DPY30

Summary

DPY30 (dpy-30 histone methyltransferase complex regulatory subunit, HGNC:24590) is a protein-coding gene on chromosome 2p22.3, encoding Protein dpy-30 homolog (Q9C005). As part of the MLL1/MLL complex, involved in the methylation of histone H3 at ‘Lys-4’, particularly trimethylation. It is a selective cancer dependency (DepMap: 31.5% of cell lines).

This gene encodes an integral core subunit of the SET1/MLL family of H3K4 methyltransferases. The encoded protein directly controls cell cycle regulators and plays an important role in the proliferation and differentiation of human hematopoietic progenitor cells.

Source: NCBI Gene 84661 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 17 total — 5 pathogenic
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 31.5% of screened cell lines
• MANE Select transcript: NM_001321209

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24590
Approved symbol	DPY30
Name	dpy-30 histone methyltransferase complex regulatory subunit
Location	2p22.3
Locus type	gene with protein product
Status	Approved
Aliases	Saf19, HDPY-30, Cps25
Ensembl gene	ENSG00000162961
Ensembl biotype	protein_coding
OMIM	612032
Entrez	84661

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 17 protein_coding, 5 protein_coding_CDS_not_defined

ENST00000295066, ENST00000342166, ENST00000414013, ENST00000422413, ENST00000430665, ENST00000446765, ENST00000452582, ENST00000873159, ENST00000873160, ENST00000873161, ENST00000873162, ENST00000873163, ENST00000873164, ENST00000873165, ENST00000922977, ENST00000922978, ENST00000922979, ENST00000922980, ENST00000922981, ENST00000922982, ENST00000922983, ENST00000922984

RefSeq mRNA: 3 — MANE Select: NM_001321209 NM_001321209, NM_001321210, NM_032574

CCDS: CCDS1777

Canonical transcript exons

ENST00000342166 — 5 exons

Exon	Start	End
ENSE00001720453	32039733	32039805
ENSE00001895154	32023905	32024256
ENSE00003698333	32039279	32039326
ENSE00003700397	32029594	32029736
ENSE00003701329	32039421	32039492

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 98.47.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 61.7056 / max 842.5898, expressed in 1823 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
27704	61.7056	1823

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	98.47	gold quality
bronchus	UBERON:0002185	98.24	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.09	gold quality
right uterine tube	UBERON:0001302	97.81	gold quality
oocyte	CL:0000023	97.63	gold quality
ventricular zone	UBERON:0003053	97.45	gold quality
ganglionic eminence	UBERON:0004023	97.40	gold quality
right adrenal gland	UBERON:0001233	97.29	gold quality
right adrenal gland cortex	UBERON:0035827	97.28	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.27	gold quality
islet of Langerhans	UBERON:0000006	97.23	gold quality
hypothalamus	UBERON:0001898	97.23	gold quality
kidney epithelium	UBERON:0004819	97.18	gold quality
left adrenal gland cortex	UBERON:0035825	97.12	gold quality
left adrenal gland	UBERON:0001234	97.10	gold quality
adrenal cortex	UBERON:0001235	96.82	gold quality
spinal cord	UBERON:0002240	96.67	gold quality
adrenal gland	UBERON:0002369	96.49	gold quality
left ventricle myocardium	UBERON:0006566	96.49	gold quality
cortical plate	UBERON:0005343	96.41	gold quality
anterior cingulate cortex	UBERON:0009835	96.40	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.24	gold quality
prefrontal cortex	UBERON:0000451	96.23	gold quality
nasal cavity mucosa	UBERON:0001826	96.19	gold quality
caput epididymis	UBERON:0004358	96.19	gold quality
left lobe of thyroid gland	UBERON:0001120	96.11	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.08	gold quality
amygdala	UBERON:0001876	96.05	gold quality
substantia nigra	UBERON:0002038	96.04	gold quality
upper arm skin	UBERON:0004263	96.04	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-9388	no	11.21
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

58 targeting DPY30, 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-25-3P	99.98	74.60	1817
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-139-5P	99.80	69.50	1399
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 31.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 19)

• hDPY-30 (dpy-30-like protein) binds ASH2L directly. The evolutionarily conserved hDPY-30, ASH2L, RBBP5 and WDR5 likely constitute a subcomplex that is shared by all human Set1-like HMT complexes. (PMID:17500065)
• The DPY-30 C-terminal domain structure, harboring the conserved DPY-30 motif, is composed of two alpha-helices linked by a sharp loop and forms a typical X-type four-helix bundle required for dimer formation. (PMID:19481096)
• First report of SPG4 associated with partial deletions of both the SPAST and DPY30 genes. The partial heterozygous deletion of DPY30 could modify the phenotypic expression of SPG4 patients with this pedigree. (PMID:20857310)
• determination of the minimum motif of Ash2L that is required for DPY30 interaction; a structural model for the Ash2L-DPY30 interaction (PMID:22231628)
• DPY30 regulates pathways in cellular senescence through ID protein expression. (PMID:23872946)
• A deletion mutation and reduced DPY30 expression in a Spastic Paraplegia type 4 Japanese family. (PMID:24690193)
• The DPY30 subunit in SET1/MLL complexes regulates the proliferation and differentiation of hematopoietic progenitor cells. (PMID:25139354)
• Based on our structural data and cross-linking results, we suggest that Dpy30 may regulate H3K4 methylation according to its copy number in COMPASS (PMID:25542209)
• these results form the basis for understanding how WRAD(DRY-30) differentially regulates SET1 family complexes in vivo. (PMID:25561738)
• results indicate that DPY30 has critical roles in the proliferation, migration, and invasion of gastric cancer cells, and suggest DPY30 might be a therapeutic target in gastric cancer (PMID:26147337)
• Dpy30 role in cellular reprogramming and its interactions with Set1 complex (PMID:26691508)
• The PKA-binding domain of AKAP8 and the C-terminal domain of DPY30, also called Dpy-30 motif, are crucial for the interaction between these proteins. A single amino acid substitution in DPY30 L69D affects its dimerization and completely abolishes its interaction with AKAP8 and BIG1. (PMID:29288530)
• In this study identify an epistatic interaction between SPAST and DPY30 that influences age at onset in spastin-hereditary spastic paraplegia. (PMID:29481671)
• The results indicated that DPY30 may act as an oncogene in EOC and thus represents a potential therapeutic target and prognostic marker in EOC. (PMID:30221689)
• These results reveal a critical role of DPY30 in glucose homeostasis. (PMID:30448059)
• A chromatin modulator sustains self-renewal and enables differentiation of postnatal neural stem and progenitor cells. (PMID:31065682)
• Mechanism for DPY30 and ASH2L intrinsically disordered regions to modulate the MLL/SET1 activity on chromatin. (PMID:34012049)
• Glioblastoma stem cells reprogram chromatin in vivo to generate selective therapeutic dependencies on DPY30 and phosphodiesterases. (PMID:34985972)
• DPY30 Promotes Proliferation and Cell Cycle Progression of Colorectal Cancer Cells via Mediating H3K4 Trimethylation. (PMID:37324189)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	dpy30	ENSDARG00000004427
mus_musculus	Dpy30	ENSMUSG00000024067
rattus_norvegicus	Dpy30	ENSRNOG00000027126

