FADS2

Chr 11

fatty acid desaturase 2

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

NCBI Gene: 9415 ENSG00000134824 UniProt: O95864

FADS2 encodes a fatty acid desaturase that catalyzes the rate-limiting step in highly unsaturated fatty acid biosynthesis, introducing double bonds into essential polyunsaturated fatty acids including linoleic and alpha-linolenic acid. Mutations cause fetal akinesia deformation sequence 2, inherited in an autosomal recessive pattern. The gene is highly constrained against loss-of-function variants (pLI 0.998), indicating that complete loss of function is likely incompatible with normal development.

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 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]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

173

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.23

LOEUF· LoF intol.

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

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?

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?

LoF OE?0.07 (0.03–0.23)

0≤0.351.4

Missense OE?0.45 (0.38–0.52)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 2 / 27.2Missense obs/exp: 118 / 263.9Syn Z: 0.64

Background carrier burden — how many people carry a rare variant somewhere in FADS2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 200

465 rare PASS variants

Rare truncating (LoF)

1 in 4,500

56 rare PASS variants

Rare synonymous (reference)

1 in 210

266 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for FADS2. 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 200	1 in 5,300
South Asian	~43k	1 in 310	1 in 670
Remaining (unassigned)	~30k	1 in 160	≈ 1 in 7,500
European (Finnish)	~27k	1 in 300	1 in 2,800
Admixed American	~22k	1 in 250	≈ 1 in 5,200
African / African American	~21k	1 in 270	1 in 1,700
East Asian	~20k	1 in 190	1 in 2,300
Ashkenazi Jewish	~13k	1 in 1,400	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 150	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): All 12 coding exons well covered in gnomAD exomes and genomes.? see exons ↓