FADS3

Chr 11

fatty acid desaturase 3

Also known as: CYB5RP, LLCDL3

NCBI Gene: 3995 ENSG00000221968 UniProt: Q9Y5Q0

The protein is a fatty acid desaturase that introduces double bonds into sphingoid bases (particularly converting sphingosine to sphinga-4,14-dienine in ceramides) and can also desaturate certain fatty acyl chains. Mutations cause autosomal recessive spinocerebellar ataxia-38, a neurological disorder affecting coordination and movement. This gene is not highly constrained against loss-of-function variants.

ResearchSummary from RefSeq, 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]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.62

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.62LOEUF

pLI 0.003

Z-score 3.00

OE 0.36 (0.21–0.62)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

2.31Z-score

OE missense 0.60 (0.53–0.69)

159 obs / 264.9 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.36 (0.21–0.62)

0≤0.351.4

Missense OE?0.60 (0.53–0.69)

0≤0.61.4

Synonymous OE?0.84

0≤1.21.6

LoF obs/exp: 9 / 25.3Missense obs/exp: 159 / 264.9Syn Z: 1.40

Background carrier burden — how many people carry a rare variant somewhere in FADS3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 160

475 rare PASS variants

Rare truncating (LoF)

1 in 4,900

63 rare PASS variants

Rare synonymous (reference)

1 in 180

247 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for FADS3. 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 280	1 in 5,800
South Asian	~43k	1 in 140	1 in 4,600
Remaining (unassigned)	~30k	1 in 170	1 in 6,000
European (Finnish)	~27k	1 in 270	≈ 1 in 8,700
Admixed American	~22k	1 in 130	1 in 3,700
African / African American	~21k	1 in 200	≈ 1 in 6,900
East Asian	~20k	1 in 220	1 in 2,000
Ashkenazi Jewish	~13k	1 in 930	none seen
Middle Eastern	~2,884	1 in 220	≈ 1 in 2,500

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 ↓