RAPSN

Summary

RAPSN (receptor associated protein of the synapse, HGNC:9863) is a protein-coding gene on chromosome 11p11.2, encoding 43 kDa receptor-associated protein of the synapse (Q13702). Postsynaptic protein required for clustering of nicotinic acetylcholine receptors (nAChRs) at the neuromuscular junction.

This gene encodes a member of a family of proteins that are receptor associated proteins of the synapse. The encoded protein contains a conserved cAMP-dependent protein kinase phosphorylation site, and plays a critical role in clustering and anchoring nicotinic acetylcholine receptors at synaptic sites by linking the receptors to the underlying postsynaptic cytoskeleton, possibly by direct association with actin or spectrin. Mutations in this gene may play a role in postsynaptic congenital myasthenic syndromes. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 5913 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neuromuscular disease (Definitive, GenCC) — +4 more curated relationships
• GWAS associations: 46
• Clinical variants (ClinVar): 763 total — 56 pathogenic, 39 likely-pathogenic
• Phenotypes (HPO): 86
• Druggable target: yes
• MANE Select transcript: NM_005055

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9863
Approved symbol	RAPSN
Name	receptor associated protein of the synapse
Location	11p11.2
Locus type	gene with protein product
Status	Approved
Aliases	RNF205, CMS1D, CMS1E
Ensembl gene	ENSG00000165917
Ensembl biotype	protein_coding
OMIM	601592
Entrez	5913

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 11 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000298854, ENST00000352508, ENST00000524487, ENST00000528356, ENST00000529341, ENST00000897203, ENST00000897204, ENST00000949301, ENST00000949302, ENST00000949303, ENST00000949304, ENST00000949305

RefSeq mRNA: 2 — MANE Select: NM_005055 NM_005055, NM_032645

CCDS: CCDS7936, CCDS7937

Canonical transcript exons

ENST00000298854 — 8 exons

Exon	Start	End
ENSE00001098094	47441823	47441921
ENSE00001098097	47442656	47442814
ENSE00001098099	47441611	47441733
ENSE00001098100	47441159	47441212
ENSE00001098101	47438732	47438931
ENSE00001272335	47447812	47448150
ENSE00002171426	47448773	47449136
ENSE00003511601	47437764	47438047

Expression profiles

Bgee: expression breadth ubiquitous, 159 present calls, max score 95.14.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.8421 / max 148.4738, expressed in 100 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
119619	0.4355	80
119620	0.1357	54
119618	0.1273	49
119616	0.0975	37
119617	0.0299	17
119615	0.0162	7

Top tissues by expression

280 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	95.14	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	94.78	gold quality
gastrocnemius	UBERON:0001388	93.79	gold quality
muscle of leg	UBERON:0001383	91.91	gold quality
muscle organ	UBERON:0001630	86.85	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	80.76	gold quality
skeletal muscle tissue	UBERON:0001134	76.66	gold quality
apex of heart	UBERON:0002098	74.16	gold quality
biceps brachii	UBERON:0001507	74.13	silver quality
muscle tissue	UBERON:0002385	72.29	gold quality
deltoid	UBERON:0001476	71.13	silver quality
quadriceps femoris	UBERON:0001377	71.07	silver quality
gluteal muscle	UBERON:0002000	71.03	silver quality
vastus lateralis	UBERON:0001379	70.56	silver quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	69.70	silver quality
right adrenal gland cortex	UBERON:0035827	68.43	gold quality
right adrenal gland	UBERON:0001233	67.20	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	66.97	gold quality
heart left ventricle	UBERON:0002084	66.71	gold quality
cardiac ventricle	UBERON:0002082	65.84	gold quality
left adrenal gland cortex	UBERON:0035825	65.66	gold quality
tibial nerve	UBERON:0001323	65.50	gold quality
left adrenal gland	UBERON:0001234	64.63	gold quality
adrenal cortex	UBERON:0001235	64.43	gold quality
granulocyte	CL:0000094	62.53	gold quality
adrenal gland	UBERON:0002369	61.75	gold quality
monocyte	CL:0000576	60.18	gold quality
mononuclear cell	CL:0000842	60.08	gold quality
lower esophagus mucosa	UBERON:0035834	59.79	gold quality
tibialis anterior	UBERON:0001385	59.56	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.19

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HR, NFKB, RELA

miRNA regulators (miRDB)

15 targeting RAPSN, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-7159-3P	99.51	70.17	1920
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-1276	99.36	68.18	1642
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-583	98.71	67.44	1791
HSA-MIR-939-5P	97.10	65.80	1579
HSA-MIR-1343-5P	96.48	66.06	1506

Literature-anchored findings (GeneRIF, showing 25)

• Rapsyn mutations in humans cause endplate acetylcholine-receptor deficiency and myasthenic syndrome (PMID:11791205)
• E-box mutations in the RAPSN promoter region may have a role in congenital myasthenic syndrome (PMID:12651869)
• Four patients from four different families with RAPSN mutations and congenital myasthenic syndrome (PMID:12730725)
• Twenty patients with the recessive form of congenital myasthenic syndrome with no mutations in the AChR subunit have been tested for this gene; five patients have been found to carry mutations. (PMID:12807980)
• Rapsyn is essential for clustering the acetylcholine receptor at the postsynaptic membrane of the neuromuscular junction. (PMID:15036330)
• recombination events may have occurred within the rapsyn gene and that this may have implications in the phenotypic expression of postsynaptic congenital myasthenic syndrome (PMID:15252722)
• These results provide the first experimental evidence that rapsyn is a direct sequence-specific target of Kaiso and delta-catenin. (PMID:15282317)
• The patient presents with an early onset sporadic congenital myasthenic syndrome was found The mutation RAPSN N88K was found heterozygously to a large deletion of about 4.5 kb disrupting the RAPSN gene. (PMID:15482960)
• Screening for the common mutation RAPSN N88K facilitates targeted genetic analysis in congenital myasthenic syndromes. (PMID:16931511)
• No CHRNA1, CHRNB1, or CHRND mutations were detected, but a homozygous RAPSN frameshift mutation, c.1177-1178delAA, was identified in a family with three children affected with lethal fetal akinesia sequence. (PMID:18179903)
• All but 1 patient presented early in life and most responded to cholinergic agonists. With early diagnosis and therapy, rapsyn deficiency has a benign course in most patients. (PMID:19620612)
• An allelic quantification on patient’s DNA identified three novel multi-exon deletions of RAPSN. (PMID:20930056)
• nAChR mobility in plasma membranes of myoblast cells during their differentiation to myotubes in the presence and absence of rapsyn (PMID:20978122)
• Investigation of mutations in RAPSN determines that patients with congenital myasthenic syndrome can be misdiagnosed with seronegative myasthenia gravis. (PMID:21305573)
• a mutation of the RAPSN gene may have a role in development of congenital myasthenic syndrome after general anaesthesia [case report] (PMID:21372719)
• Two siblings affected with typical congenital myasthenic syndrome harbor the common heterozygous (-38A-G) E-box mutation associated with a previously unreported heterozygous p.224 insT, causing an insertion of threonine in the TPR6 domain. (PMID:22326364)
• These findings uncover a new link between rapsyn, lysosome positioning, exocytosis and plasma membrane integrity. (PMID:26330529)
• Hypomethylation of CpG sites in RPTOR, MGRN1 and RAPSN in blood is associated with breast cancer. (PMID:27577081)
• Mutations in RAPSN and COLQ are the most common causes of congenital myasthenic syndrome in Israel. (PMID:28024842)
• Report attributes the RAPSN mutation c.484G > A, identified in a homozygous state, to causing fetal akinesia deformation sequence. (PMID:28495245)
• In investigating how N88K missense mutation in Rapsn impairs the neuromuscular junction, the authors uncovered a novel signaling pathway by which Agrin-LRP4-MuSK induces tyrosine phosphorylation of Rapsn, which is required for its self-association and E3 ligase activity. (PMID:31549961)
• The association between RAPSN methylation in peripheral blood and breast cancer in the Chinese population. (PMID:33958711)
• Membraneless condensates by Rapsn phase separation as a platform for neuromuscular junction formation. (PMID:34033754)
• The role of Rapsyn in neuromuscular junction and congenital myasthenic syndrome. (PMID:36815443)
• Delineation of molecular characteristics of congenital myasthenic syndromes in Indian families and review of literature. (PMID:37646703)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rapsn	ENSDARG00000041133
mus_musculus	Rapsn	ENSMUSG00000002104
rattus_norvegicus	Rapsn	ENSRNOG00000011208
drosophila_melanogaster	CG1909	FBGN0039911
caenorhabditis_elegans		WBGENE00004507

Paralogs (6): TTC28 (ENSG00000100154), GPSM2 (ENSG00000121957), TTC29 (ENSG00000137473), GPSM1 (ENSG00000160360), TTC24 (ENSG00000187862), GPSM3 (ENSG00000213654)

Protein

Protein identifiers

43 kDa receptor-associated protein of the synapse — Q13702 (reviewed: Q13702)

Alternative names: 43 kDa postsynaptic protein, Acetylcholine receptor-associated 43 kDa protein, RING finger protein 205

All UniProt accessions (7): A0A0S2Z4A2, A0A0S2Z4A6, A0A0S2Z4F8, A0A0S2Z4M9, Q13702, E9PJP9, E9PK11

UniProt curated annotations — full annotation on UniProt →

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.

