SYNJ1

synaptojanin 1, the group of Phosphoinositide phosphatases

Basic information

Region (hg38): 21:32628759-32728040

Links

ENSG00000159082 ∙ NCBI:8867 ∙ OMIM:604297 ∙ HGNC:11503 ∙ Uniprot:O43426 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• early-onset Parkinson disease 20 (Strong), mode of inheritance: AR
• young-onset Parkinson disease (Supportive), mode of inheritance: AR
• atypical juvenile parkinsonism (Supportive), mode of inheritance: AR
• undetermined early-onset epileptic encephalopathy (Supportive), mode of inheritance: AD
• developmental and epileptic encephalopathy, 53 (Moderate), mode of inheritance: AR
• early-onset Parkinson disease 20 (Strong), mode of inheritance: AR
• developmental and epileptic encephalopathy, 53 (Strong), mode of inheritance: AR
• early-onset Parkinson disease 20 (Moderate), mode of inheritance: AR
• genetic developmental and epileptic encephalopathy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Developmental and epileptic encephalopathy 53; Parkinson disease 20, early-onset	AR	Neurologic	For Parkinson disease 20, response to levodopa has been described	Neurologic	23804563; 23804577; 27435091

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SYNJ1 gene.

• Early-onset_Parkinson_disease_20 (1058 variants)
• Developmental_and_epileptic_encephalopathy,_53 (1057 variants)
• not_provided (146 variants)
• Inborn_genetic_diseases (111 variants)
• SYNJ1-related_disorder (18 variants)
• not_specified (6 variants)
• Developmental_and_epileptic_encephalopathy,_1 (4 variants)
• Young-onset_Parkinson_disease (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SYNJ1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000203446.3. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	269	5	277
missense	2	1	495	26	2	526
nonsense	12	3	2			17
start loss						0
frameshift	17	2	1			20
splice donor/acceptor (+/-2bp)	1	8	2	1		12
Total	32	14	503	296	7

Highest pathogenic variant AF is 0.0000116291

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SYNJ1	protein_coding	protein_coding	ENST00000433931	32	99291

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.427	0.573	125687	0	61	125748	0.000243

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.25	667	852	0.783	0.0000446	10473
Missense in Polyphen		214	356.61	0.60009		4369
Synonymous	0.409	295	304	0.970	0.0000163	3181
Loss of Function	6.61	19	84.5	0.225	0.00000480	994

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000677	0.000674
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000223	0.000217
Finnish	0.0000953	0.0000924
European (Non-Finnish)	0.000194	0.000193
Middle Eastern	0.000223	0.000217
South Asian	0.000588	0.000588
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Phosphatase that acts on various phosphoinositides, including phosphatidylinositol 4-phosphate, phosphatidylinositol (4,5)-bisphosphate and phosphatidylinositol (3,4,5)-trisphosphate (PubMed:27435091). Has a role in clathrin-mediated endocytosis (By similarity). Hydrolyzes PIP2 bound to actin regulatory proteins resulting in the rearrangement of actin filaments downstream of tyrosine kinase and ASH/GRB2 (By similarity). {ECO:0000250|UniProtKB:O18964, ECO:0000250|UniProtKB:Q62910, ECO:0000269|PubMed:27435091}.
• Disease: DISEASE: Parkinson disease 20, early-onset (PARK20) [MIM:615530]: An early-onset form of Parkinson disease, a complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability, as well as by a clinically significant response to treatment with levodopa. The pathology involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. PARK20 is characterized by young adult-onset of parkinsonism. Additional features may include seizures, cognitive decline, abnormal eye movements, and dystonia. {ECO:0000269|PubMed:23804563, ECO:0000269|PubMed:23804577, ECO:0000269|PubMed:27496670}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Epileptic encephalopathy, early infantile, 53 (EIEE53) [MIM:617389]: A form of epileptic encephalopathy, a heterogeneous group of severe childhood onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. EIEE53 inheritance is autosomal recessive. {ECO:0000269|PubMed:27435091}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Inositol phosphate metabolism - Homo sapiens (human);Phosphatidylinositol signaling system - Homo sapiens (human);Phosphatidylinositol Phosphate Metabolism;Joubert syndrome;EGF-EGFR Signaling Pathway;D-<i>myo</i>-inositol (1,3,4)-trisphosphate biosynthesis;superpathway of D-<i>myo</i>-inositol (1,4,5)-trisphosphate metabolism;Vesicle-mediated transport;endocytotic role of ndk phosphins and dynamin;Membrane Trafficking;Metabolism of lipids;1D-<i>myo</i>-inositol hexakisphosphate biosynthesis II (mammalian);Inositol phosphate metabolism;3-phosphoinositide degradation;D-<i>myo</i>-inositol (1,4,5)-trisphosphate degradation;Metabolism;superpathway of inositol phosphate compounds;Clathrin-mediated endocytosis;Synthesis of IP3 and IP4 in the cytosol;Inositol phosphate metabolism;Synthesis of PIPs at the plasma membrane;PI Metabolism;Phospholipid metabolism;Synthesis of IP2, IP, and Ins in the cytosol;Internalization of ErbB1;EPHB forward signaling (Consensus)

Recessive Scores

• pRec: 0.121

Intolerance Scores

• loftool: 0.0251
• rvis_EVS: 0.5
• rvis_percentile_EVS: 79.67

Haploinsufficiency Scores

• pHI: 0.724
• hipred: Y
• hipred_score: 0.685
• ghis: 0.590

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.988

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Synj1
• Phenotype: vision/eye 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); 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); growth/size/body region phenotype

Zebrafish Information Network

• Gene name: synj1
• Affected structure: neuromast hair cell
• Phenotype tag: abnormal
• Phenotype quality: amount

Gene ontology

• Biological process: phosphatidylinositol biosynthetic process;neurotransmitter transport;brain development;learning;synaptic vesicle priming;synaptic vesicle uncoating;phosphatidylinositol-3-phosphate biosynthetic process;inositol phosphate metabolic process;phosphatidylinositol metabolic process;inositol phosphate dephosphorylation;phosphatidylinositol dephosphorylation;synaptic vesicle endocytosis;synaptic vesicle transport;membrane organization;positive regulation of endosome organization
• Cellular component: cytosol;microtubule;vesicle membrane;membrane coat;clathrin coat of coated pit;terminal bouton;perinuclear region of cytoplasm;synaptic membrane;presynapse;postsynapse
• Molecular function: RNA binding;phosphatidylinositol-3-phosphatase activity;phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity;SH3 domain binding;phosphatidylinositol phosphate 5-phosphatase activity;phosphatidylinositol phosphate 4-phosphatase activity;phosphatidylinositol-4-phosphate phosphatase activity;phosphatidylinositol-3,5-bisphosphate 5-phosphatase activity;phosphatidylinositol-3,5-bisphosphate 3-phosphatase activity;inositol-1,4,5-trisphosphate 5-phosphatase activity;inositol-1,3,4,5-tetrakisphosphate 5-phosphatase activity