CHNG3_MIR7-2
- Gene
- MIR7-2
- Disease
- CHNG3
- Inheritance
- AD
- Classification
- Strong
- Total Score
- 13.5
- Publications Reviewed
- 2
- Publication Span
- Last Updated
- 08/18/2025
- Curator(s)
- Macayla Weiner, Laurel Hiatt
Description
Noncoding TTTG STR changes at 15q26.1 between DET1 and MIR7-2/MIR1179 are associated with autosomal dominant CHNG3/resistance to TSH, presenting as congenital nongoitrous hypothyroidism and/or multinodular goiter. Two 2024 studies reported recurrent (TTTG)3 deletions and STR SNVs segregating in families and enriched in congenital hypothyroidism/MNG cohorts, with locus-specific functional evidence that the STR has thyroid-specific regulatory activity and that pathogenic STR variants disrupt or activate regulatory programs affecting MIR7-2/MIR1179 expression in thyroid tissue.
Genetic evidence
Total: 12
| Singular Evidence | Probands | PMID:38714869 | 6 | STR3 or STR4* variants in the 15q TTTG STR were identified in 12 unrelated RTSH families; all 76 phenotypically assessed affected participants were heterozygous for STRmut, with 6 additional STRmut carriers whose pretreatment thyroid phenotype could not be assessed. |
| Collective Evidence | Segregation | PMID:38714868 | 1.5 | Linkage analysis in family A identified a chr15q26.1 critical interval overlapping the TTTG STR (GRCh38 chr15:86,206,051-89,412,131; maximum LOD score 4.8), with the (TTTG)3 allele tracking with thyroid abnormalities in the pedigree. |
| Statistics | Case-control data | PMID:38714868 | 6 | In a congenital hypothyroidism cohort, (TTTG)3/SNV variants were found in 137/989 cases (13.9%) versus 3/38,722 Japanese population controls (P<1e-300); an independent MNG cohort also showed enrichment (3/33 cases; P<1.2e-8 versus controls). |
Experimental evidence
Total: 1.5
| Function | Regulatory impact | PMID:38714868 | 0.5 | Locus-specific regulatory evidence: snATAC-seq placed the (TTTG)4 region in thyroid-selective open chromatin, and luciferase assays in FRTL-5 and HEK293 cells showed WT repressor activity that was attenuated by (TTTG)3/SNV variants. |
| Functional Alteration | Patient cells | PMID:38714868 | 1 | Patient-derived thyroid tissue from an adult (TTTG)3 carrier with MNG showed benign nodular pathology, heterogeneous follicle size, increased resorptive vacuoles, and thyroglobulin staining. |
Note: Maximum score caps apply at evidence type, category, and supercategory levels, so section totals may be lower than the raw sum of row scores.