MORF4L1

Summary

MORF4L1 (mortality factor 4 like 1, HGNC:16989) is a protein-coding gene on chromosome 15q25.1, encoding Mortality factor 4-like protein 1 (Q9UBU8). Component of the NuA4 histone acetyltransferase (HAT) complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A.

Predicted to enable chromatin binding activity. Involved in double-strand break repair via homologous recombination; positive regulation of double-strand break repair via homologous recombination; and regulation of cell cycle. Located in nuclear speck. Part of NuA4 histone acetyltransferase complex; Sin3-type complex; and nucleosome.

Source: NCBI Gene 10933 — RefSeq curated summary.

At a glance

• GWAS associations: 15
• Clinical variants (ClinVar): 50 total
• Druggable target: yes
• MANE Select transcript: NM_006791

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16989
Approved symbol	MORF4L1
Name	mortality factor 4 like 1
Location	15q25.1
Locus type	gene with protein product
Status	Approved
Aliases	MRG15, MORFRG15, HsT17725, Eaf3, MEAF3
Ensembl gene	ENSG00000185787
Ensembl biotype	protein_coding
OMIM	607303
Entrez	10933

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 23 protein_coding, 7 retained_intron, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000331268, ENST00000379535, ENST00000426013, ENST00000557961, ENST00000558502, ENST00000558522, ENST00000558539, ENST00000558746, ENST00000558830, ENST00000558893, ENST00000558923, ENST00000559158, ENST00000559244, ENST00000559258, ENST00000559345, ENST00000559619, ENST00000559690, ENST00000559697, ENST00000559751, ENST00000559930, ENST00000560422, ENST00000560710, ENST00000561171, ENST00000715745, ENST00000715746, ENST00000715747, ENST00000718282, ENST00000878183, ENST00000878184, ENST00000878185, ENST00000878186, ENST00000924053, ENST00000924054, ENST00000924055, ENST00000957655

RefSeq mRNA: 5 — MANE Select: NM_006791 NM_001265603, NM_001265604, NM_001265605, NM_006791, NM_206839

CCDS: CCDS10307, CCDS32304, CCDS58393

Canonical transcript exons

ENST00000426013 — 12 exons

Exon	Start	End
ENSE00001335501	78894058	78894230
ENSE00003460739	78891484	78891572
ENSE00003502207	78886141	78886227
ENSE00003505562	78894820	78894904
ENSE00003578788	78878213	78878259
ENSE00003589042	78880512	78880579
ENSE00003608400	78890989	78891014
ENSE00003616166	78893539	78893627
ENSE00003640788	78892212	78892313
ENSE00003664625	78887269	78887349
ENSE00004027796	78896983	78898139
ENSE00004034621	78872890	78873057

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 99.84.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 78.5492 / max 1706.3043, expressed in 1821 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
147927	29.6560	1779
147925	24.0615	1804
147926	21.8813	1794
147928	1.3190	718
147922	0.7147	123
147929	0.5346	207
147924	0.1876	57
147923	0.1216	19
147921	0.0563	24
147931	0.0166	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lateral nuclear group of thalamus	UBERON:0002736	99.84	gold quality
choroid plexus epithelium	UBERON:0003911	99.83	gold quality
substantia nigra pars compacta	UBERON:0001965	99.79	gold quality
cerebellar vermis	UBERON:0004720	99.79	gold quality
adult organism	UBERON:0007023	99.77	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.76	gold quality
tibia	UBERON:0000979	99.75	gold quality
pons	UBERON:0000988	99.75	gold quality
germinal epithelium of ovary	UBERON:0001304	99.74	gold quality
secondary oocyte	CL:0000655	99.72	gold quality
caput epididymis	UBERON:0004358	99.71	gold quality
medial globus pallidus	UBERON:0002477	99.70	gold quality
left testis	UBERON:0004533	99.70	gold quality
superior vestibular nucleus	UBERON:0007227	99.70	gold quality
oocyte	CL:0000023	99.69	gold quality
parietal pleura	UBERON:0002400	99.69	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	99.69	gold quality
cauda epididymis	UBERON:0004360	99.69	gold quality
right testis	UBERON:0004534	99.69	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	99.68	gold quality
amniotic fluid	UBERON:0000173	99.68	gold quality
globus pallidus	UBERON:0001875	99.68	gold quality
orbitofrontal cortex	UBERON:0004167	99.68	gold quality
pleura	UBERON:0000977	99.67	gold quality
visceral pleura	UBERON:0002401	99.67	gold quality
lateral globus pallidus	UBERON:0002476	99.67	gold quality
bronchial epithelial cell	CL:0002328	99.66	gold quality
medulla oblongata	UBERON:0001896	99.65	gold quality
postcentral gyrus	UBERON:0002581	99.65	gold quality
dorsal plus ventral thalamus	UBERON:0001897	99.64	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-CURD-88	yes	24.13
E-MTAB-7316	yes	15.35
E-MTAB-8142	yes	12.65
E-MTAB-10042	yes	7.84
E-HCAD-9	yes	5.02
E-GEOD-130148	yes	4.73
E-MTAB-6108	no	776.48
E-HCAD-5	no	7.73
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ELF4, MAF

