FDFT1

farnesyl-diphosphate farnesyltransferase 1

Basic information

Region (hg38): 8:11795573-11839395

Links

ENSG00000079459 ∙ NCBI:2222 ∙ OMIM:184420 ∙ HGNC:3629 ∙ Uniprot:P37268 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• squalene synthase deficiency (Limited), mode of inheritance: AR
• squalene synthase deficiency (Limited), mode of inheritance: AR
• squalene synthase deficiency (Limited), mode of inheritance: AR
• retinitis pigmentosa (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Squalene synthase deficiency	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Cardiovascular; Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic	29909962

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FDFT1 gene.

• not_specified (84 variants)
• FDFT1-related_disorder (28 variants)
• not_provided (26 variants)
• Squalene_synthase_deficiency (7 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FDFT1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004462.5. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				13	3	16
missense			84	3	2	89
nonsense		1				1
start loss						0
frameshift			1			1
splice donor/acceptor (+/-2bp)			2			2
Total	0	1	87	16	5

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FDFT1	protein_coding	protein_coding	ENST00000220584	8	43737

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.10e-15	0.00625	125700	0	48	125748	0.000191

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-3.88	408	239	1.71	0.0000129	2754
Missense in Polyphen		105	78.436	1.3387		962
Synonymous	-7.30	172	86.0	2.00	0.00000452	768
Loss of Function	-0.394	21	19.1	1.10	8.96e-7	233

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000346	0.000341
Ashkenazi Jewish	0.000203	0.000198
East Asian	0.000329	0.000326
Finnish	0.0000464	0.0000462
European (Non-Finnish)	0.000249	0.000246
Middle Eastern	0.000329	0.000326
South Asian	0.000100	0.0000980
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Pathway: Steroid biosynthesis - Homo sapiens (human);Bisphosphonate Pathway, Pharmacodynamics;Statin Pathway, Pharmacodynamics;Simvastatin Action Pathway;Pravastatin Action Pathway;Atorvastatin Action Pathway;Hyper-IgD syndrome;Cholesteryl ester storage disease;Lysosomal Acid Lipase Deficiency (Wolman Disease);Alendronate Action Pathway;Rosuvastatin Action Pathway;Lovastatin Action Pathway;Mevalonic aciduria;Wolman disease;Risedronate Action Pathway;Cerivastatin Action Pathway;Pamidronate Action Pathway;Fluvastatin Action Pathway;Smith-Lemli-Opitz Syndrome (SLOS);Chondrodysplasia Punctata II, X Linked Dominant (CDPX2);CHILD Syndrome;Desmosterolosis;Hypercholesterolemia;Steroid Biosynthesis;Zoledronate Action Pathway;Ibandronate Action Pathway;Cholesterol Biosynthesis;Sterol Regulatory Element-Binding Proteins (SREBP) signalling;Activation of gene expression by SREBF (SREBP);Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha);Demo complete;Statin Pathway;Metabolism of lipids;Regulation of cholesterol biosynthesis by SREBP (SREBF);Squalene and cholesterol biosynthesis;Metabolism;cholesterol biosynthesis III (via desmosterol);cholesterol biosynthesis II (via 24,25-dihydrolanosterol);superpathway of cholesterol biosynthesis;Metabolism of steroids;epoxysqualene biosynthesis;cholesterol biosynthesis I;Steroids metabolism;Cholesterol biosynthesis;Activation of gene expression by SREBF (SREBP) (Consensus)

Recessive Scores

• pRec: 0.267

Intolerance Scores

• loftool: 0.320
• rvis_EVS: -1.13
• rvis_percentile_EVS: 6.48

Haploinsufficiency Scores

• pHI: 0.181
• ghis: 0.622

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.999

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Fdft1
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; growth/size/body region phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); skeleton phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype

Gene ontology

• Biological process: steroid biosynthetic process;cholesterol biosynthetic process;ergosterol biosynthetic process;isoprenoid biosynthetic process;regulation of lipid metabolic process;farnesyl diphosphate metabolic process;regulation of cholesterol biosynthetic process
• Cellular component: endoplasmic reticulum;endoplasmic reticulum membrane;integral component of membrane
• Molecular function: farnesyl-diphosphate farnesyltransferase activity;protein binding;squalene synthase activity