Fetal akinesia deformation sequence 2

Summary

Fetal akinesia deformation sequence 2 (MONDO:0100102) is a disease caused by RAPSN (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: RAPSN (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 95

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	fetal akinesia deformation sequence 2
Mondo ID	MONDO:0100102
OMIM	618388
DOID	DOID:0111378
UMLS	C4760576
MedGen	1678048
GARD	0016495
Is cancer (heuristic)	no

Also known as: FADS2

Data availability: 95 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › fetal akinesia deformation sequence › fetal akinesia deformation sequence 2

Related subtypes (4): fetal akinesia syndrome, X-linked, fetal akinesia deformation sequence 1, fetal akinesia deformation sequence 3, fetal akinesia deformation sequence 4

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

95 retrieved; paginated sample, class counts are floors:

25 pathogenic/likely pathogenic, 19 uncertain significance, 18 likely pathogenic, 13 conflicting classifications of pathogenicity, 12 pathogenic, 6 benign, 1 benign/likely benign, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1067929	NM_005055.5(RAPSN):c.531+1G>T	RAPSN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070359	NM_005055.5(RAPSN):c.418C>T (p.Gln140Ter)	RAPSN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1072315	NM_005055.5(RAPSN):c.599G>A (p.Trp200Ter)	RAPSN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1073877	NM_005055.5(RAPSN):c.291C>A (p.Cys97Ter)	RAPSN	Pathogenic	criteria provided, multiple submitters, no conflicts
1073878	NM_005055.5(RAPSN):c.46dup (p.Leu16fs)	RAPSN	Pathogenic	criteria provided, multiple submitters, no conflicts
1323519	NM_005055.5(RAPSN):c.300_319del (p.His100fs)	RAPSN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1324987	NM_005055.5(RAPSN):c.679G>T (p.Glu227Ter)	RAPSN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1416981	NM_005055.5(RAPSN):c.712C>T (p.Gln238Ter)	RAPSN	Pathogenic	criteria provided, multiple submitters, no conflicts
1455976	NM_005055.5(RAPSN):c.210del (p.Ile70fs)	RAPSN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1481997	NM_005055.5(RAPSN):c.966+1_966+2delinsAG	RAPSN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
190252	NM_005055.5(RAPSN):c.1083_1084dup (p.Tyr362fs)	RAPSN	Pathogenic	criteria provided, multiple submitters, no conflicts
197248	NM_005055.5(RAPSN):c.737C>T (p.Ala246Val)	RAPSN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2137088	NM_005055.5(RAPSN):c.990_993del (p.His329_Cys330insTer)	RAPSN	Pathogenic	criteria provided, multiple submitters, no conflicts
2506372	NM_005055.5(RAPSN):c.912+1G>A	RAPSN	Pathogenic	criteria provided, single submitter
264677	NM_005055.5(RAPSN):c.-199C>G	RAPSN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2678224	NM_005055.5(RAPSN):c.288del (p.Cys97fs)	RAPSN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2678233	NM_005055.5(RAPSN):c.690+1G>A	RAPSN	Pathogenic	criteria provided, single submitter
2678235	NM_005055.5(RAPSN):c.192+2T>G	RAPSN	Pathogenic	criteria provided, multiple submitters, no conflicts
2949109	NM_005055.5(RAPSN):c.733C>T (p.Gln245Ter)	RAPSN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
381702	NM_005055.5(RAPSN):c.439G>A (p.Glu147Lys)	RAPSN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
476121	NM_005055.5(RAPSN):c.370C>T (p.Gln124Ter)	RAPSN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
545747	NM_005055.5(RAPSN):c.1177_1178del (p.Asn393fs)	RAPSN	Pathogenic	criteria provided, multiple submitters, no conflicts
632161	NM_005055.5(RAPSN):c.1029_1045del (p.Glu344fs)	RAPSN	Pathogenic	criteria provided, multiple submitters, no conflicts
664620	NM_005055.5(RAPSN):c.997G>T (p.Glu333Ter)	RAPSN	Pathogenic	criteria provided, multiple submitters, no conflicts
802677	NM_005055.5(RAPSN):c.61C>T (p.Gln21Ter)	RAPSN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
8046	NM_005055.5(RAPSN):c.264C>A (p.Asn88Lys)	RAPSN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
8047	NM_005055.5(RAPSN):c.41T>C (p.Leu14Pro)	RAPSN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
8048	NM_005055.5(RAPSN):c.549_553dup (p.Phe185fs)	RAPSN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
8051	NM_005055.5(RAPSN):c.-210A>G	RAPSN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
8054	NM_005055.5(RAPSN):c.490C>T (p.Arg164Cys)	RAPSN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
RAPSN	Definitive	Autosomal recessive	fetal akinesia deformation sequence 2	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RAPSN	Orphanet:33108	Lethal multiple pterygium syndrome
RAPSN	Orphanet:98913	Postsynaptic congenital myasthenic syndrome
RAPSN	Orphanet:994	Fetal akinesia deformation sequence

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RAPSN	HGNC:9863	ENSG00000165917	Q13702	43 kDa receptor-associated protein of the synapse	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RAPSN	43 kDa receptor-associated protein of the synapse	Postsynaptic protein required for clustering of nicotinic acetylcholine receptors (nAChRs) at the neuromuscular junction.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RAPSN	Transcription factor	no		Postsynaptic, Znf_RING, TPR-like_helical_dom_sf

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
gastrocnemius	1
hindlimb stylopod muscle	1
male germ line stem cell (sensu Vertebrata) in testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RAPSN	159	tissue_specific	marker	hindlimb stylopod muscle, male germ line stem cell (sensu Vertebrata) in testis, gastrocnemius

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RAPSN	715

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
RAPSN	Q13702	93.29

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of postsynaptic membrane organization	1	16852.0×	3e-04	RAPSN
establishment of protein localization to postsynaptic membrane	1	16852.0×	3e-04	RAPSN
positive regulation of motor neuron apoptotic process	1	8426.0×	4e-04	RAPSN
positive regulation of neuromuscular synaptic transmission	1	5617.3×	4e-04	RAPSN
skeletal muscle acetylcholine-gated channel clustering	1	1872.4×	1e-03	RAPSN
motor neuron apoptotic process	1	1123.5×	0.001	RAPSN
synaptic transmission, cholinergic	1	802.5×	0.001	RAPSN
neurotransmitter receptor localization to postsynaptic specialization membrane	1	802.5×	0.001	RAPSN
chemical synaptic transmission	1	77.3×	0.013	RAPSN

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RAPSN	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
RAPSN	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	RAPSN

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
RAPSN	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.