MOS

Summary

MOS (MOS proto-oncogene, serine/threonine kinase, HGNC:7199) is a protein-coding gene on chromosome 8q12.1, encoding Proto-oncogene serine/threonine-protein kinase mos (P00540). Serine/threonine kinase involved in the regulation of MAPK signaling.

MOS is a serine/threonine kinase that activates the MAP kinase cascade through direct phosphorylation of the MAP kinase activator MEK (MAP2K1; MIM 176872) (Prasad et al., 2008 [PubMed 18246541]).

Source: NCBI Gene 4342 — RefSeq curated summary.

At a glance

• Gene–disease (curated): oocyte/zygote/embryo maturation arrest 20 (Strong, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 59 total — 7 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 4
• Druggable target: yes
• MANE Select transcript: NM_005372

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7199
Approved symbol	MOS
Name	MOS proto-oncogene, serine/threonine kinase
Location	8q12.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000172680
Ensembl biotype	protein_coding
OMIM	190060
Entrez	4342

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000311923

RefSeq mRNA: 1 — MANE Select: NM_005372 NM_005372

CCDS: CCDS6164

Canonical transcript exons

ENST00000311923 — 1 exons

Exon	Start	End
ENSE00001198383	56112942	56113982

Expression profiles

Bgee: expression breadth broad, 17 present calls, max score 95.61.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	95.61	gold quality
secondary oocyte	CL:0000655	93.85	gold quality
pancreatic ductal cell	CL:0002079	66.93	silver quality
tibialis anterior	UBERON:0001385	61.08	silver quality
ileal mucosa	UBERON:0000331	58.35	silver quality
decidua	UBERON:0002450	56.55	gold quality
deltoid	UBERON:0001476	53.43	silver quality
skin of hip	UBERON:0001554	53.16	silver quality
hair follicle	UBERON:0002073	52.43	gold quality
quadriceps femoris	UBERON:0001377	50.55	gold quality
frontal pole	UBERON:0002795	50.41	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality
Brodmann (1909) area 10	UBERON:0013541	50.18	gold quality
metanephric glomerulus	UBERON:0004736	49.61	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
cerebellar vermis	UBERON:0004720	49.25	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
vastus lateralis	UBERON:0001379	49.11	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
myocardium	UBERON:0002349	48.87	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality
oviduct epithelium	UBERON:0004804	48.21	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality
kidney epithelium	UBERON:0004819	48.11	gold quality
upper arm skin	UBERON:0004263	48.06	gold quality
cervix epithelium	UBERON:0004801	48.04	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.65

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 10)

• the Mos/MAPK pathway is not essential for initiating goldfish oocyte maturation despite its general function as a cytostatic factor (CSF). (PMID:11180847)
• multiple meiotic genes are aberrantly activated during mitotic catastrophe in p53 mutated lymphoma cells after irradiation; the coordinated expression of MOS and REC8 regulate the extent of arrested mitoses and polyploidy (PMID:16401344)
• These results clarify the direct link of the classical Mos-MAPK (mitogen-activated protein kinase) pathway to Erp1 in meiotic arrest of vertebrate oocytes. (PMID:17410130)
• Mos 3’ UTR regulatory differences underlie species-specific temporal patterns of Mos mRNA cytoplasmic polyadenylation and translational recruitment during oocyte maturation. (PMID:18246541)
• Cdc2 and Mos regulate Emi2 stability to promote the meiosis I-meiosis II transition (PMID:18550795)
• In the absence of p53, Mos knockdown prevents multipolar mitoses and exerts genome-stabilizing effects. (PMID:20186124)
• among the candidate genes, DNA methylation of MOS may reflect the duration of H. pylori exposure and may be a marker for the development of gastric cancer. (PMID:22252584)
• High methylation level in MOS is associated with intestinal metaplasia. (PMID:23595635)
• approach identified 18 kinase and kinase-related genes whose overexpression can substitute for EGFR in EGFR-dependent PC9 cells, and these genes include seven of nine Src family kinase genes, FGFR1, FGFR2, ITK, NTRK1, NTRK2, MOS, MST1R, and RAF1. (PMID:25512530)
• MOS mutation causes female infertility with large polar body oocytes. (PMID:36403623)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mos	ENSDARG00000069744
mus_musculus	Mos	ENSMUSG00000078365
rattus_norvegicus	Mos	ENSRNOG00000008567
drosophila_melanogaster	Mos	FBGN0033773
caenorhabditis_elegans		WBGENE00013149

