HBA-LCR alpha-globin locus control region [Homo sapiens (human)] - Gene

Summary

Gene symbol: HBA-LCR
Gene description: alpha-globin locus control region
Gene type: biological region
Feature type(s): misc_feature: conserved_region
protein_bind
regulatory: DNase_I_hypersensitive_site, enhancer, locus_control_region, silencer, transcriptional_cis_regulatory_region
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: alpha-LCR
Summary: 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]
Orthologs: mouse all
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Genomic context

Location:: 16p13.3

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	16	NC_000016.10 (87808..152854)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	16	NC_060940.1 (81410..146425)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	16	NC_000016.9 (137807..202853)

Chromosome 16 - NC_000016.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Our observations suggest that variants of the alpha-globin gene cluster might account for some of the phenotypic heterogeneity of sickle cell anaemia and HbAS.
Title: Haemolysis in sickle cell anaemia: effects of polymorphisms in α-globin gene regulatory elements.

Submit: New GeneRIF Correction

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See Variation Viewer (GRCh37.p13)

General gene information

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Other Names

ATAC-STARR-seq lymphoblastoid active region 10201
ATAC-STARR-seq lymphoblastoid silent region 6902
CRISPRi-validated cis-regulatory element chr16.29
CRISPRi-validated cis-regulatory element chr16.30
MED14-independent group 3 enhancer GRCh37_chr16:163229-164428
alpha-globin DCR
alpha-globin dominant control region
alpha-locus controlling region

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.