HBS1L

Chr 6

HBS1 like translational GTPase

Also known as: EF-1a, ERFS, HBS1, HSPC276, eRF3c

NCBI Gene: 10767ENSG00000112339UniProt: Q9Y450

This gene encodes a member of the GTP-binding elongation factor family. It is expressed in multiple tissues with the highest expression in heart and skeletal muscle. The intergenic region of this gene and the MYB gene has been identified to be a quantitative trait locus (QTL) controlling fetal hemoglobin level, and this region influnces erythrocyte, platelet, and monocyte counts as well as erythrocyte volume and hemoglobin content. DNA polymorphisms at this region associate with fetal hemoglobin levels and pain crises in sickle cell disease. A single nucleotide polymorphism in exon 1 of this gene is significantly associated with severity in beta-thalassemia/Hemoglobin E. Multiple alternatively spliced transcript variants encoding different protein isoforms have been found for this gene. [provided by RefSeq, May 2009]

88
ClinVar variants
15
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— HBS1L
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
15 Pathogenic / Likely Pathogenic· 67 VUS of 88 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.68LOEUF
pLI 0.000
Z-score 3.17
OE 0.46 (0.31–0.68)
Tolerant

Typical tolerance to LoF variation

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.
0.89Z-score
OE missense 0.87 (0.79–0.95)
316 obs / 363.8 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.0.46 (0.31–0.68)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.87 (0.79–0.95)
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.0.93
0≤1.21.6
LoF obs/exp: 18 / 39.5Missense obs/exp: 316 / 363.8Syn Z: 0.63

ClinVar Variant Classifications

88 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15
VUS67
Likely Benign3
Benign3
15
Pathogenic
67
VUS
3
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
15
0
15
Likely Pathogenic
0
0
0
0
0
VUS
0
66
1
0
67
Likely Benign
0
0
1
2
3
Benign
0
2
1
0
3
Total06818288

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

View in ClinVar →

Protein Context — Lollipop Plot

HBS1L · 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
HBS1-LIKE PROTEIN; HBS1L
MIM #612450 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Synthetic lethality of mRNA quality control complexes in cancer.
Prindle V et al.·Nature
2025
Genetic Variation and Sickle Cell Disease Severity: A Systematic Review and Meta-Analysis.
Kirkham JK et al.·JAMA Netw Open
2023Meta-analysis
Safety and efficacy of thalidomide in patients with transfusion-dependent β-thalassemia: a randomized clinical trial.
Chen JM et al.·Signal Transduct Target Ther
2021Clinical trial
Mammalian Hbs1L deficiency causes congenital anomalies and developmental delay associated with Pelota depletion and 80S monosome accumulation.
O'Connell AE et al.·PLoS Genet
2019
Fetal haemoglobin induction in sickle cell disease.
Paikari A et al.·Br J Haematol
2018Review
Association Between KLF1, BCL11A and HBS1L-MYB Polymorphisms and Phenotypes With β-Thalassemia Patients in Hainan.
Hu J et al.·Mol Genet Genomic Med
2025Cohort
Predictive SNPs for β(0)-thalassemia/HbE disease severity.
Munkongdee T et al.·Sci Rep
2021
Disruption of the Hbs1l-Myb locus causes hereditary persistence of fetal hemoglobin in a mouse model.
Suzuki M et al.·Mol Cell Biol
2013Functional
Epigenetic Insights and Potential Modifiers as Therapeutic Targets in β-Thalassemia.
Zakaria NA et al.·Biomolecules
2021Review
DNA polymorphisms at the BCL11A, HBS1L-MYB, and beta-globin loci associate with fetal hemoglobin levels and pain crises in sickle cell disease.
Lettre G et al.·Proc Natl Acad Sci U S A
2008
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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