ELL

Summary

ELL (elongation factor for RNA polymerase II, HGNC:23114) is a protein-coding gene on chromosome 19p13.11, encoding RNA polymerase II elongation factor ELL (P55199). Elongation factor component of the super elongation complex (SEC), a complex required to increase the catalytic rate of RNA polymerase II transcription by suppressing transient pausing by the polymerase at multiple sites along the DNA. It is a common-essential gene (DepMap: required in 94.0% of cancer cell lines).

Enables phosphatase binding activity. Involved in positive regulation of DNA-templated transcription and snRNA transcription. Located in cytosol; euchromatin; and nuclear body. Part of transcription elongation factor complex.

Source: NCBI Gene 8178 — RefSeq curated summary.

At a glance

• GWAS associations: 24
• Clinical variants (ClinVar): 114 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): activating (oncogene-like) across 2 cancer types
• Cancer dependency (DepMap): dependent in 94.0% of screened cell lines (common-essential)
• MANE Select transcript: NM_006532

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23114
Approved symbol	ELL
Name	elongation factor for RNA polymerase II
Location	19p13.11
Locus type	gene with protein product
Status	Approved
Aliases	Men, ELL1, PPP1R68
Ensembl gene	ENSG00000105656
Ensembl biotype	protein_coding
OMIM	600284
Entrez	8178

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 4 protein_coding, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000262809, ENST00000594635, ENST00000596124, ENST00000596915, ENST00000608165, ENST00000610152, ENST00000884359, ENST00000955167

RefSeq mRNA: 1 — MANE Select: NM_006532 NM_006532

CCDS: CCDS12380

Canonical transcript exons

ENST00000262809 — 12 exons

Exon	Start	End
ENSE00001123665	18521921	18522070
ENSE00003045463	18442663	18444868
ENSE00003477457	18465797	18465918
ENSE00003688826	18465412	18465575
ENSE00003697004	18472835	18472882
ENSE00003702900	18446309	18446480
ENSE00003703201	18461578	18461852
ENSE00003703320	18450477	18450975
ENSE00003706220	18446748	18446814
ENSE00003707118	18458205	18458329
ENSE00003707651	18451552	18451648
ENSE00003708694	18445224	18445268

Expression profiles

Bgee: expression breadth ubiquitous, 187 present calls, max score 90.70.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.8678 / max 849.8855, expressed in 1810 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
180016	21.7848	1810
180010	0.0543	31
180008	0.0131	4
180007	0.0084	2
180009	0.0054	2
180006	0.0016	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	90.70	gold quality
left testis	UBERON:0004533	90.66	gold quality
buccal mucosa cell	CL:0002336	90.59	gold quality
sperm	CL:0000019	88.75	gold quality
sural nerve	UBERON:0015488	87.42	gold quality
male germ cell	CL:0000015	87.02	gold quality
blood	UBERON:0000178	86.88	gold quality
testis	UBERON:0000473	86.87	gold quality
granulocyte	CL:0000094	86.19	gold quality
gastrocnemius	UBERON:0001388	86.02	gold quality
hindlimb stylopod muscle	UBERON:0004252	85.93	gold quality
muscle of leg	UBERON:0001383	85.19	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.12	gold quality
skin of leg	UBERON:0001511	83.48	gold quality
monocyte	CL:0000576	83.32	gold quality
omental fat pad	UBERON:0010414	83.18	gold quality
peritoneum	UBERON:0002358	83.10	gold quality
leukocyte	CL:0000738	83.04	gold quality
mononuclear cell	CL:0000842	82.83	gold quality
popliteal artery	UBERON:0002250	82.72	gold quality
tibial artery	UBERON:0007610	82.71	gold quality
right lobe of liver	UBERON:0001114	82.70	gold quality
spleen	UBERON:0002106	82.62	gold quality
skin of abdomen	UBERON:0001416	82.61	gold quality
ascending aorta	UBERON:0001496	82.53	gold quality
aorta	UBERON:0000947	82.44	gold quality
descending thoracic aorta	UBERON:0002345	82.44	gold quality
thoracic aorta	UBERON:0001515	82.41	gold quality
lower esophagus mucosa	UBERON:0035834	82.19	gold quality
upper lobe of left lung	UBERON:0008952	82.15	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.92

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

4 targets.

Target	Regulation
BAX	Repression
CDKN1A	Repression
E2F1	Repression
MDM2	Repression

Upstream regulators (CollecTRI, top): EAF1, EAF2, VDR

miRNA regulators (miRDB)

121 targeting ELL, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
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-4531	99.99	69.70	3181
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-493-5P	99.96	72.47	2382
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-424-5P	99.89	71.90	2641

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 94.0% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 14)

• In the Acute Myeloid Leukemia patients, detected MLL rearrangements consisting of MLL/AF6, MLL/AF9, MLL/AF17 , MLL/ELL and MLL partial tandem duplication. MLL rearrangement include chromosome translocation and partial tandem duplication. (PMID:16086288)
• ELL (Eleven-Nineteen Lysine-rich Leukemia) acts as a transcription factor for direct thrombospondin-1 regulation (PMID:19447890)
• Our findings suggest that ELL and HIF-1alpha are binding partners and can modulate the functions of each other in hypoxia. (PMID:20166137)
• ELL has an early and essential role during rapid high-amplitude gene expression that is required for both Pol II pause site entry and release (PMID:22252557)
• Studies indicate that the super elongation complex (SEC) consisting of ELL, P-TEFb (CDK9) and MLL required for rapid transcriptional induction in the presence or absence of paused RNA polymerase II (Pol II). (PMID:22895430)
• ELL is an essential player for RNA Pol II restart during cellular DNA damage response. (PMID:24127601)
• eleven-nineteen lysine-rich leukemia protein enhanced E2F1 deacetylation via recruitment of histone deacetylase 1 (PMID:24344198)
• The Tax oncogene enhances ELL incorporation into p300 and P-TEFb containing protein complexes to activate transcription. (PMID:26188510)
• This work reveals a previously unrecognized function for ELL as an E3 ubiquitin ligase for c-Myc and a potential tumour suppressor. (PMID:27009366)
• The results indicate that p53 interferes with the interaction between ELL/EAF and ICE1 and represses transcription of small nuclear RNA genes by Pol II. (PMID:27268141)
• E1A-associated p300 protein -mediated site-specific acetylation increases, whereas histone deacetylase 3-mediated deacetylation decreases, transcriptional elongation factor ELL stability through polyubiquitylation by the E3 ubiquitin ligase Siah1. Knockdown of human cell cycle and apoptosis regulator 2 reduces ELL levels and expression of a significant number of genes, including those involved in glucose metabolism. (PMID:32152128)
• ELL Facilitates RNA Polymerase II-Mediated Transcription of Human Epidermal Proliferation Genes. (PMID:33157094)
• ATM-mediated ELL phosphorylation enhances its self-association through increased EAF1 interaction and inhibits global transcription during genotoxic stress. (PMID:36305813)
• Stratification and therapeutic potential of ELL in cytogenetic normal acute myeloid leukemia. (PMID:36543308)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ell	ENSDARG00000000568
mus_musculus	Ell	ENSMUSG00000070002
rattus_norvegicus	Ell	ENSRNOG00000019824
drosophila_melanogaster	Su(Tpl)	FBGN0014037
caenorhabditis_elegans		WBGENE00021281

Paralogs (5): OCEL1 (ENSG00000099330), ELL2 (ENSG00000118985), ELL3 (ENSG00000128886), MARVELD2 (ENSG00000152939), OCLN (ENSG00000197822)

Protein

Protein identifiers

RNA polymerase II elongation factor ELL — P55199 (reviewed: P55199)

Alternative names: Eleven-nineteen lysine-rich leukemia protein

All UniProt accessions (3): P55199, U3KQ90, U3KQA3

UniProt curated annotations — full annotation on UniProt →

Function. Elongation factor component of the super elongation complex (SEC), a complex required to increase the catalytic rate of RNA polymerase II transcription by suppressing transient pausing by the polymerase at multiple sites along the DNA. Elongation factor component of the little elongation complex (LEC), a complex required to regulate small nuclear RNA (snRNA) gene transcription by RNA polymerase II and III. Specifically required for stimulating the elongation step of RNA polymerase II- and III-dependent snRNA gene transcription. ELL also plays an early role before its assembly into in the SEC complex by stabilizing RNA polymerase II recruitment/initiation and entry into the pause site. Required to stabilize the pre-initiation complex and early elongation.

Subunit / interactions. Component of the super elongation complex (SEC), at least composed of EAF1, EAF2, CDK9, MLLT3/AF9, AFF (AFF1 or AFF4), the P-TEFb complex and ELL (ELL, ELL2 or ELL3). Component of the little elongation complex (LEC), at least composed of ELL (ELL, ELL2 or ELL3), ZC3H8, ICE1 and ICE2. Interacts with AFF4; the interaction is direct. Interacts with EAF1 and EAF2. Interacts with ICE1 (via N-terminus domain). Interacts with ICE2. Interacts with USPL1.

Subcellular location. Nucleus. Nucleus speckle. Cajal body.

Tissue specificity. Expressed in all tissues tested. Highest levels found in placenta, skeletal muscle, testis and peripheral blood leukocytes.

Disease relevance. A chromosomal aberration involving ELL is found in acute leukemias. Translocation t(11;19)(q23;p13.1) with KMT2A/MLL1. The result is a rogue activator protein.

Similarity. Belongs to the ELL/occludin family.

RefSeq proteins (1): NP_006523* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010844	Occludin_ELL	Domain
IPR019464	ELL_N	Domain
IPR031176	ELL/occludin	Family
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR042065	E3_ELL-like	Homologous_superfamily

Pfam: PF07303, PF10390

UniProt features (27 total): compositionally biased region 6, helix 5, modified residue 4, strand 3, sequence variant 2, region of interest 2, initiator methionine 1, chain 1, site 1, domain 1, short sequence motif 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2DOA	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P55199-F1	69.31	0.34

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 (1): 46 (kmt2a/mll1 fusion point (in acute myeloid leukemia patient))

Post-translational modifications (4): 2, 180, 309, 561

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-112382	Formation of RNA Pol II elongation complex
R-HSA-167152	Formation of HIV elongation complex in the absence of HIV Tat
R-HSA-167200	Formation of HIV-1 elongation complex containing HIV-1 Tat
R-HSA-167238	Pausing and recovery of Tat-mediated HIV elongation
R-HSA-167243	Tat-mediated HIV elongation arrest and recovery
R-HSA-167246	Tat-mediated elongation of the HIV-1 transcript
R-HSA-167287	HIV elongation arrest and recovery
R-HSA-167290	Pausing and recovery of HIV elongation
R-HSA-674695	RNA Polymerase II Pre-transcription Events
R-HSA-6781827	Transcription-Coupled Nucleotide Excision Repair (TC-NER)
R-HSA-6796648	TP53 Regulates Transcription of DNA Repair Genes
R-HSA-6807505	RNA polymerase II transcribes snRNA genes
R-HSA-75955	RNA Polymerase II Transcription Elongation

MSigDB gene sets: 230 (showing top): GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, HOEGERKORP_CD44_TARGETS_TEMPORAL_DN, GOBP_TRANSCRIPTION_BY_RNA_POLYMERASE_III, CAGCTG_AP4_Q5, MODULE_503, REACTOME_HIV_INFECTION, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT, MODULE_195, BRN2_01, BACH2_01, MODULE_123, TGANTCA_AP1_C, MODULE_147, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_UP

GO Biological Process (7): in utero embryonic development (GO:0001701), transcription elongation by RNA polymerase II (GO:0006368), positive regulation of DNA-templated transcription, elongation (GO:0032786), positive regulation of transcription elongation by RNA polymerase II (GO:0032968), snRNA transcription by RNA polymerase II (GO:0042795), snRNA transcription by RNA polymerase III (GO:0042796), positive regulation of transcription by RNA polymerase III (GO:0045945)

GO Molecular Function (3): cis-regulatory region sequence-specific DNA binding (GO:0000987), phosphatase binding (GO:0019902), protein binding (GO:0005515)