miRNA regulators (miRDB)

43 targeting MORF4L1, 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-574-5P	100.00	66.01	989
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-96-5P	99.95	72.80	2140
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-1255A	99.74	68.09	744
HSA-MIR-1255B-5P	99.74	68.16	741
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-1179	99.71	68.70	1040
HSA-MIR-518A-5P	99.70	69.01	2209

Literature-anchored findings (GeneRIF, showing 17)

• a novel chromodomain protein that is present in two distinct multiprotein complexes involved in transcriptional activation (PMID:12397079)
• Site-directed mutagenesis studies of a prototypic MRG domain from human MRG15 based on the X-ray structure and bioinformatics identify key residues involved in the binding of PAM14 and MRGBP. (PMID:16407074)
• identify MRG15 residues that form a shallow hydrophobic pocket to interact with the N-terminal 50 residues of PAM14 through primarily hydrophobic interactions (PMID:17008723)
• The MRG15 chromo domain may function as an adaptor module which can bind to a modified histone H3 in a mode different from that of the HP1/Pc chromo domains. (PMID:17135209)
• MORF4 has a role in cellular aging, and MRG15 associates with both histone deacetylases and histone acetyl transferase complexes [review] (PMID:17460191)
• RBP2 associates with MRG15 complex to maintain reduced H3K4 methylation at transcribed regions, which may ensure the transcriptional elongation state (PMID:17573780)
• MRG15 is a novel PALB2-interacting factor involved in homologous recombination (PMID:19553677)
• gene deficiency reduces DNA repair and increase sensitivity to DNA-crosslinking agents (PMID:20332121)
• it seems unlikely that any constitutional changes in MRG15 confer an increased risk for breast cancer. (PMID:20844547)
• While the present study expands on the role of MRG15 in the control of genomic stability, weak associations can not be ruled out for potential low-penetrance variants at MORF4L1 and breast cancer risk among BRCA2 mutation carriers (PMID:21466675)
• Both MRG15 CD and Pf1 PHD1 bind to their targets with >100 muM affinity. (PMID:22728643)
• PALB2 associates with active genes through its major binding partner, MRG15, which recognizes histone H3 trimethylated at lysine 36 (H3K36me3) by the SETD2 methyltransferase (PMID:28673974)
• ASH1L activation by MRG15 represents a delicate regulatory mechanism for how a cofactor activates an SET domain HMTase by releasing autoinhibition (PMID:30827841)
• Ash1L stimulates H3K36 methyltransferase activity through Mrg15 binding (PMID:30827843)
• Structural Insight into the Mechanism of PALB2 Interaction with MRG15. (PMID:34946951)
• MRG15 aggravates non-alcoholic steatohepatitis progression by regulating the mitochondrial proteolytic degradation of TUFM. (PMID:35985547)
• MRG15 activates histone methyltransferase activity of ASH1L by recruiting it to the nucleosomes. (PMID:37527654)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	morf4l1	ENSDARG00000041155
mus_musculus	Morf4l1	ENSMUSG00000062270
rattus_norvegicus	Morf4l1	ENSRNOG00000058412
drosophila_melanogaster	MRG15	FBGN0027378

Paralogs (3): MSL3 (ENSG00000005302), MORF4L2 (ENSG00000123562), MSL3B (ENSG00000293137)

Protein

Protein identifiers

Mortality factor 4-like protein 1 — Q9UBU8 (reviewed: Q9UBU8)

Alternative names: MORF-related gene 15 protein, Protein MSL3-1, Transcription factor-like protein MRG15

All UniProt accessions (10): B3KTM8, Q9UBU8, H0YLJ3, H0YLV1, H0YM21, H0YMJ0, H0YMT8, H0YNE0, H0YNI8, H0YNX3

UniProt curated annotations — full annotation on UniProt →

Function. Component of the NuA4 histone acetyltransferase (HAT) complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair. The NuA4 complex ATPase and helicase activities seem to be, at least in part, contributed by the association of RUVBL1 and RUVBL2 with EP400. NuA4 may also play a direct role in DNA repair when directly recruited to sites of DNA damage. As part of the SIN3B complex represses transcription and counteracts the histone acetyltransferase activity of EP300 through the recognition H3K27ac marks by PHF12 and the activity of the histone deacetylase HDAC2. SIN3B complex is recruited downstream of the constitutively active genes transcriptional start sites through interaction with histones and mitigates histone acetylation and RNA polymerase II progression within transcribed regions contributing to the regulation of transcription. Required for homologous recombination repair (HRR) and resistance to mitomycin C (MMC). Involved in the localization of PALB2, BRCA2 and RAD51, but not BRCA1, to DNA-damage foci.

Subunit / interactions. Component of the NuA4 histone acetyltransferase complex which contains the catalytic subunit KAT5/TIP60 and the subunits EP400, TRRAP/PAF400, BRD8/SMAP, EPC1, DMAP1/DNMAP1, RUVBL1/TIP49, RUVBL2, ING3, actin, ACTL6A/BAF53A, MORF4L1/MRG15, MORF4L2/MRGX, MRGBP, YEATS4/GAS41, VPS72/YL1 and MEAF6. The NuA4 complex interacts with MYC and the adenovirus E1A protein. MORF4L1 may also participate in the formation of NuA4 related complexes which lack the KAT5/TIP60 catalytic subunit, but which include the SWI/SNF related protein SRCAP. Component of the mSin3A histone deacetylase complex, which includes SIN3A, HDAC2, ARID4B, MORF4L1, RBBP4/RbAp48, and RBBP7/RbAp46. May also interact with PHF12 and one or more as yet undefined members of the TLE (transducin-like enhancer of split) family of transcriptional repressors. Component of the SIN3B complex, which includes SIN3B, HDAC2 or HDAC1, PHF12 and MORF4L1. Interacts with RB1 and KAT8. Interacts with the N-terminus of MRFAP1. Found in a complex composed of MORF4L1, MRFAP1 and RB1. Interacts with the entire BRCA complex, which contains BRCA1, PALB2, BRCA2 and RAD51. Interacts with PALB2. Forms a complex with MSL1 and NUPR1.

Subcellular location. Nucleus.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9UBU8-1	1	yes
Q9UBU8-2	2
Q9UBU8-3	3

RefSeq proteins (5): NP_001252532, NP_001252533, NP_001252534, NP_006782, NP_996670 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008676	MRG	Family
IPR016197	Chromo-like_dom_sf	Homologous_superfamily
IPR025995	Tudor-knot	Domain
IPR026541	MRG_dom	Domain
IPR038217	MRG_C_sf	Homologous_superfamily

Pfam: PF05712, PF11717

UniProt features (45 total): helix 14, strand 11, region of interest 6, mutagenesis site 4, domain 2, splice variant 2, sequence conflict 2, chain 1, modified residue 1, turn 1, short sequence motif 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
2F5J	X-RAY DIFFRACTION	2.2
2F5K	X-RAY DIFFRACTION	2.2
2AQL	X-RAY DIFFRACTION	2.3
6INE	X-RAY DIFFRACTION	2.6
7S4A	X-RAY DIFFRACTION	2.69
6AGO	X-RAY DIFFRACTION	3.1
8C60	ELECTRON MICROSCOPY	3.4
8BPA	ELECTRON MICROSCOPY	3.7
2EFI	SOLUTION NMR
2LKM	SOLUTION NMR
2N1D	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UBU8-F1	73.78	0.42

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 (1): 143

Mutagenesis-validated functional residues (4):

Position	Phenotype
208	abolishes binding to mrfap1.
234	no effect on mrfap1 binding.
251	no effect on mrfap1 binding.
254	reduces binding to mrfap1.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-3214847	HATs acetylate histones
R-HSA-3247509	Chromatin modifying enzymes
R-HSA-4839726	Chromatin organization

