GH-LCR
Chr 17ARADgrowth hormone locus control region
This element represents a locus control region (LCR) that can confer copy number-dependent, position-independent expression on members of the human growth hormone gene cluster in transgenic assays. It regulates expression of the GH1 (growth hormone 1), CSHL1 (chorionic somatomammotropin hormone-like 1), CSH1 (chorionic somatomammotropin hormone 1 (placental lactogen)), GH2 (growth hormone 2) and CSH2 (chorionic somatomammotropin hormone 2) genes in this cluster. This LCR spans approximately 40 kb upstream of the GH1 gene and is characterized by five major DNase I hypersensitive sites (HSI-HSV). It overlaps the CD79B (CD79b molecule, immunoglobulin-associated beta) gene, and also the 3' end of the SCN4A (sodium channel, voltage gated, type IV alpha subunit) gene. This LCR includes several transcription factor binding sites as well as subregions with enhancer, enhancer-blocking and boundary element activity. Three subregions were shown to be active enhancers by ChIP-STARR-seq in naive human embryonic stem cells, where all are marked by the H3K4me1 histone modification and one is additionally marked by H3K27ac. A subregion was also validated as a functional repressive element by Sharpr-MPRA (Systematic high-resolution activation and repression profiling with reporter tiling using massively parallel reporter assays) in HepG2 liver carcinoma cells (group: HepG2 Repressive non-DNase unmatched - State 20:ReprD, Polycomb repression w. Duke DNase/promoter and conservation enriched). This locus also includes seven accessible chromatin subregions, six of which were validated as enhancers and one 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) MPRA in GM12878 lymphoblastoid cells. Polymorphisms in this LCR may be associated with isolated growth hormone deficiency (IGHD), affecting serum IGF-I levels and height. [provided by RefSeq, May 2023]
Primary Disease Associations & Inheritance
Some data sources returned errors (2)
ensembl: Error: Ensembl fetch failed: 400 for https://rest.ensembl.org/lookup/symbol/homo_sapiens/GH-LCR?content-type=application/json&expand=1
gnomad: Error: Gene not found
Population Genetics & Constraint
Constraint data not available from gnomAD.
ClinVar Variant Classifications
486 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 | 3 | 0 | 0 | 0 | 3 |
Likely Pathogenic | 8 | 6 | 3 | 0 | 17 |
VUS | 3 | 242 | 21 | 5 | 271 |
Likely Benign | 0 | 3 | 57 | 88 | 148 |
Benign | 0 | 0 | 44 | 0 | 44 |
Conflicting | — | 3 | |||
| Total | 14 | 251 | 125 | 93 | 486 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
GH-LCR · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No open access results found
External Resources
Links to major genomics databases and tools