CBLL1

Chr 7

Cbl proto-oncogene like 1

Also known as: HAKAI, RNF188

NCBI Gene: 79872ENSG00000105879UniProt: Q75N03

This gene encodes an E3 ubiquitin-ligase for the E-cadherin complex and mediates its ubiquitination, endocytosis, and degradation in the lysosomes. The encoded protein contains a RING-finger domain and is also thought to have a role in control of cell proliferation. A related pseudogene has been identified on chromosome X. Alternative splicing results in a non-coding transcript variant. [provided by RefSeq, Aug 2011]

61
ClinVar variants
20
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— CBLL1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
20 Pathogenic / Likely Pathogenic· 40 VUS of 61 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.
0.14LOEUF
pLI 0.999
Z-score 4.20
OE 0.00 (0.00–0.14)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

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.
1.34Z-score
OE missense 0.78 (0.69–0.87)
222 obs / 285.7 exp
Tolerant

Mild missense constraint

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 (0.00–0.14)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.78 (0.69–0.87)
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.1.21
0≤1.21.6
LoF obs/exp: 0 / 20.5Missense obs/exp: 222 / 285.7Syn Z: -1.56

ClinVar Variant Classifications

61 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20
VUS40
Likely Benign1
20
Pathogenic
40
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
20
0
20
Likely Pathogenic
0
0
0
0
0
VUS
0
37
3
0
40
Likely Benign
0
1
0
0
1
Benign
0
0
0
0
0
Total03823061

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

View in ClinVar →

Protein Context — Lollipop Plot

CBLL1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Characteristics of n6-methyladenosine (m6A) regulators and role of FTO/TNC in scleroderma.
Yu Y et al.·Gene
2024
Comprehensive Analysis of Aberrant m6A RNA Modifications Identifies Prognostic Biomarkers in Non-Small Cell Lung Cancer.
Li Y et al.·Int J Med Sci
2025
Expression patterns of eight RNA-modified regulators correlating with immune infiltrates during the progression of osteoarthritis.
Chen Z et al.·Front Immunol
2023
m6A Regulator-mediated RNA Methylation Modulates Immune Microenvironment of Hepatitis B Virus-related Acute Liver Failure.
Li D et al.·Inflammation
2023
m6A regulator-mediated RNA methylation modification patterns are involved in immune microenvironment regulation of periodontitis.
Zhang X et al.·J Cell Mol Med
2021
Human m(6)A-mRNA and lncRNA epitranscriptomic microarray reveal function of RNA methylation in hemoglobin H-constant spring disease.
Ruan H et al.·Sci Rep
2021
Gene signature of m6A-related targets to predict prognosis and immunotherapy response in ovarian cancer.
Tan W et al.·J Cancer Res Clin Oncol
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
CBLL1 promotes endometrial stromal cell senescence via inhibiting PTEN in recurrent spontaneous abortion.
Liu X et al.·FASEB J
2024
Stratification of Colorectal Patients Based on Survival Analysis Shows the Value of Consensus Molecular Subtypes and Reveals the CBLL1 Gene as a Biomarker of CMS2 Tumours.
Alfonsín G et al.·Int J Mol Sci
2024🔓 Open AccessCohort
CBLL1 is hypomethylated and correlates with cortical thickness in transgender men before gender affirming hormone treatment.
Fernández R et al.·Sci Rep
2023🔓 Open Access
Circ_0072083 interference enhances growth-inhibiting effects of cisplatin in non-small-cell lung cancer cells via miR-545-3p/CBLL1 axis.
Li H et al.·Cancer Cell Int
2020🔓 Open Access
Downregulation of long non-coding RNA XIST inhibits cell proliferation, migration, invasion and EMT by regulating miR-212-3p/CBLL1 axis in non-small cell lung cancer cells.
Qiu HB et al.·Eur Rev Med Pharmacol Sci
2019
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