GREB1

protein-coding

growth regulating estrogen receptor binding 1

Gene summary

This gene is an estrogen-responsive gene that is an early response gene in the estrogen receptor-regulated pathway. It is thought to play an important role in hormone-responsive tissues and cancer. Three alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

MANE transcript

NM_014668.4

Inheritance

—

ClinVar variants

U:323B:35

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.35

Max pathogenic AF

—

Genomic locus

chr2:11,482,341-11,642,788

External References & Databases

Ensembl (ENSG00000196208)

Transcript & Mutation Effects

hg38 • Region Span ~160.4 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 GREB1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 327

not providedTotal: 21

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014668.4. 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			3 clinvar	12 clinvar	3 clinvar	18
missense			317 clinvar	17 clinvar	3 clinvar	337
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	323	29	6	358

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 66 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014668.4	RefSeq	NP_055483.2	32	MANE Select
ENST00000381486.7	Ensembl	ENSP00000370896.2	32	MANE Select
NM_033090.3	RefSeq	NP_149081.1	10	Standard
NM_148903.3	RefSeq	NP_683701.2	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Ectoderm Differentiation
Signal Transduction
downregulated of mta-3 in er-negative breast tumors
Signaling by Nuclear Receptors
Estrogen-dependent gene expression

Cellular Component

nucleoplasm
integral component of membrane
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000381486
Coding exons: 32
Length: 108673
Individuals with no LoFs: 125686
Homozygous LoFs: 0
Heterozygous LoFs: 62
Defined: 125748
p: 0.000247

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.68	1022	1.18e+3	0.862	0.0000764	12657
Missense (PolyPhen)		374	507.65	0.73672		5428
Synonymous	-0.693	562	541	1.04	0.0000406	3930
Loss of Function	5.62	31	87.9	0.353	0.00000419	1012

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00026	0.00025	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00022	0.00022	rare
Finnish	0.00037	0.00037	rare
European (Non-Finnish)	0.00031	0.00030	rare
South Asian	0.00026	0.00026	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play a role in estrogen-stimulated cell proliferation. Acts as a regulator of hormone-dependent cancer growth in breast and prostate cancers.;

Intolerance Scores

LoFtool: 0.471
RVIS EVS: -0.05
RVIS percentile EVS: 48.93

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.471

Gene Damage Prediction

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