Subcellular location. Cell membrane. Postsynaptic cell membrane. Cytoplasm. Cytoskeleton.

Post-translational modifications. Ubiquitinated by the BCR(KLHL8) complex, leading to its degradation.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry. Fetal akinesia deformation sequence 2 (FADS2) [MIM:618388] 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. FADS2 inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. A cysteine-rich region homologous to part of the regulatory domain of protein kinase C may be important in interactions of this protein with the lipid bilayer.

Similarity. Belongs to the RAPsyn family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q13702-1	1	yes
Q13702-2	2

RefSeq proteins (2): NP_005046, NP_116034 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001237	Postsynaptic	Family
IPR001841	Znf_RING	Domain
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR018293	Postsynaptic_CS	Conserved_site
IPR019568	Rapsyn_myristoylation/link_N	Domain
IPR019734	TPR_rpt	Repeat
IPR052480	RAPsyn	Family

Pfam: PF10579, PF13181, PF13639

UniProt features (28 total): sequence variant 10, repeat 7, sequence conflict 4, modified residue 2, initiator methionine 1, chain 1, lipid moiety-binding region 1, splice variant 1, zinc finger region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13702-F1	93.29	0.82

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (3): 196, 405, 2

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 324 (showing top): GOBP_NEUROMUSCULAR_JUNCTION_DEVELOPMENT, MULLIGHAN_NPM1_SIGNATURE_3_UP, MODULE_274, GCANCTGNY_MYOD_Q6, GOBP_SYNAPTIC_TRANSMISSION_CHOLINERGIC, GOBP_CELLULAR_COMPONENT_MAINTENANCE, CAGCTG_AP4_Q5, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GOBP_CELL_CELL_SIGNALING, GOBP_CELL_JUNCTION_ORGANIZATION, GOBP_POSTSYNAPTIC_MEMBRANE_ORGANIZATION, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_MEMBRANE, COATES_MACROPHAGE_M1_VS_M2_UP, TGACATY_UNKNOWN, GOBP_SYNAPTIC_SIGNALING

GO Biological Process (11): chemical synaptic transmission (GO:0007268), synaptic transmission, cholinergic (GO:0007271), skeletal muscle acetylcholine-gated channel clustering (GO:0071340), motor neuron apoptotic process (GO:0097049), neurotransmitter receptor localization to postsynaptic specialization membrane (GO:0099645), positive regulation of neuromuscular synaptic transmission (GO:1900075), regulation of postsynaptic membrane organization (GO:1901626), establishment of protein localization to postsynaptic membrane (GO:1903540), positive regulation of motor neuron apoptotic process (GO:2000673), neuromuscular junction development (GO:0007528), maintenance of postsynaptic specialization structure (GO:0098880)

GO Molecular Function (8): zinc ion binding (GO:0008270), acetylcholine receptor binding (GO:0033130), ionotropic glutamate receptor binding (GO:0035255), protein-membrane adaptor activity (GO:0043495), structural constituent of postsynaptic specialization (GO:0098879), protein binding (GO:0005515), protein-macromolecule adaptor activity (GO:0030674), metal ion binding (GO:0046872)

GO Cellular Component (11): Golgi apparatus (GO:0005794), centrosome (GO:0005813), cytosol (GO:0005829), plasma membrane (GO:0005886), neuromuscular junction (GO:0031594), postsynaptic specialization membrane (GO:0099634), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), membrane (GO:0016020), synapse (GO:0045202), postsynaptic membrane (GO:0045211)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
postsynaptic membrane organization	2
postsynaptic specialization	2
cytoplasm	2
synaptic membrane	2
anterograde trans-synaptic signaling	1
chemical synaptic transmission	1
neuromuscular junction development	1
receptor clustering	1
neuron apoptotic process	1
protein-containing complex localization	1
receptor localization to synapse	1
regulation of postsynaptic membrane neurotransmitter receptor levels	1
protein localization to postsynaptic specialization membrane	1
neuromuscular synaptic transmission	1
positive regulation of synaptic transmission	1
regulation of neuromuscular synaptic transmission	1
regulation of cellular component organization	1
establishment of protein localization to membrane	1
positive regulation of neuron apoptotic process	1
motor neuron apoptotic process	1
regulation of motor neuron apoptotic process	1
synapse organization	1
postsynaptic density organization	1
maintenance of synapse structure	1
transition metal ion binding	1
signaling receptor binding	1
glutamate receptor binding	1
protein-macromolecule adaptor activity	1
maintenance of postsynaptic specialization structure	1
structural constituent of postsynapse	1
binding	1
protein binding	1
molecular adaptor activity	1
cation binding	1
endomembrane system	1
intracellular membrane-bounded organelle	1
centriole	1
microtubule organizing center	1
membrane	1

Protein interactions and networks

STRING

684 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RAPSN	MUSK	O15146	990
RAPSN	AGRN	O00468	989
RAPSN	DOK7	Q18PE1	983
RAPSN	CHRND	Q07001	915
RAPSN	CHRNB1	P11230	910
RAPSN	CHRNE	Q04844	903
RAPSN	UTRN	P46939	887
RAPSN	CHRNG	P07510	882
RAPSN	COLQ	Q9Y215	879
RAPSN	CHRNA1	P02708	864
RAPSN	DAG1	Q14118	824
RAPSN	ZBTB33	Q86T24	814
RAPSN	CTNND2	Q9UQB3	799
RAPSN	RNF103	O00237	785
RAPSN	MACF1	Q9UPN3	749

IntAct

5 interactions, top by confidence:

A	B	Type	Score
DLG1	RAPSN	psi-mi:“MI:0407”(direct interaction)	0.440
RAPSN	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.400
RAPSN	UBE2Z	psi-mi:“MI:0915”(physical association)	0.370
RAPSN	ZZEF1	psi-mi:“MI:0914”(association)	0.350

BioGRID (26): HERC1 (Affinity Capture-MS), RAPSN (Affinity Capture-Western), RAPSN (Biochemical Activity), RAPSN (Two-hybrid), DAG1 (Co-localization), RAPSN (Two-hybrid), RAPSN (Negative Genetic), KCMF1 (Affinity Capture-MS), UBR4 (Affinity Capture-MS), TUSC2 (Affinity Capture-MS), HERC1 (Affinity Capture-MS), HSPA2 (Affinity Capture-MS), ZZEF1 (Affinity Capture-MS), CCT2 (Affinity Capture-MS), TCP1 (Affinity Capture-MS)

ESM2 similar proteins: A1A4R8, A4IG72, B0BNG0, B3DNN5, E7F590, F8VPK0, P09108, P12672, P49754, P54319, Q0IIZ5, Q13702, Q15006, Q17QZ7, Q28G25, Q3SYS9, Q3UR70, Q4G074, Q4QR29, Q5E993, Q5E9L7, Q5F3K0, Q5KU39, Q5R882, Q5RBW9, Q62018, Q6DEU9, Q6DFB8, Q6P3X3, Q6PD62, Q6PGP7, Q6TGY8, Q6ZPU9, Q7T3P8, Q8BGZ4, Q8CD92, Q8CEF1, Q8TAM2, Q8VD72, Q8VY89

Diamond homologs: O42393, P09108, P12672, Q13702, Q09485, Q4R8N7

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	RAPSN	ubiquitination
KLHL8	“down-regulates quantity by destabilization”	RAPSN	binding
“Cullin 3-RBX1-Skp1”	“down-regulates quantity by destabilization”	RAPSN	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

763 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	56
Likely pathogenic	39
Uncertain significance	237
Likely benign	334
Benign	19

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1073877	NM_005055.5(RAPSN):c.291C>A (p.Cys97Ter)	Pathogenic
1073878	NM_005055.5(RAPSN):c.46dup (p.Leu16fs)	Pathogenic
1405025	NM_005055.5(RAPSN):c.537C>A (p.Tyr179Ter)	Pathogenic
1407552	NM_005055.5(RAPSN):c.7C>T (p.Gln3Ter)	Pathogenic
1416981	NM_005055.5(RAPSN):c.712C>T (p.Gln238Ter)	Pathogenic
1426829	NM_005055.5(RAPSN):c.318C>A (p.Cys106Ter)	Pathogenic
1454224	NM_005055.5(RAPSN):c.297del (p.His100fs)	Pathogenic
1457721	NM_005055.5(RAPSN):c.546_547dup (p.Leu183fs)	Pathogenic
1458342	NM_005055.5(RAPSN):c.1185del (p.Thr396fs)	Pathogenic
1458494	NC_000011.9:g.(?47469557)(47478800_?)del	Pathogenic
190252	NM_005055.5(RAPSN):c.1083_1084dup (p.Tyr362fs)	Pathogenic
1997927	NM_005055.5(RAPSN):c.22C>T (p.Gln8Ter)	Pathogenic
2034351	NM_005055.5(RAPSN):c.424_425insTGTCTCCTCTATATAAATGCGTAGGGGTTTTAGTTAAATGTCCTTTGAAGTATACTTGAGGAGGGTGACGGGCGGTGTGTACGCGCTTCAGGGCCCTGTTCAACTAAGCACTCTACCCTGTTCAACTAAG (p.Ala142delinsValSerProLeuTyrLysCysValGlyValLeuValLysCysProLeuLysTyrThrTer)	Pathogenic
2077373	NM_005055.5(RAPSN):c.1168del (p.Cys390fs)	Pathogenic
2099531	NM_005055.5(RAPSN):c.79C>T (p.Gln27Ter)	Pathogenic
2137088	NM_005055.5(RAPSN):c.990_993del (p.His329_Cys330insTer)	Pathogenic
2137089	NM_005055.5(RAPSN):c.973C>T (p.Gln325Ter)	Pathogenic
2137090	NM_005055.5(RAPSN):c.358del (p.Gln120fs)	Pathogenic
2152107	NM_005055.5(RAPSN):c.1166+1G>C	Pathogenic
2163124	NM_005055.5(RAPSN):c.1166+2T>G	Pathogenic
2166080	NM_005055.5(RAPSN):c.3G>T (p.Met1Ile)	Pathogenic
2425285	NC_000011.9:g.(?47460273)(47460492_?)del	Pathogenic
2425286	NC_000011.9:g.(?47459516)(47459608_?)del	Pathogenic
2425287	NC_000011.9:g.(?47462700)(47463483_?)del	Pathogenic
2425289	NC_000011.9:g.(?47467519)(47469609_?)del	Pathogenic
2425290	NC_000011.9:g.(?47469354)(47470726_?)del	Pathogenic
2500291	NM_005055.5(RAPSN):c.123del (p.Arg42fs)	Pathogenic
2506372	NM_005055.5(RAPSN):c.912+1G>A	Pathogenic
2678233	NM_005055.5(RAPSN):c.690+1G>A	Pathogenic
2678235	NM_005055.5(RAPSN):c.192+2T>G	Pathogenic

SpliceAI

1181 predictions. Top by Δscore:

Variant	Effect	Δscore
11:47438726:CCCCA:C	donor_loss	1.0000
11:47438727:CCCAC:C	donor_loss	1.0000
11:47438728:CCA:C	donor_loss	1.0000
11:47438729:CACCT:C	donor_loss	1.0000
11:47438730:A:C	donor_loss	1.0000
11:47438731:C:CG	donor_loss	1.0000
11:47438759:AGGG:A	donor_gain	1.0000
11:47438929:CAG:C	acceptor_gain	1.0000
11:47438940:C:CT	acceptor_gain	1.0000
11:47438955:C:CT	acceptor_gain	1.0000
11:47438958:C:CT	acceptor_gain	1.0000
11:47438959:A:T	acceptor_gain	1.0000
11:47438960:G:GC	acceptor_gain	1.0000
11:47441605:CCTCA:C	donor_loss	1.0000
11:47441606:CTCAC:C	donor_loss	1.0000
11:47441607:TCAC:T	donor_loss	1.0000
11:47441608:CAC:C	donor_loss	1.0000
11:47441609:A:AG	donor_loss	1.0000
11:47441625:T:TA	donor_gain	1.0000
11:47441730:CTGT:C	acceptor_gain	1.0000
11:47441742:CCAGG:C	acceptor_gain	1.0000
11:47441743:C:CT	acceptor_gain	1.0000
11:47441744:A:T	acceptor_gain	1.0000
11:47441817:CCTCA:C	donor_loss	1.0000
11:47441818:CTCA:C	donor_loss	1.0000
11:47441819:TCAC:T	donor_loss	1.0000
11:47441820:CACC:C	donor_loss	1.0000
11:47441821:ACCT:A	donor_gain	1.0000
11:47441822:CCTC:C	donor_gain	1.0000
11:47441822:CCTCC:C	donor_loss	1.0000

AlphaMissense

2718 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:47447954:C:T	G130D	1.000
11:47447955:C:G	G130R	1.000
11:47441854:G:T	A253D	0.999
11:47441868:G:C	C248W	0.999
11:47442722:G:C	S208R	0.999
11:47442722:G:T	S208R	0.999
11:47442724:T:G	S208R	0.999
11:47447898:C:G	A149P	0.999
11:47447954:C:A	G130V	0.999
11:47447963:A:G	L127P	0.999
11:47448025:G:C	C106W	0.999
11:47448067:G:C	S92R	0.999
11:47448067:G:T	S92R	0.999
11:47448069:T:G	S92R	0.999
11:47448074:G:T	A90E	0.999
11:47448075:C:G	A90P	0.999
11:47448077:A:G	L89P	0.999
11:47448083:A:G	L87P	0.999
11:47448088:G:C	S85R	0.999
11:47448088:G:T	S85R	0.999
11:47448090:T:G	S85R	0.999
11:47448880:A:G	W29R	0.999
11:47448880:A:T	W29R	0.999
11:47438019:A:G	C399R	0.998
11:47438802:A:G	C366R	0.998
11:47438810:C:T	C363Y	0.998
11:47438811:A:G	C363R	0.998
11:47441709:C:G	A272P	0.998
11:47441842:C:G	R257P	0.998
11:47441870:A:G	C248R	0.998