Paralogs (23): MAP3K9 (ENSG00000006432), TESK2 (ENSG00000070759), MAP3K13 (ENSG00000073803), ARAF (ENSG00000078061), MAP3K20 (ENSG00000091436), RIPK2 (ENSG00000104312), LIMK1 (ENSG00000106683), TESK1 (ENSG00000107140), TNNI3K (ENSG00000116783), RIPK3 (ENSG00000129465), MAP3K10 (ENSG00000130758), RAF1 (ENSG00000132155), RIPK1 (ENSG00000137275), MAP3K12 (ENSG00000139625), KSR1 (ENSG00000141068), MAP3K21 (ENSG00000143674), BRAF (ENSG00000157764), ILK (ENSG00000166333), MLKL (ENSG00000168404), KSR2 (ENSG00000171435), MAP3K11 (ENSG00000173327), LIMK2 (ENSG00000182541), LRRK2 (ENSG00000188906)

Protein

Protein identifiers

Proto-oncogene serine/threonine-protein kinase mos — P00540 (reviewed: P00540)

Alternative names: Oocyte maturation factor mos, Proto-oncogene c-Mos

All UniProt accessions (1): P00540

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine kinase involved in the regulation of MAPK signaling. Is an activator of the ERK1/2 signaling cascade playing an essential role in the stimulation of oocyte maturation.

Subunit / interactions. Interacts with MAP2K1/MEK1.

Subcellular location. Cytoplasm.

Tissue specificity. Highly expressed in oocytes. Lower expression is detected in early embryo.

Disease relevance. Oocyte/zygote/embryo maturation arrest 20 (OZEMA20) [MIM:620383] An autosomal recessive, female infertility disorder characterized by early embryonic arrest and fragmentation. Early embryo fragmentation is defined by the presence of anucleate cell fragments derived from the blastomeres. Excessive embryo fragmentation is associated with deleterious outcomes, including decreased implantation rate. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.

RefSeq proteins (1): NP_005363* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR051681	Ser/Thr_Kinases-Pseudokinases	Family

Pfam: PF00069

Enzyme classification (BRENDA):

• EC 2.7.10.2 — non-specific protein-tyrosine kinase (BRENDA: 41 organisms, 396 substrates, 479 inhibitors, 43 Km, 32 kcat entries)

Substrate kinetics (BRENDA)

6 substrates with measured Km, best-characterized 6. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.014–17.64	12
[KDSRC KINASE]-L-TYROSINE	0.0057–0.24	12
POLY(GLU4-TYR)	0.018–0.659	10
EEEEYIQ[DP]-8-HYDROXY-5-(N,N-DIMETHYLSULFONAMIDO	0.057	1
S1 PEPTIDE	0.037	1
EEEEY	—	0

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (18 total): sequence variant 13, binding site 2, chain 1, domain 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P00540-F1	80.98	0.64

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): 201 (proton acceptor)

Ligand- & substrate-binding residues (2): 66–74; 87

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 154 (showing top): GOBP_MEIOTIC_CHROMOSOME_SEGREGATION, GOBP_CHROMOSOME_ORGANIZATION, GOBP_ESTABLISHMENT_OF_SPINDLE_ORIENTATION, GOBP_NEGATIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, WANG_CLIM2_TARGETS_UP, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_REGULATION_OF_NUCLEAR_DIVISION, KEGG_MAPK_SIGNALING_PATHWAY, GOBP_REGULATION_OF_MEIOTIC_NUCLEAR_DIVISION, GOBP_SPINDLE_LOCALIZATION, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_OOGENESIS, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_CHROMOSOME_SEPARATION, GOBP_REGULATION_OF_MEIOTIC_CELL_CYCLE

GO Biological Process (11): MAPK cascade (GO:0000165), meiotic spindle organization (GO:0000212), oocyte maturation (GO:0001556), chromatin organization (GO:0006325), signal transduction (GO:0007165), regulation of meiotic nuclear division (GO:0040020), positive regulation of MAPK cascade (GO:0043410), establishment of meiotic spindle orientation (GO:0051296), positive regulation of ERK1 and ERK2 cascade (GO:0070374), negative regulation of metaphase/anaphase transition of meiotic cell cycle (GO:1902103), protein phosphorylation (GO:0006468)