Protein

Protein identifiers

Protein dpy-30 homolog — Q9C005 (reviewed: Q9C005)

Alternative names: Dpy-30-like protein

All UniProt accessions (1): Q9C005

UniProt curated annotations — full annotation on UniProt →

Function. As part of the MLL1/MLL complex, involved in the methylation of histone H3 at ‘Lys-4’, particularly trimethylation. Histone H3 ‘Lys-4’ methylation represents a specific tag for epigenetic transcriptional activation. May play some role in histone H3 acetylation. In a teratocarcinoma cell, plays a crucial role in retinoic acid-induced differentiation along the neural lineage, regulating gene induction and H3 ‘Lys-4’ methylation at key developmental loci. May also play an indirect or direct role in endosomal transport.

Subunit / interactions. Homodimer. Core component of several methyltransferase-containing complexes including MLL1/MLL, MLL2/3 (also named ASCOM complex) and MLL4/WBP7. Each complex is at least composed of ASH2L, RBBP5, WDR5, DPY30, one or more specific histone methyltransferases (KMT2A/MLL1, KMT2D/MLL2, KMT2C/MLL3 and KMT2B/MLL4), and the facultative components MEN1, HCFC1, HCFC2, NCOA6, KDM6A, PAXIP1/PTIP, PAGR1 and alpha- and beta-tubulin. Interacts with ASH2L; the interaction is direct. Interacts with ARFGEF1. Component of the SET1 complex, at least composed of the catalytic subunit (SETD1A or SETD1B), WDR5, WDR82, RBBP5, ASH2L/ASH2, CXXC1/CFP1, HCFC1 and DPY30.

Subcellular location. Nucleus. Golgi apparatus. trans-Golgi network.

Similarity. Belongs to the dpy-30 family.

RefSeq proteins (2): NP_001308138, NP_115963 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007858	Dpy-30_motif	Conserved_site
IPR037856	Sdc1/DPY30	Family
IPR049629	DPY30_SDC1_DD	Domain

Pfam: PF05186

UniProt features (13 total): helix 6, modified residue 3, chain 1, region of interest 1, cross-link 1, turn 1

Structure

Experimental structures (PDB)

12 structures.

PDB	Method	Resolution (Å)
3G36	X-RAY DIFFRACTION	1.2
4RT4	X-RAY DIFFRACTION	2
4RTA	X-RAY DIFFRACTION	2.12
4RIQ	X-RAY DIFFRACTION	2.23
6E2H	X-RAY DIFFRACTION	2.24
9YM8	ELECTRON MICROSCOPY	3.43
9YMF	ELECTRON MICROSCOPY	3.45
9YL3	ELECTRON MICROSCOPY	3.5
9YLE	ELECTRON MICROSCOPY	3.63
9YLY	ELECTRON MICROSCOPY	3.77
7UD5	ELECTRON MICROSCOPY	4.25
6PWV	ELECTRON MICROSCOPY	6.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9C005-F1	75.98	0.48

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 (4): 1, 19, 35, 35

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-201722	Formation of the beta-catenin:TCF transactivating complex
R-HSA-3214841	PKMTs methylate histone lysines
R-HSA-3769402	Deactivation of the beta-catenin transactivating complex
R-HSA-5617472	Activation of anterior HOX genes in hindbrain development during early embryogenesis
R-HSA-8936459	RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function
R-HSA-9772755	Formation of WDR5-containing histone-modifying complexes
R-HSA-9818564	Epigenetic regulation of gene expression by MLL3 and MLL4 complexes
R-HSA-9841922	MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis
R-HSA-9909649	Regulation of PD-L1(CD274) transcription
R-HSA-9944997	Loss of Function of KMT2D in MLL4 Complex Formation in Kabuki Syndrome
R-HSA-9976102	Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)

MSigDB gene sets: 184 (showing top): TGCGCANK_UNKNOWN, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, MODULE_151, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_VESICLE_MEDIATED_TRANSPORT, EFC_Q6, GOCC_TRANS_GOLGI_NETWORK, OCT1_03, GOBP_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, GOBP_TRANSCRIPTION_INITIATION_AT_RNA_POLYMERASE_II_PROMOTER, ZHANG_BREAST_CANCER_PROGENITORS_UP, GOBP_CHROMATIN_REMODELING, DANG_BOUND_BY_MYC, GOBP_EPIGENETIC_REGULATION_OF_GENE_EXPRESSION, MODULE_114

GO Biological Process (3): endosomal transport (GO:0016197), transcription initiation-coupled chromatin remodeling (GO:0045815), chromatin organization (GO:0006325)

GO Molecular Function (3): identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), protein binding (GO:0005515)

