RALA

Chr 7AD

RAS like proto-oncogene A

Also known as: HINCONS, RAL

NCBI Gene: 5898ENSG00000006451UniProt: P11233

The product of this gene belongs to the small GTPase superfamily, Ras family of proteins. GTP-binding proteins mediate the transmembrane signaling initiated by the occupancy of certain cell surface receptors. This gene encodes a low molecular mass ras-like GTP-binding protein that shares about 50% similarity with other ras proteins. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Hiatt-Neu-Cooper neurodevelopmental syndromeMIM #619311
AD
150
ClinVar variants
36
Pathogenic / LP
0.97
pLI score· haploinsufficient
0
Active trials
Clinical Summary— RALA
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Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
36 Pathogenic / Likely Pathogenic· 50 VUS of 150 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.27LOEUF
pLI 0.973
Z-score 3.09
OE 0.00 (0.00–0.27)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.70Z-score
OE missense 0.27 (0.20–0.37)
29 obs / 108.1 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.27)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.27 (0.20–0.37)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.80
0≤1.21.6
LoF obs/exp: 0 / 11.1Missense obs/exp: 29 / 108.1Syn Z: 1.00

ClinVar Variant Classifications

150 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic12
VUS50
Likely Benign51
Benign12
Conflicting1
24
Pathogenic
12
Likely Pathogenic
50
VUS
51
Likely Benign
12
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
4
20
0
24
Likely Pathogenic
0
8
4
0
12
VUS
3
36
10
1
50
Likely Benign
0
2
19
30
51
Benign
0
5
6
1
12
Conflicting
—1
Total3555932150

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

View in ClinVar →

Protein Context — Lollipop Plot

RALA · protein map & ClinVar variants

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

Gene2Phenotype Curations

RALA-related neurodevelopmental syndrome

strong
ADUndeterminedUncertain
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Hiatt-Neu-Cooper neurodevelopmental syndrome

MIM #619311

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Pathogenic bacteria exploit transferrin receptor transcytosis to penetrate the blood-brain barrier.
Cheng Z et al.·Proc Natl Acad Sci U S A
2023
Identification of RALA as a Therapeutic Target and Prognostic Predictor of Osteosarcoma.
Fan G et al.·Biomed Res Int
2023
KRAS-related proteins in pancreatic cancer.
Mann KM et al.·Pharmacol Ther
2016Review
RalA is overactivated in medulloblastoma.
Ginn KF et al.·J Neurooncol
2016
Dysregulation of RalA signaling through dual regulatory mechanisms exerts its oncogenic functions in hepatocellular carcinoma.
Tian L et al.·Hepatology
2022Functional
Systematic pan-cancer analysis identifies RALA as a tumor targeting immune therapeutic and prognostic marker.
Jin H et al.·Front Immunol
2022
RalA and RalB relocalization to depolarized mitochondria depends on clathrin-mediated endocytosis and facilitates TBK1 activation.
Pollock SR et al.·PLoS One
2019
Robot-assisted laparoscopic adrenalectomy: Extended application in children.
Taghavi K et al.·Eur J Surg Oncol
2024
BQU57 suppresses IL-1β-induced apoptosis and extracellular matrix degradation in nucleus pulposus cells by blocking the NF-κB signaling pathway.
Qiu X et al.·Cell Signal
2025
Novel De Novo RALA Missense Variants Expand the Genotype Spectrum of Hiatt-Neu-Cooper Neurodevelopmental Syndrome.
Dainelli A et al.·Mol Genet Genomic Med
2025Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
DNA vaccination for cervical cancer; a novel technology platform of RALA mediated gene delivery via polymeric microneedles.
Ali AA et al.·Nanomedicine
2026
Development of RALA-Based Mannosylated Nanocarriers for Targeted Delivery of Minicircle DNA Vaccines Encoding HPV-16 Oncogenes.
Giusti A et al.·Vaccines (Basel)
2025🔓 Open Access
Unimolecular Micelle for MLN8237 Delivery to Target AURKA-RalA Crosstalk for Ras-Driven Tumor Suppression in Mice Xenografts.
Singh K et al.·Biomacromolecules
2025
A novel 20 (R) dammarane panaxadiol-indole-2 ',3' -dione derivative was found to inhibit the growth and migration of colorectal cancer cells by inhibiting EGFR-mediated RalA/EMT pathway.
Tan H et al.·Eur J Med Chem
2025
CRISPR-Cas9 mediated RALA knockout and reconstitution: insights into the detection and role of RALA S194 phosphorylation in Ras-dependent and Ras-independent cancers.
Konde MV et al.·Biol Open
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools