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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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RAB3IL1
RAB3A interacting protein like 1
Chromosome 11 · 11q12.2-q12.3
NCBI Gene: 5866Ensembl: ENSG00000167994.14HGNC: HGNC:9780UniProt: Q8TBN0
27PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
guanyl-nucleotide exchange factor activityprotein bindingidentical protein bindingcytosolovarian neoplasmmigraine disorderpoisoninghypertension
✦AI Summary

RAB3IL1 (RAB3A interacting protein like 1) is a guanine nucleotide exchange factor (GEF) that activates small GTPases regulating intracellular trafficking and exocytosis. As a GEF, RAB3IL1 catalyzes the exchange of GDP to GTP on multiple Rab proteins, converting them to their active forms 1. RAB3IL1 functions as a dual Rab-binding protein, serving as a GEF for Rab3A, Rab8A, and Rab8B, while also binding Rab11a and Rab11b through a distinct carboxy-terminal domain 1. In human sperm exocytosis, GRAB (the protein product encoded by RAB3IL1) is recruited by the Rab27A-Rabphilin3a complex and exhibits GEF activity toward Rab3A during the acrosome reaction 2. Regarding disease relevance, RAB3IL1 has been implicated in multiple pathologies. Genetic variants in RAB3IL1 are associated with autism spectrum disorder and language impairments, with structural equation modeling identifying rs2524290 as a causal SNP linking ASD with language deficits 3. RAB3IL1 was identified as a novel ferroptosis regulator in male infertility; Rab3il1 knockdown induces ferroptosis via SLC7A11 translocation, disrupting the blood-testis barrier in idiopathic non-obstructive azoospermia 4. RAB3IL1 additionally serves as a hub gene in unstable atherosclerotic plaque progression 5 and functions as a prognostic indicator for hepatocellular carcinoma outcome 6. These findings position RAB3IL1 as a multifunctional protein relevant to neurodevelopmental, reproductive, cardiovascular, and oncological diseases.

Sources cited
1
RAB3IL1 variant rs2524290 is a causal SNP linking autism spectrum disorder with language impairments through structural equation modeling
PMID: 40483526
2
RAB3IL1 regulates ferroptosis and autophagy in spermatogenic cells; Rab3il1 knockdown induces ferroptosis via SLC7A11 translocation and disrupts blood-testis barrier in male infertility
PMID: 40503859
3
RAB3IL1/GRAB functions as a GEF for Rab3A, Rab8A, and Rab8B, and also binds Rab11a and Rab11b through a distinct carboxy-terminal domain
PMID: 24140058
4
GRAB/RAB3IL1 exhibits GEF activity toward Rab3A and is recruited by Rab27A-Rabphilin3a complex during human sperm exocytosis
PMID: 30599141
5
RAB3IL1 is identified as a hub gene in unstable atherosclerotic plaque progression
PMID: 33011223
6
RAB3IL1 is one of nine mRNAs identified as a prognostic indicator for hepatocellular carcinoma mortality
PMID: 32032609
Disease Associationsⓘ20
ovarian neoplasmOpen Targets
0.31Weak
migraine disorderOpen Targets
0.30Weak
poisoningOpen Targets
0.22Weak
hypertensionOpen Targets
0.15Weak
primary familial polycythemia due to EPO receptor mutationOpen Targets
0.05Suggestive
hemoglobin D diseaseOpen Targets
0.05Suggestive
hereditary persistence of fetal hemoglobin-sickle cell disease syndromeOpen Targets
0.05Suggestive
Hereditary persistence of fetal hemoglobin - beta-thalassemiaOpen Targets
0.05Suggestive
Pyruvate kinase hyperactivityOpen Targets
0.05Suggestive
hemolytic anemia due to diphosphoglycerate mutase deficiencyOpen Targets
0.05Suggestive
dehydrated hereditary stomatocytosisOpen Targets
0.05Suggestive
alpha thalassemia-intellectual disability syndrome type 1Open Targets
0.04Suggestive
Alpha-thalassemia - intellectual disability syndrome linked to chromosome 16Open Targets
0.04Suggestive
dominant beta-thalassemiaOpen Targets
0.04Suggestive
Hemoglobin E - beta-thalassemiaOpen Targets
0.04Suggestive
hemoglobin E-beta-thalassemia syndromeOpen Targets
0.04Suggestive
delta-beta-thalassemiaOpen Targets
0.04Suggestive
Autosomal dominant methemoglobinemiaOpen Targets
0.04Suggestive
hemoglobin E diseaseOpen Targets
0.04Suggestive
hemoglobin C-beta-thalassemia syndromeOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
RAB8BProtein interaction99%A2MProtein interaction95%RAB8AProtein interaction92%RAB11AProtein interaction92%RAB3IPProtein interaction87%IP6K1Protein interaction85%
Tissue Expression6 tissues
Ovary
100%
Bone Marrow
67%
Heart
40%
Lung
25%
Liver
19%
Brain
7%
Gene Interaction Network
Click a node to explore
RAB3IL1RAB8BA2MRAB8ARAB11ARAB3IPIP6K1
PROTEIN STRUCTURE
Preparing viewer…
PDB4LI0 · 3.30 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.15LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.88 [0.67–1.15]
RankingsWhere RAB3IL1 stands among ~20K protein-coding genes
  • #12,656of 20,598
    Most Researched27
  • #12,024of 17,882
    Most Constrained (LOEUF)1.15
Genes detectedRAB3IL1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Unraveling genetic risk contributions to nonverbal status in autism spectrum disorder probands.
PMID: 40483526
Behav Brain Funct · 2025
1.00
2
Global gene expression profiling in congenital diaphragmatic hernia (CDH) patients.
PMID: 35260975
Funct Integr Genomics · 2022
0.90
3
RAB3IL1: a key regulator in the autophagy-ferroptosis axis of male infertility†.
PMID: 40503859
Biol Reprod · 2025
0.80
4
Identification of hub genes in unstable atherosclerotic plaque by conjoint analysis of bioinformatics.
PMID: 33011223
Life Sci · 2020
0.70
5
A novel genomic-clinicopathologic nomogram to improve prognosis prediction of hepatocellular carcinoma.
PMID: 32032609
Clin Chim Acta · 2020
0.60