GO Cellular Component (9): nucleus (GO:0005634), nucleoplasm (GO:0005654), Golgi apparatus (GO:0005794), trans-Golgi network (GO:0005802), histone methyltransferase complex (GO:0035097), MLL1/2 complex (GO:0044665), MLL3/4 complex (GO:0044666), Set1C/COMPASS complex (GO:0048188), MLL1 complex (GO:0071339)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
TCF dependent signaling in response to WNT	2
Epigenetic regulation by WDR5-containing histone modifying complexes	2
Chromatin modifying enzymes	1
Activation of HOX genes during differentiation	1
Transcriptional regulation by RUNX1	1
Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes	1
Regulation of PD-L1(CD274) expression	1
Loss of Function of KMT2D in Kabuki Syndrome	1
Differentiation of T cells	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
histone methyltransferase complex	3
intracellular membrane-bounded organelle	2
vesicle-mediated transport	1
intracellular transport	1
transcription initiation at RNA polymerase II promoter	1
positive regulation of gene expression, epigenetic	1
cellular component organization	1
protein binding	1
identical protein binding	1
protein dimerization activity	1
binding	1
nuclear lumen	1
cellular anatomical structure	1
cytoplasm	1
endomembrane system	1
Golgi apparatus subcompartment	1
nucleoplasm	1
methyltransferase complex	1
nuclear protein-containing complex	1
MLL1/2 complex	1

Protein interactions and networks

STRING

3388 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DPY30	RBBP5	Q15291	999
DPY30	ASH2L	Q9UBL3	999
DPY30	WDR5	P61964	999
DPY30	KMT2C	Q8NEZ4	991
DPY30	SETD1A	O15047	983
DPY30	SETD1B	Q9UPS6	978
DPY30	CXXC1	Q9P0U4	973
DPY30	HCFC1	P51610	943
DPY30	PAGR1	Q9BTK6	934
DPY30	PAXIP1	Q6ZW49	924
DPY30	NCOA6	Q14686	921
DPY30	WDR82	Q6UXN9	879
DPY30	KDM6A	O15550	808
DPY30	KMT2A	Q03164	785
DPY30	AKAP8	O43823	765

IntAct

227 interactions, top by confidence:

A	B	Type	Score
DPY30	ASH2L	psi-mi:“MI:0915”(physical association)	0.970
ASH2L	DPY30	psi-mi:“MI:0915”(physical association)	0.970
DPY30	ASH2L	psi-mi:“MI:0407”(direct interaction)	0.970
ASH2L	WDR5	psi-mi:“MI:0915”(physical association)	0.950
DPY30	WDR5	psi-mi:“MI:0914”(association)	0.860
RBBP5	KMT2D	psi-mi:“MI:0914”(association)	0.840
DPY30	DPY30	psi-mi:“MI:0915”(physical association)	0.830
DPY30	DPY30	psi-mi:“MI:0407”(direct interaction)	0.830
DPY30	ASH2L	psi-mi:“MI:0407”(direct interaction)	0.740
	WDR5	psi-mi:“MI:0914”(association)	0.730
DPY30	PSMD14	psi-mi:“MI:0915”(physical association)	0.720
PSMD14	DPY30	psi-mi:“MI:0915”(physical association)	0.720
DPY30	RBBP5	psi-mi:“MI:0914”(association)	0.690
NFIC	NFIB	psi-mi:“MI:2364”(proximity)	0.690
GTF2I	DPY30	psi-mi:“MI:0915”(physical association)	0.670
DYDC1	DPY30	psi-mi:“MI:0915”(physical association)	0.670

BioGRID (279): DPY30 (Reconstituted Complex), DPY30 (Two-hybrid), DPY30 (Two-hybrid), DPY30 (Two-hybrid), DPY30 (Two-hybrid), DPY30 (Affinity Capture-Western), DPY30 (Affinity Capture-Western), DPY30 (Affinity Capture-Western), DPY30 (Protein-peptide), DPY30 (Affinity Capture-MS), DPY30 (Two-hybrid), DPY30 (Two-hybrid), DYDC1 (Two-hybrid), DPY30 (Two-hybrid), DPY30 (Affinity Capture-MS)

ESM2 similar proteins: A0JMA8, A1A5P5, A6NNX1, E7F187, O43150, O46470, O54829, O94376, P45966, P47822, P49758, P49802, P49803, Q0VIA1, Q23288, Q23679, Q2KI89, Q2NKU6, Q32PB2, Q3KNY5, Q3ZCF2, Q4R6I5, Q4R6W4, Q5M6W3, Q5R629, Q5R6P5, Q5U245, Q5XIR8, Q61Z20, Q626S1, Q6CT76, Q6CVN3, Q6DJ25, Q6IP67, Q6IQX0, Q6VBQ6, Q758M1, Q7SIG6, Q7YTB0, Q80Y84

Diamond homologs: O74861, P56597, Q03323, Q10661, Q2NKU6, Q8K3E7, Q99LT0, Q9C005, Q9D2H2, Q9VKQ9, Q95JP6, Q96M32, Q99MH5, B0TC77, B2A4G2, B3QS41, Q6DGQ8, Q6FD71, Q73NP0, Q8XHU4, C5CGI1, O29581, Q0SQG5, Q0TMR7, B1I3R5

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
DPY30	“form complex”	“MLL/SET subcomplex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 138 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
Formation of WDR5-containing histone-modifying complexes	14	44.3×	2e-17
Deactivation of the beta-catenin transactivating complex	7	19.4×	5e-06
Epigenetic regulation of gene expression by MLL3 and MLL4 complexes	8	18.8×	2e-06
PKMTs methylate histone lysines	7	13.4×	5e-05
Formation of the beta-catenin:TCF transactivating complex	9	12.9×	3e-06
Epigenetic regulation by WDR5-containing histone modifying complexes	7	12.9×	6e-05
Nonhomologous End-Joining (NHEJ)	6	12.0×	5e-04
Activation of anterior HOX genes in hindbrain development during early embryogenesis	11	12.0×	4e-07

GO biological processes:

GO term	Partners	Fold	FDR
transcription initiation-coupled chromatin remodeling	5	17.4×	1e-03
heterochromatin formation	6	13.9×	6e-04
nucleosome assembly	8	10.2×	2e-04
DNA replication	6	9.0×	4e-03
chromatin remodeling	12	8.0×	1e-05
DNA repair	9	5.2×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	0
Uncertain significance	10
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
219058	Single allele	Pathogenic
219095	Single allele	Pathogenic
4081879	NC_000002.12:g.32024174_32184348del	Pathogenic
4081952	NC_000002.12:g.32024173_32184348del	Pathogenic
60107	GRCh38/hg38 2p23.1-22.3(chr2:31368632-32087629)x1	Pathogenic

SpliceAI

3394 predictions. Top by Δscore:

Variant	Effect	Δscore
2:31869839:GATAC:G	donor_loss	1.0000
2:31869840:ATACT:A	donor_loss	1.0000
2:31869841:TACT:T	donor_loss	1.0000
2:31869842:AC:A	donor_loss	1.0000
2:31869843:CTC:C	donor_loss	1.0000
2:31869844:T:TA	donor_loss	1.0000
2:31869845:CACAT:C	donor_loss	1.0000
2:31869846:A:AC	donor_gain	1.0000
2:31869847:C:CC	donor_gain	1.0000
2:31883477:CATG:C	acceptor_gain	1.0000
2:31891985:AACTT:A	donor_loss	1.0000
2:31891986:ACTT:A	donor_loss	1.0000
2:31891987:CTTAC:C	donor_loss	1.0000
2:31891988:TTAC:T	donor_loss	1.0000
2:31891989:TA:T	donor_loss	1.0000
2:31891990:A:AC	donor_gain	1.0000
2:31891990:A:C	donor_loss	1.0000
2:31891990:AC:A	donor_gain	1.0000
2:31891990:ACC:A	donor_gain	1.0000
2:31891991:C:CA	donor_loss	1.0000
2:31891991:C:CC	donor_gain	1.0000
2:31891991:CC:C	donor_gain	1.0000
2:31891991:CCC:C	donor_gain	1.0000
2:31892050:A:AC	donor_gain	1.0000
2:31892051:C:CC	donor_gain	1.0000
2:31892130:TATGG:T	acceptor_gain	1.0000
2:31892132:TGG:T	acceptor_gain	1.0000
2:31892133:GG:G	acceptor_gain	1.0000
2:31892135:C:CC	acceptor_gain	1.0000
2:31892136:T:C	acceptor_gain	1.0000

AlphaMissense

636 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:32024221:A:G	L88P	1.000
2:32024221:A:T	L88H	1.000
2:32024230:G:T	A85E	1.000
2:32024235:A:C	F83L	1.000
2:32024235:A:T	F83L	1.000
2:32024237:A:G	F83L	1.000
2:32024245:G:T	P80H	1.000
2:32029594:C:G	R76T	1.000
2:32029606:A:G	L72P	1.000
2:32029606:A:T	L72H	1.000
2:32029613:C:G	A70P	1.000
2:32029615:A:G	L69P	1.000
2:32029618:C:T	G68E	1.000
2:32029619:C:G	G68R	1.000
2:32029619:C:T	G68R	1.000
2:32029627:A:G	L65S	1.000
2:32029639:A:T	V61D	1.000
2:32029645:T:G	Q59P	1.000
2:32029648:T:A	D58V	1.000
2:32029649:C:G	D58H	1.000
2:32029651:A:G	L57P	1.000
2:32029651:A:T	L57Q	1.000
2:32029655:A:C	Y56D	1.000
2:32029655:A:G	Y56H	1.000
2:32029661:G:A	R54C	1.000
2:32029661:G:T	R54S	1.000
2:32024221:A:C	L88R	0.999
2:32024231:C:G	A85P	0.999
2:32024233:A:G	L84P	0.999
2:32024233:A:T	L84Q	0.999

dbSNP variants (sampled 300 via entrez): RS1000012918 (2:32038291 G>C), RS1000198294 (2:32041139 G>A,C), RS1000540144 (2:32039890 G>T), RS1000839266 (2:32035038 G>A), RS1000874182 (2:32012279 A>C,G), RS1000911418 (2:32040132 A>G), RS1000919902 (2:32016725 G>A), RS1000925064 (2:32039187 C>G), RS1000978585 (2:32039017 A>G), RS1001037020 (2:32018020 T>C), RS1001219931 (2:32035592 A>T), RS1001324162 (2:32041141 C>T), RS1001524278 (2:32014719 G>A), RS1001579816 (2:32021222 C>G,T), RS1001672640 (2:32035435 C>T)

Disease associations

OMIM: gene MIM:612032 | disease phenotypes: MIM:182601, MIM:616050, MIM:616115

GenCC curated gene-disease

Mondo (3): hereditary spastic paraplegia 4 (MONDO:0008438), periodic fever-infantile enterocolitis-autoinflammatory syndrome (MONDO:0014472), familial cold autoinflammatory syndrome 4 (MONDO:0014498)

Orphanet (4): Autosomal dominant spastic paraplegia type 4 (Orphanet:100985), Periodic fever-infantile enterocolitis-autoinflammatory syndrome (Orphanet:436166), Familial cold urticaria (Orphanet:47045), NLRC4-related familial cold autoinflammatory syndrome (Orphanet:576349)

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002255_2	Inflammatory biomarkers	3.000000e-19
GCST006661_237	Male-pattern baldness	7.000000e-26
GCST009736_2	Interleukin-18 levels	3.000000e-19

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004812	interleukin-1 beta measurement
EFO:0004581	interleukin 18 measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536865	Spastic paraplegia 4, autosomal dominant (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4106124 (PROTEIN-PROTEIN INTERACTION)

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

ChEMBL bioactivities

34 potent at pChembl≥5 of 34 total, top 34 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.90	IC50	12.6	nM	CHEMBL4073865
7.90	IC50	12.7	nM	CHEMBL4103117
7.82	IC50	15.2	nM	CHEMBL4648206
7.66	IC50	21.8	nM	CHEMBL4646694
7.59	IC50	25.5	nM	CHEMBL4645555
7.53	IC50	29.6	nM	CHEMBL4632716
7.33	IC50	46.8	nM	CHEMBL4649421
7.25	IC50	55.6	nM	CHEMBL4633548
7.18	IC50	66.5	nM	CHEMBL4641078
7.14	IC50	72.4	nM	CHEMBL4643465
7.07	IC50	84.8	nM	CHEMBL4094433
7.00	IC50	99.5	nM	CHEMBL4637676
6.92	IC50	119	nM	CHEMBL4636460
6.91	IC50	124	nM	CHEMBL4102238
6.90	IC50	127	nM	CHEMBL4638858
6.88	IC50	132	nM	CHEMBL4647930
6.86	IC50	138	nM	CHEMBL4092028
6.86	IC50	138.4	nM	CHEMBL4638624
6.82	IC50	150.2	nM	CHEMBL4635991
6.72	IC50	190	nM	CHEMBL4064300
6.70	IC50	201	nM	CHEMBL4649846
6.67	IC50	216	nM	CHEMBL4072805
6.63	IC50	234	nM	CHEMBL4635424
6.43	IC50	373	nM	CHEMBL4099772
6.35	IC50	451	nM	CHEMBL4641985
6.34	IC50	452	nM	CHEMBL4084272
6.32	IC50	477	nM	CHEMBL4086696
6.24	IC50	578	nM	CHEMBL3799591
6.23	IC50	592	nM	CHEMBL4633905
6.14	IC50	724	nM	S-ADENOSYLHOMOCYSTEINE
6.13	IC50	744	nM	CHEMBL4078842
5.90	IC50	1259	nM	CHEMBL4065250
5.82	IC50	1527	nM	CHEMBL4099696
5.75	IC50	1800	nM	CHEMBL4078836

PubChem BioAssay actives

34 with measured affinity, of 42 total; 34 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-[(3R,6S,9S,12R)-9-[3-(diaminomethylideneamino)propyl]-6-ethyl-12-methyl-2,5,8,11-tetraoxo-3-phenyl-1,4,7,10-tetrazacyclotetradec-12-yl]-2-methylpropanamide;2,2,2-trifluoroacetic acid	1449556: Inhibition of human N-terminal GST-tagged MLL1 (3735 to 3973 residues) interaction with human full length N-terminal 6xHis-tagged ASH2L/N-terminal 6xHis-tagged human full length RbBP5/human N-terminal 6xHis-tagged WDR5/human full length N-terminal 6xHis-tagged DPY30 assessed as decrease in H3K4me1-2 methylation preincubated for 30 mins followed by SAM/nucleosome mixture addition measured after 120 mins in absence of light by AlphaLISA assay	ic50	0.0126	uM
N-[(3R,6S,9S,12R)-6-ethyl-12-methyl-9-[3-[(N’-methylcarbamimidoyl)amino]propyl]-2,5,8,11-tetraoxo-3-phenyl-1,4,7,10-tetrazacyclotetradec-12-yl]-2-methylpropanamide;2,2,2-trifluoroacetic acid	1449556: Inhibition of human N-terminal GST-tagged MLL1 (3735 to 3973 residues) interaction with human full length N-terminal 6xHis-tagged ASH2L/N-terminal 6xHis-tagged human full length RbBP5/human N-terminal 6xHis-tagged WDR5/human full length N-terminal 6xHis-tagged DPY30 assessed as decrease in H3K4me1-2 methylation preincubated for 30 mins followed by SAM/nucleosome mixture addition measured after 120 mins in absence of light by AlphaLISA assay	ic50	0.0127	uM
(2S)-2-amino-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-[[1-(thiophen-3-ylmethyl)azetidin-3-yl]methyl]amino]butanoic acid	1658842: Inhibition of recombinant human MLL1 complex (MLL1/Ash2L/RbBP5/WDR5/DPY-30) expressed in Escherichia coli Rosetta 2 (DE3) cells using H3 (1 to 21) peptide as substrate incubated for 1 hr in presence of 3[H] SAM by AlphaLISA assay	ic50	0.0152	uM
(2S)-2-amino-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-[[1-(furan-3-ylmethyl)azetidin-3-yl]methyl]amino]butanoic acid	1658842: Inhibition of recombinant human MLL1 complex (MLL1/Ash2L/RbBP5/WDR5/DPY-30) expressed in Escherichia coli Rosetta 2 (DE3) cells using H3 (1 to 21) peptide as substrate incubated for 1 hr in presence of 3[H] SAM by AlphaLISA assay	ic50	0.0218	uM
(2S)-2-amino-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-[[1-(3-cyclopentylpropyl)azetidin-3-yl]methyl]amino]butanoic acid	1658842: Inhibition of recombinant human MLL1 complex (MLL1/Ash2L/RbBP5/WDR5/DPY-30) expressed in Escherichia coli Rosetta 2 (DE3) cells using H3 (1 to 21) peptide as substrate incubated for 1 hr in presence of 3[H] SAM by AlphaLISA assay	ic50	0.0255	uM
(2S)-2-amino-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-[[1-(3-phenylpropyl)azetidin-3-yl]methyl]amino]butanoic acid	1658842: Inhibition of recombinant human MLL1 complex (MLL1/Ash2L/RbBP5/WDR5/DPY-30) expressed in Escherichia coli Rosetta 2 (DE3) cells using H3 (1 to 21) peptide as substrate incubated for 1 hr in presence of 3[H] SAM by AlphaLISA assay	ic50	0.0296	uM
(2S)-2-amino-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-[(1-benzylazetidin-3-yl)methyl]amino]butanoic acid	1658842: Inhibition of recombinant human MLL1 complex (MLL1/Ash2L/RbBP5/WDR5/DPY-30) expressed in Escherichia coli Rosetta 2 (DE3) cells using H3 (1 to 21) peptide as substrate incubated for 1 hr in presence of 3[H] SAM by AlphaLISA assay	ic50	0.0468	uM
(2S)-2-amino-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-[[1-[(4-chlorophenyl)methyl]azetidin-3-yl]methyl]amino]butanoic acid	1658842: Inhibition of recombinant human MLL1 complex (MLL1/Ash2L/RbBP5/WDR5/DPY-30) expressed in Escherichia coli Rosetta 2 (DE3) cells using H3 (1 to 21) peptide as substrate incubated for 1 hr in presence of 3[H] SAM by AlphaLISA assay	ic50	0.0556	uM
(2S)-2-amino-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-[[1-(thiophen-2-ylmethyl)azetidin-3-yl]methyl]amino]butanoic acid	1658842: Inhibition of recombinant human MLL1 complex (MLL1/Ash2L/RbBP5/WDR5/DPY-30) expressed in Escherichia coli Rosetta 2 (DE3) cells using H3 (1 to 21) peptide as substrate incubated for 1 hr in presence of 3[H] SAM by AlphaLISA assay	ic50	0.0665	uM
(2S)-2-amino-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-[(1-butylazetidin-3-yl)methyl]amino]butanoic acid	1658842: Inhibition of recombinant human MLL1 complex (MLL1/Ash2L/RbBP5/WDR5/DPY-30) expressed in Escherichia coli Rosetta 2 (DE3) cells using H3 (1 to 21) peptide as substrate incubated for 1 hr in presence of 3[H] SAM by AlphaLISA assay	ic50	0.0724	uM
N-[(3R,6S,9S,12R)-9-[3-(diaminomethylideneamino)propyl]-6-ethyl-12-methyl-2,5,8,11-tetraoxo-3-phenyl-1,4,7,10-tetrazacyclopentadec-12-yl]-2-methylpropanamide;2,2,2-trifluoroacetic acid	1449556: Inhibition of human N-terminal GST-tagged MLL1 (3735 to 3973 residues) interaction with human full length N-terminal 6xHis-tagged ASH2L/N-terminal 6xHis-tagged human full length RbBP5/human N-terminal 6xHis-tagged WDR5/human full length N-terminal 6xHis-tagged DPY30 assessed as decrease in H3K4me1-2 methylation preincubated for 30 mins followed by SAM/nucleosome mixture addition measured after 120 mins in absence of light by AlphaLISA assay	ic50	0.0848	uM
(2S)-2-amino-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-[[1-[(3-chlorophenyl)methyl]azetidin-3-yl]methyl]amino]butanoic acid	1658842: Inhibition of recombinant human MLL1 complex (MLL1/Ash2L/RbBP5/WDR5/DPY-30) expressed in Escherichia coli Rosetta 2 (DE3) cells using H3 (1 to 21) peptide as substrate incubated for 1 hr in presence of 3[H] SAM by AlphaLISA assay	ic50	0.0995	uM
(2S)-2-amino-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-[[1-(1-benzofuran-3-ylmethyl)azetidin-3-yl]methyl]amino]butanoic acid	1658842: Inhibition of recombinant human MLL1 complex (MLL1/Ash2L/RbBP5/WDR5/DPY-30) expressed in Escherichia coli Rosetta 2 (DE3) cells using H3 (1 to 21) peptide as substrate incubated for 1 hr in presence of 3[H] SAM by AlphaLISA assay	ic50	0.1190	uM
N-[(3R,6S,9S,12R)-3-(4-chlorophenyl)-9-[3-(diaminomethylideneamino)propyl]-6-ethyl-1,12-dimethyl-2,5,8,11-tetraoxo-1,4,7,10-tetrazacyclohexadec-12-yl]-2-methylpropanamide;2,2,2-trifluoroacetic acid	1449556: Inhibition of human N-terminal GST-tagged MLL1 (3735 to 3973 residues) interaction with human full length N-terminal 6xHis-tagged ASH2L/N-terminal 6xHis-tagged human full length RbBP5/human N-terminal 6xHis-tagged WDR5/human full length N-terminal 6xHis-tagged DPY30 assessed as decrease in H3K4me1-2 methylation preincubated for 30 mins followed by SAM/nucleosome mixture addition measured after 120 mins in absence of light by AlphaLISA assay	ic50	0.1240	uM
(2S)-2-amino-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-[3-(3-cyclopentylpropylamino)cyclobutyl]amino]butanoic acid	1658842: Inhibition of recombinant human MLL1 complex (MLL1/Ash2L/RbBP5/WDR5/DPY-30) expressed in Escherichia coli Rosetta 2 (DE3) cells using H3 (1 to 21) peptide as substrate incubated for 1 hr in presence of 3[H] SAM by AlphaLISA assay	ic50	0.1270	uM
(2S)-2-amino-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-[[1-(2-phenylethyl)triazol-4-yl]methyl]amino]butanoic acid	1658842: Inhibition of recombinant human MLL1 complex (MLL1/Ash2L/RbBP5/WDR5/DPY-30) expressed in Escherichia coli Rosetta 2 (DE3) cells using H3 (1 to 21) peptide as substrate incubated for 1 hr in presence of 3[H] SAM by AlphaLISA assay	ic50	0.1320	uM
N-[(3R,6S,9S,12R)-9-[3-(diaminomethylideneamino)propyl]-6-ethyl-3-(4-fluorophenyl)-1,12-dimethyl-2,5,8,11-tetraoxo-1,4,7,10-tetrazacyclohexadec-12-yl]-2-methylpropanamide;2,2,2-trifluoroacetic acid	1449556: Inhibition of human N-terminal GST-tagged MLL1 (3735 to 3973 residues) interaction with human full length N-terminal 6xHis-tagged ASH2L/N-terminal 6xHis-tagged human full length RbBP5/human N-terminal 6xHis-tagged WDR5/human full length N-terminal 6xHis-tagged DPY30 assessed as decrease in H3K4me1-2 methylation preincubated for 30 mins followed by SAM/nucleosome mixture addition measured after 120 mins in absence of light by AlphaLISA assay	ic50	0.1380	uM
(2S)-2-amino-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-[[1-(3,3-diphenylpropyl)azetidin-3-yl]methyl]amino]butanoic acid	1658842: Inhibition of recombinant human MLL1 complex (MLL1/Ash2L/RbBP5/WDR5/DPY-30) expressed in Escherichia coli Rosetta 2 (DE3) cells using H3 (1 to 21) peptide as substrate incubated for 1 hr in presence of 3[H] SAM by AlphaLISA assay	ic50	0.1384	uM
