DHDDS

dehydrodolichyl diphosphate synthase subunit, the group of Dehydrodolichyl diphosphate synthase

Basic information

Region (hg38): 1:26432281-26471306

Links

ENSG00000117682 ∙ NCBI:79947 ∙ OMIM:608172 ∙ HGNC:20603 ∙ Uniprot:Q86SQ9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• retinitis pigmentosa 59 (Limited), mode of inheritance: AR
• retinitis pigmentosa (Supportive), mode of inheritance: AD
• undetermined early-onset epileptic encephalopathy (Supportive), mode of inheritance: AD
• developmental delay and seizures with or without movement abnormalities (Strong), mode of inheritance: AD
• retinitis pigmentosa 59 (Definitive), mode of inheritance: AR
• retinitis pigmentosa 59 (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Developmental delay and seizures with or without movement abnormalities; Retinitis pigmentosa 59	AD/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	Neurologic; Ophthalmologic	21295282; 21295283; 29100083

ClinVar

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

• Retinitis pigmentosa 59 (370 variants)
• Retinitis pigmentosa (60 variants)
• not provided (44 variants)
• Developmental delay and seizures with or without movement abnormalities (13 variants)
• Inborn genetic diseases (12 variants)
• Retinitis Pigmentosa, Recessive (8 variants)
• not specified (7 variants)
• Developmental delay and seizures with or without movement abnormalities;Retinitis pigmentosa 59 (3 variants)
• See cases (2 variants)
• Retinitis pigmentosa 59;Developmental delay and seizures with or without movement abnormalities (2 variants)
• DHDDS-related condition (2 variants)
• Seizure (1 variants)
• Congenital disorder of glycosylation, type Ibb (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DHDDS 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			2	118	1	121
missense	6	5	145		1	157
nonsense	1	4	6			11
start loss			1			1
frameshift	4	3	3			10
inframe indel			1			1
splice donor/acceptor (+/-2bp)		2	1			3
splice region		1	8	25	1	35
non coding		1	45	52	11	109
Total	11	15	204	170	13

Highest pathogenic variant AF is 0.000125

Variants in DHDDS

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

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

Position	Type	Phenotype	Significance	ClinVar
1-26432282-G-A		Retinitis pigmentosa	Benign (Jan 13, 2018)
1-26432289-C-T		Retinitis pigmentosa	Uncertain significance (Jan 12, 2018)
1-26432313-G-A		Retinitis pigmentosa	Likely benign (Jan 12, 2018)
1-26432658-A-G			Benign (Jul 27, 2018)
1-26432893-T-G		Retinitis pigmentosa	Uncertain significance (Jan 12, 2018)
1-26432909-G-A		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
1-26432944-CTA-C		Retinitis pigmentosa 59	Uncertain significance (Oct 05, 2023)
1-26432951-A-G		Retinitis pigmentosa 59	Likely benign (Oct 27, 2023)
1-26432957-C-T		Retinitis pigmentosa 59	Likely benign (Apr 28, 2023)
1-26432964-G-A		Retinitis pigmentosa 59	Uncertain significance (Jan 10, 2024)
1-26432965-G-A		Retinitis pigmentosa 59	Uncertain significance (May 08, 2020)
1-26432967-G-C		Retinitis pigmentosa 59	Uncertain significance (Dec 11, 2023)
1-26432978-T-C		Retinitis pigmentosa 59 • DHDDS-related disorder	Likely benign (Jan 17, 2024)
1-26432985-C-A		Retinitis pigmentosa 59	Likely benign (Aug 18, 2023)
1-26432985-C-G		Inborn genetic diseases	Uncertain significance (Jun 06, 2023)
1-26432985-C-T			Uncertain significance (May 25, 2022)
1-26432987-G-A		Retinitis pigmentosa 59	Likely benign (Jun 14, 2022)
1-26432987-G-C		Retinitis pigmentosa 59	Likely benign (Jul 06, 2021)
1-26432989-T-A		Retinitis pigmentosa 59	Uncertain significance (Oct 19, 2023)
1-26432990-C-T		Retinitis pigmentosa 59	Likely benign (Nov 10, 2020)
1-26432996-C-T		Retinitis pigmentosa 59	Likely benign (Sep 15, 2022)
1-26432998-A-G		Retinitis pigmentosa • Retinitis pigmentosa 59	Uncertain significance (Oct 28, 2022)
1-26432999-C-A			Uncertain significance (Nov 02, 2022)
1-26433001-T-G		Retinitis pigmentosa 59	Uncertain significance (Aug 10, 2023)
1-26433002-C-T		Retinitis pigmentosa 59 • DHDDS-related disorder	Likely benign (Jan 10, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DHDDS	protein_coding	protein_coding	ENST00000360009	8	39013

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.245	0.754	125741	0	7	125748	0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.09	152	195	0.780	0.0000128	2177
Missense in Polyphen		36	69.348	0.51912		718
Synonymous	0.968	65	75.7	0.858	0.00000436	654
Loss of Function	3.18	5	20.6	0.243	0.00000124	208

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000867	0.0000867
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000264	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: With NUS1, forms the dehydrodolichyl diphosphate synthase (DDS) complex, an essential component of the dolichol monophosphate (Dol-P) biosynthetic machinery. Both subunits contribute to enzymatic activity, i.e. condensation of multiple copies of isopentenyl pyrophosphate (IPP) to farnesyl pyrophosphate (FPP) to produce dehydrodolichyl diphosphate (Dedol- PP), a precursor of dolichol phosphate which is utilized as a sugar carrier in protein glycosylation in the endoplasmic reticulum (ER) (PubMed:25066056, PubMed:28842490). Regulates the glycosylation and stability of nascent NPC2, thereby promoting trafficking of LDL-derived cholesterol (PubMed:21572394). {ECO:0000269|PubMed:21572394, ECO:0000269|PubMed:25066056, ECO:0000269|PubMed:28842490}.
• Disease: DISEASE: Developmental delay and seizures with or without movement abnormalities (DEDSM) [MIM:617836]: An autosomal dominant neurodevelopmental disorder characterized by global developmental delay, variable intellectual disability, and early-onset seizures with a myoclonic component. Most patients have delayed motor development and show abnormal movements, including ataxia, dystonia, and tremor. {ECO:0000269|PubMed:29100083}. Note=The disease may be caused by mutations affecting the gene represented in this entry.
• Pathway: Terpenoid backbone biosynthesis - Homo sapiens (human);Post-translational protein modification;Metabolism of proteins;dolichol and dolichyl phosphate biosynthesis;Synthesis of Dolichyl-phosphate;Synthesis of substrates in N-glycan biosythesis;Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein;Asparagine N-linked glycosylation (Consensus)

Recessive Scores

• pRec: 0.825

Intolerance Scores

• loftool: 0.468
• rvis_EVS: -0.09
• rvis_percentile_EVS: 46.74

Haploinsufficiency Scores

• pHI: 0.136
• hipred: Y
• hipred_score: 0.728
• ghis: 0.557

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.962

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dhdds
• 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)

Zebrafish Information Network

• Gene name: dhdds
• Affected structure: retinal cone cell
• Phenotype tag: abnormal
• Phenotype quality: absent

Gene ontology

• Biological process: dolichyl diphosphate biosynthetic process;polyprenol biosynthetic process
• Cellular component: endoplasmic reticulum;endoplasmic reticulum membrane;dehydrodolichyl diphosphate synthase complex
• Molecular function: polyprenyltransferase activity;protein binding;dehydrodolichyl diphosphate synthase activity