GO Cellular Component (9): euchromatin (GO:0000791), nucleoplasm (GO:0005654), cytosol (GO:0005829), transcription elongation factor complex (GO:0008023), Cajal body (GO:0015030), nuclear body (GO:0016604), nuclear speck (GO:0016607), histone locus body (GO:0035363), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Transcription of the HIV genome	5
RNA Polymerase II Transcription	3
RNA Polymerase II Transcription Elongation	1
Tat-mediated elongation of the HIV-1 transcript	1
HIV Transcription Elongation	1
Nucleotide Excision Repair	1
Transcriptional Regulation by TP53	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nuclear ribonucleoprotein granule	3
DNA-templated transcription elongation	2
transcription by RNA polymerase II	2
positive regulation of DNA-templated transcription	2
snRNA transcription	2
transcription by RNA polymerase III	2
cellular anatomical structure	2
nucleoplasm	2
chordate embryonic development	1
regulation of DNA-templated transcription elongation	1
transcription elongation by RNA polymerase II	1
positive regulation of DNA-templated transcription, elongation	1
regulation of transcription elongation by RNA polymerase II	1
positive regulation of transcription by RNA polymerase II	1
regulation of transcription by RNA polymerase III	1
transcription cis-regulatory region binding	1
enzyme binding	1
binding	1
chromatin	1
nuclear lumen	1
cytoplasm	1
nuclear protein-containing complex	1
intracellular membraneless organelle	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1375 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ELL	MLLT1	Q03111	999
ELL	MLLT3	P42568	998
ELL	AFF1	P51825	998
ELL	AFF4	Q9UHB7	997
ELL	CCNT1	O60563	977
ELL	EAF2	Q96CJ1	967
ELL	EAF1	Q96JC9	951
ELL	CDK9	P50750	950
ELL	VPS36	Q86VN1	948
ELL	SNF8	Q96H20	931
ELL	VPS25	Q9BRG1	927
ELL	MLLT10	P55197	916
ELL	MED26	O95402	915
ELL	MLLT6	P55198	831
ELL	AFDN	P55196	809

IntAct

90 interactions, top by confidence:

A	B	Type	Score
EAF1	ELL2	psi-mi:“MI:0914”(association)	0.840
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
AFF4	ELL2	psi-mi:“MI:0914”(association)	0.730
MLLT3	CDK9	psi-mi:“MI:0914”(association)	0.730
ELL3	CCNT1	psi-mi:“MI:0914”(association)	0.640
SNRPA1	HTATSF1	psi-mi:“MI:0914”(association)	0.640
DYNLL2	BLTP3B	psi-mi:“MI:0914”(association)	0.640
CAMKV	AP3B1	psi-mi:“MI:0914”(association)	0.640
MLLT1	ELL2	psi-mi:“MI:0914”(association)	0.640
SNRPA1	U2SURP	psi-mi:“MI:0914”(association)	0.640
ICE1	ELL	psi-mi:“MI:0915”(physical association)	0.620
ICE2	ELL	psi-mi:“MI:0915”(physical association)	0.620
ELL	ICE2	psi-mi:“MI:0914”(association)	0.620
ICE2	ELL	psi-mi:“MI:0914”(association)	0.620
ICE1	ELL	psi-mi:“MI:0914”(association)	0.620
ELL	SNF8	psi-mi:“MI:0407”(direct interaction)	0.600

BioGRID (158): USPL1 (Affinity Capture-Western), ELL (Affinity Capture-Western), ELL (Affinity Capture-MS), ELL (Affinity Capture-MS), ELL (Affinity Capture-MS), ELL (Affinity Capture-MS), ELL (Affinity Capture-MS), ELL (Affinity Capture-MS), ELL (Affinity Capture-MS), ELL (Affinity Capture-MS), ELL (Affinity Capture-MS), ELL (Affinity Capture-MS), ELL (Affinity Capture-MS), ELL (Affinity Capture-MS), ELL (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GU71, A6QPI4, B2RV13, D4A6L0, E1BBQ2, F1LQY6, G3UW36, O08856, P15382, P53801, P55199, P56182, Q08CB3, Q0VF94, Q148E1, Q17RQ9, Q2KJ58, Q32Q90, Q4R5F9, Q4V8A6, Q4VA36, Q5I0I4, Q5NVI6, Q5R8Q2, Q5T6X4, Q5T848, Q5XII8, Q68EN5, Q6P767, Q8C419, Q8CHT6, Q8R143, Q8R1T1, Q8TBN0, Q8VDV3, Q8WUX9, Q90YH8, Q91WM6, Q91ZP9, Q96IL0

Diamond homologs: F1MGG3, O00472, O08856, P55199, Q0IHQ3, Q3UKU1, Q3UZP0, Q5XFX8, Q80VR2, Q8N4S9, Q9HB65, Q9VW51, Q28793, Q91049, Q6P6T5, Q9H607, Q9PUN1, Q8VCR9, Q16625, Q28269, Q5RFS5, Q61146

