MPHOSPH8

Summary

MPHOSPH8 (M-phase phosphoprotein 8, HGNC:29810) is a protein-coding gene on chromosome 13q12.11, encoding M-phase phosphoprotein 8 (Q99549). Heterochromatin component that specifically recognizes and binds methylated ‘Lys-9’ of histone H3 (H3K9me) and promotes recruitment of proteins that mediate epigenetic repression.

Enables chromatin binding activity; histone reader activity; and methylated histone binding activity. Involved in negative regulation of gene expression via chromosomal CpG island methylation and transposable element silencing by heterochromatin formation. Located in several cellular components, including cytosol; heterochromatin; and nuclear lumen. Part of nucleosome.

Source: NCBI Gene 54737 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 111 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_017520

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29810
Approved symbol	MPHOSPH8
Name	M-phase phosphoprotein 8
Location	13q12.11
Locus type	gene with protein product
Status	Approved
Aliases	mpp8, HSMPP8
Ensembl gene	ENSG00000196199
Ensembl biotype	protein_coding
OMIM	611626
Entrez	54737

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 8 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000361479, ENST00000414242, ENST00000449056, ENST00000467481, ENST00000496525, ENST00000890362, ENST00000937069, ENST00000937070, ENST00000971229, ENST00000971230

RefSeq mRNA: 1 — MANE Select: NM_017520 NM_017520

CCDS: CCDS9287

Canonical transcript exons

ENST00000361479 — 14 exons

Exon	Start	End
ENSE00000678074	19670236	19670363
ENSE00000678075	19668377	19668531
ENSE00000678076	19666425	19666579
ENSE00001598583	19661698	19661838
ENSE00001599859	19642115	19642270
ENSE00001621634	19671834	19673441
ENSE00001712974	19663040	19663126
ENSE00001780084	19650003	19650260
ENSE00001784636	19646443	19647291
ENSE00001785657	19648422	19648521
ENSE00001856160	19633659	19633961
ENSE00003495450	19658995	19659120
ENSE00003506436	19671206	19671289
ENSE00003517090	19659201	19659289

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 97.56.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.3901 / max 2224.8102, expressed in 1760 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
134280	22.3901	1760

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	97.56	gold quality
calcaneal tendon	UBERON:0003701	97.09	gold quality
sural nerve	UBERON:0015488	96.76	gold quality
left ovary	UBERON:0002119	96.45	gold quality
right ovary	UBERON:0002118	96.25	gold quality
endocervix	UBERON:0000458	96.00	gold quality
ovary	UBERON:0000992	95.94	gold quality
tendon	UBERON:0000043	95.90	gold quality
cerebellar hemisphere	UBERON:0002245	95.78	gold quality
mucosa of stomach	UBERON:0001199	95.77	gold quality
body of uterus	UBERON:0009853	95.71	gold quality
cerebellar cortex	UBERON:0002129	95.61	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.58	gold quality
popliteal artery	UBERON:0002250	95.53	gold quality
tibial artery	UBERON:0007610	95.53	gold quality
right lung	UBERON:0002167	95.43	gold quality
descending thoracic aorta	UBERON:0002345	95.40	gold quality
aorta	UBERON:0000947	95.24	gold quality
right coronary artery	UBERON:0001625	95.21	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.20	gold quality
secondary oocyte	CL:0000655	95.17	gold quality
tibial nerve	UBERON:0001323	95.12	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.03	gold quality
lymph node	UBERON:0000029	95.02	gold quality
lower esophagus	UBERON:0013473	94.91	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.91	gold quality
thoracic aorta	UBERON:0001515	94.88	gold quality
ascending aorta	UBERON:0001496	94.87	gold quality
right uterine tube	UBERON:0001302	94.85	gold quality
body of pancreas	UBERON:0001150	94.76	gold quality

Single-cell (SCXA)

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

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

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

72 targeting MPHOSPH8, 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-3613-3P	100.00	76.36	7965
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488

Literature-anchored findings (GeneRIF, showing 12)

• MPP8 mediates E-cadherin gene silencing and promotes breast tumour cell motility and invasion. (PMID:20871592)
• We determined the crystal structure of MPP8 chromodomain in complex with H3K9me3 peptide. MPP8 interacts with at least six histone H3 residues from glutamine 5 to serine 10. (PMID:21419134)
• These findings reveal the molecular mechanism of selective binding of human MPP8 chromodomain to methylated histone H3K9. (PMID:22022377)
• these results indicate that the chromatin association of MPP8 is regulated by Cdk-dependent phosphorylation. (PMID:23416073)
• interaction of HN with MPP8 may play a role in oncogenesis because MPP8 increases tumor cell motility and invasion (PMID:23532874)
• Knockdown analysis of MPP8 in HeLa cells resulted in derepression of a set of genes that are normally expressed in spermatogonia, spermatids and mature sperm, thereby indicating a role for this molecule in silencing testis-related genes in somatic cells. (PMID:25660450)
• findings demonstrate MPP8 and SIRT1 reciprocally regulate each other’s function at multiple molecular layers through physical interaction; disruption of MPP8-SIRT1 interaction de-represses E cadherin expression and reduces cell motility and invasiveness suggesting this interplay plays critical role in MPP8- and SIRT1-mediated epithelial-mesenchymal transition (PMID:25870236)
• this study identified the HUSH (human silencing hub) complex, comprising three poorly characterized proteins, TASOR, MPP8, and periphilin; this complex is absent from Drosophila but is conserved from fish to humans. (PMID:26022416)
• The haploid screen identified HUSH, an epigenetic heterochromatin repressor complex composed of three subunits, TASOR, MPP8 and Periphilin. (Review) (PMID:26853531)
• The study demonstrated that MPP8 was associated with non-small cell lung cancer cell proliferation through regulation of HOXA5. (PMID:29412790)
• M-phase phosphoprotein 8 promotes gastric cancer growth and metastasis via p53/Bcl-2 and EMT-related signaling pathways. (PMID:31692032)
• MPP8 Promotes Proliferation and Restrains Apoptosis in Osteosarcoma by Regulating p38alphaMAPK Pathway. (PMID:33596786)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	mphosph8	ENSDARG00000005576
mus_musculus	Mphosph8	ENSMUSG00000079184
drosophila_melanogaster	CG9121	FBGN0031675

Paralogs (7): ASB4 (ENSG00000005981), ASB3 (ENSG00000115239), ASB15 (ENSG00000146809), ASB10 (ENSG00000146926), ASB16 (ENSG00000161664), ASB18 (ENSG00000182177), ASB14 (ENSG00000239388)

Protein

Protein identifiers

M-phase phosphoprotein 8 — Q99549 (reviewed: Q99549)

Alternative names: Two hybrid-associated protein 3 with RanBPM

All UniProt accessions (3): A0A0A0MT47, Q99549, H0Y6J1

UniProt curated annotations — full annotation on UniProt →

Function. Heterochromatin component that specifically recognizes and binds methylated ‘Lys-9’ of histone H3 (H3K9me) and promotes recruitment of proteins that mediate epigenetic repression. As part of the HUSH complex, promotes epigenetic repression of mobile genetic elements, such as retroviruses and transposable elements: the HUSH complex mainly represses LINE-1 (L1) retrotransposons that are still capable of transposition. Silencing events often occur within introns of transcriptionally active genes, and lead to the down-regulation of host gene expression. MPHOSPH8 mediates recruitment of the HUSH complex to H3K9me3 sites: the HUSH complex is recruited to genomic loci rich in H3K9me3 and is required to maintain transcriptional silencing by promoting recruitment of SETDB1, a histone methyltransferase that mediates further deposition of H3K9me3, as well as MORC2, a chromatin remodeler that compacts chromatin. The HUSH complex is also involved in the silencing of unintegrated retroviral DNA by being recruited by ZNF638: some part of the retroviral DNA formed immediately after infection remains unintegrated in the host genome and is transcriptionally repressed. As part of the HUSH2 complex, promotes epigenetic repression of interferon-stimulated genes. Binds H3K9me and promotes DNA methylation by recruiting DNMT3A to target CpG sites; these can be situated within the coding region of the gene. Mediates silencing of E-cadherin (CDH1) and protocadherin genes in the nervous system.

Subunit / interactions. Homodimer. Interacts (via chromo domain) with histone H3K9me3. Has the highest affinity for H3K9me3, and lesser affinity for H3K9me2 and H3K9me1. Component of the HUSH complex; composed of TASOR, PPHLN1 and MPHOSPH8. Component of the HUSH2 complex; composed of TASOR2, PPHLN1 and MPHOSPH8. Interacts with DNMT3, EHMT1 and SETDB1. Interacts with MORC2; the interaction associates MORC2 with the HUSH complex which recruits MORC2 to heterochromatic loci. Interacts with ZNF638; leading to recruitment of the HUSH complex to unintegrated retroviral DNA. Interacts with humanin. Interacts with HDGFL2.

Subcellular location. Nucleus. Chromosome.

Post-translational modifications. Phosphorylated in M (mitotic) phase. Phosphorylation by CDK1 promotes dissociation from chromatin.

Domain organisation. The chromo domain mediates interaction with methylated ‘Lys-9’ of histone H3 (H3K9me), with the highest affinity for the trimethylated form (H3K9me3).

Isoforms (2)

UniProt ID	Names	Canonical?
Q99549-1	1	yes
Q99549-2	2

RefSeq proteins (1): NP_059990* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000953	Chromo/chromo_shadow_dom	Domain
IPR002110	Ankyrin_rpt	Repeat
IPR016197	Chromo-like_dom_sf	Homologous_superfamily
IPR023779	Chromodomain_CS	Conserved_site
IPR023780	Chromo_domain	Domain
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily
IPR050889	Dendritic_Spine_Reg/Scaffold	Family

Pfam: PF00023, PF00385, PF12796

UniProt features (78 total): modified residue 21, helix 14, strand 13, compositionally biased region 8, region of interest 5, mutagenesis site 5, repeat 4, sequence conflict 2, chain 1, domain 1, site 1, disulfide bond 1, splice variant 1, turn 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
6V2S	X-RAY DIFFRACTION	1.6
9H77	X-RAY DIFFRACTION	2.01
7M5U	X-RAY DIFFRACTION	2.02
3LWE	X-RAY DIFFRACTION	2.05
3R93	X-RAY DIFFRACTION	2.06
3SVM	X-RAY DIFFRACTION	2.31
3QO2	X-RAY DIFFRACTION	2.49
8QFB	X-RAY DIFFRACTION	3.04

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99549-F1	56.12	0.20

Antibody-complex structures (SAbDab): 1 — 9H77

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): 59 (interaction with histone h3k9me3)

Post-translational modifications (21): 1, 51, 85, 136, 138, 144, 149, 164, 188, 189, 192, 266, 272, 279, 319, 334, 385, 392, 400, 403 …

Disulfide bonds (1): 799

Mutagenesis-validated functional residues (5):

Position	Phenotype
80	abolishes interaction with histone h3k9me3 and prevents recruitment of the hush complex to heterochromatin. impaired abi
149	in sta mutant; fails to dissociate from chromatin during early mitosis; when associated with a-164; a-334 and a-385.
164	in sta mutant; fails to dissociate from chromatin during early mitosis; when associated with a-149; a-334 and a-385.
334	in sta mutant; fails to dissociate from chromatin during early mitosis; when associated with a-149; a-164 and a-385.
385	in sta mutant; fails to dissociate from chromatin during early mitosis; when associated with a-149; a-164; and a-334.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-9764725	Negative Regulation of CDH1 Gene Transcription
R-HSA-9843970	Regulation of endogenous retroelements by the Human Silencing Hub (HUSH) complex
R-HSA-212165	Epigenetic regulation of gene expression
R-HSA-74160	Gene expression (Transcription)
R-HSA-9842860	Regulation of endogenous retroelements

MSigDB gene sets: 151 (showing top): MULLIGHAN_NPM1_SIGNATURE_3_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_NEGATIVE_REGULATION_OF_TYPE_I_INTERFERON_PRODUCTION, BROWNE_HCMV_INFECTION_16HR_UP, BROWNE_HCMV_INFECTION_12HR_UP, REACTOME_ADHERENS_JUNCTIONS_INTERACTIONS, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_CYTOKINE_PRODUCTION, MORF_EPHA7, MORF_RAB3A, ZHANG_BREAST_CANCER_PROGENITORS_UP, MORF_WNT1, GOBP_CHROMATIN_REMODELING

GO Biological Process (5): negative regulation of type I interferon production (GO:0032480), negative regulation of gene expression via chromosomal CpG island methylation (GO:0044027), negative regulation of gene expression, epigenetic (GO:0045814), constitutive heterochromatin formation (GO:0140719), transposable element silencing by heterochromatin formation (GO:0141005)

GO Molecular Function (3): chromatin binding (GO:0003682), histone H3K9me2/3 reader activity (GO:0062072), protein binding (GO:0005515)

GO Cellular Component (12): chromatin (GO:0000785), nucleosome (GO:0000786), heterochromatin (GO:0000792), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), HUSH complex (GO:0140283), HUSH2 complex (GO:0140286), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Regulation of CDH1 Gene Transcription	1
Regulation of endogenous retroelements	1
Gene expression (Transcription)	1
Epigenetic regulation of gene expression	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
binding	2
chromatin	2
nuclear lumen	2
intracellular membraneless organelle	2
chromatin silencing complex	2
negative regulation of cytokine production	1
regulation of type I interferon production	1
type I interferon production	1
negative regulation of gene expression, epigenetic	1
negative regulation of gene expression	1
epigenetic regulation of gene expression	1
heterochromatin formation	1
transposable element silencing	1
constitutive heterochromatin formation	1
histone H3 reader activity	1
chromosome	1
protein-DNA complex	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

2867 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MPHOSPH8	TASOR	Q9UK61	996
MPHOSPH8	PPHLN1	Q8NEY8	985
MPHOSPH8	RANBP9	Q96S59	929
MPHOSPH8	DNMT3A	Q9Y6K1	867
MPHOSPH8	GID8	Q9NWU2	858
MPHOSPH8	SETDB1	Q15047	775
MPHOSPH8	MKLN1	Q9UL63	758
MPHOSPH8	H3-3A	P06351	754
MPHOSPH8	H3C1	P02295	753
MPHOSPH8	H3-5	Q6NXT2	752
MPHOSPH8	H3-7	Q5TEC6	752
MPHOSPH8	H3C14	Q71DI3	751
MPHOSPH8	H3-4	Q16695	750
MPHOSPH8	MORC2	Q9Y6X9	697
MPHOSPH8	ATF7IP	Q6VMQ6	690

IntAct

49 interactions, top by confidence:

A	B	Type	Score
SETDB1	MPHOSPH8	psi-mi:“MI:0914”(association)	0.560
MPHOSPH8	H3C1	psi-mi:“MI:0407”(direct interaction)	0.560
SETDB1	MPHOSPH8	psi-mi:“MI:0915”(physical association)	0.560
MPHOSPH8	SETDB1	psi-mi:“MI:0915”(physical association)	0.560
MPHOSPH8	EHMT1	psi-mi:“MI:0915”(physical association)	0.560
EHMT1	MPHOSPH8	psi-mi:“MI:0915”(physical association)	0.560
ZNF597	HCFC1	psi-mi:“MI:0914”(association)	0.530
DAXX	TNRC18	psi-mi:“MI:0914”(association)	0.530
TASOR	MPHOSPH8	psi-mi:“MI:0915”(physical association)	0.500
	CBX5	psi-mi:“MI:0914”(association)	0.500
MPHOSPH8		psi-mi:“MI:0915”(physical association)	0.500
MPHOSPH8	HCFC1	psi-mi:“MI:0914”(association)	0.350
MATR3	BCLAF3	psi-mi:“MI:0914”(association)	0.350
YIPF5	SSR3	psi-mi:“MI:0914”(association)	0.350
Srsf1	SRRM1	psi-mi:“MI:0914”(association)	0.350
PPHLN1	MPHOSPH8	psi-mi:“MI:0914”(association)	0.350
TASOR	PPHLN1	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
H2BC21	SMCHD1	psi-mi:“MI:0914”(association)	0.350
HMGN5	SMCHD1	psi-mi:“MI:0914”(association)	0.350
SSRP1	DDX39A	psi-mi:“MI:0914”(association)	0.350
TOP1	DDX39A	psi-mi:“MI:0914”(association)	0.350
ERH	BCLAF3	psi-mi:“MI:0914”(association)	0.350
DAXX	SETD1A	psi-mi:“MI:0914”(association)	0.350

BioGRID (133): MPHOSPH8 (Affinity Capture-RNA), MPHOSPH8 (Affinity Capture-RNA), MPHOSPH8 (Affinity Capture-RNA), MPHOSPH8 (Affinity Capture-MS), MPHOSPH8 (Affinity Capture-MS), MPHOSPH8 (Affinity Capture-MS), MPHOSPH8 (Proximity Label-MS), ERCC6 (Affinity Capture-MS), HCFC1 (Affinity Capture-MS), ILF3 (Affinity Capture-MS), NOP2 (Affinity Capture-MS), NUMA1 (Affinity Capture-MS), RPL24 (Affinity Capture-MS), MRPS12 (Affinity Capture-MS), RPS11 (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8GR68, A2CG63, E6ZGB4, F7AQ22, F8VPQ2, G3V8T1, O75151, O75376, O75475, O88974, O96028, P29374, Q0VEE6, Q0VGB7, Q15047, Q2TB10, Q3TYA6, Q4KKX4, Q4LE39, Q5F363, Q5HYC2, Q5JSH3, Q5R9U6, Q5XJV7, Q5XXA9, Q5ZMU6, Q60974, Q62315, Q66T72, Q6DCQ0, Q6INA9, Q6NVE8, Q6P7W0, Q6P949, Q6P964, Q812D1, Q8BVE8, Q8MJG1, Q8QG78, Q8VBW5

Diamond homologs: A0A0P0VUY4, B1Q3J6, C0SQ89, D4ZX35, G3V8T1, J9VQZ0, O23273, O33481, O49139, P13864, P16668, P23737, P25265, P26358, P31033, P34881, P50196, Q24K09, Q27746, Q3TYA6, Q57983, Q5KQL9, Q7Y1I7, Q8LPU5, Q8N8U2, Q92072, Q94F87, Q94F88, Q99549, Q9ARI6, Q9AXT8, Q9M0S8, Q9T0I1, Q9WTK2, G5EDE2, G5EET5, P23198, P45973, P94147, Q13185

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MPHOSPH8	“form complex”	“HUSH epigenetic repressor complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 51 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
Regulation of endogenous retroelements by the Human Silencing Hub (HUSH) complex	7	35.7×	9e-08
mRNA Splicing	5	17.2×	3e-04
CHD1 and CHD2 subfamily	5	17.0×	3e-04
Regulation of endogenous retroelements by KRAB-ZFP proteins	5	16.7×	3e-04
Processing of Capped Intron-Containing Pre-mRNA	6	15.4×	1e-04
Dengue Virus-Host Interactions	10	14.3×	9e-08
mRNA Polyadenylation	5	13.7×	6e-04
mRNA Splicing - Major Pathway	7	11.9×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
nucleosome assembly	5	14.6×	2e-03
mRNA splicing, via spliceosome	7	13.4×	7e-05
RNA splicing	5	9.2×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	80
Likely benign	11
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
815567	GRCh37/hg19 13q11-12.12(chr13:19436286-24970361)x1	Pathogenic

SpliceAI

2102 predictions. Top by Δscore:

Variant	Effect	Δscore
13:19633957:AGGGG:A	donor_gain	1.0000
13:19633958:GGGG:G	donor_gain	1.0000
13:19633958:GGGGG:G	donor_gain	1.0000
13:19633959:GGG:G	donor_gain	1.0000
13:19633959:GGGG:G	donor_gain	1.0000
13:19633960:GG:G	donor_gain	1.0000
13:19633960:GGG:G	donor_gain	1.0000
13:19633960:GGGTA:G	donor_loss	1.0000
13:19633961:GG:G	donor_gain	1.0000
13:19633962:G:GG	donor_gain	1.0000
13:19633963:T:G	donor_loss	1.0000
13:19642101:A:AG	acceptor_gain	1.0000
13:19642102:T:G	acceptor_gain	1.0000
13:19642108:A:AG	acceptor_gain	1.0000
13:19642109:T:G	acceptor_gain	1.0000
13:19642110:A:AG	acceptor_gain	1.0000
13:19642110:AACAG:A	acceptor_gain	1.0000
13:19642111:A:G	acceptor_gain	1.0000
13:19642112:CAGG:C	acceptor_loss	1.0000
13:19642113:A:AG	acceptor_gain	1.0000
13:19642113:AG:A	acceptor_gain	1.0000
13:19642113:AGG:A	acceptor_gain	1.0000
13:19642114:G:GA	acceptor_gain	1.0000
13:19642114:G:GT	acceptor_loss	1.0000
13:19642114:GG:G	acceptor_gain	1.0000
13:19642114:GGG:G	acceptor_gain	1.0000
13:19642114:GGGT:G	acceptor_gain	1.0000
13:19642114:GGGTA:G	acceptor_gain	1.0000
13:19642222:G:GT	donor_gain	1.0000
13:19642258:G:GT	donor_gain	1.0000

