OSM

protein-coding

oncostatin M, the group of Interleukin 6 type cytokine family

Gene summary

This gene encodes a member of the leukemia inhibitory factor/oncostatin-M (LIF/OSM) family of proteins. The encoded preproprotein is proteolytically processed to generate the mature protein. This protein is a secreted cytokine and growth regulator that inhibits the proliferation of a number of tumor cell lines. This protein also regulates the production of other cytokines, including interleukin 6, granulocyte-colony stimulating factor and granulocyte-macrophage colony stimulating factor in endothelial cells. This gene and the related gene, leukemia inhibitory factor, also present on chromosome 22, may have resulted from the duplication of a common ancestral gene. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Jan 2016]

MANE transcript

NM_020530.6

Inheritance

—

ClinVar variants

P:1U:53B:7

Top phenotype

Autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr22:30,262,829-30,266,851

External References & Databases

Ensembl (ENSG00000099985)

Transcript & Mutation Effects

hg38 • Region Span ~4.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to OSM variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 58

Autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020530.6. 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			51 clinvar	7 clinvar		58
nonsense		1 clinvar				1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	1	53	7	0	61

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 9 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020530.6	RefSeq	NP_065391.1	3	MANE Select
ENST00000215781.3	Ensembl	ENSP00000215781.2	3	MANE Select
NM_001319108.2	RefSeq	NP_001306037.1	2	Standard
ENST00000403389.1	Ensembl	ENSP00000383893.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

PI3K-Akt signaling pathway - Homo sapiens (human)
Jak-STAT signaling pathway - Homo sapiens (human)
Cytokine-cytokine receptor interaction - Homo sapiens (human)
JAK-STAT-Core
Adipogenesis

Biological Process

positive regulation of acute inflammatory response
immune response
multicellular organism development
cell population proliferation
positive regulation of cell population proliferation

Molecular Function

cytokine activity
oncostatin-M receptor binding
growth factor activity

Cellular Component

extracellular region
extracellular space

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000215781
Coding exons: 3
Length: 4012
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	0.294	152	163	0.935	0.0000104	1625
Missense (PolyPhen)		33	41.545	0.79431		463
Synonymous	0.781	60	68.2	0.880	0.00000404	533
Loss of Function	1.54	0	2.77	0.00	1.17e-7	32

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

Function: FUNCTION: Growth regulator. Inhibits the proliferation of a number of tumor cell lines. Stimulates proliferation of AIDS-KS cells. It regulates cytokine production, including IL-6, G-CSF and GM-CSF from endothelial cells. Uses both type I OSM receptor (heterodimers composed of LIPR and IL6ST) and type II OSM receptor (heterodimers composed of OSMR and IL6ST). Involved in the maturation of fetal hepatocytes, thereby promoting liver development and regeneration (By similarity). {ECO:0000250, ECO:0000269|PubMed:1542792, ECO:0000269|PubMed:1542793}.;

Recessive Scores

pRec: 0.717

Intolerance Scores

LoFtool: 0.557
RVIS EVS: -0.25
RVIS percentile EVS: 35.75

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.944

Gene Damage Prediction

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