FADS1

Chr 11AR

fatty acid desaturase 1

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

NCBI Gene: 3992 ENSG00000149485 UniProt: O60427 OMIM: 208150

The FADS1 protein is a fatty acid desaturase that introduces double bonds into fatty acyl chains, specifically converting precursor fatty acids into highly unsaturated fatty acids including arachidonate, which is critical for inflammatory responses and membrane phospholipid biosynthesis. Mutations cause fetal akinesia deformation sequence 1, an autosomal recessive disorder characterized by reduced fetal movement and resulting deformations. The gene shows significant constraint against loss-of-function variants (LOEUF 0.445), indicating that biallelic mutations are likely required for disease manifestation.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Fetal akinesia deformation sequence 1MIM #208150

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Fetal akinesia deformation sequence 1; no ClinGen or GenCC tier

Active trials

129

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

—

LOEUF

—

Mechanism

Some data sources returned errors (1)

gnomad: Error: gnomAD API error: 400

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in FADS1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 270

423 rare PASS variants

Rare truncating (LoF)

1 in 650

63 rare PASS variants

Rare synonymous (reference)

1 in 240

260 rare PASS variants

Rare missense and truncating variants are carried at similar rates in FADS1; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 410	1 in 770
South Asian	~43k	1 in 220	1 in 1,700
Remaining (unassigned)	~30k	1 in 320	1 in 620
European (Finnish)	~27k	1 in 700	≈ 1 in 8,900
Admixed American	~22k	1 in 330	1 in 710
African / African American	~21k	1 in 230	1 in 1,900
East Asian	~20k	1 in 350	1 in 3,500
Ashkenazi Jewish	~13k	1 in 1,600	1 in 1,400
Middle Eastern	~2,884	1 in 160	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 11 of 12 coding exons well covered in gnomAD exomes; exon 2 marginal. Genomes: all 12.? see exons ↓