21701590 T>A,C), RS1000136836 (10:21610506 T>C), RS1000141295 (10:21552667 C>G,T), RS1000158698 (10:21651379 G>A)

Disease associations

OMIM: gene MIM:602409 | disease phenotypes: MIM:601626

GenCC curated gene-disease

Mondo (1): acute myeloid leukemia (MONDO:0018874)

Orphanet (1): Acute myeloid leukemia (Orphanet:519)

HPO phenotypes

3 total (3 of 3 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001442	Typified by somatic mosaicism
HP:0004808	Acute myeloid leukemia

GWAS associations

29 associations (top):

Study	Trait	p-value
GCST001184_1	Meningioma	2.000000e-14
GCST001937_11	Breast cancer	4.000000e-14
GCST001941_14	Ovarian cancer	2.000000e-08
GCST001941_15	Ovarian cancer	1.000000e-07
GCST002748_8	Epithelial ovarian cancer	1.000000e-09
GCST003170_5	Subcutaneous adipose tissue	1.000000e-08
GCST005829_11	Hand grip strength	2.000000e-13
GCST005830_14	Hand grip strength	4.000000e-16
GCST007147_6	Lateral ventricular volume in normal aging	2.000000e-08
GCST007209_12	Gallstone disease	4.000000e-12
GCST008512_27	Multisite chronic pain	3.000000e-08
GCST008647_14	Urinary sodium excretion	4.000000e-11
GCST009597_195	Multiple sclerosis	4.000000e-06
GCST009602_80	Metabolic syndrome	2.000000e-08
GCST009640_36	Urinary albumin-to-creatinine ratio	2.000000e-09
GCST010135_27	Oily fish consumption	2.000000e-19
GCST010136_13	Fruit consumption	1.000000e-08
GCST010136_20	Fruit consumption	3.000000e-08
GCST010136_26	Fruit consumption	5.000000e-20
GCST010138_13	Raw vegetable consumption	2.000000e-11
GCST010140_44	Pork consumption	2.000000e-19
GCST010142_54	Fish- and plant-related diet	8.000000e-17
GCST010142_65	Fish- and plant-related diet	5.000000e-11
GCST010142_85	Fish- and plant-related diet	2.000000e-24
GCST010703_303	Brain morphology (MOSTest)	1.000000e-27
GCST010988_438	Adult body size	2.000000e-20
GCST011122_66	Walking pace	9.000000e-13
GCST011703_98	Smoking initiation	8.000000e-11
GCST012332_27	Multisite chronic pain	4.000000e-08

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0006941	grip strength measurement
EFO:0008487	lateral ventricle volume measurement
EFO:0010100	multisite chronic pain
EFO:0009282	sodium measurement
EFO:0000195	metabolic syndrome
EFO:0007778	urinary albumin to creatinine ratio
EFO:0008111	diet measurement
EFO:0004346	neuroimaging measurement
EFO:0005670	smoking initiation

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D015470	Leukemia, Myeloid, Acute	C04.557.337.539.275; C15.378.508.539.275

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, decreases methylation, affects cotreatment, increases expression	9
bisphenol A	increases methylation, decreases expression, affects cotreatment	3
Acetaminophen	decreases expression	2
Formaldehyde	decreases expression	2
Phenylmercuric Acetate	decreases expression, affects cotreatment	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
FR900359	increases phosphorylation	1
uranyl acetate	affects expression	1
trichostatin A	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
tanespimycin	affects cotreatment, decreases expression	1
monomethylarsonous acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, affects expression	1
dorsomorphin	affects cotreatment, decreases expression, affects expression	1
VER 155008	affects cotreatment, decreases expression	1
Arsenic Trioxide	increases expression	1
Fulvestrant	increases methylation, affects cotreatment	1
Vorinostat	increases expression	1
Leflunomide	increases expression	1
Arsenic	affects methylation	1
Cadmium	increases abundance, increases expression	1
Dexamethasone	decreases expression, affects cotreatment	1
Diethylstilbestrol	increases expression	1
Doxorubicin	decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, decreases expression	1

Cellosaurus cell lines

52 cell lines: 52 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_0007	U-937	Cancer cell line	Male
CVCL_1775	TUR	Cancer cell line	Male
CVCL_2082	JOSK-I	Cancer cell line	Male
CVCL_2083	JOSK-M	Cancer cell line	Male
CVCL_2810	U-937 cl1-14	Cancer cell line	Male
CVCL_2811	U-937 cl1-22	Cancer cell line	Male
CVCL_2Z95	U937-DC-SIGN	Cancer cell line	Male
CVCL_3680	EL 1	Cancer cell line	Male
CVCL_4V23	U937/ara-C	Cancer cell line	Male
CVCL_6444	SC [Human contaminated U-937]	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00199147	PHASE4	UNKNOWN	Efficacy of G-CSF-Priming in Elderly AML Patients
NCT00304447	PHASE4	COMPLETED	Study Evaluating the Effect of Corticosteroids on Mylotarg® Infusion-Related Adverse Events in Patients With Leukemia
NCT00464217	PHASE4	COMPLETED	Treatment of the Acute Myeloblastic Leukaemia in Patients Over 65 Years
NCT00487448	PHASE4	COMPLETED	SMD_FLAG-IDA_98: FLAG-IDA in Induction Treatment of High Risk Myelodysplastic Syndromes or Secondary Acute Myeloblastic Leukemia
NCT00488709	PHASE4	COMPLETED	Fludarabine, Cytarabine, Topotecan in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia
NCT00686543	PHASE4	COMPLETED	Oral Posaconazole in High Risk Patients With Gastrointestinal Dysfunction (Study P05115)
NCT01041040	PHASE4	COMPLETED	LAM07: Study to Analyze the Efficacy of a Risk Adapted Treatment Strategy, Including Gemtuzumab Ozogamicin (GO) During Consolidation, for Patients With Acute Myeloid Leukemia (AML)
NCT01198054	PHASE4	TERMINATED	LENA-LMA-5:Lenalidomide in Acute Myeloid Leukemia (AML)
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
NCT01347996	PHASE4	COMPLETED	Maintenance Therapy With Ceplene® (Histamine) and IL-2 on Immune Response and MRD in Acute Myeloid Leukemia
NCT01587430	PHASE4	UNKNOWN	3 Anthracyclines, 2 Types of Consolidation With Different ARA-C Doses and Maintenance in Adult Acute Myeloid Leukemia
NCT01819792	PHASE4	COMPLETED	Respiratory Viral Infections During Acute Myeloid Leukemia (AML)Chemotherapy Related Aplasia
NCT02024308	PHASE4	UNKNOWN	AML1-ETO Acute Myeloid Leukemia With Fludarabine and Cytarabine Chemotherapy
NCT02027064	PHASE4	UNKNOWN	Interferon for the Intervention of Molecular Relapse in t (8; 21) AML After Allo-HSCT
NCT02277847	PHASE4	UNKNOWN	Idarubicin at Different Dosages as Induction Therapy for Newly Diagnosed Acute Myeloid Leukaemia
NCT02386800	PHASE4	ACTIVE_NOT_RECRUITING	CINC424A2X01B Rollover Protocol
NCT02926586	PHASE4	COMPLETED	Fludarabine and Cytarabine Versus High-dose Cytarabine for CBF-AML
NCT02933333	PHASE4	UNKNOWN	G-CSF Alone or Combination With GM-CSF on Prevention and Treatment of Infection in Children With Malignant Tumor
NCT03026842	PHASE4	UNKNOWN	Decitabine Versus Conventional Chemotherapy for Maintenance Therapy of Acute Myeloid Leukemia With t(8;21)
NCT03150134	PHASE4	UNKNOWN	Early Tapering of Immunosuppressive Agents to Immunomodulation to Improve Survival of AML Patients
NCT05144243	PHASE4	ACTIVE_NOT_RECRUITING	Study to Assess Adverse Events and Change in Disease State of Oral Venetoclax in Combination With Subcutaneous (SC) Azacitidine in Newly Diagnosed Adult Participants With Acute Myeloid Leukemia (AML) Who Are Ineligible for Intensive Chemotherapy in China
NCT06370000	PHASE4	RECRUITING	Oral Azacitidine in Transplant-Eligible Patients With Acute Myeloid Leukemia (AML) Suffering From Health-Inequality
NCT06571825	PHASE4	RECRUITING	RIC Allo-HSCT vs. Venetoclax-Based Consolidation in Elderly AML Patients After First CR
NCT07016165	PHASE4	RECRUITING	Ciprofloxacin vs Ceftazidime for Empirical Treatment of High-Risk Neutropenic Fever in Children With Hematologic Malignancies
NCT07044687	PHASE4	RECRUITING	Study to Assess Adverse Events and Change in Disease Activity of Oral Venetoclax in Combination With Subcutaneous (SC) or Intravenous (IV) Azacitidine in Newly Diagnosed Adult Participants With Acute Myeloid Leukemia (AML) Who Are Ineligible for Standard Induction Therapy in India
NCT07486713	PHASE4	RECRUITING	Olutasidenib DDI Study in Patients With IDH1 Mutation Positive Malignancies
NCT07561892	PHASE4	RECRUITING	Study of the Effectiveness and Safety of Daunorubicin /Idarubicin ± Silibinin in Treating Newly Diagnosed AML (Non-M3).
NCT00000589	PHASE3	COMPLETED	Trial to Reduce Alloimmunization to Platelets (TRAP)
NCT00044486	PHASE3	COMPLETED	Prophylaxis Trial of Posaconazole Versus Standard Azole Therapy for Neutropenic Patients (Study P01899)
NCT00093990	PHASE3	COMPLETED	Tipifarnib Versus Best Supportive Care in the Treatment of Newly Diagnosed Acute Myeloid Leukemia (AML)
NCT00125606	PHASE3	TERMINATED	Phase 3 Trial for AML Patients in CR2 Comparing 8Gy TBI /Fludarabine to Conditioning With TBI 12Gy/Cyclophosphamide
NCT00136084	PHASE3	COMPLETED	Treatment of Patients With Newly Diagnosed Acute Myeloid Leukemia or Myelodysplasia
NCT00146120	PHASE3	COMPLETED	Risk-Adapted Therapy of Acute Myeloid Leukemia of Adults (18-60 Years) According to the Cytogenetic Result
NCT00150878	PHASE3	TERMINATED	Standard vs. Reduced-Intensity Conditioning in Patients With Acute Myeloid Leukemia in First Remission
NCT00151255	PHASE3	COMPLETED	All-Trans Retinoic Acid in Combination With Standard Induction and Consolidation Therapy in Older Patients With Newly Diagnosed Acute Myeloid Leukemia
NCT00152139	PHASE3	COMPLETED	Stem Cell Transplantation for Patients With Hematologic Malignancies
NCT00152594	PHASE3	TERMINATED	Voriconazole or Placebo in the Prophylaxis of Lung Infiltrates in Patients Undergoing Induction Chemotherapy for Acute Myelogenous Leukemia
NCT00186966	PHASE3	COMPLETED	Treatment of Children and Adolescents With Refractory or Relapsed Acute Myeloid Leukemia
NCT00226512	PHASE3	WITHDRAWN	To Determine the Role of Adding Campath-1H or ATG Given In-vivo in Addition to Fludarabine and Low Dose Busulfex on Outcome in Patients Treated With Reduced Intensity Conditioning
NCT00260832	PHASE3	COMPLETED	Trial of Decitabine in Patients With Acute Myeloid Leukemia