RALBP1

Chr 18

ralA binding protein 1

Also known as: RIP1, RLIP1, RLIP76

NCBI Gene: 10928ENSG00000017797UniProt: Q15311

RALBP1 encodes a multifunctional protein that acts as a downstream effector of RAL GTPases, functioning as a GTPase-activating protein for CDC42 and RAC1, regulating receptor-mediated endocytosis, and controlling mitochondrial fission during mitosis. The gene shows high constraint against loss-of-function variants (LOEUF 0.449), but no established human disease associations have been reported for RALBP1 mutations based on the provided information.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
3
Pubs (1 yr)
103
P/LP submissions
0%
P/LP missense
0.45
LOEUF
DN
Mechanism· predicted
Clinical Summary— RALBP1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.
📋
ClinVar Variants
98 unique Pathogenic / Likely Pathogenic· 81 VUS of 200 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.45LOEUF
pLI 0.147
Z-score 3.94
OE 0.25 (0.14–0.45)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.01Z-score
OE missense 0.70 (0.63–0.78)
254 obs / 361.3 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.25 (0.14–0.45)
0≤0.351.4
Missense OE0.70 (0.63–0.78)
0≤0.61.4
Synonymous OE0.95
0≤1.21.6
LoF obs/exp: 8 / 32.1Missense obs/exp: 254 / 361.3Syn Z: 0.49
DN
0.6162th %ile
GOF
0.6247th %ile
LOF
0.4331th %ile

The Badonyi & Marsh model scores gain-of-function highest, but genomic evidence most strongly supports dominant-negative as the primary mechanism.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

200 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic96
Likely Pathogenic2
VUS81
Likely Benign8
Benign2
96
Pathogenic
2
Likely Pathogenic
81
VUS
8
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
96
0
96
Likely Pathogenic
0
0
2
0
2
VUS
0
73
8
0
81
Likely Benign
0
3
1
4
8
Benign
0
2
0
0
2
Total0781074189

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

RALBP1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
ALKBH5 suppresses gastric cancer tumorigenesis and metastasis by inhibiting the translation of uncapped WRAP53 RNA isoforms in an m6A-dependent manner
Zheng Z et al.·Mol Cancer
2025
Haploinsufficiency Interactions of RALBP1 and TP53 in Carcinogenesis
Awasthi S·Cancers (Basel)
2021
Histone lactylation leads to perioperative neurocognitive disorders by promoting the expression of Ralbp1 and inducing excessive mitochondrial fission in hippocampal neurons.
Meng F et al.·Cell Mol Life Sci
2026
MDR1 Inhibition Reverses Doxorubicin-Resistance in Six Doxorubicin-Resistant Canine Prostate and Bladder Cancer Cell Lines
Packeiser EM et al.·Int J Mol Sci
2023
Abnormal interaction of Rlip with mutant APP/Abeta and phosphorylated tau reduces wild-type Rlip levels and disrupt Rlip function in Alzheimer's disease.
Baig J et al.·Biochim Biophys Acta Mol Basis Dis
2023
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients