GRB14

protein-coding

growth factor receptor bound protein 14, the group of Pleckstrin homology domain containing|SH2 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 insulin receptors and insulin-like growth-factor receptors. This protein likely has an inhibitory effect on receptor tyrosine kinase signaling and, in particular, on insulin receptor signaling. This gene may play a role in signaling pathways that regulate growth and metabolism. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

MANE transcript

NM_004490.3

Inheritance

—

ClinVar variants

U:93B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.27

Max pathogenic AF

—

Genomic locus

chr2:164,492,417-164,621,482

External References & Databases

Ensembl (ENSG00000115290)

Transcript & Mutation Effects

hg38 • Region Span ~129.1 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 GRB14 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 89

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004490.3. 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	1 clinvar	4
missense			90 clinvar	1 clinvar		91
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	93	2	1	96

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 43 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004490.3	RefSeq	NP_004481.2	14	MANE Select
ENST00000263915.8	Ensembl	ENSP00000263915.3	14	MANE Select
NM_001303422.2	RefSeq	NP_001290351.1	13	Standard
ENST00000424693.1	Ensembl	ENSP00000401702.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Angiogenesis overview
Rac1-Pak1-p38-MMP-2 pathway
Insulin Signaling
EGFR1
Tie2 Signaling

Biological Process

signal transduction
positive regulation of signal transduction
negative regulation of insulin receptor signaling pathway
leukocyte migration

Molecular Function

SH3/SH2 adaptor activity
receptor tyrosine kinase binding
identical protein binding
protein homodimerization activity

Cellular Component

cytoplasm
cytosol
plasma membrane
endosome membrane
intracellular membrane-bounded organelle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000263915
Coding exons: 14
Length: 129037
Individuals with no LoFs: 125706
Homozygous LoFs: 0
Heterozygous LoFs: 40
Defined: 125746
p: 0.000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0449	265	263	1.01	0.0000136	3534
Missense (PolyPhen)		71	80.919	0.87742		1061
Synonymous	-0.808	105	95.0	1.11	0.00000545	994
Loss of Function	3.63	8	29.1	0.275	0.00000147	367

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000069	0.000062	rare
Latino/Admixed American	0.00017	0.00017	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0	0.0	absent
Finnish	0.00042	0.00042	rare
European (Non-Finnish)	0.00019	0.00018	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Adapter protein which modulates coupling of cell surface receptor kinases with specific signaling pathways. Binds to, and suppresses signals from, the activated insulin receptor (INSR). Potent inhibitor of insulin-stimulated MAPK3 phosphorylation. Plays a critical role regulating PDPK1 membrane translocation in response to insulin stimulation and serves as an adapter protein to recruit PDPK1 to activated insulin receptor, thus promoting PKB/AKT1 phosphorylation and transduction of the insulin signal. {ECO:0000269|PubMed:15210700, ECO:0000269|PubMed:19648926}.;

Recessive Scores

pRec: 0.164

Intolerance Scores

LoFtool: 0.777
RVIS EVS: -0.18
RVIS percentile EVS: 40.45

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.790

Gene Damage Prediction

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