MOS

protein-coding

MOS proto-oncogene, serine/threonine kinase

Gene summary

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]).[supplied by OMIM, Jul 2009]

MANE transcript

NM_005372.1

Inheritance

ClinVar variants

P:10U:47B:3

Top phenotype

Oocyte/zygote/embryo maturation arrest 20

gnomAD constraint

pLI —, LoF o/e 0.14

Max pathogenic AF

—

Genomic locus

chr8:56,112,942-56,113,982

External References & Databases

Ensembl (ENSG00000172680)

Transcript & Mutation Effects

hg38 • Region Span ~1.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

oocyte/zygote/embryo maturation arrest 20LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0957278

Submitter: Labcorp Genetics (formerly Invitae)

oocyte/zygote/embryo maturation arrest 20STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0957278

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Oocyte/zygote/embryo maturation arrest 20AR

Manifestation: Obstetric

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 34779126; 34997960; 35670744

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MOS variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 43

Oocyte/zygote/embryo maturation arrest 20Total: 13

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005372.1. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				2 clinvar		2
missense	5 clinvar	1 clinvar	45 clinvar	1 clinvar		52
nonsense	1 clinvar	1 clinvar	2 clinvar			4
start loss						0
frameshift		2 clinvar				2
splice donor/acceptor (+/-2bp)						0
Total	6	4	47	3	0	60

Highest pathogenic variant AF is 0.0000018587199

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005372.1	RefSeq	NP_005363.1	1	MANE Select
ENST00000311923.1	Ensembl	ENSP00000310722.1	1	MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Oocyte meiosis - Homo sapiens (human)
Regulation of actin cytoskeleton - Homo sapiens (human)
Progesterone-mediated oocyte maturation - Homo sapiens (human)
Preimplantation Embryo
MAPK Signaling Pathway

Biological Process

MAPK cascade
activation of MAPKK activity
activation of MAPK activity
meiotic spindle organization
chromatin organization

Molecular Function

protein serine/threonine kinase activity
MAP kinase kinase kinase activity
protein binding
ATP binding

Cellular Component

cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000311923
Coding exons: 1
Length: 1041
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.15	177	225	0.785	0.0000142	2177
Missense (PolyPhen)		74	103.95	0.71187		1038
Synonymous	1.49	85	104	0.815	0.00000686	771
Loss of Function	2.10	1	6.98	0.143	3.46e-7	83

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.212

Intolerance Scores

LoFtool: 0.308
RVIS EVS: 0.02
RVIS percentile EVS: 55.22

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.890

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium