FADS1

Chr 11AR

fatty acid desaturase 1

Also known as: D5D, FADS6, FADSD5, LLCDL1, TU12

NCBI Gene: 3992ENSG00000149485UniProt: O60427

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 FADS1 and FADS2 at 11q12-q13.1; this cluster is thought to have arisen evolutionarily from gene duplication based on its similar exon/intron organization. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Fetal akinesia deformation sequence 1MIM #208150
AR
36
ClinVar variants
8
Pathogenic / LP
0.37
pLI score
2
Active trials
Clinical Summary— FADS1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.23) despite low pLI — interpret in context.
📋
ClinVar Variants
8 Pathogenic / Likely Pathogenic· 23 VUS of 36 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Missense constrained — critical functional residues
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.
0.45LOEUF
pLI 0.374
Z-score 3.70
OE 0.23 (0.12–0.45)
Moderately constrained

More LoF-intolerant than ~75% 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.
3.67Z-score
OE missense 0.37 (0.31–0.43)
98 obs / 267.0 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.0.23 (0.12–0.45)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.37 (0.31–0.43)
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.0.81
0≤1.21.6
LoF obs/exp: 6 / 26.6Missense obs/exp: 98 / 267.0Syn Z: 1.56

ClinVar Variant Classifications

36 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic3
VUS23
Likely Benign5
5
Pathogenic
3
Likely Pathogenic
23
VUS
5
Likely 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
21
2
0
23
Likely Benign
0
2
1
2
5
Benign
0
0
0
0
0
Total02311236

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

View in ClinVar →

Protein Context — Lollipop Plot

FADS1 · 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 1

MIM #208150

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
FADS1/2 control lipid metabolism and ferroptosis susceptibility in triple-negative breast cancer.
Lorito N et al.·EMBO Mol Med
2024
FADS1 Genetic Variant and Omega-3 Supplementation Are Associated with Changes in Fatty Acid Composition in Red Blood Cells of Subjects with Obesity.
Reyes-Pérez SD et al.·Nutrients
2024
Genetic variation influencing DNA methylation provides insights into molecular mechanisms regulating genomic function.
Hawe JS et al.·Nat Genet
2022Functional
Genetics of aortic valve disease.
Ackah RL et al.·Curr Opin Cardiol
2023Review
Exploring clinical and genetic evidence in association between unsaturated fatty acids and acne.
Zhang L et al.·Eur J Nutr
2025
Causal association between polyunsaturated fatty acids and acne: a two-sample Mendelian randomization study.
Kim BR et al.·Br J Dermatol
2025
Metabolic Interplay in Acute Lung Injury: PARK7 Integrates FADS1/2-Dependent PUFA Metabolism and H3K14 Lactylation to Attenuate Endothelial Ferroptosis and Dysfunction.
Xu J et al.·Adv Sci (Weinh)
2025
Integrating a multi-omics strategy framework to screen potential targets in cognitive impairment-related epilepsy.
Xu C et al.·Methods
2025
A comprehensive study of genetic regulation and disease associations of plasma circulatory microRNAs using population-level data.
Mustafa R et al.·Genome Biol
2024
Integrated network pharmacology and metabolomics analysis to reveal the potential mechanism of Ershen Wan in ameliorating ulcerative colitis.
Wang M et al.·J Ethnopharmacol
2025Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
SPP1⁺ macrophage-FADS1⁺ tumor cell crosstalk via the PDGFB-PDGFRB axis drives liver metastasis in colorectal cancer.
Zhao P et al.·Transl Oncol
2026🔓 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
Targeting FADS1-mediated lipid metabolism and signaling: a novel therapeutic strategy for precision oncology in colorectal and esophageal cancers.
Lian J et al.·Cell Death Discov
2025🔓 Open Access
Impact of fatty acid desaturase 1 (FADS1) on chronic kidney disease via very low-density lipoprotein: A drug target-related mediation Mendelian randomization study.
Zuo Y et al.·J Clin Lipidol
2025
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Heart Health MarkersCardiovascular DiseasesOmega 3 Fatty Acids

Omega-3D: Omega-3 for Diet-Driven Health Disparities

RECRUITING
NCT07078344Phase PHASE2University of ArizonaStarted 2025-07-31
Omega-3 Fatty Acids and Safflower Oil PlaceboSafflower Oil Placebo and Omega-3 Fatty Acids
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