EPSTI1

protein-coding

epithelial stromal interaction 1

Gene summary

The protein encoded by this gene has been shown to promote tumor invasion and metastasis in some invasive cancer cells when overexpressed. Expression of this gene has been shown to be upregulated by direct binding of the Kruppel like factor 8 protein to promoter sequences. The translated protein interacts with the amino terminal region of the valosin containing protein gene product, resulting in the nuclear translocation of the nuclear factor kappa B subunit 1 gene product, and activation of target genes. Overexpression of this gene has been observed in some breast cancers and in some individuals with systemic lupus erythematosus (SLE). [provided by RefSeq, Sep 2016]

MANE transcript

NM_033255.5

Inheritance

—

ClinVar variants

U:56B:2

Top phenotype

Prostate cancer

gnomAD constraint

pLI —, LoF o/e 1.29

Max pathogenic AF

—

Genomic locus

chr13:42,886,388-42,992,271

External References & Databases

Ensembl (ENSG00000133106)

Transcript & Mutation Effects

hg38 • Region Span ~105.9 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 EPSTI1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 57

not providedTotal: 2

Prostate cancerTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_033255.5. 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			1 clinvar			1
missense			51 clinvar	1 clinvar	1 clinvar	53
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	56	1	1	58

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 28 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_033255.5	RefSeq	NP_150280.1	11	MANE Select
ENST00000313624.12	Ensembl	ENSP00000318643.7	11	MANE Select
NM_001002264.4	RefSeq	NP_001002264.1	13	Standard
NM_001330543.2	RefSeq	NP_001317472.1	12	Standard

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000313640
Coding exons: 13
Length: 105884
Individuals with no LoFs: 125237
Homozygous LoFs: 2
Heterozygous LoFs: 509
Defined: 125748
p: 0.00203

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.425	231	214	1.08	0.0000103	2687
Missense (PolyPhen)		50	53.363	0.93698		755
Synonymous	0.130	79	80.5	0.982	0.00000399	746
Loss of Function	-1.38	33	25.5	1.29	0.00000114	305

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00031	rare
Latino/Admixed American	0.00091	0.00090	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00077	0.00076	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.0011	0.0010	notable
South Asian	0.011	0.011	notable
Other	0.0016	0.0016	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a role in M1 macrophage polarization and is required for the proper regulation of gene expression during M1 versus M2 macrophage differentiation (By similarity). Might play a role in RELA/p65 and STAT1 phosphorylation and nuclear localization upon activation of macrophages (By similarity). {ECO:0000250|UniProtKB:Q8VDI1}.;

Recessive Scores

pRec: 0.0744

Intolerance Scores

LoFtool: 0.321
RVIS EVS: 0.37
RVIS percentile EVS: 75.43

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0209

Gene Damage Prediction

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