(2S)-2-amino-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-[[1-[(2-chlorophenyl)methyl]azetidin-3-yl]methyl]amino]butanoic acid	1658842: Inhibition of recombinant human MLL1 complex (MLL1/Ash2L/RbBP5/WDR5/DPY-30) expressed in Escherichia coli Rosetta 2 (DE3) cells using H3 (1 to 21) peptide as substrate incubated for 1 hr in presence of 3[H] SAM by AlphaLISA assay	ic50	0.1502	uM
N-[(3R,6S,9S,12R)-9-[3-(diaminomethylideneamino)propyl]-6-ethyl-1,12-dimethyl-2,5,8,11-tetraoxo-3-phenyl-1,4,7,10-tetrazacyclohexadec-12-yl]-2-methylpropanamide;2,2,2-trifluoroacetic acid	1449556: Inhibition of human N-terminal GST-tagged MLL1 (3735 to 3973 residues) interaction with human full length N-terminal 6xHis-tagged ASH2L/N-terminal 6xHis-tagged human full length RbBP5/human N-terminal 6xHis-tagged WDR5/human full length N-terminal 6xHis-tagged DPY30 assessed as decrease in H3K4me1-2 methylation preincubated for 30 mins followed by SAM/nucleosome mixture addition measured after 120 mins in absence of light by AlphaLISA assay	ic50	0.1900	uM
(2S)-2-amino-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-[3-(3-phenylpropylamino)propyl]amino]butanoic acid	1658842: Inhibition of recombinant human MLL1 complex (MLL1/Ash2L/RbBP5/WDR5/DPY-30) expressed in Escherichia coli Rosetta 2 (DE3) cells using H3 (1 to 21) peptide as substrate incubated for 1 hr in presence of 3[H] SAM by AlphaLISA assay	ic50	0.2010	uM
N-[(3R,6S,9S,12R)-6-ethyl-12-methyl-9-[3-[(N’-methylcarbamimidoyl)amino]propyl]-2,5,8,11-tetraoxo-3-phenyl-1,4,7,10-tetrazacyclooctadec-12-yl]-2-methylpropanamide;2,2,2-trifluoroacetic acid	1449556: Inhibition of human N-terminal GST-tagged MLL1 (3735 to 3973 residues) interaction with human full length N-terminal 6xHis-tagged ASH2L/N-terminal 6xHis-tagged human full length RbBP5/human N-terminal 6xHis-tagged WDR5/human full length N-terminal 6xHis-tagged DPY30 assessed as decrease in H3K4me1-2 methylation preincubated for 30 mins followed by SAM/nucleosome mixture addition measured after 120 mins in absence of light by AlphaLISA assay	ic50	0.2160	uM
(2S)-2-amino-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-[1-(3-cyclopentylpropyl)azetidin-3-yl]amino]butanoic acid	1658842: Inhibition of recombinant human MLL1 complex (MLL1/Ash2L/RbBP5/WDR5/DPY-30) expressed in Escherichia coli Rosetta 2 (DE3) cells using H3 (1 to 21) peptide as substrate incubated for 1 hr in presence of 3[H] SAM by AlphaLISA assay	ic50	0.2340	uM
N-[(3R,6S,9S,12R)-9-[3-(diaminomethylideneamino)propyl]-6-ethyl-12-methyl-2,5,8,11-tetraoxo-3-phenyl-1,4,7,10-tetrazacyclohexadec-12-yl]-2-methylpropanamide;2,2,2-trifluoroacetic acid	1449556: Inhibition of human N-terminal GST-tagged MLL1 (3735 to 3973 residues) interaction with human full length N-terminal 6xHis-tagged ASH2L/N-terminal 6xHis-tagged human full length RbBP5/human N-terminal 6xHis-tagged WDR5/human full length N-terminal 6xHis-tagged DPY30 assessed as decrease in H3K4me1-2 methylation preincubated for 30 mins followed by SAM/nucleosome mixture addition measured after 120 mins in absence of light by AlphaLISA assay	ic50	0.3730	uM
(2S)-2-amino-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-[3-[(3-phenylpropylamino)methyl]cyclobutyl]amino]butanoic acid	1658842: Inhibition of recombinant human MLL1 complex (MLL1/Ash2L/RbBP5/WDR5/DPY-30) expressed in Escherichia coli Rosetta 2 (DE3) cells using H3 (1 to 21) peptide as substrate incubated for 1 hr in presence of 3[H] SAM by AlphaLISA assay	ic50	0.4510	uM
N-[(3R,6S,9S,12R)-6-ethyl-12-methyl-9-[3-[(N’-methylcarbamimidoyl)amino]propyl]-2,5,8,11-tetraoxo-3-phenyl-1,4,7,10-tetrazacyclohexadec-12-yl]-2-methylpropanamide;2,2,2-trifluoroacetic acid	1449556: Inhibition of human N-terminal GST-tagged MLL1 (3735 to 3973 residues) interaction with human full length N-terminal 6xHis-tagged ASH2L/N-terminal 6xHis-tagged human full length RbBP5/human N-terminal 6xHis-tagged WDR5/human full length N-terminal 6xHis-tagged DPY30 assessed as decrease in H3K4me1-2 methylation preincubated for 30 mins followed by SAM/nucleosome mixture addition measured after 120 mins in absence of light by AlphaLISA assay	ic50	0.4520	uM
N-[(3S,6S,9S,12R)-6-ethyl-12-methyl-9-[3-[(N’-methylcarbamimidoyl)amino]propyl]-2,5,8,11-tetraoxo-3-phenyl-1,4,7,10-tetrazacyclotetradec-12-yl]-2-methylpropanamide;2,2,2-trifluoroacetic acid	1449556: Inhibition of human N-terminal GST-tagged MLL1 (3735 to 3973 residues) interaction with human full length N-terminal 6xHis-tagged ASH2L/N-terminal 6xHis-tagged human full length RbBP5/human N-terminal 6xHis-tagged WDR5/human full length N-terminal 6xHis-tagged DPY30 assessed as decrease in H3K4me1-2 methylation preincubated for 30 mins followed by SAM/nucleosome mixture addition measured after 120 mins in absence of light by AlphaLISA assay	ic50	0.4770	uM
N-benzhydryl-1-[[(2S)-5-(diaminomethylideneamino)-2-[[2-ethyl-2-(2-methylpropanoylamino)butanoyl]amino]pentanoyl]amino]cyclopentane-1-carboxamide	1449556: Inhibition of human N-terminal GST-tagged MLL1 (3735 to 3973 residues) interaction with human full length N-terminal 6xHis-tagged ASH2L/N-terminal 6xHis-tagged human full length RbBP5/human N-terminal 6xHis-tagged WDR5/human full length N-terminal 6xHis-tagged DPY30 assessed as decrease in H3K4me1-2 methylation preincubated for 30 mins followed by SAM/nucleosome mixture addition measured after 120 mins in absence of light by AlphaLISA assay	ic50	0.5780	uM
(2S)-2-amino-4-[2-aminoethyl-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl]amino]butanoic acid	1658842: Inhibition of recombinant human MLL1 complex (MLL1/Ash2L/RbBP5/WDR5/DPY-30) expressed in Escherichia coli Rosetta 2 (DE3) cells using H3 (1 to 21) peptide as substrate incubated for 1 hr in presence of 3[H] SAM by AlphaLISA assay	ic50	0.5920	uM
(2S)-2-amino-4-[[(2S,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methylsulfanyl]butanoic acid	1658842: Inhibition of recombinant human MLL1 complex (MLL1/Ash2L/RbBP5/WDR5/DPY-30) expressed in Escherichia coli Rosetta 2 (DE3) cells using H3 (1 to 21) peptide as substrate incubated for 1 hr in presence of 3[H] SAM by AlphaLISA assay	ic50	0.7240	uM
N-[(3R,6S,9S,12R)-6-ethyl-12-methyl-9-[3-[(N’-methylcarbamimidoyl)amino]propyl]-2,5,8,11-tetraoxo-3-phenyl-1,4,7,10-tetrazacycloicos-12-yl]-2-methylpropanamide;2,2,2-trifluoroacetic acid	1449556: Inhibition of human N-terminal GST-tagged MLL1 (3735 to 3973 residues) interaction with human full length N-terminal 6xHis-tagged ASH2L/N-terminal 6xHis-tagged human full length RbBP5/human N-terminal 6xHis-tagged WDR5/human full length N-terminal 6xHis-tagged DPY30 assessed as decrease in H3K4me1-2 methylation preincubated for 30 mins followed by SAM/nucleosome mixture addition measured after 120 mins in absence of light by AlphaLISA assay	ic50	0.7440	uM
N-[(3R,6S,9S,12R)-9-[3-[(N,N’-dimethylcarbamimidoyl)amino]propyl]-6-ethyl-12-methyl-2,5,8,11-tetraoxo-3-phenyl-1,4,7,10-tetrazacyclohexadec-12-yl]-2-methylpropanamide;2,2,2-trifluoroacetic acid	1449556: Inhibition of human N-terminal GST-tagged MLL1 (3735 to 3973 residues) interaction with human full length N-terminal 6xHis-tagged ASH2L/N-terminal 6xHis-tagged human full length RbBP5/human N-terminal 6xHis-tagged WDR5/human full length N-terminal 6xHis-tagged DPY30 assessed as decrease in H3K4me1-2 methylation preincubated for 30 mins followed by SAM/nucleosome mixture addition measured after 120 mins in absence of light by AlphaLISA assay	ic50	1.2590	uM
N-[(3R,6S,9S,12R)-9-[3-(diaminomethylideneamino)propyl]-6-ethyl-12-methyl-2,5,8,11-tetraoxo-3-phenyl-1,4,7,10-tetrazacycloheptadec-12-yl]-2-methylpropanamide;2,2,2-trifluoroacetic acid	1449556: Inhibition of human N-terminal GST-tagged MLL1 (3735 to 3973 residues) interaction with human full length N-terminal 6xHis-tagged ASH2L/N-terminal 6xHis-tagged human full length RbBP5/human N-terminal 6xHis-tagged WDR5/human full length N-terminal 6xHis-tagged DPY30 assessed as decrease in H3K4me1-2 methylation preincubated for 30 mins followed by SAM/nucleosome mixture addition measured after 120 mins in absence of light by AlphaLISA assay	ic50	1.5270	uM
N-[(3R,6S,9S,12R)-9-[3-(diaminomethylideneamino)propyl]-6-ethyl-2,5,8,11-tetraoxo-3-phenyl-1,4,7,10-tetrazacyclotetradec-12-yl]-2-methylpropanamide;2,2,2-trifluoroacetic acid	1449556: Inhibition of human N-terminal GST-tagged MLL1 (3735 to 3973 residues) interaction with human full length N-terminal 6xHis-tagged ASH2L/N-terminal 6xHis-tagged human full length RbBP5/human N-terminal 6xHis-tagged WDR5/human full length N-terminal 6xHis-tagged DPY30 assessed as decrease in H3K4me1-2 methylation preincubated for 30 mins followed by SAM/nucleosome mixture addition measured after 120 mins in absence of light by AlphaLISA assay	ic50	1.8000	uM

