FADS2

Chr 11AR

fatty acid desaturase 2

Also known as: D6D, DES6, FADSD6, LLCDL2, SLL0262, TU13

NCBI Gene: 9415ENSG00000134824UniProt: O95864

The protein encoded by this gene is a member of the fatty acid desaturase (FADS) gene family. Desaturase enzymes regulate unsaturation of fatty acids through the introduction of double bonds between defined carbons of the fatty acyl chain. FADS family members are considered fusion products composed of an N-terminal cytochrome b5-like domain and a C-terminal multiple membrane-spanning desaturase portion, both of which are characterized by conserved histidine motifs. This gene is clustered with family members at 11q12-q13.1; this cluster is thought to have arisen evolutionarily from gene duplication based on its similar exon/intron organization. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013]

Primary Disease Associations & Inheritance

Fetal akinesia deformation sequence 2MIM #618388
AR
43
ClinVar variants
8
Pathogenic / LP
1.00
pLI score· haploinsufficient
1
Active trials
Clinical Summary— FADS2
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
8 Pathogenic / Likely Pathogenic· 28 VUS of 43 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.23LOEUF
pLI 0.998
Z-score 4.48
OE 0.07 (0.03–0.23)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
3.19Z-score
OE missense 0.45 (0.38–0.52)
118 obs / 263.9 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.07 (0.03–0.23)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.45 (0.38–0.52)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.92
0≤1.21.6
LoF obs/exp: 2 / 27.2Missense obs/exp: 118 / 263.9Syn Z: 0.64

ClinVar Variant Classifications

43 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic3
VUS28
Likely Benign4
Benign3
5
Pathogenic
3
Likely Pathogenic
28
VUS
4
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
5
0
5
Likely Pathogenic
0
0
3
0
3
VUS
0
26
2
0
28
Likely Benign
0
1
1
2
4
Benign
0
0
2
1
3
Total02713343

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

FADS2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

2 OMIM entries

OMIM

Fetal akinesia deformation sequence 2

MIM #618388

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Zeb1 mediates EMT/plasticity-associated ferroptosis sensitivity in cancer cells by regulating lipogenic enzyme expression and phospholipid composition.
Schwab A et al.·Nat Cell Biol
2024
Discovery of a potent SCAP degrader that ameliorates HFD-induced obesity, hyperlipidemia and insulin resistance via an autophagy-independent lysosomal pathway.
Zheng ZG et al.·Autophagy
2021
Inhibition of cannabinoid receptor type 1 sensitizes triple-negative breast cancer cells to ferroptosis via regulating fatty acid metabolism.
Li P et al.·Cell Death Dis
2022
Exploring clinical and genetic evidence in association between unsaturated fatty acids and acne.
Zhang L et al.·Eur J Nutr
2025
Effect modification of FADS2 polymorphisms on the association between breastfeeding and intelligence: results from a collaborative meta-analysis.
Hartwig FP et al.·Int J Epidemiol
2019Meta-analysis
Differential regulation of FADS2 by EZH2 reveals a metabolic vulnerability in ovarian cancer treatment.
Guo Z et al.·EBioMedicine
2025
Uncovering the molecular networks of ferroptosis in the pathogenesis of type 2 diabetes and its complications: a multi-omics investigation.
Dong C et al.·Mol Med
2024
FADS2 confers SCD1 inhibition resistance to cancer cells by modulating the ER stress response.
Ikeda T et al.·Sci Rep
2024
FADS2 inhibits colorectal cancer cell proliferation by regulating ferroptosis through SLC7A11/GPX4.
Yang Q et al.·Mol Biol Rep
2025
Gene-Environment Interactions in Inflammatory Bowel Disease: A Systematic Review of Human Epidemiologic Studies.
Bai J et al.·J Crohns Colitis
2025Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Association of FADS2 polymorphism rs174538 with fatty acid metabolism and disease severity in Japanese patients with Crohn's disease.
Matsuzawa H et al.·World J Gastroenterol
2026🔓 Open AccessCohort
SLBP promotes lung adenocarcinoma progression by inhibiting ferroptosis and reprogramming glutamine metabolism via FADS2 interaction.
Yan W et al.·Exp Cell Res
2026
Novel organoid-based exploration reveals the role of LMTK3/FADS2 signaling in metastatic breast cancer progression in felines and humans.
Yamamoto H et al.·Sci Rep
2025🔓 Open Access
FADS1 and FADS2 Gene Polymorphisms Affect Omega-3 and Omega-6 Erythrocyte Fatty Acid Composition and Influence the Association Between Dietary Fatty Acid Intake and Lipid Profile in Brazilian Adults.
Batista LD et al.·Metabolites
2025🔓 Open Access
Liquiritin in Chaihu-shugan-san alleviates Parkinson's Disease via PPARα-mediated inhibition of SCD1/FADS2-dependent Ferroptosis.
Cai Y et al.·Phytomedicine
2025
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Breast Cancer

Anti-Inflammatory Diet in BRC Patients on Aromatase Inhibitors

RECRUITING
NCT06214598Phase NAUniversity of BelgradeStarted 2024-03-01
SupplementAI dietPlacebo

External Resources

Links to major genomics databases and tools