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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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GRAP
GRB2 related adaptor protein
Chromosome 17 · 17p11.2
NCBI Gene: 10750Ensembl: ENSG00000154016.14HGNC: HGNC:4562UniProt: I3L2P9
25PubMed Papers
21Diseases
0Drugs
1Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingsensory perception of soundsignal transductionphosphotyrosine residue bindinghearing loss, autosomal recessiveAlzheimer diseasesevere combined immunodeficiency due to CARD11 deficiencyreticular dysgenesis
✦AI Summary

GRAP (GRB2-related adaptor protein) is a conserved adaptor protein that couples receptor and cytoplasmic tyrosine kinase signaling to the Ras/ERK MAP kinase pathway 1. The protein contains SH2 and SH3 domains characteristic of the GRB2 family 2, which enable phosphotyrosine binding and recruitment of downstream signaling molecules. In human B cells, GRAP amplifies BCR-induced ITAM signaling and connects it to Ras-controlled Erk activation, functioning largely independently of phospholipase C-γ activity 1. Critically, GRAP plays an essential role in auditory function. The protein is expressed in mouse inner ear neuronal fibers innervating cochlear and utricular hair cells 3. Loss of the Drosophila GRAP homolog (drk) in the hearing organ causes scolopidium abnormalities and deficits in negative geotaxis behavior, defects suppressible by wild-type but not mutant human GRAP 3. GRAP mutations (c.311A>T; p.Gln104Leu) cosegregate with autosomal recessive nonsyndromic deafness (DFNB114), establishing a causative link 3. Additionally, GRAP is implicated in pulmonary arterial hypertension, where m6A-modified GRAP mRNA is upregulated but protein is downregulated; GRAP overexpression alleviates HPASMC proliferation through Ras/ERK inhibition 4.

Sources cited
1
GRAP connects BCR signaling to Ras/ERK MAP kinase pathway activation in human B cells
PMID: 29523808
2
GRAP contains SH2-SH3 domain structure characteristic of adaptor proteins
PMID: 9878555
3
GRAP mutations cause autosomal recessive deafness; GRAP is expressed in inner ear and required for auditory function
PMID: 30610177
4
GRAP is involved in pulmonary arterial hypertension pathogenesis through Ras/ERK signaling regulation
PMID: 35972996
⚠Limited data available — This gene has 4 indexed publications. Summary and analysis may be incomplete.
Disease Associationsⓘ21
hearing loss, autosomal recessiveOpen Targets
0.44Moderate
Alzheimer diseaseOpen Targets
0.12Weak
severe combined immunodeficiency due to CARD11 deficiencyOpen Targets
0.05Suggestive
reticular dysgenesisOpen Targets
0.04Suggestive
combined immunodeficiency due to CTPS1 deficiencyOpen Targets
0.04Suggestive
immunodeficiency 18Open Targets
0.04Suggestive
Wiskott-Aldrich syndromeOpen Targets
0.04Suggestive
Chronic mucocutaneous candidosisOpen Targets
0.04Suggestive
immunodeficiency 81Open Targets
0.04Suggestive
immunodeficiency 112Open Targets
0.03Suggestive
autoimmune lymphoproliferative syndrome type 2BOpen Targets
0.03Suggestive
Autoimmune lymphoproliferative syndrome with recurrent viral infectionsOpen Targets
0.03Suggestive
ovarian dysfunctionOpen Targets
0.02Suggestive
oral squamous cell carcinomaOpen Targets
0.01Suggestive
systemic juvenile idiopathic arthritisOpen Targets
0.01Suggestive
Sjogren syndromeOpen Targets
0.01Suggestive
T-cell acute lymphoblastic leukemiaOpen Targets
0.01Suggestive
non-alcoholic steatohepatitisOpen Targets
0.01Suggestive
pulmonary arterial hypertensionOpen Targets
0.01Suggestive
myeloid sarcomaOpen Targets
0.01Suggestive
Deafness, autosomal recessive, 114UniProt
Pathogenic Variants1
NM_006613.4(GRAP):c.311A>T (p.Gln104Leu)Likely pathogenic
Hearing loss, autosomal recessive 114
★☆☆☆2019→ Residue 104
View on ClinVar ↗
Related Genes
LATProtein interaction100%PLCG1Protein interaction100%GRB2Protein interaction100%FYB1Protein interaction97%LCP2Protein interaction97%SOS1Protein interaction97%
Tissue Expression6 tissues
Lung
100%
Brain
67%
Bone Marrow
56%
Liver
43%
Heart
21%
Ovary
16%
Gene Interaction Network
Click a node to explore
GRAPLATPLCG1GRB2FYB1LCP2SOS1
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q13588
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.35LoF Tolerant
pLIⓘ
0.08Tolerant
Observed/Expected LoF0.60 [0.29–1.35]
RankingsWhere GRAP stands among ~20K protein-coding genes
  • #12,985of 20,598
    Most Researched25
  • #5,313of 5,498
    Most Pathogenic Variants1
  • #14,128of 17,882
    Most Constrained (LOEUF)1.35
Genes detectedGRAP
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
The Richmond Agitation-Sedation Scale: validity and reliability in adult intensive care unit patients.
PMID: 12421743
Am J Respir Crit Care Med · 2002
1.00
2
Grb2 and GRAP connect the B cell antigen receptor to Erk MAP kinase activation in human B cells.
PMID: 29523808
Sci Rep · 2018
0.90
3
Molecular cloning and expression of human grap-2, a novel leukocyte-specific SH2- and SH3-containing adaptor-like protein that binds to gab-1.
PMID: 9878555
Biochem Biophys Res Commun · 1998
0.80
4
Detection of Grb-2-related adaptor protein gene (GRAP) and peptide molecule in salivary glands of MRL/lpr mice and patients with Sjögren's syndrome.
PMID: 15174222
J Int Med Res · 2004
0.70
5
Dysfunction of
PMID: 30610177
Proc Natl Acad Sci U S A · 2019
0.60