GGPS1

geranylgeranyl diphosphate synthase 1

Basic information

Region (hg38): 1:235327349-235344532

Links

ENSG00000152904 ∙ NCBI:9453 ∙ OMIM:606982 ∙ HGNC:4249 ∙ Uniprot:O95749 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• muscular dystrophy, congenital hearing loss, and ovarian insufficiency syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Muscular dystrophy, congenital hearing loss, and ovarian insufficiency syndrome	AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Endocrine; Musculoskeletal; Obstetric; Pulmonary	32403198

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GGPS1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GGPS1 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			9			9
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	9	0	0

Variants in GGPS1

This is a list of pathogenic ClinVar variants found in the GGPS1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-235335307-C-T		Muscular dystrophy, congenital hearing loss, and ovarian insufficiency syndrome	Uncertain significance (Sep 11, 2023)
1-235335308-C-T		not specified	Uncertain significance (Dec 16, 2022)
1-235335313-A-G		not specified	Uncertain significance (Feb 05, 2024)
1-235342039-A-G		Muscular dystrophy, congenital hearing loss, and ovarian insufficiency syndrome	Uncertain significance (Feb 06, 2024)
1-235342105-C-A		not specified	Uncertain significance (Sep 23, 2023)
1-235342138-A-G		Myopathy;Sensorineural hearing loss disorder	Uncertain significance (Jan 14, 2020)
1-235342269-G-A		Muscular dystrophy, congenital hearing loss, and ovarian insufficiency syndrome	Uncertain significance (Feb 06, 2024)
1-235342380-G-A		not specified	Uncertain significance (Apr 26, 2024)
1-235342465-G-A		not specified	Uncertain significance (Dec 14, 2022)
1-235342596-A-G		not specified	Uncertain significance (Oct 03, 2022)
1-235342633-G-A		Muscular dystrophy, congenital hearing loss, and ovarian insufficiency syndrome	Uncertain significance (-)
1-235342639-T-G		Myopathy with tubular aggregates	Likely pathogenic (Mar 01, 2024)
1-235342645-A-G		Muscular dystrophy, congenital hearing loss, and ovarian insufficiency syndrome	Pathogenic (Sep 08, 2021)
1-235342650-C-G		Muscular dystrophy, congenital hearing loss, and ovarian insufficiency syndrome	Pathogenic (Sep 08, 2021)
1-235342651-G-A		Myopathy;Sensorineural hearing loss disorder;Premature ovarian insufficiency • Muscular dystrophy, congenital hearing loss, and ovarian insufficiency syndrome	Conflicting classifications of pathogenicity (Sep 08, 2021)
1-235342657-C-A		not specified	Uncertain significance (Jan 30, 2024)
1-235342723-T-G		Muscular dystrophy, congenital hearing loss, and ovarian insufficiency syndrome	Pathogenic (Oct 10, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GGPS1	protein_coding	protein_coding	ENST00000282841	3	17183

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.269	0.727	125733	0	15	125748	0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.22	113	156	0.726	0.00000777	1980
Missense in Polyphen		23	49.328	0.46626		649
Synonymous	-0.935	65	56.1	1.16	0.00000266	555
Loss of Function	2.43	3	12.1	0.248	5.91e-7	158

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000914	0.0000904
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000708	0.0000703
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000988	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the trans-addition of the three molecules of IPP onto DMAPP to form geranylgeranyl pyrophosphate, an important precursor of carotenoids and geranylated proteins.
• Pathway: Terpenoid backbone biosynthesis - Homo sapiens (human);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;Activation of gene expression by SREBF (SREBP);Metabolism of lipids;Regulation of cholesterol biosynthesis by SREBP (SREBF);<i>trans, trans</i>-farnesyl diphosphate biosynthesis;Metabolism;superpathway of cholesterol biosynthesis;Metabolism of steroids;Steroids metabolism;Cholesterol biosynthesis;Activation of gene expression by SREBF (SREBP);geranylgeranyldiphosphate biosynthesis;superpathway of geranylgeranyldiphosphate biosynthesis I (via mevalonate) (Consensus)

Recessive Scores

• pRec: 0.173

Intolerance Scores

• loftool: 0.618
• rvis_EVS: -0.32
• rvis_percentile_EVS: 31.46

Haploinsufficiency Scores

• pHI: 0.221
• hipred: Y
• hipred_score: 0.591
• ghis: 0.640

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.939

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ggps1
• 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); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); homeostasis/metabolism phenotype

Gene ontology

• Biological process: cholesterol biosynthetic process;isoprenoid metabolic process;geranyl diphosphate biosynthetic process;geranylgeranyl diphosphate biosynthetic process;farnesyl diphosphate biosynthetic process;regulation of cholesterol biosynthetic process
• Cellular component: cytosol
• Molecular function: dimethylallyltranstransferase activity;farnesyltranstransferase activity;geranyltranstransferase activity;protein binding;identical protein binding;metal ion binding