GO Molecular Function (9): protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), MAP kinase kinase kinase activity (GO:0004709), ATP binding (GO:0005524), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
meiotic cell cycle	2
MAPK cascade	2
protein kinase activity	2
intracellular signaling cassette	1
spindle organization	1
meiotic cell cycle process	1
developmental process involved in reproduction	1
cell maturation	1
oocyte development	1
cellular component organization	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
regulation of cell cycle process	1
regulation of meiotic cell cycle	1
regulation of nuclear division	1
meiotic nuclear division	1
regulation of MAPK cascade	1
positive regulation of intracellular signal transduction	1
establishment of spindle orientation	1
establishment of meiotic spindle localization	1
positive regulation of MAPK cascade	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	1
metaphase/anaphase transition of meiotic cell cycle	1
negative regulation of meiotic cell cycle phase transition	1
negative regulation of metaphase/anaphase transition of cell cycle	1
regulation of metaphase/anaphase transition of meiotic cell cycle	1
negative regulation of meiotic chromosome separation	1
phosphorylation	1
protein modification process	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
protein serine/threonine kinase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1

Protein interactions and networks

STRING

1019 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MOS	CPEB1	Q9BZB8	724
MOS	MSI1	O43347	668
MOS	MT-CYB	P00156	521
MOS	GDF9	O60383	477
MOS	BMP15	O95972	425
MOS	MT-ND4	P03905	425
MOS	MC1R	Q01726	425
MOS	RAG1	P15918	419
MOS	MAD2L1	Q13257	390
MOS	RAG2	P55895	376
MOS	BTG4	Q9NY30	376
MOS	TGS1	Q96RS0	366
MOS	PLAG1	Q6DJT9	366
MOS	BBOF1	Q8ND07	366
MOS	OR12D3	Q9UGF7	366

IntAct

223 interactions, top by confidence:

A	B	Type	Score
MOS	HOMER3	psi-mi:“MI:0915”(physical association)	0.790
HOMER3	MOS	psi-mi:“MI:0915”(physical association)	0.790
MOS	CALCOCO2	psi-mi:“MI:0915”(physical association)	0.780
CALCOCO2	MOS	psi-mi:“MI:0915”(physical association)	0.780
MTMR9	MOS	psi-mi:“MI:0915”(physical association)	0.740
MOS	MTMR9	psi-mi:“MI:0915”(physical association)	0.740
MOS	PPP2R5A	psi-mi:“MI:0915”(physical association)	0.740
MOS	FKBP5	psi-mi:“MI:0915”(physical association)	0.740
MOS	KRT15	psi-mi:“MI:0915”(physical association)	0.720
MOS	GOLGA2	psi-mi:“MI:0915”(physical association)	0.720
MOS	TRAF1	psi-mi:“MI:0915”(physical association)	0.720
MOS	USHBP1	psi-mi:“MI:0915”(physical association)	0.720
KRT15	MOS	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (100): MOS (Two-hybrid), MOS (Two-hybrid), MOS (Two-hybrid), MOS (Two-hybrid), MOS (Two-hybrid), MOS (Two-hybrid), TRIM27 (Two-hybrid), TRAF1 (Two-hybrid), HOMER3 (Two-hybrid), SEC24C (Two-hybrid), CALCOCO2 (Two-hybrid), MID2 (Two-hybrid), CCNDBP1 (Two-hybrid), C17orf59 (Two-hybrid), CCDC136 (Two-hybrid)

ESM2 similar proteins: D0N4E2, O08605, O22558, O61661, P00536, P00537, P00538, P00539, P00540, P07331, P10421, P10650, P10741, P11730, P12965, P32593, P50118, P53684, Q10KY3, Q13555, Q17QV9, Q2MHE4, Q4G050, Q4V7Q6, Q58D94, Q5JJY4, Q5R667, Q5U2N4, Q6AVM3, Q6F3A6, Q7TNL3, Q7TNL4, Q7XIM0, Q7XJR9, Q8AX00, Q8AX01, Q8AX02, Q8CDB0, Q8GVC7, Q8N2I9

Diamond homologs: A0A509AKL0, A1Z9X0, A2CI34, A2CI35, A5K0N4, O73792, P00537, P00538, P00540, P04409, P05128, P05129, P05696, P06245, P09215, P0CD62, P10102, P16879, P17252, P20444, P28582, P28867, P32593, P43298, P63318, P63319, P83099, P83741, P93050, P93759, Q02111, Q04759, Q05655, Q12469, Q1L6Q1, Q20CR4, Q2MHE4, Q38868, Q38872, Q38873

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
PKA	“down-regulates activity”	MOS	phosphorylation
MOS	“up-regulates activity”	MAP2K1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 59 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 the cornified envelope	7	16.2×	5e-05
Keratinization	8	11.7×	5e-05

GO biological processes:

