GeneBe

FDPS

protein-coding

farnesyl diphosphate synthase

Gene summary

This gene encodes an enzyme that catalyzes the production of geranyl pyrophosphate and farnesyl pyrophosphate from isopentenyl pyrophosphate and dimethylallyl pyrophosphate. The resulting product, farnesyl pyrophosphate, is a key intermediate in cholesterol and sterol biosynthesis, a substrate for protein farnesylation and geranylgeranylation, and a ligand or agonist for certain hormone receptors and growth receptors. Drugs that inhibit this enzyme prevent the post-translational modifications of small GTPases and have been used to treat diseases related to bone resorption. Multiple pseudogenes have been found on chromosomes 1, 7, 14, 15, 21 and X. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2008]

MANE transcript

NM_002004.4

Inheritance

AD

ClinVar variants

P:4U:68B:11

Top phenotype

Porokeratosis 9, multiple types

gnomAD constraint

pLI —, LoF o/e 0.35

Max pathogenic AF

—

Genomic locus

chr1:155,308,748-155,320,666

External References & Databases

Ensembl (ENSG00000160752)NCBI Gene (2224)OMIM (134629)HGNC:3631GenCCUniProt (P14324)AlphaFoldClinVar (FDPS)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~11.9 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

porokeratosis 9, multiple typesSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0014713

Submitter: Labcorp Genetics (formerly Invitae)

disseminated superficial actinic porokeratosisSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0019212

Submitter: Orphanet

porokeratosis 9, multiple typesMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0014713

Submitter: Ambry Genetics

porokeratosis 9, multiple typesSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0014713

Submitter: Genomics England PanelApp

porokeratosis 9, multiple typesMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0014713

Submitter: G2P

Clinical Genomic Database (CGD)

Porokeratosis 9, multiple typesAD

Manifestation: Dermatologic

Intervention: General

Rationale: 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

Refs: 26202976Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FDPS variants in ClinVar

5 Conditions Cataloged
not specifiedTotal: 51
FDPS-related disorderTotal: 5
Porokeratosis 9, multiple typesTotal: 3
not providedTotal: 2
response to aminobisphosphonatesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002004.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
7
clinvar
6
clinvar
1
clinvar
 14
missense
1
clinvar
58
clinvar
2
clinvar
2
clinvar
 63
nonsense
1
clinvar
 1
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
2
clinvar
1
clinvar
2
clinvar
 5
Total31688383

Highest pathogenic variant AF is 0.000018008328

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 93 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_002004.4RefSeqNP_001995.110MANE Select
ENST00000368356.9EnsemblENSP00000357340.410MANE Select
NM_001135821.2RefSeqNP_001129293.110Standard
NM_001135822.2RefSeqNP_001129294.19Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Mevalonate pathway
  • Influenza A - Homo sapiens (human)
  • HTLV-I infection - Homo sapiens (human)
  • Terpenoid backbone biosynthesis - Homo sapiens (human)
  • Bisphosphonate Pathway, Pharmacodynamics

Biological Process

  • cholesterol biosynthetic process
  • viral process
  • geranyl diphosphate biosynthetic process
  • farnesyl diphosphate biosynthetic process
  • regulation of cholesterol biosynthetic process

Molecular Function

  • RNA binding
  • dimethylallyltranstransferase activity
  • geranyltranstransferase activity
  • metal ion binding

Cellular Component

  • nucleoplasm
  • cytoplasm
  • cytosol

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000356657
Coding exons
10
Length
11919
Individuals with no LoFs
125728
Homozygous LoFs
0
Heterozygous LoFs
20
Defined
125748
p
0.0000795
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.091932410.8020.00001382703
Missense (PolyPhen)3856.0640.6778764
Synonymous1.927397.00.7520.00000540824
Loss of Function2.90823.00.3480.00000102252

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American0.000200.00020rare
Ashkenazi Jewish00.0absent
East Asian0.000110.00011rare
Finnish0.0000920.000092rare
European (Non-Finnish)0.0000350.000035rare
South Asian0.000160.00016rare
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Key enzyme in isoprenoid biosynthesis which catalyzes the formation of farnesyl diphosphate (FPP), a precursor for several classes of essential metabolites including sterols, dolichols, carotenoids, and ubiquinones. FPP also serves as substrate for protein farnesylation and geranylgeranylation. Catalyzes the sequential condensation of isopentenyl pyrophosphate with the allylic pyrophosphates, dimethylallyl pyrophosphate, and then with the resultant geranylpyrophosphate to the ultimate product farnesyl pyrophosphate.;
Disease
DISEASE: Porokeratosis 9, multiple types (POROK9) [MIM:616631]: A form of porokeratosis, a disorder of faulty keratinization characterized by one or more atrophic patches surrounded by a distinctive hyperkeratotic ridgelike border called the cornoid lamella. The keratotic lesions can progress to overt cutaneous neoplasms, typically squamous cell carcinomas. Multiple clinical variants of porokeratosis are recognized, including porokeratosis of Mibelli, linear porokeratosis, disseminated superficial actinic porokeratosis, palmoplantar porokeratosis, and punctate porokeratosis. Different clinical presentations can be observed among members of the same family. Individuals expressing more than one variant have also been reported. {ECO:0000269|PubMed:26202976}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.351

Intolerance Scores

LoFtool
0.943
RVIS EVS
0.57
RVIS percentile EVS
81.99

Essentials

Essential (CRISPR)
E
Essential (CRISPR2)
N
Essential (gene trap)
E
Indispensability pred.
E
Indispensability score
0.998

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
Feedback | API | MCP | Annotate VCF | Sitemap | About | Privacy & Terms
For research and educational, non-commercial use only. Not for clinical or diagnostic use. GeneBe does not provide medical advice. Data use for AI modeling is prohibited: if used, the cost is $0.001 per byte of downloaded uncompressed data.