dbSNP variants (sampled 300 via entrez): RS1000586592 (11:47450358 A>AT), RS1000668477 (11:47450010 C>A,G), RS1000763492 (11:47450362 C>A,T), RS1000855871 (11:47446236 A>C), RS1000975833 (11:47444332 G>A), RS1002270699 (11:47447270 C>A), RS1002410627 (11:47440754 T>A), RS1002622854 (11:47447106 G>A), RS1002976952 (11:47441369 G>A), RS1003034735 (11:47447863 C>A,T), RS1003096262 (11:47444015 G>A), RS1003219191 (11:47448384 A>G), RS1003415849 (11:47442252 A>G), RS1003432180 (11:47442483 A>C,T), RS1003454786 (11:47443617 G>A)

Disease associations

OMIM: gene MIM:601592 | disease phenotypes: MIM:616326, MIM:208150, MIM:601462, MIM:618388, MIM:617468, MIM:608931

GenCC curated gene-disease

Disease	Classification	Inheritance
neuromuscular disease	Definitive	Autosomal recessive
fetal akinesia deformation sequence 2	Definitive	Autosomal recessive
congenital myasthenic syndrome 11	Strong	Autosomal recessive
postsynaptic congenital myasthenic syndrome	Supportive	Autosomal recessive
fetal akinesia deformation sequence 1	Supportive	Autosomal recessive

Mondo (10): congenital myasthenic syndrome 11 (MONDO:0014588), fetal akinesia deformation sequence 1 (MONDO:0100101), congenital myasthenic syndrome (MONDO:0018940), fetal akinesia deformation sequence 2 (MONDO:0100102), hydrops fetalis (MONDO:0015193), arthrogryposis multiplex congenita (MONDO:0015168), myopathy (MONDO:0005336), congenital myasthenic syndrome 4C (MONDO:0012157), neuromuscular disease (MONDO:0019056), postsynaptic congenital myasthenic syndrome (MONDO:0020344)

Orphanet (4): Congenital myasthenic syndrome (Orphanet:590), Fetal akinesia deformation sequence (Orphanet:994), Hydrops fetalis (Orphanet:1041), Arthrogryposis multiplex congenita (Orphanet:1037)

HPO phenotypes

86 total (30 of 86 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000175	Cleft palate
HP:0000218	High palate
HP:0000276	Long face
HP:0000316	Hypertelorism
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000431	Wide nasal bridge
HP:0000475	Broad neck
HP:0000476	Cystic hygroma
HP:0000494	Downslanted palpebral fissures
HP:0000496	Abnormality of eye movement
HP:0000508	Ptosis
HP:0000597	Ophthalmoparesis
HP:0000651	Diplopia
HP:0000961	Cyanosis
HP:0001059	Pterygium
HP:0001252	Hypotonia
HP:0001262	Excessive daytime somnolence
HP:0001305	Dandy-Walker malformation
HP:0001315	Reduced tendon reflexes
HP:0001319	Neonatal hypotonia
HP:0001324	Muscle weakness
HP:0001371	Flexion contracture
HP:0001446	Abnormality of the musculature of the upper limbs
HP:0001508	Failure to thrive
HP:0001511	Intrauterine growth retardation
HP:0001558	Decreased fetal movement

GWAS associations

46 associations (top):

Study	Trait	p-value
GCST002580_7	Intraocular pressure	5.000000e-09
GCST004630_249	Mean corpuscular hemoglobin	5.000000e-09
GCST004776_59	Systolic blood pressure	3.000000e-07
GCST004777_25	Diastolic blood pressure	7.000000e-08
GCST005170_27	Intraocular pressure	1.000000e-19
GCST005232_56	Neuroticism	1.000000e-16
GCST005580_146	Intraocular pressure	6.000000e-30
GCST005905_14	Global electrical heterogeneity phenotypes	6.000000e-09
GCST005973_42	White blood cell count	9.000000e-09
GCST006258_12	Diastolic blood pressure	9.000000e-19
GCST006259_19	Systolic blood pressure	4.000000e-13
GCST006716_13	Alcohol use disorder (total score)	6.000000e-09
GCST006923_11	Loneliness	1.000000e-07
GCST006924_13	Loneliness (MTAG)	1.000000e-08
GCST007293_118	Body fat distribution (arm fat ratio)	3.000000e-08
GCST007293_19	Body fat distribution (arm fat ratio)	2.000000e-10
GCST007293_45	Body fat distribution (arm fat ratio)	5.000000e-14
GCST007294_28	Body fat distribution (trunk fat ratio)	6.000000e-09
GCST007294_9	Body fat distribution (trunk fat ratio)	4.000000e-06
GCST007295_159	Body fat distribution (leg fat ratio)	1.000000e-18
GCST007295_24	Body fat distribution (leg fat ratio)	7.000000e-08
GCST007295_50	Body fat distribution (leg fat ratio)	2.000000e-12
GCST007328_14	Alcohol consumption (drinks per week)	7.000000e-17
GCST007559_27	Sleep duration (short sleep)	4.000000e-08
GCST007709_286	General factor of neuroticism	3.000000e-09
GCST007825_4	Alzheimer’s disease or fasting glucose levels (pleiotropy)	3.000000e-16
GCST008163_556	Height	2.000000e-06
GCST008357_37	Mood instability	9.000000e-14
GCST008811_6	Alcohol consumption (drinks per week)	2.000000e-10
GCST010002_238	Refractive error	2.000000e-14

EFO canonical traits (18, from GWAS)

EFO ID	Trait name
EFO:0004695	intraocular pressure measurement
EFO:0004527	mean corpuscular hemoglobin
EFO:0006335	systolic blood pressure
EFO:0006336	diastolic blood pressure
EFO:0007660	neuroticism measurement
EFO:0004327	electrocardiography
EFO:0009458	alcohol use disorder measurement
EFO:0007865	loneliness measurement
EFO:0004341	body fat distribution
EFO:0008475	mood instability measurement
EFO:0008111	diet measurement
EFO:0004346	neuroimaging measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0005213	central corneal thickness
EFO:0004842	eosinophil count
EFO:0007991	eosinophil percentage of leukocytes
EFO:0009188	Red cell distribution width

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D015160	Hydrops Fetalis	C12.050.703.277.060.480; C15.378.295.480; C15.378.420.826.100.350; C16.300.060.480; C16.320.365.826.100.350; C20.306.480; C23.888.277.395
D020294	Myasthenic Syndromes, Congenital	C10.668.758.800; C16.320.590
D009468	Neuromuscular Diseases	C10.668
C563831	Myasthenic Syndrome, Congenital, Ie (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2163166 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
incobotulinumtoxinA	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Benzo(a)pyrene	decreases methylation, affects methylation	1
Estradiol	decreases expression	1
Ozone	affects expression, increases abundance	1
Quercetin	increases expression	1
Urethane	decreases expression	1
Valproic Acid	increases methylation	1
Okadaic Acid	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2167635	Binding	Binding affinity to RAPsyn assessed as photoincorporation at 1.7 uM by SDS-PAGE followed by fluorography analysis	p-(4-Azipentyl)propofol: a potent photoreactive general anesthetic derivative of propofol. — J Med Chem

Cellosaurus cell lines

2 cell lines: 1 cancer cell line, 1 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E0WP	Ubigene K-562 RAPSN KO	Cancer cell line	Female
CVCL_YK79	SDQLCHi018-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