GO term	Partners	Fold	FDR
morphogenesis of an epithelium	7	48.1×	2e-08
intermediate filament organization	8	38.5×	1e-08
epithelial cell differentiation	7	24.6×	2e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	2
Uncertain significance	47
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (9)

Variant ID	HGVS	Classification
2502325	NM_005372.1(MOS):c.285C>A (p.Asn95Lys)	Pathogenic
2502326	NM_005372.1(MOS):c.416T>C (p.Met139Thr)	Pathogenic
2502327	NM_005372.1(MOS):c.737G>A (p.Arg246His)	Pathogenic
2502329	NM_005372.1(MOS):c.960C>A (p.Cys320Ter)	Pathogenic
2502331	NM_005372.1(MOS):c.956G>A (p.Arg319His)	Pathogenic
2502332	NM_005372.1(MOS):c.791C>G (p.Ser264Cys)	Pathogenic
2502334	NM_005372.1(MOS):c.591T>G (p.Ile197Met)	Pathogenic
2502330	NM_005372.1(MOS):c.467del (p.Gly156fs)	Likely pathogenic
4849341	NM_005372.1(MOS):c.755_759del (p.Lys252fs)	Likely pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

2201 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:56113722:C:A	K87N	0.998
8:56113722:C:G	K87N	0.998
8:56113326:G:C	D219E	0.996
8:56113326:G:T	D219E	0.996
8:56113770:A:C	F71L	0.995
8:56113770:A:T	F71L	0.995
8:56113772:A:G	F71L	0.995
8:56113327:T:A	D219V	0.993
8:56113724:T:C	K87E	0.990
8:56113327:T:G	D219A	0.989
8:56113380:G:C	D201E	0.989
8:56113380:G:T	D201E	0.989
8:56113381:T:A	D201V	0.987
8:56113381:T:G	D201A	0.986
8:56113754:C:G	A77P	0.985
8:56113175:A:G	W270R	0.984
8:56113175:A:T	W270R	0.984
8:56113328:C:G	D219H	0.984
8:56113723:T:G	K87T	0.984
8:56112999:C:A	R328S	0.983
8:56112999:C:G	R328S	0.983
8:56113327:T:C	D219G	0.983
8:56113615:G:T	A123D	0.983
8:56113729:G:T	A85D	0.983
8:56113374:C:A	K203N	0.982
8:56113374:C:G	K203N	0.982
8:56113417:A:G	L189P	0.982
8:56113723:T:A	K87M	0.981
8:56113202:C:G	D261H	0.980
8:56113381:T:C	D201G	0.980

dbSNP variants (sampled 300 via entrez): RS1001479929 (8:56114753 C>T), RS1001553591 (8:56114532 A>T), RS1003224361 (8:56112802 A>G), RS1003699574 (8:56112787 G>A), RS1003894136 (8:56113750 G>A), RS1004155193 (8:56112527 A>AT), RS1004932283 (8:56114776 C>A,G,T), RS1005860764 (8:56114919 G>T), RS1005913178 (8:56114651 T>G), RS1007590650 (8:56112831 A>G), RS1009068425 (8:56115231 T>C), RS1009854974 (8:56115708 T>A,G), RS1010382078 (8:56115425 T>A), RS1012461545 (8:56112504 G>A), RS1013583092 (8:56112752 A>G)

Disease associations

OMIM: gene MIM:190060 | disease phenotypes: MIM:620383

GenCC curated gene-disease

Disease	Classification	Inheritance
oocyte/zygote/embryo maturation arrest 20	Strong	Autosomal recessive

Mondo (1): oocyte/zygote/embryo maturation arrest 20 (MONDO:0957278)

Orphanet (0):

HPO phenotypes

4 total (4 of 4 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000141	Amenorrhea
HP:0008222	Female infertility
HP:0011462	Young adult onset

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST000175_46	Height	7.000000e-08
GCST010002_300	Refractive error	1.000000e-19

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1075184 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — MOS family

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, decreases methylation, increases methylation	1
arsenite	increases methylation	1
epigallocatechin gallate	increases expression	1
scriptaid	affects expression	1
bisphenol S	decreases methylation	1
theaflavin-3,3’-digallate	affects expression	1
Resveratrol	affects cotreatment, decreases expression	1
Fulvestrant	decreases methylation, affects cotreatment	1
Atrazine	increases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression, increases abundance	1
Caffeine	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Diethylhexyl Phthalate	increases expression	1
Oxygen	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Quercetin	affects cotreatment, increases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	decreases expression, increases abundance	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1116720	Binding	Inhibition of MOS at 5 uM	Structure-activity relationship study of EphB3 receptor tyrosine kinase inhibitors. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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