RAPSN

receptor associated protein of the synapse, the group of Ring finger proteins

Basic information

Region (hg38): 11:47437764-47449143

Links

ENSG00000165917 ∙ NCBI:5913 ∙ OMIM:601592 ∙ HGNC:9863 ∙ Uniprot:Q13702 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital myasthenic syndrome 11 (Strong), mode of inheritance: AR
• congenital myasthenic syndrome 11 (Strong), mode of inheritance: AR
• fetal akinesia deformation sequence 1 (Supportive), mode of inheritance: AR
• postsynaptic congenital myasthenic syndrome (Supportive), mode of inheritance: AR
• fetal akinesia deformation sequence 2 (Strong), mode of inheritance: AR
• congenital myasthenic syndrome 11 (Strong), mode of inheritance: AR
• fetal akinesia deformation sequence 2 (Definitive), mode of inheritance: AR
• neuromuscular disease (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Myasthenic syndrome, congenital 11, associated with acetylcholine receptor deficiency	AR	Musculoskeletal; Neurologic; Pharmacogenomic	Prophylactic medications (anticholinesterase therapy) in order to prevent apneic episodes/sudden respiratory insufficiency secondary to fever/infections can be effective; Most individuals with CMS benefit from AChE inhibitors and/or potassium channel blocker 3,4-diaminopyridine (3,4-DAP), though caution must be used in giving 3,4-DAP to young children and individuals with fast-channel syndromes; Some individuals with SCCMS are treated with quinidine, which has some major side effects and may be detrimental in individuals with AChR deficiency	Musculoskeletal; Neurologic	12651869; 14504330; 15286164; 18179903; 18252226; 19261599; 20930056; 25194721; 25792100

ClinVar

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

• Congenital_myasthenic_syndrome_11 (598 variants)
• Fetal_akinesia_deformation_sequence_1 (580 variants)
• Congenital_myasthenic_syndrome (143 variants)
• not_provided (116 variants)
• Fetal_akinesia_deformation_sequence_2 (86 variants)
• Inborn_genetic_diseases (60 variants)
• not_specified (25 variants)
• RAPSN-related_disorder (22 variants)
• Hydrops_fetalis (2 variants)
• Arthrogryposis_multiplex_congenita (2 variants)
• Myopathy (2 variants)
• Global_developmental_delay (1 variants)
• Congenital_Myasthenic_Syndrome,_Recessive (1 variants)
• Congenital_myasthenic_syndrome_4C (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RAPSN gene is commonly pathogenic or not. These statistics are base on transcript: NM_000005055.5. 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			6	211	1	218
missense	3	26	210	7	2	248
nonsense	20	9	1			30
start loss	2					2
frameshift	17	18	1			36
splice donor/acceptor (+/-2bp)	7	9				16
Total	49	62	218	218	3

Highest pathogenic variant AF is 0.002027891

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RAPSN	protein_coding	protein_coding	ENST00000298854	8	11423

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00151	0.993	125725	0	16	125741	0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.548	233	258	0.904	0.0000176	2672
Missense in Polyphen		85	90.859	0.93552		899
Synonymous	0.0638	112	113	0.992	0.00000825	783
Loss of Function	2.41	8	19.5	0.411	8.43e-7	221

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000298	0.000298
Ashkenazi Jewish	0.00	0.00
East Asian	0.000326	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.0000443	0.0000440
Middle Eastern	0.000326	0.000163
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Postsynaptic protein required for clustering of nicotinic acetylcholine receptors (nAChRs) at the neuromuscular junction. It may link the receptor to the underlying postsynaptic cytoskeleton, possibly by direct association with actin or spectrin.
• Disease: DISEASE: Myasthenic syndrome, congenital, 11, associated with acetylcholine receptor deficiency (CMS11) [MIM:616326]: A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS11 is an autosomal recessive disorder of postsynaptic neuromuscular transmission, due to deficiency of AChR at the endplate that results in low amplitude of the miniature endplate potential and current. {ECO:0000269|PubMed:11791205, ECO:0000269|PubMed:12730725, ECO:0000269|PubMed:12796535, ECO:0000269|PubMed:12929188, ECO:0000269|PubMed:14504330, ECO:0000269|PubMed:15036330, ECO:0000269|PubMed:15328566, ECO:0000269|PubMed:16931511, ECO:0000269|PubMed:17594401}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Fetal akinesia deformation sequence (FADS) [MIM:208150]: A clinically and genetically heterogeneous group of disorders with congenital malformations related to impaired fetal movement. Clinical features include fetal akinesia, intrauterine growth retardation, polyhydramnios, arthrogryposis, pulmonary hypoplasia, craniofacial abnormalities, and cryptorchidism. {ECO:0000269|PubMed:18179903, ECO:0000269|PubMed:18252226}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: role of nicotinic acetylcholine receptors in the regulation of apoptosis;agrin in postsynaptic differentiation (Consensus)

Intolerance Scores

• loftool: 0.256
• rvis_EVS: 0.22
• rvis_percentile_EVS: 68.38

Haploinsufficiency Scores

• pHI: 0.574
• hipred: N
• hipred_score: 0.415
• ghis: 0.481

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.724

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rapsn
• Phenotype: muscle phenotype; homeostasis/metabolism phenotype; respiratory system 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); 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)

Zebrafish Information Network

• Gene name: rapsn
• Affected structure: CaP motoneuron
• Phenotype tag: abnormal
• Phenotype quality: process quality

Gene ontology

• Biological process: chemical synaptic transmission;synaptic transmission, cholinergic;positive regulation of neuron apoptotic process;positive regulation of neuromuscular synaptic transmission;regulation of postsynaptic membrane organization;establishment of protein localization to postsynaptic membrane
• Cellular component: Golgi apparatus;centrosome;cytosol;plasma membrane;cell junction;neuromuscular junction;postsynaptic specialization membrane
• Molecular function: acetylcholine receptor binding;ionotropic glutamate receptor binding;protein membrane anchor;metal ion binding