266 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00331656	PHASE4	UNKNOWN	Comparative Study of Non-Invasive Mask Ventilation vs Cuirass Ventilation in Patients With Acute Respiratory Failure.
NCT00994552	PHASE4	UNKNOWN	Comparison of Pressure Support and Pressure Control Ventilation in Chronic Respiratory Failure
NCT00120055	PHASE4	COMPLETED	Association Between Systemic Exposure of Atorvastatin and Metabolites and Atorvastatin-induced Myotoxicity
NCT03633565	PHASE4	UNKNOWN	Comparative Study of Strategies for Management of Duchenne Myopathy (DM)
NCT00839033	PHASE3	TERMINATED	Evaluation of a Mechanical Device During Acute Respiratory Failure in Patients With Neuromuscular Disorders
NCT00942227	PHASE3	COMPLETED	The Value of Traction in Treatment of Lumbar Radiculopathy
NCT00979108	PHASE3	COMPLETED	The Value of Traction in the Treatment of Cervical Radiculopathy
NCT01826487	PHASE3	COMPLETED	Phase 3 Study of Ataluren in Participants With Nonsense Mutation Duchenne Muscular Dystrophy (nmDMD)
NCT02090959	PHASE3	TERMINATED	An Extension Study of Ataluren (PTC124) in Participants With Nonsense Mutation Dystrophinopathy
NCT02436096	PHASE3	COMPLETED	A Study to Evaluate eFFIcacy and Safety of Sublingual TNX-102 SL Tablet Taken at Bedtime in Patients With fibRoMyalgia
NCT02829814	PHASE3	TERMINATED	Repeat of: A Study to Evaluate Efficacy and Safety of Sublingual TNX-102 SL Tablet Taken at Bedtime in Patients With Fibromyalgia
NCT03179631	PHASE3	COMPLETED	Long-Term Outcomes of Ataluren in Duchenne Muscular Dystrophy
NCT05126758	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Deramiocel (CAP-1002) in Ambulatory and Non-Ambulatory Patients With Duchenne Muscular Dystrophy
NCT05156320	PHASE3	COMPLETED	Efficacy and Safety of Apitegromab in Patients With Later-Onset Spinal Muscular Atrophy Treated With Nusinersen or Risdiplam
NCT05337553	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Efficacy and Safety of Taldefgrobep Alfa in Participants With Spinal Muscular Atrophy
NCT05626855	PHASE3	ACTIVE_NOT_RECRUITING	Long-Term Safety & Efficacy of Apitegromab in Patients With SMA Who Completed Previous Trials of Apitegromab
NCT06672237	PHASE3	RECRUITING	A Phase 3 Study of NTLA-2001 in ATTRv-PN
NCT01225614	PHASE3	UNKNOWN	Efficacy and Tolerance of Early Launching of Nocturnal Non Invasive
NCT01074359	PHASE2	TERMINATED	Safety and Efficacy Study of A0001 in Patients With the A3243G Mitochondrial DNA Point Mutation
NCT01371149	PHASE2	COMPLETED	Patient -Ventilator Interaction in Chronic Respiratory Failure
NCT02022072	PHASE2	TERMINATED	Evaluation of Vital Capacity
NCT03127514	PHASE2	COMPLETED	AMX0035 in Patients With Amyotrophic Lateral Sclerosis (ALS)
NCT03406780	PHASE2	COMPLETED	A Study of CAP-1002 in Ambulatory and Non-Ambulatory Patients With Duchenne Muscular Dystrophy
NCT03921528	PHASE2	COMPLETED	An Active Treatment Study of SRK-015 in Patients With Type 2 or Type 3 Spinal Muscular Atrophy
NCT05479981	PHASE2	COMPLETED	Extension of AOC 1001-CS1 (MARINA) Study in Adult Myotonic Dystrophy Type 1 (DM1) Patients
NCT06339580	PHASE2	RECRUITING	Assessment of Volume-targeted Ventilation in Patients With Neuromuscular Disease
NCT07071935	PHASE2	NOT_YET_RECRUITING	A Clinical Trial of Early Ventilation in Amyotrophic Lateral Sclerosis (EVENT ALS)
NCT07287189	PHASE2	RECRUITING	Phase 2 Study of SAT-3247 in Pediatric Ambulatory Patients
NCT00252252	PHASE1	COMPLETED	AutoVPAP Versus VPAP; Assessment of Sleep and Ventilation
NCT01560741	PHASE1	UNKNOWN	Telemedicine and Ventilator Titration in Chronic Respiratory Patients Initiating Non-invasive Ventilation
NCT01621984	PHASE1	COMPLETED	Therapeutic Riding and Neuromuscular Disease
NCT01758510	PHASE1	COMPLETED	Safety Study of HLA-haplo Matched Allogenic Bone Marrow Derived Stem Cell Treatment in Amyotrophic Lateral Sclerosis
NCT03440034	PHASE1	COMPLETED	Study of Pioglitazone in Sporadic Inclusion Body Myositis
NCT05730842	PHASE1	COMPLETED	Absorption, Metabolism, Excretion and Absolute Bioavailability of EDG-5506 in Healthy Volunteers
NCT01203592	PHASE1	COMPLETED	Efficacy of Albuterol in the Treatment of Congenital Myasthenic Syndromes
NCT06436742	PHASE1	RECRUITING	A Phase 1b Study to Investigate Safety and Tolerability of ARGX-119 in Adult Participants With DOK7-Congenital Myasthenic Syndromes (CMS)
NCT07226726	PHASE1	RECRUITING	Patients With Congenital Myasthenic Syndrome Will be Treated With Mesenchymal Stem Cell Exosome Solution
NCT02986698	PHASE1	TERMINATED	In Utero Hematopoietic Stem Cell Transplantation for Alpha-thalassemia Major (ATM)
NCT00278564	PHASE1	TERMINATED	Stem Cell Transplantation in Idiopathic Inflammatory Myopathy Diseases
NCT03272802	PHASE2/PHASE3	UNKNOWN	Treatment Effect of Edaravone in Patients With Amyotrophic Lateral Sclerosis (ALS)