GRB7

protein-coding

growth factor receptor bound protein 7, the group of SH2 domain containing|Pleckstrin homology domain containing

Gene summary

The product of this gene belongs to a small family of adapter proteins that are known to interact with a number of receptor tyrosine kinases and signaling molecules. This gene encodes a growth factor receptor-binding protein that interacts with epidermal growth factor receptor (EGFR) and ephrin receptors. The protein plays a role in the integrin signaling pathway and cell migration by binding with focal adhesion kinase (FAK). Several transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jun 2011]

MANE transcript

NM_005310.5

Inheritance

—

ClinVar variants

U:73B:8

Top phenotype

High myopia

gnomAD constraint

pLI —, LoF o/e 0.47

Max pathogenic AF

—

Genomic locus

chr17:39,737,927-39,747,291

External References & Databases

Ensembl (ENSG00000141738)

Transcript & Mutation Effects

hg38 • Region Span ~9.4 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 GRB7 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 67

not providedTotal: 9

High myopiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005310.5. 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	2 clinvar	1 clinvar	4
missense			68 clinvar	2 clinvar	3 clinvar	73
nonsense						0
start loss			1 clinvar			1
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	73	4	4	81

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 83 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005310.5	RefSeq	NP_005301.2	14	MANE Select
ENST00000309156.9	Ensembl	ENSP00000310771.4	14	MANE Select
NM_001030002.3	RefSeq	NP_001025173.1	14	Standard
NM_001242442.2	RefSeq	NP_001229371.2	15	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Angiogenesis overview
Kit receptor signaling pathway
Rac1-Pak1-p38-MMP-2 pathway
Developmental Biology
Signal Transduction

Biological Process

epidermal growth factor receptor signaling pathway
axon guidance
positive regulation of signal transduction
negative regulation of translation
positive regulation of cell migration

Molecular Function

RNA binding
SH3/SH2 adaptor activity
protein binding
protein kinase binding
phosphatidylinositol binding

Cellular Component

cytosol
plasma membrane
focal adhesion
cytoplasmic stress granule
cell projection

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000445327
Coding exons: 15
Length: 9365
Individuals with no LoFs: 125649
Homozygous LoFs: 0
Heterozygous LoFs: 98
Defined: 125747
p: 0.000390

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.677	324	360	0.900	0.0000237	3589
Missense (PolyPhen)		124	144.79	0.85641		1390
Synonymous	-0.183	144	141	1.02	0.00000893	1130
Loss of Function	2.73	15	31.6	0.475	0.00000166	324

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00014	0.00012	rare
Latino/Admixed American	0.0015	0.0015	notable
Ashkenazi Jewish	0.00030	0.00030	rare
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00029	0.00028	rare
South Asian	0.000099	0.000098	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Adapter protein that interacts with the cytoplasmic domain of numerous receptor kinases and modulates down-stream signaling. Promotes activation of down-stream protein kinases, including STAT3, AKT1, MAPK1 and/or MAPK3. Promotes activation of HRAS. Plays a role in signal transduction in response to EGF. Plays a role in the regulation of cell proliferation and cell migration. Plays a role in the assembly and stability of RNA stress granules. Binds to the 5'UTR of target mRNA molecules and represses translation of target mRNA species, when not phosphorylated. Phosphorylation impairs RNA binding and promotes stress granule disassembly during recovery after cellular stress (By similarity). {ECO:0000250, ECO:0000269|PubMed:10893408, ECO:0000269|PubMed:12021278, ECO:0000269|PubMed:12223469, ECO:0000269|PubMed:20622016}.;

Recessive Scores

pRec: 0.277

Intolerance Scores

LoFtool: 0.793
RVIS EVS: 0.07
RVIS percentile EVS: 59.16

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.930

Gene Damage Prediction

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