AlphaMissense

5739 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:19642139:T:A	W80R	1.000
13:19642139:T:C	W80R	1.000
13:19642134:T:A	V78D	0.999
13:19642137:G:C	R79P	0.999
13:19642140:G:C	W80S	0.999
13:19642141:G:C	W80C	0.999
13:19642141:G:T	W80C	0.999
13:19642169:T:A	W90R	0.999
13:19642169:T:C	W90R	0.999
13:19661732:C:A	A609D	0.999
13:19661765:T:C	L620P	0.999
13:19661828:C:A	A641D	0.999
13:19661830:G:C	A642P	0.999
13:19663065:T:C	L653P	0.999
13:19642188:T:C	L96P	0.998
13:19659061:T:C	F548S	0.998
13:19661729:C:A	A608D	0.998
13:19661731:G:C	A609P	0.998
13:19661756:T:C	L617P	0.998
13:19661816:C:A	A637D	0.998
13:19661819:T:A	L638H	0.998
13:19661827:G:C	A641P	0.998
13:19663073:G:C	A656P	0.998
13:19666425:G:C	A674P	0.998
13:19666428:T:C	C675R	0.998
13:19666429:G:A	C675Y	0.998
13:19666430:T:G	C675W	0.998
13:19642127:T:G	Y76D	0.997
13:19659255:T:C	L586P	0.997
13:19661819:T:C	L638P	0.997

dbSNP variants (sampled 300 via entrez): RS1000077422 (13:19672533 T>A,C), RS1000197650 (13:19646752 T>A,C), RS1000457086 (13:19649917 T>C), RS1000509589 (13:19656373 A>C), RS1000580413 (13:19655045 A>T), RS1000600752 (13:19642394 C>G), RS1000670685 (13:19643574 C>G), RS1000718229 (13:19662488 C>T), RS1000762440 (13:19647887 A>T), RS1000793453 (13:19648210 G>T), RS1000919782 (13:19635927 A>G), RS1000946505 (13:19656111 G>A), RS1000963963 (13:19650855 A>G,T), RS1000970120 (13:19635769 A>G), RS1001014976 (13:19650651 T>C)

Disease associations

OMIM: gene MIM:611626 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST011973_7	Colorectal cancer	9.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1741210 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, decreases expression	2
Valproic Acid	affects expression	2
FR900359	affects phosphorylation	1
methylmercuric chloride	decreases expression, increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
coumarin	affects phosphorylation	1
pentabromodiphenyl ether	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Zoledronic Acid	affects cotreatment, increases expression	1
Fluvastatin	affects cotreatment, increases expression	1
Acetaminophen	decreases expression	1
Amphotericin B	decreases expression	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	increases expression	1
Caffeine	increases phosphorylation	1
Diuron	decreases expression	1
Estradiol	decreases expression	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Polychlorinated Biphenyls	affects expression	1
Tetrachlorodibenzodioxin	affects expression	1
Dronabinol	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
tert-Butylhydroperoxide	decreases expression	1

ChEMBL screening assays

3 unique, capped per target: 2 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1738402	Functional	PUBCHEM_BIOASSAY: qHTS Validation Assay for Inhibitors for MPP8 Chromodomain Interactions with Methylated Histone Tails. (Class of assay: confirmatory)	PubChem BioAssay data set
CHEMBL5373012	Binding	Displacement of Biotin-p53K381acK382me2 from MPP8 chromodomain (unknown origin) by TR-FRET assay	Discovery of a 53BP1 Small Molecule Antagonist Using a Focused DNA-Encoded Library Screen. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D9KN	Ubigene HEK293 MPHOSPH8 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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