FDFT1

Chr 8AR

farnesyl-diphosphate farnesyltransferase 1

Also known as: DGPT, ERG9, SQS, SQSD, SS

The protein catalyzes the condensation of two farnesyl pyrophosphate molecules to form squalene, serving as the first committed enzyme in cholesterol biosynthesis. Mutations cause squalene synthase deficiency, an autosomal recessive disorder affecting cholesterol metabolism. This gene shows very high constraint against loss-of-function variants (pLI ~1.0), indicating that complete loss of protein function is typically incompatible with normal development.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.571 OMIM phenotype
Clinical SummaryFDFT1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.57LOEUF
pLI 0.000
Z-score -0.39
OE 1.10 (0.781.57)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-3.88Z-score
OE missense 1.71 (1.571.85)
408 obs / 239.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.10 (0.781.57)
00.351.4
Missense OE1.71 (1.571.85)
00.61.4
Synonymous OE2.00
01.21.6
LoF obs/exp: 21 / 19.1Missense obs/exp: 408 / 239.0Syn Z: -7.30
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedFDFT1-related defect in cholesterol biosynthesisLOFAR
limitedFDFT1-related retinitis pigmentosaOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.5869th %ile
GOF
0.6930th %ile
LOF
0.2678th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

FDFT1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →