OS9

protein-coding

OS9 endoplasmic reticulum lectin, the group of MRH domain containing

Gene summary

This gene encodes a protein that is highly expressed in osteosarcomas. This protein binds to the hypoxia-inducible factor 1 (HIF-1), a key regulator of the hypoxic response and angiogenesis, and promotes the degradation of one of its subunits. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

MANE transcript

NM_006812.4

Inheritance

—

ClinVar variants

U:115B:8

Top phenotype

Hereditary cancer

gnomAD constraint

pLI —, LoF o/e 0.54

Max pathogenic AF

—

Genomic locus

chr12:57,693,841-57,728,342

External References & Databases

Ensembl (ENSG00000135506)

Transcript & Mutation Effects

hg38 • Region Span ~34.5 kb

Loading mutation effect viewer...

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 OS9 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 112

not providedTotal: 8

Hereditary cancerTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006812.4. 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	1 clinvar	3
missense			110 clinvar	4 clinvar	1 clinvar	115
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	115	6	2	123

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 177 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006812.4	RefSeq	NP_006803.1	15	MANE Select
ENST00000315970.12	Ensembl	ENSP00000318165.7	15	MANE Select
NM_001017956.3	RefSeq	NP_001017956.1	14	Standard
NM_001017957.3	RefSeq	NP_001017957.1	14	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Protein processing in endoplasmic reticulum - Homo sapiens (human)
Disorders of transmembrane transporters
Disease
Signal Transduction
Defective CFTR causes cystic fibrosis

Biological Process

ubiquitin-dependent protein catabolic process
protein targeting
protein retention in ER lumen
protein ubiquitination
ubiquitin-dependent ERAD pathway

Molecular Function

protease binding
protein binding
carbohydrate binding

Cellular Component

Hrd1p ubiquitin ligase complex
endoplasmic reticulum
endoplasmic reticulum lumen
endoplasmic reticulum membrane
endoplasmic reticulum quality control compartment

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000315970
Coding exons: 15
Length: 27603
Individuals with no LoFs: 125709
Homozygous LoFs: 0
Heterozygous LoFs: 39
Defined: 125748
p: 0.000155

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.05	343	402	0.853	0.0000238	4339
Missense (PolyPhen)		88	119.54	0.73613		1236
Synonymous	1.51	128	152	0.844	0.00000846	1292
Loss of Function	2.61	20	37.1	0.538	0.00000180	439

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00020	0.00020	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00033	0.00033	rare
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.00016	0.00016	rare
South Asian	0.000068	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Lectin which functions in endoplasmic reticulum (ER) quality control and ER-associated degradation (ERAD). May bind terminally misfolded non-glycosylated proteins as well as improperly folded glycoproteins, retain them in the ER, and possibly transfer them to the ubiquitination machinery and promote their degradation. Possible targets include TRPV4. {ECO:0000269|PubMed:17932042, ECO:0000269|PubMed:18264092, ECO:0000269|PubMed:18417469, ECO:0000269|PubMed:19084021, ECO:0000269|PubMed:19346256, ECO:0000269|PubMed:21172656}.;

Intolerance Scores

LoFtool: 0.971
RVIS EVS: -0.82
RVIS percentile EVS: 11.88

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.700

Gene Damage Prediction

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