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
dicrotophos	decreases expression	1
2,4,6-tribromophenol	increases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
sodium arsenite	increases expression	1
aflatoxin B2	increases methylation	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
azoxystrobin	increases expression	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	increases expression	1
picoxystrobin	increases expression	1
MT19c compound	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Carbamazepine	affects expression	1
Doxorubicin	decreases expression	1
Estradiol	decreases expression	1
Ivermectin	decreases expression	1
Quercetin	decreases expression	1
Rotenone	increases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4017369	Binding	Inhibition of human N-terminal GST-tagged MLL1 (3735 to 3973 residues) interaction with human full length N-terminal 6xHis-tagged ASH2L/N-terminal 6xHis-tagged human full length RbBP5/human N-terminal 6xHis-tagged WDR5/human full length N-t	Discovery of a Highly Potent, Cell-Permeable Macrocyclic Peptidomimetic (MM-589) Targeting the WD Repeat Domain 5 Protein (WDR5)-Mixed Lineage Leukemia (MLL) Protein-Protein Interaction. — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03204773	Not specified	COMPLETED	Studying Non-motor Symptoms in HSP
NCT04712812	Not specified	RECRUITING	Registry and Natural History Study for Early Onset Hereditary Spastic Paraplegia
NCT06553976	Not specified	RECRUITING	Spastic Paraplegia - Centers of Excellence Research Network