HBA-LCR
Chr 16alpha-globin locus control region
Also known as: alpha-LCR
This genomic region regulates developmental stage- and erythroid lineage-specific expression of the HBZ (hemoglobin, zeta), HBA2 (hemoglobin, alpha 2), HBA1 (hemoglobin, alpha 1) and HBQ1 (hemoglobin, theta 1) genes within the alpha-globin gene cluster. This region has properties of a locus control region (LCR) in that it can confer high-level and chromosomal position-independent expression on members of the alpha-globin gene cluster in a transgene assay, but unlike other LCRs, such as that regulating the beta-globin gene cluster, it lacks the ability to confer copy number-dependent expression on the linked genes. This region overlaps the NPRL3 (NPR3-like, GATOR1 complex subunit) gene, which is transcribed in the opposite orientation compared to the downstream alpha-globin genes. This regulatory region is characterized by multiple erythroid-specific DNase I hypersensitive sites, including HS-48, HS-40, HS-33, HS-10 and HS-8, where the HS-40 site represents an enhancer and is the major cis-acting regulatory element. HS-40 binds transcription factors and mediates looping with the promoters of the alpha-globin genes during erythroid development. The HS-40 element has also been used to enhance erythroid expression of beta-globin family members in gene therapy vectors for beta-chain hemoglobinopathies. Mutations in this regulatory region result in alpha thalassemias and alpha hemoglobinopathies. This locus also includes two accessible chromatin subregions, one of which was validated as an enhancer and the other as a silencer based on their ability to activate or repress an origin of replication minimal core promoter by the ATAC-STARR-seq (assay for transposase-accessible chromatin with self-transcribing active regulatory region sequencing) massively parallel reporter assay (MPRA) in GM12878 lymphoblastoid cells. [provided by RefSeq, May 2023]
Some data sources returned errors (3)
ensembl: Error: Ensembl fetch failed: 400 for https://rest.ensembl.org/lookup/symbol/homo_sapiens/HBA-LCR?content-type=application/json&expand=1
clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi
gnomad: Error: Gene not found
Population Genetics & Constraint
Constraint data not available from gnomAD.
ClinVar Variant Classifications
974 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 9 | 0 | 4 | 0 | 13 |
Likely Pathogenic | 5 | 0 | 0 | 0 | 5 |
VUS | 0 | 37 | 5 | 0 | 42 |
Likely Benign | 1 | 1 | 9 | 14 | 25 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 15 | 38 | 18 | 14 | 85 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
HBA-LCR · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
OMIM — Genotype-Phenotype
No OMIM entries found.
External Resources
Links to major genomics databases and tools
Variant Interpretation
Population Databases
Gene Resources
Expert Curation
No publications found for HBA-LCR
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools