FDFT1

Chr 8AR

farnesyl-diphosphate farnesyltransferase 1

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

NCBI Gene: 2222ENSG00000079459UniProt: P37268

This gene encodes a membrane-associated enzyme located at a branch point in the mevalonate pathway. The encoded protein is the first specific enzyme in cholesterol biosynthesis, catalyzing the dimerization of two molecules of farnesyl diphosphate in a two-step reaction to form squalene. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Squalene synthase deficiencyMIM #618156
AR
280
ClinVar variants
119
Pathogenic / LP
0.00
pLI score
2
Active trials
Clinical Summary— FDFT1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
119 Pathogenic / Likely Pathogenic· 113 VUS of 280 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
Tolerant — LoF & missense variants common in population
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.
1.57LOEUF
pLI 0.000
Z-score -0.39
OE 1.10 (0.78–1.57)
Tolerant

Highly tolerant — LoF variants common in population

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.
-3.88Z-score
OE missense 1.71 (1.57–1.85)
408 obs / 239.0 exp
Tolerant

Tolerant to missense variation

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.1.10 (0.78–1.57)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.71 (1.57–1.85)
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.2.00
0≤1.21.6
LoF obs/exp: 21 / 19.1Missense obs/exp: 408 / 239.0Syn Z: -7.30

ClinVar Variant Classifications

280 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic109
Likely Pathogenic10
VUS113
Likely Benign31
Benign16
Conflicting1
109
Pathogenic
10
Likely Pathogenic
113
VUS
31
Likely Benign
16
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
109
0
109
Likely Pathogenic
0
0
10
0
10
VUS
3
91
19
0
113
Likely Benign
0
6
10
15
31
Benign
0
3
6
7
16
Conflicting
—1
Total310015422280

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

View 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.

Gene2Phenotype Curations

FDFT1-related defect in cholesterol biosynthesis

limited
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

FDFT1-related retinitis pigmentosa

limited
ARUndeterminedAltered Gene Product Structure
Eye
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Squalene synthase deficiency

MIM #618156

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — FDFT1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Targeting FDFT1 Reduces Cholesterol and Bile Acid Production and Delays Hepatocellular Carcinoma Progression Through the HNF4A/ALDOB/AKT1 Axis.
Cai D et al.·Adv Sci (Weinh)
2025
Gene-specific somatic epigenetic mosaicism of FDFT1 underlies a non-hereditary localized form of porokeratosis.
Saito S et al.·Am J Hum Genet
2024
FDFT1 maintains glioblastoma stem cells through activation of the Akt pathway.
Mo H et al.·Stem Cell Res Ther
2024
Artemisitene induces apoptosis of breast cancer cells by targeting FDFT1 and inhibits the growth of breast cancer patient-derived organoids.
Chen D et al.·Phytomedicine
2024
Raman spectroscopy biochemical characterisation of bladder cancer cisplatin resistance regulated by FDFT1: a review.
Kanmalar M et al.·Cell Mol Biol Lett
2022Review
MicroRNA-146b-5p/FDFT1 mediates cisplatin sensitivity in bladder cancer by redirecting cholesterol biosynthesis to the non-sterol branch.
Azhar NA et al.·Int J Biochem Cell Biol
2024
Identification of Ferroptosis-Related Prognostic Models and FDFT1 as a Potential Ferroptosis Driver in Colorectal Cancer.
Duan L et al.·Curr Med Chem
2026Functional
The mechanism and clinical application of farnesyl diphosphate farnesyltransferase 1 in cancer metabolism.
Li N et al.·Biochem Biophys Res Commun
2024Review
Exclusion of CTSB and FDFT1 as positional and functional candidate genes for keratolytic winter erythema (KWE).
Hobbs A et al.·J Dermatol Sci
2012Functional
Multiomic molecular patterns of lipid dysregulation in a subphenotype of sepsis with higher shock incidence and mortality.
Augustin B et al.·Crit Care
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Rare DiseasesAlbinismIntellectual Disability

Implementation of Long-read Sequencing for the Diagnosis of Rare Diseases.

NOT YET RECRUITING
NCT07400913University Hospital, BordeauxStarted 2026-02
Long-read sequencing
Castration-Resistant Prostate CarcinomaMetastatic Castration-Resistant Prostate CarcinomaRefractory Prostate Carcinoma

Testing the Effect of M1774 on Hard-to-Treat Refractory SPOP-mutant Prostate Cancer

ACTIVE NOT RECRUITING
NCT05828082Phase PHASE2National Cancer Institute (NCI)Started 2023-10-16
Biopsy ProcedureBiospecimen CollectionComputed Tomography

External Resources

Links to major genomics databases and tools