PDYN

prodynorphin, the group of Neuropeptides

Basic information

Region (hg38): 20:1978756-1994285

Previous symbols: [ "SCA23" ]

Links

ENSG00000101327 ∙ NCBI:5173 ∙ OMIM:131340 ∙ HGNC:8820 ∙ Uniprot:P01213 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spinocerebellar ataxia type 23 (Supportive), mode of inheritance: AD
• spinocerebellar ataxia type 23 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spinocerebellar ataxia 23	AD	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	15306549; 21035104

ClinVar

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

• not provided (99 variants)
• Spinocerebellar ataxia type 23 (71 variants)
• not specified (19 variants)
• Inborn genetic diseases (8 variants)
• Autosomal dominant cerebellar ataxia (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PDYN 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	19	4	25
missense			61	6	2	69
nonsense			1			1
start loss			1			1
frameshift			2			2
inframe indel			1			1
splice donor/acceptor (+/-2bp)			2			2
splice region			1	1		2
non coding			27	2	19	48
Total	0	0	97	27	25

Variants in PDYN

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

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

Position	Type	Phenotype	Significance	ClinVar
20-1978791-G-A		Spinocerebellar ataxia type 23	Uncertain significance (Jan 12, 2018)
20-1978866-G-C		Spinocerebellar ataxia type 23	Benign (Jan 13, 2018)
20-1978880-C-T		Spinocerebellar ataxia type 23	Benign (Jan 13, 2018)
20-1978927-G-A		Spinocerebellar ataxia type 23	Benign (Jan 13, 2018)
20-1978929-G-A		Spinocerebellar ataxia type 23	Uncertain significance (Jan 12, 2018)
20-1978929-G-T		Spinocerebellar ataxia type 23	Benign (Jan 12, 2018)
20-1978987-C-G		Spinocerebellar ataxia type 23	Uncertain significance (Jan 12, 2018)
20-1979049-A-C		Spinocerebellar ataxia type 23	Uncertain significance (Jan 13, 2018)
20-1979085-T-A		Autosomal dominant cerebellar ataxia	Likely benign (Jun 14, 2016)
20-1979166-A-C		Spinocerebellar ataxia type 23	Uncertain significance (Jan 12, 2018)
20-1979252-C-T		Spinocerebellar ataxia type 23	Conflicting classifications of pathogenicity (Apr 01, 2023)
20-1979258-G-A		Spinocerebellar ataxia type 23	Uncertain significance (Mar 02, 2018)
20-1979293-G-A		Spinocerebellar ataxia type 23	Benign (Jan 13, 2018)
20-1979294-T-C		Spinocerebellar ataxia type 23	Benign (Jan 12, 2018)
20-1979451-G-T		Spinocerebellar ataxia type 23	Uncertain significance (Jan 13, 2018)
20-1979476-A-G		Spinocerebellar ataxia type 23	Uncertain significance (Jan 12, 2018)
20-1979487-G-C		Spinocerebellar ataxia type 23	Benign (Jan 13, 2018)
20-1979496-T-C		Spinocerebellar ataxia type 23	Uncertain significance (Jan 13, 2018)
20-1979552-A-G		Spinocerebellar ataxia type 23	Benign (Jan 12, 2018)
20-1979563-C-G		Spinocerebellar ataxia type 23	Conflicting classifications of pathogenicity (Aug 01, 2022)
20-1979580-A-G		Spinocerebellar ataxia type 23	Benign (Jan 13, 2018)
20-1979619-AAGTC-A		Autosomal dominant cerebellar ataxia	Uncertain significance (Jun 14, 2016)
20-1979652-A-G		Spinocerebellar ataxia type 23	Uncertain significance (Jan 13, 2018)
20-1979653-T-A		Spinocerebellar ataxia type 23	Uncertain significance (Jan 12, 2018)
20-1979667-A-G		Spinocerebellar ataxia type 23	Benign (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PDYN	protein_coding	protein_coding	ENST00000217305	2	15330

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000170	0.468	125676	1	71	125748	0.000286

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.527	159	141	1.12	0.00000904	1644
Missense in Polyphen		59	49.926	1.1817		495
Synonymous	-0.607	66	60.0	1.10	0.00000343	515
Loss of Function	0.295	6	6.83	0.878	2.99e-7	100

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000550	0.000550
Ashkenazi Jewish	0.000198	0.000198
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000211	0.000211
Middle Eastern	0.00	0.00
South Asian	0.000817	0.000784
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Leu-enkephalins compete with and mimic the effects of opiate drugs. They play a role in a number of physiologic functions, including pain perception and responses to stress (By similarity). {ECO:0000250}.; FUNCTION: Leumorphin has a typical opiod activity and may have anti-apoptotic effect. {ECO:0000250}.
• Disease: DISEASE: Spinocerebellar ataxia 23 (SCA23) [MIM:610245]: Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA23 is an adult-onset autosomal dominant form characterized by slowly progressive gait and limb ataxia, with variable additional features, including peripheral neuropathy and dysarthria. {ECO:0000269|PubMed:21035104, ECO:0000269|PubMed:21712028, ECO:0000269|PubMed:23108490, ECO:0000269|PubMed:23471613}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Amphetamine addiction - Homo sapiens (human);Alcoholism - Homo sapiens (human);Cocaine addiction - Homo sapiens (human);Spinal Cord Injury;Signaling by GPCR;Signal Transduction;Peptide ligand-binding receptors;Class A/1 (Rhodopsin-like receptors);GPCR ligand binding;G-protein activation;Opioid Signalling;G alpha (i) signalling events;GPCR downstream signalling (Consensus)

Recessive Scores

• pRec: 0.187

Intolerance Scores

• loftool: 0.213
• rvis_EVS: 0.57
• rvis_percentile_EVS: 82.08

Haploinsufficiency Scores

• pHI: 0.120
• hipred: N
• hipred_score: 0.180

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.126

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pdyn
• Phenotype: adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); 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); growth/size/body region phenotype; homeostasis/metabolism phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); digestive/alimentary phenotype; skeleton phenotype

Gene ontology

• Biological process: G protein-coupled receptor signaling pathway;neuropeptide signaling pathway;chemical synaptic transmission;regulation of signaling receptor activity
• Cellular component: extracellular region;plasma membrane;dendrite;neuronal cell body;axon terminus
• Molecular function: opioid peptide activity;opioid receptor binding