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
EAF1	up-regulates	ELL	binding
EAF2	up-regulates	ELL	binding
ELL	“form complex”	ELL/ICE1	binding
ELL	“form complex”	ELL/ICE2	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 80 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 RNA Pol II elongation complex	11	35.5×	6e-13
RNA Polymerase II Transcription Elongation	11	35.5×	6e-13
HIV Transcription Elongation	6	33.6×	8e-07
RNA polymerase II transcribes snRNA genes	12	30.9×	4e-13
RNA Polymerase II Pre-transcription Events	13	29.8×	7e-14
Formation of HIV-1 elongation complex containing HIV-1 Tat	6	25.9×	3e-06
Tat-mediated elongation of the HIV-1 transcript	6	25.9×	3e-06
Formation of HIV elongation complex in the absence of HIV Tat	6	24.8×	3e-06

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of transcription elongation by RNA polymerase II	9	39.2×	6e-10
transcription elongation by RNA polymerase II	6	38.6×	1e-06
transcription initiation at RNA polymerase II promoter	5	27.1×	1e-04
mRNA splicing, via spliceosome	6	8.0×	5e-03
transcription by RNA polymerase II	7	7.2×	4e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 2 cancer types — MEL, OVT.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	91
Likely benign	9
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

3016 predictions. Top by Δscore:

Variant	Effect	Δscore
19:18444864:TTGGT:T	acceptor_gain	1.0000
19:18444865:TGGT:T	acceptor_gain	1.0000
19:18444866:GGT:G	acceptor_gain	1.0000
19:18444867:GT:G	acceptor_gain	1.0000
19:18444869:C:CC	acceptor_gain	1.0000
19:18444870:T:G	acceptor_loss	1.0000
19:18445221:CACCT:C	donor_loss	1.0000
19:18445222:A:AC	donor_gain	1.0000
19:18445222:AC:A	donor_gain	1.0000
19:18445223:C:CC	donor_gain	1.0000
19:18445223:CC:C	donor_gain	1.0000
19:18445223:CCT:C	donor_gain	1.0000
19:18445223:CCTT:C	donor_gain	1.0000
19:18445223:CCTTT:C	donor_gain	1.0000
19:18445265:TAGT:T	acceptor_gain	1.0000
19:18445266:AGT:A	acceptor_gain	1.0000
19:18445267:GT:G	acceptor_gain	1.0000
19:18445269:C:CA	acceptor_loss	1.0000
19:18445269:C:CC	acceptor_gain	1.0000
19:18445270:T:A	acceptor_loss	1.0000
19:18446304:TCTA:T	donor_loss	1.0000
19:18446307:AC:A	donor_loss	1.0000
19:18446308:C:CT	donor_loss	1.0000
19:18446312:ATACT:A	donor_gain	1.0000
19:18446314:A:AC	donor_gain	1.0000
19:18446314:ACT:A	donor_gain	1.0000
19:18446315:C:CC	donor_gain	1.0000
19:18446315:CTC:C	donor_gain	1.0000
19:18446317:C:CA	donor_gain	1.0000
19:18446477:CTTC:C	acceptor_gain	1.0000

AlphaMissense

4030 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:18444813:A:G	L602P	1.000
19:18446426:G:C	F529L	1.000
19:18446426:G:T	F529L	1.000
19:18446428:A:G	F529L	1.000
19:18444800:C:A	K606N	0.999
19:18444800:C:G	K606N	0.999
19:18444813:A:T	L602Q	0.999
19:18444815:C:A	K601N	0.999
19:18444815:C:G	K601N	0.999
19:18444825:A:G	L598P	0.999
19:18446407:A:G	Y536H	0.999
19:18446427:A:G	F529S	0.999
19:18458257:A:G	W273R	0.999
19:18458257:A:T	W273R	0.999
19:18444802:T:C	K606E	0.998
19:18444823:G:C	H599D	0.998
19:18446363:G:C	F550L	0.998
19:18446363:G:T	F550L	0.998
19:18446365:A:G	F550L	0.998
19:18446395:G:C	H540D	0.998
19:18446397:A:G	L539P	0.998
19:18446406:T:C	Y536C	0.998
19:18446406:T:G	Y536S	0.998
19:18446407:A:C	Y536D	0.998
19:18446427:A:C	F529C	0.998
19:18446435:C:A	K526N	0.998
19:18446435:C:G	K526N	0.998
19:18446448:C:G	R522P	0.998
19:18446449:G:T	R522S	0.998
19:18458255:C:A	W273C	0.998

