SCR-LIP-000240 · Claim · machine-readable JSON →
This review identifies specific lipedema-associated variants in AKR1C genes, including the familial AKR1C1 p.Leu213Gln (L213Q) mutation segregating across three generations and reducing catalytic efficiency ~50%, the gain-of-function AKR1C2 Ser320PheTer2 mutation, AKR1C2 overexpression in 24% (5/21) of patients without coding mutations, and regulatory SNPs rs28571848 (glucocorticoid receptor site) and rs34477787 (RORα site) that increase AKR1C2/AKR1C3 expression and truncal fat mass independent of BMI.
Claim at a glance
- Type
- clinical association
- Knowledge state
- Emerging
- Evidence certainty
- low (GRADE)
- Evidence
- 2 source(s)
- Answers
- 1 question(s)
- Dates
- 2026-05-31 → 2026-06-12
Structured evidence, machine-compiled — not a verdict.
Auto-compiled by the Layer 1 surveillance loop; not yet human-reviewed. anthropic/claude-opus-4.8 · 2026-05-31
Evidence over time
Evidence (2)
- From rare familial mutations to multifactorial disease: aldo-keto reductase 1C enzymes as a central biological pathway in lipedema — Vainberg et al. (2026) ✓ verified — consistent · review · 2026 · reading confidence: high
“Variante AKR1C1 p.Leu213Gln (L213Q) — descrita por Michelini et al. — segrega com lipedema em 3 gerações”
The article directly reviews specific genetic variants and inheritance patterns in lipedema (familial AKR1C1 L213Q segregating in 3 generations, AKR1C2 mutation, regulatory SNPs), proposing a mono-to-multifactorial genetic model. As a narra - Aldo-Keto Reductase 1C1 (AKR1C1) as the First Mutated Gene in a Family with Nonsyndromic Primary Lipedema — Michelini et al. (2020) ✓ verified — consistent · case series · 2020 · reading confidence: high
“Variante AKR1C1 c.638T>A; p.L213Q identificada exclusivamente nas 3 pacientes afetadas e ausente nos 9 membros não afetados da família”
The article directly identifies a specific genetic variant (AKR1C1 p.L213Q) and an autosomal dominant inheritance pattern in a single lipedema family, directly addressing the question; evidence is from one family with functional predictions
Context (PECO)
Answers these questions
Gaps & caveats
Auto-ingested single source; not yet human-reviewed.
Change log
- 2026-05-31 — created · auto-ingested for SQ-LIP-000025
- 2026-05-31 — evidence added · corroborated by DOI:10.3390/ijms21176264
- 2026-06-12 — disputed evidence reviewed · Human review: synthesis — this source supports the claim's direction; the specific variant(s)/figure(s) it lacks are present in a sibling source (per-claim integrity clean). Accepted.