PDE6D

phosphodiesterase 6D, the group of Phosphodiesterases

Basic information

Region (hg38): 2:231732433-231786272

Links

ENSG00000156973 ∙ NCBI:5147 ∙ OMIM:602676 ∙ HGNC:8788 ∙ Uniprot:O43924 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Joubert syndrome 22 (Moderate), mode of inheritance: AR
• Joubert syndrome 22 (Strong), mode of inheritance: AR
• orofaciodigital syndrome type 6 (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Joubert syndrome 22	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	Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic; Renal	24166846

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PDE6D gene.

• Joubert syndrome 22 (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PDE6D 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				18		18
missense			18	2		20
nonsense	1					1
start loss						0
frameshift	3	1				4
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			2	4		6
non coding				9		9
Total	4	1	18	29	0

Highest pathogenic variant AF is 0.00000657

Variants in PDE6D

This is a list of pathogenic ClinVar variants found in the PDE6D region.

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

Position	Type	Phenotype	Significance	ClinVar
2-231732981-T-C		Joubert syndrome 22	Uncertain significance (Jul 05, 2022)
2-231732996-C-T		Joubert syndrome 22	Likely benign (Feb 03, 2025)
2-231732997-G-A		Joubert syndrome 22	Likely benign (Dec 13, 2023)
2-231732999-C-T		PDE6D-related disorder • Joubert syndrome 22	Likely benign (Jan 20, 2025)
2-231733000-G-A		Joubert syndrome 22	Likely benign (Oct 03, 2023)
2-231733003-A-G			Likely benign (Jul 20, 2018)
2-231733015-T-A		Joubert syndrome 22	Uncertain significance (Apr 13, 2021)
2-231733040-G-T		Joubert syndrome 22	Likely benign (Nov 15, 2022)
2-231737174-C-A		Joubert syndrome 22	Likely benign (Jan 25, 2025)
2-231737179-T-G		Joubert syndrome 22	Benign/Likely benign (Jan 20, 2025)
2-231737190-A-AC		Joubert syndrome 22	Pathogenic/Likely pathogenic (Dec 29, 2020)
2-231737194-C-T		Joubert syndrome 22	Uncertain significance (Aug 01, 2022)
2-231737195-G-A		Joubert syndrome 22	Likely benign (Dec 03, 2021)
2-231737199-G-T		Joubert syndrome 22	Uncertain significance (Aug 26, 2021)
2-231737209-T-C		Inborn genetic diseases	Uncertain significance (Jun 28, 2023)
2-231737213-G-A		Joubert syndrome 22	Likely benign (Dec 10, 2023)
2-231737215-AC-A		Joubert syndrome 22	Pathogenic (Jun 01, 2022)
2-231737225-T-C			Likely benign (Jun 01, 2018)
2-231737230-C-T		Joubert syndrome 22	Uncertain significance (Sep 06, 2022)
2-231737247-G-A		Joubert syndrome 22	Uncertain significance (Oct 13, 2020)
2-231737254-T-G		Joubert syndrome 22	Uncertain significance (Feb 24, 2022)
2-231737260-T-C		Joubert syndrome 22	Uncertain significance (Jul 04, 2022)
2-231737295-G-A		Joubert syndrome 22	Uncertain significance (Jul 26, 2022)
2-231738020-G-A		Joubert syndrome 22	Likely benign (Dec 17, 2024)
2-231738020-GC-G		Joubert syndrome 22	Likely pathogenic (Apr 05, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PDE6D	protein_coding	protein_coding	ENST00000287600	5	53848

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00642	0.919	125738	0	10	125748	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.60	45	87.0	0.517	0.00000490	991
Missense in Polyphen		9	29.734	0.30269		356
Synonymous	0.157	30	31.1	0.964	0.00000195	275
Loss of Function	1.54	5	10.3	0.484	5.99e-7	101

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000906	0.0000905
Ashkenazi Jewish	0.0000995	0.0000992
East Asian	0.0000548	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000442	0.0000439
Middle Eastern	0.0000548	0.0000544
South Asian	0.0000328	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Promotes the release of prenylated target proteins from cellular membranes (PubMed:9712853). Modulates the activity of prenylated or palmitoylated Ras family members by regulating their subcellular location (PubMed:22002721, PubMed:23698361). Required for normal ciliary targeting of farnesylated target proteins, such as INPP5E (PubMed:24166846). Modulates the subcellular location of target proteins by acting as a GTP specific dissociation inhibitor (GDI) (By similarity). Increases the affinity of ARL3 for GTP by several orders of magnitude. Stabilizes ARL3-GTP by decreasing the nucleotide dissociation rate (By similarity). {ECO:0000250|UniProtKB:O55057, ECO:0000269|PubMed:10518933, ECO:0000269|PubMed:22002721, ECO:0000269|PubMed:23559067, ECO:0000269|PubMed:23698361, ECO:0000269|PubMed:24166846, ECO:0000269|PubMed:9712853}.
• Pathway: Purine metabolism - Homo sapiens (human);Phosphodiesterases in neuronal function;Purine nucleotides nucleosides metabolism;ARL13B-mediated ciliary trafficking of INPP5E;Cargo trafficking to the periciliary membrane;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.191

Intolerance Scores

• loftool: 0.500
• rvis_EVS: 0.48
• rvis_percentile_EVS: 78.95

Haploinsufficiency Scores

• pHI: 0.392
• hipred: Y
• hipred_score: 0.705

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.995

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pde6d
• Phenotype: normal 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); vision/eye phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: pde6d
• Affected structure: pronephric tubule
• Phenotype tag: abnormal
• Phenotype quality: distended

Gene ontology

• Biological process: visual perception;negative regulation of GTPase activity;response to stimulus
• Cellular component: cytosol;cytoskeleton;cilium;cytoplasmic vesicle membrane;cytoplasmic vesicle
• Molecular function: 3',5'-cyclic-nucleotide phosphodiesterase activity;GTPase inhibitor activity;protein binding;Rab GTPase binding