CPLX1

complexin 1

Basic information

Region (hg38): 4:784957-826129

Links

ENSG00000168993 ∙ NCBI:10815 ∙ OMIM:605032 ∙ HGNC:2309 ∙ Uniprot:O14810 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• familial infantile myoclonic epilepsy (Supportive), mode of inheritance: AR
• developmental and epileptic encephalopathy, 63 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Developmental and epileptic encephalopathy 63	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	26539891; 28422131

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CPLX1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CPLX1 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	16		18
missense			25	1		26
nonsense		2	1			3
start loss						0
frameshift		1				1
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			2	1	1	4
non coding				10	2	12
Total	0	3	29	27	2

Variants in CPLX1

This is a list of pathogenic ClinVar variants found in the CPLX1 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-786498-C-G		Developmental and epileptic encephalopathy, 63	Benign (Jul 14, 2021)
4-786500-G-T		CPLX1-related disorder	Likely benign (Sep 19, 2022)
4-786501-C-T			Uncertain significance (Mar 26, 2022)
4-786507-C-G			Uncertain significance (Jul 15, 2022)
4-786510-G-C			Likely benign (Sep 27, 2022)
4-786524-G-T		Developmental and epileptic encephalopathy, 63	Conflicting classifications of pathogenicity (Dec 02, 2021)
4-786526-G-T			Uncertain significance (Dec 06, 2022)
4-786531-G-A			Likely benign (Mar 15, 2022)
4-786539-A-G		Inborn genetic diseases	Uncertain significance (Aug 31, 2022)
4-786553-T-C			Uncertain significance (Aug 07, 2022)
4-786557-G-A		CPLX1-related disorder	Likely benign (Aug 24, 2023)
4-786564-C-G		Inborn genetic diseases	Uncertain significance (Jul 06, 2022)
4-786564-C-CTCG			Uncertain significance (Aug 27, 2022)
4-786566-C-T		Inborn genetic diseases	Uncertain significance (Apr 20, 2023)
4-786567-G-C		Inborn genetic diseases	Uncertain significance (Jun 11, 2024)
4-786570-C-G		Inborn genetic diseases	Uncertain significance (May 30, 2024)
4-786573-C-T			Likely benign (Jul 19, 2022)
4-786580-A-G		Inborn genetic diseases	Uncertain significance (Sep 28, 2022)
4-786584-C-A		Abnormal brain morphology • Developmental and epileptic encephalopathy, 63	Likely pathogenic (Oct 15, 2018)
4-786584-C-G			Uncertain significance (Mar 01, 2020)
4-786591-G-T		Developmental and epileptic encephalopathy, 63	Pathogenic/Likely pathogenic (Oct 15, 2018)
4-786595-C-T			Uncertain significance (Oct 13, 2022)
4-786598-G-A			Likely benign (Dec 31, 2019)
4-786632-C-A		Inborn genetic diseases	Uncertain significance (Feb 17, 2022)
4-786635-C-T		Inborn genetic diseases	Uncertain significance (Sep 27, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CPLX1	protein_coding	protein_coding	ENST00000304062	3	41242

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.825	0.172	122001	0	3	122004	0.0000123

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.351	93	83.9	1.11	0.00000463	871
Missense in Polyphen		48	38.58	1.2442		401
Synonymous	-1.98	51	35.9	1.42	0.00000219	238
Loss of Function	2.22	0	5.75	0.00	2.44e-7	75

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000273	0.0000273
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Positively regulates a late step in exocytosis of various cytoplasmic vesicles, such as synaptic vesicles and other secretory vesicles (PubMed:21785414). Organizes the SNAREs into a cross-linked zigzag topology that, when interposed between the vesicle and plasma membranes, is incompatible with fusion, thereby preventing SNAREs from releasing neurotransmitters until an action potential arrives at the synapse (PubMed:21785414). Also involved in glucose-induced secretion of insulin by pancreatic beta-cells. Essential for motor behavior. {ECO:0000250|UniProtKB:P63040, ECO:0000269|PubMed:21785414}.
• Pathway: Synaptic vesicle cycle - Homo sapiens (human);Synaptic Vesicle Pathway;Neuronal System;Glutamate Neurotransmitter Release Cycle;Dopamine Neurotransmitter Release Cycle;Acetylcholine Neurotransmitter Release Cycle;GABA synthesis, release, reuptake and degradation;Neurotransmitter release cycle;Transmission across Chemical Synapses;Serotonin Neurotransmitter Release Cycle;Norepinephrine Neurotransmitter Release Cycle (Consensus)

Intolerance Scores

• rvis_EVS: -0.16
• rvis_percentile_EVS: 41.25

Haploinsufficiency Scores

• hipred: Y
• hipred_score: 0.793
• ghis: 0.630

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.731

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cplx1
• Phenotype: hearing/vestibular/ear 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); reproductive system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cellular phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: exocytosis;chemical synaptic transmission;synaptic vesicle exocytosis;regulation of exocytosis;insulin secretion;regulation of synaptic vesicle fusion to presynaptic active zone membrane;regulation of neurotransmitter secretion;exocytic insertion of neurotransmitter receptor to postsynaptic membrane
• Cellular component: cytosol;dendrite;SNARE complex;neuronal cell body;terminal bouton;calyx of Held;synaptobrevin 2-SNAP-25-syntaxin-1a-complexin I complex;synaptobrevin 2-SNAP-25-syntaxin-3-complexin complex;Schaffer collateral - CA1 synapse;postsynapse;glutamatergic synapse
• Molecular function: SNARE binding;neurotransmitter transporter activity;protein binding;syntaxin-1 binding