MSigDB gene sets: 205 (showing top): GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_REGULATION_OF_DNA_RECOMBINATION, CMYB_01, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, KYNG_DNA_DAMAGE_DN, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR_VIA_HOMOLOGOUS_RECOMBINATION, GGGTGGRR_PAX4_03, GOBP_REGULATION_OF_DNA_REPAIR, CATTTCA_MIR203, GOBP_REGULATION_OF_CELL_CYCLE, CAATGCA_MIR33, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, GOBP_DNA_DAMAGE_RESPONSE

GO Biological Process (13): double-strand break repair via homologous recombination (GO:0000724), chromatin organization (GO:0006325), regulation of apoptotic process (GO:0042981), positive regulation of DNA-templated transcription (GO:0045893), fibroblast proliferation (GO:0048144), regulation of cell cycle (GO:0051726), positive regulation of double-strand break repair via homologous recombination (GO:1905168), regulation of double-strand break repair (GO:2000779), DNA repair (GO:0006281), DNA recombination (GO:0006310), regulation of DNA-templated transcription (GO:0006355), DNA damage response (GO:0006974), cell population proliferation (GO:0008283)

GO Molecular Function (2): chromatin binding (GO:0003682), protein binding (GO:0005515)

GO Cellular Component (6): nucleosome (GO:0000786), nucleoplasm (GO:0005654), nuclear speck (GO:0016607), NuA4 histone acetyltransferase complex (GO:0035267), Sin3-type complex (GO:0070822), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Chromatin modifying enzymes	1
Chromatin organization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
double-strand break repair	2
DNA-templated transcription	2
DNA metabolic process	2
binding	2
chromatin	2
recombinational repair	1
cellular component organization	1
apoptotic process	1
regulation of programmed cell death	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
cell population proliferation	1
cell cycle	1
regulation of cellular process	1
double-strand break repair via homologous recombination	1
regulation of double-strand break repair via homologous recombination	1
positive regulation of DNA recombination	1
positive regulation of double-strand break repair	1
regulation of DNA repair	1
DNA damage response	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cellular response to stress	1
cellular process	1
protein-DNA complex	1
nuclear lumen	1
cellular anatomical structure	1
nuclear ribonucleoprotein granule	1
H4/H2A histone acetyltransferase complex	1
histone deacetylase complex	1
nuclear chromosome	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2642 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MORF4L1	MRGBP	Q9NV56	998
MORF4L1	KAT5	Q92993	959
MORF4L1	MEAF6	Q9HAF1	959
MORF4L1	ING3	Q9NXR8	933
MORF4L1	HDAC1	Q13547	928
MORF4L1	YEATS4	O95619	927
MORF4L1	HDAC2	Q92769	898
MORF4L1	HDAC3	O15379	893
MORF4L1	HDAC8	Q9BY41	892
MORF4L1	PHF12	Q96QT6	882
MORF4L1	PTBP1	P26599	882
MORF4L1	SIN3A	Q96ST3	869
MORF4L1	DMAP1	Q9NPF5	854
MORF4L1	MRFAP1	Q9Y605	853
MORF4L1	BRD8	Q9H0E9	849

IntAct

214 interactions, top by confidence:

A	B	Type	Score
PALB2	BRCA2	psi-mi:“MI:0914”(association)	0.970
MRGBP	MORF4L1	psi-mi:“MI:0915”(physical association)	0.910
MRFAP1L1	MORF4L1	psi-mi:“MI:0915”(physical association)	0.900
MORF4L1	MRFAP1L1	psi-mi:“MI:0915”(physical association)	0.900
MORF4L1	MRFAP1	psi-mi:“MI:0915”(physical association)	0.900
MRFAP1	MORF4L1	psi-mi:“MI:0915”(physical association)	0.900
TAB1	MAP3K7	psi-mi:“MI:0914”(association)	0.900
RUVBL1	ZNHIT1	psi-mi:“MI:0914”(association)	0.860
TSC2	YWHAH	psi-mi:“MI:0914”(association)	0.850
YEATS4	ZNHIT1	psi-mi:“MI:0914”(association)	0.790
H2AZ1	ZNHIT1	psi-mi:“MI:0914”(association)	0.770
TRRAP	ATXN7	psi-mi:“MI:0914”(association)	0.740
MBTD1	YEATS4	psi-mi:“MI:0914”(association)	0.730

BioGRID (524): MORF4L1 (Two-hybrid), MORF4L1 (Two-hybrid), MORF4L1 (Two-hybrid), MORF4L1 (Two-hybrid), MORF4L1 (Two-hybrid), MORF4L1 (Two-hybrid), MORF4L1 (Two-hybrid), MORF4L1 (Two-hybrid), MORF4L1 (Two-hybrid), MORF4L1 (Two-hybrid), MORF4L1 (Two-hybrid), RACGAP1 (Two-hybrid), THAP1 (Two-hybrid), MRGBP (Two-hybrid), PBXIP1 (Two-hybrid)

ESM2 similar proteins: A2A432, A6H5Z3, A9X1D0, B0VX69, B1MTJ4, B2KI88, B5FW36, C1FXW2, E2R766, E2RBS6, F1LSG8, O43242, O54923, O55047, O70133, P60762, Q13098, Q13619, Q13620, Q29425, Q2KJ46, Q3TCH7, Q4V860, Q5NVP9, Q5R5J4, Q5RAN1, Q5RB36, Q5VIR6, Q5ZKV9, Q5ZLD7, Q5ZML9, Q6AYU1, Q6NRT5, Q6NZH6, Q86TU7, Q8CCB4, Q8CI71, Q8K4Q0, Q8N122, Q8R3S6

Diamond homologs: A5A6J5, A7DTF0, G3X992, O13953, P0C860, P0CO86, P0CO87, P60762, Q12432, Q15014, Q4P827, Q4R578, Q4V3E2, Q4WPW2, Q54RM0, Q59K07, Q5BBV4, Q5NVP9, Q5R6Y9, Q5R905, Q6AYG1, Q6AYU1, Q6BT38, Q6C9M9, Q6CND0, Q6QI89, Q75AH9, Q8N5Y2, Q94C32, Q9R0Q4, Q9UBU8, Q9WVG9, Q9Y0I1, P50536, Q9NBL2, A2CG63, F8VPQ2, P29374, Q4LE39, Q6FN68

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
MORF4L1	“form complex”	Sin3B_complex	binding
MORF4L1	“form complex”	“NuA4 complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 125 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
HATs acetylate histones	17	18.7×	8e-15
Chromatin organization	14	15.9×	4e-11
Chromosome Maintenance	5	14.7×	2e-03
Chromatin modifying enzymes	14	14.1×	1e-10
Deubiquitination	7	12.1×	2e-04
DNA Repair	7	9.6×	8e-04
Epigenetic regulation of gene expression	7	6.9×	3e-03
Ub-specific processing proteases	8	5.9×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
regulation of double-strand break repair	14	74.6×	5e-21
positive regulation of double-strand break repair via homologous recombination	14	49.2×	4e-18
regulation of DNA replication	7	23.5×	2e-06
cellular response to estradiol stimulus	5	18.9×	4e-04
positive regulation of DNA repair	5	16.4×	8e-04
regulation of embryonic development	5	15.2×	1e-03
regulation of apoptotic process	18	13.8×	2e-13
regulation of DNA repair	5	12.7×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	28
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1849 predictions. Top by Δscore:

Variant	Effect	Δscore
15:78872903:G:GT	donor_gain	1.0000
15:78878207:TTACA:T	acceptor_loss	1.0000
15:78878208:TACAG:T	acceptor_loss	1.0000
15:78878210:CAGGT:C	acceptor_loss	1.0000
15:78878211:A:AG	acceptor_gain	1.0000
15:78878212:G:A	acceptor_loss	1.0000
15:78878212:G:GG	acceptor_gain	1.0000
15:78878212:GGT:G	acceptor_gain	1.0000
15:78878260:G:C	donor_loss	1.0000
15:78880502:T:TA	acceptor_gain	1.0000
15:78880505:A:AG	acceptor_gain	1.0000
15:78880508:TCA:T	acceptor_loss	1.0000
15:78880510:A:AG	acceptor_gain	1.0000
15:78880510:AGT:A	acceptor_gain	1.0000
15:78880510:AGTGT:A	acceptor_gain	1.0000
15:78880511:G:A	acceptor_loss	1.0000
15:78880511:G:GA	acceptor_gain	1.0000
15:78880511:GT:G	acceptor_gain	1.0000
15:78880511:GTG:G	acceptor_gain	1.0000
15:78880511:GTGT:G	acceptor_gain	1.0000
15:78880511:GTGTG:G	acceptor_gain	1.0000
15:78880575:AAAAA:A	donor_gain	1.0000
15:78880576:AAAA:A	donor_gain	1.0000
15:78880577:AAA:A	donor_gain	1.0000
15:78880578:AA:A	donor_gain	1.0000
15:78880579:AG:A	donor_loss	1.0000
15:78880580:G:GG	donor_gain	1.0000
15:78880581:TG:T	donor_loss	1.0000
15:78880582:GAG:G	donor_loss	1.0000
15:78880583:AG:A	donor_loss	1.0000