dbSNP variants (sampled 300 via entrez): RS1000063108 (19:18444100 T>C), RS1000070979 (19:18448025 A>G), RS1000074114 (19:18474348 GC>G), RS1000112395 (19:18485328 C>A), RS1000113227 (19:18522789 A>G), RS1000122499 (19:18496643 C>T), RS1000144592 (19:18522576 G>A), RS1000167042 (19:18494102 CAA>C,CAAA), RS1000194680 (19:18501081 T>G), RS1000225932 (19:18500817 G>A,T), RS1000285916 (19:18510565 C>T), RS1000289095 (19:18507151 G>A), RS1000297554 (19:18473879 C>A), RS1000308070 (19:18468842 G>A), RS1000359867 (19:18468483 T>A,C)

Disease associations

OMIM: gene MIM:600284 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

24 associations (top):

Study	Trait	p-value
GCST001937_26	Breast cancer	5.000000e-15
GCST004602_269	Mean corpuscular volume	4.000000e-16
GCST004605_80	Mean corpuscular hemoglobin concentration	4.000000e-10
GCST004630_62	Mean corpuscular hemoglobin	1.000000e-22
GCST004988_184	Breast cancer	5.000000e-28
GCST005194_161	Coronary artery disease	4.000000e-12
GCST006626_12	Pulse pressure	2.000000e-12
GCST007511_22	Alzheimer’s disease (late onset)	2.000000e-06
GCST010241_210	Apolipoprotein A1 levels	1.000000e-09
GCST010242_68	HDL cholesterol levels	4.000000e-09
GCST011369_25	Iron status biomarkers (ferritin levels)	3.000000e-11
GCST90002389_400	Lymphocyte percentage of white cells	3.000000e-22
GCST90002390_687	Mean corpuscular hemoglobin	8.000000e-49
GCST90002391_112	Mean corpuscular hemoglobin concentration	5.000000e-34
GCST90002392_88	Mean corpuscular volume	4.000000e-31
GCST90002393_654	Monocyte count	2.000000e-36
GCST90002403_284	Red blood cell count	5.000000e-11
GCST90002403_285	Red blood cell count	4.000000e-12
GCST90002404_572	Red cell distribution width	1.000000e-11
GCST90002406_497	Reticulocyte fraction of red cells	1.000000e-12
GCST90013663_86	Alanine aminotransferase levels	2.000000e-09
GCST90013664_50	Aspartate aminotransferase levels	1.000000e-11
GCST90020024_539	A body shape index	1.000000e-08
GCST90020027_275	Waist-hip index	2.000000e-08

EFO canonical traits (14, from GWAS)

EFO ID	Trait name
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0004527	mean corpuscular hemoglobin
EFO:0005763	pulse pressure measurement
EFO:1001870	late-onset Alzheimers disease
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004459	ferritin measurement
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0005091	monocyte count
EFO:0004305	erythrocyte count
EFO:0009188	Red cell distribution width
EFO:0004736	aspartate aminotransferase measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725004 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

3 potent at pChembl≥5 of 3 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.21	Kd	62	nM	MOLIBRESIB
7.18	Kd	66	nM	MOLIBRESIB
6.96	IC50	110	nM	MOLIBRESIB

PubChem BioAssay actives

3 with measured affinity, of 8 total; 1 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
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2174622: Binding affinity to ELL (unknown origin) assessed as apparent dissociation constant	kd	0.0620	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	2
Air Pollutants	affects expression, increases abundance, increases expression	2
Valproic Acid	increases methylation, affects cotreatment, increases expression	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
benzo(e)pyrene	increases methylation	1
cupric oxide	increases expression	1
di-n-butylphosphoric acid	affects expression	1
cylindrospermopsin	increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases methylation	1
Caffeine	affects phosphorylation	1
Diazinon	increases methylation	1
Doxorubicin	decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Methapyrilene	increases methylation	1
Methotrexate	decreases expression	1
Ozone	affects expression, increases abundance	1
Silver	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	increases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	decreases expression	1
Copper Sulfate	increases expression	1
Acrylamide	increases expression	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5696852	Binding	Binding affinity to ELL (unknown origin) assessed as apparent dissociation constant	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Clinical trials (associated diseases)

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