AlphaMissense

2131 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:78878225:T:C	L18P	1.000
15:78878227:T:C	C19R	1.000
15:78878228:G:A	C19Y	1.000
15:78878229:C:G	C19W	1.000
15:78878230:T:C	F20L	1.000
15:78878232:T:A	F20L	1.000
15:78878232:T:G	F20L	1.000
15:78878237:G:A	G22E	1.000
15:78878246:T:A	L25H	1.000
15:78878254:G:C	A28P	1.000
15:78880548:T:C	Y42H	1.000
15:78880548:T:G	Y42D	1.000
15:78880555:T:A	I44K	1.000
15:78886151:T:A	W95R	1.000
15:78886151:T:C	W95R	1.000
15:78886153:G:C	W95C	1.000
15:78886153:G:T	W95C	1.000
15:78886155:T:A	V96D	1.000
15:78886167:G:C	R100T	1.000
15:78886167:G:T	R100I	1.000
15:78886168:A:C	R100S	1.000
15:78886168:A:T	R100S	1.000
15:78886173:T:C	L102P	1.000
15:78886212:T:C	L115P	1.000
15:78892240:T:A	V195D	1.000
15:78892264:T:A	L203Q	1.000
15:78892264:T:C	L203P	1.000
15:78892266:A:G	K204E	1.000
15:78892268:A:C	K204N	1.000
15:78892268:A:T	K204N	1.000

dbSNP variants (sampled 300 via entrez): RS1000105446 (15:78873188 C>G,T), RS1000137768 (15:78873330 C>A,G,T), RS1000294617 (15:78896549 C>A,G,T), RS1000315172 (15:78877245 C>G,T), RS1000452756 (15:78874585 T>C), RS1000479099 (15:78871013 C>G), RS1000516340 (15:78871196 G>A,C), RS1000558104 (15:78887083 G>T), RS1000606492 (15:78877424 C>A,T), RS1000619030 (15:78892809 A>G), RS1000807759 (15:78893279 A>G), RS1000908059 (15:78886880 G>A,C), RS1000915566 (15:78888804 CTT>C), RS1001107462 (15:78873926 T>G), RS1001138429 (15:78874174 C>G)

Disease associations

OMIM: gene MIM:607303 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST000999_1	Coronary heart disease	4.000000e-09
GCST004744_40	Lung adenocarcinoma	3.000000e-09
GCST004748_5	Lung cancer	4.000000e-12
GCST004749_45	Lung cancer in ever smokers	4.000000e-08
GCST004750_9	Squamous cell lung carcinoma	4.000000e-07
GCST007096_33	Pulse pressure	3.000000e-15
GCST007097_51	Pulse pressure	2.000000e-07
GCST007097_52	Pulse pressure	2.000000e-08
GCST007269_284	Pulse pressure	3.000000e-12
GCST010002_101	Refractive error	8.000000e-84
GCST010480_14	Coronary artery disease	1.000000e-08
GCST010866_62	Coronary artery disease	4.000000e-44
GCST011364_24	Myocardial infarction	3.000000e-09
GCST011365_44	Myocardial infarction	2.000000e-17
GCST011656_18	Lung cancer	1.000000e-12

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005763	pulse pressure measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4630863 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Particulate Matter	decreases expression, increases abundance	2
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
beta-lapachone	increases expression	1
arsenite	increases reaction, affects binding	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	decreases expression	1
avobenzone	increases expression	1
CPG-oligonucleotide	decreases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Vehicle Emissions	decreases expression, increases abundance	1
Benzo(a)pyrene	decreases methylation	1
Cadmium	affects expression	1
Cisplatin	decreases expression	1
Doxorubicin	increases expression	1
Ivermectin	decreases expression	1
Ribonucleotides	affects binding	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4610339	Binding	Binding affinity to recombinant human MORF4L1 by microarray based assay	Pan-specific and partially selective dye-labeled peptidic inhibitors of the polycomb paralog proteins. — Bioorg Med Chem

Clinical trials (associated diseases)

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