Atrial fibrillation, familial, 15

Summary

Atrial fibrillation, familial, 15 (MONDO:0014340) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 7

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	atrial fibrillation, familial, 15
Mondo ID	MONDO:0014340
OMIM	615770
UMLS	C4014269
MedGen	862706
GARD	0016010
Is cancer (heuristic)	no

Also known as: ATFB15 · atrial fibrillation 15 · atrial fibrillation, familial, 15 · atrial fibrillation, familial, type 15 · familial atrial fibrillation caused by mutation in NUP155 · NUP155 familial atrial fibrillation

Data availability: 7 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › heart disorder › cardiac rhythm disease › atrial fibrillation › familial atrial fibrillation › atrial fibrillation, familial, 15

Related subtypes (17): atrial fibrillation, familial, 3, atrial fibrillation, familial, 1, atrial fibrillation, familial, 2, atrial fibrillation, familial, 4, atrial fibrillation, familial, 5, atrial fibrillation, familial, 6, atrial fibrillation, familial, 7, atrial fibrillation, familial, 8, atrial fibrillation, familial, 9, atrial fibrillation, familial, 10, atrial fibrillation, familial, 11, atrial fibrillation, familial, 12, atrial fibrillation, familial, 13, atrial fibrillation, familial, 14, atrial fibrillation, familial, 18, atrial fibrillation, familial, 17, atrial fibrillation, familial, 16

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

7 retrieved; paginated sample, class counts are floors:

5 uncertain significance, 1 benign, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
127142	NM_153485.3(NUP155):c.1172G>A (p.Arg391His)	NUP155	Pathogenic	no assertion criteria provided
1032504	NM_153485.3(NUP155):c.3226C>T (p.Arg1076Cys)	NUP155	Uncertain significance	criteria provided, single submitter
3242595	NM_153485.3(NUP155):c.1304A>G (p.Asn435Ser)	NUP155	Uncertain significance	criteria provided, single submitter
3362422	NM_153485.3(NUP155):c.3247C>T (p.Arg1083Trp)	NUP155	Uncertain significance	criteria provided, single submitter
870608	NM_153485.3(NUP155):c.1204G>A (p.Val402Met)	NUP155	Uncertain significance	criteria provided, single submitter
977374	NM_153485.3(NUP155):c.1348A>G (p.Met450Val)	NUP155	Uncertain significance	criteria provided, multiple submitters, no conflicts
1180961	NM_153485.3(NUP155):c.201G>A (p.Leu67=)	NUP155	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 1 · 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
NUP155	Supportive	Autosomal dominant	familial atrial fibrillation	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NUP155	Orphanet:334	Hereditary atrial fibrillation

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
NUP155	HGNC:8063	ENSG00000113569	O75694	Nuclear pore complex protein Nup155	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NUP155	Nuclear pore complex protein Nup155	Essential component of nuclear pore complex.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NUP155	Other/Unknown	no		Nucleoporin_Nup155, Nucleoporin_Nup133/Nup155_C, Nucleoporin_Nup133/Nup155_N

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
left testis	1
male germ cell	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NUP155	238	ubiquitous	marker	sperm, male germ cell, left testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NUP155	3,663

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NUP155	O75694	10

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 31. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways 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.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Postmitotic nuclear pore complex (NPC) reformation	1	407.9×	0.006	NUP155
IPs transport between nucleus and cytosol	1	380.7×	0.006	NUP155
IP3 and IP4 transport between cytosol and nucleus	1	380.7×	0.006	NUP155
IP6 and IP7 transport between cytosol and nucleus	1	380.7×	0.006	NUP155
Transport of Ribonucleoproteins into the Host Nucleus	1	356.9×	0.006	NUP155
Regulation of Glucokinase by Glucokinase Regulatory Protein	1	356.9×	0.006	NUP155
Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC)	1	356.9×	0.006	NUP155
NEP/NS2 Interacts with the Cellular Export Machinery	1	346.1×	0.006	NUP155
Nuclear import of Rev protein	1	335.9×	0.006	NUP155
Vpr-mediated nuclear import of PICs	1	335.9×	0.006	NUP155
Transport of the SLBP independent Mature mRNA	1	326.3×	0.006	NUP155
SUMOylation of SUMOylation proteins	1	326.3×	0.006	NUP155
Transport of the SLBP Dependant Mature mRNA	1	317.2×	0.006	NUP155
Rev-mediated nuclear export of HIV RNA	1	317.2×	0.006	NUP155
Nuclear Pore Complex (NPC) Disassembly	1	308.6×	0.006	NUP155
SUMOylation of ubiquitinylation proteins	1	292.8×	0.006	NUP155
NS1 Mediated Effects on Host Pathways	1	285.5×	0.006	NUP155
Transport of Mature mRNA Derived from an Intronless Transcript	1	271.9×	0.006	NUP155
Viral Messenger RNA Synthesis	1	259.6×	0.006	NUP155
SUMOylation of DNA replication proteins	1	248.3×	0.006	NUP155
SUMOylation of RNA binding proteins	1	237.9×	0.006	NUP155
snRNP Assembly	1	211.5×	0.007	NUP155
tRNA processing in the nucleus	1	196.9×	0.007	NUP155
SUMOylation of chromatin organization proteins	1	158.6×	0.008	NUP155
Transport of Mature mRNA derived from an Intron-Containing Transcript	1	152.3×	0.008	NUP155
ISG15 antiviral mechanism	1	150.3×	0.008	NUP155
SUMOylation of DNA damage response and repair proteins	1	146.4×	0.008	NUP155
Regulation of HSF1-mediated heat shock response	1	139.3×	0.008	NUP155
HCMV Late Events	1	98.5×	0.011	NUP155
SARS-CoV-2 activates/modulates innate and adaptive immune responses	1	89.2×	0.012	NUP155

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
transcription-dependent tethering of RNA polymerase II gene DNA at nuclear periphery	1	4213.0×	0.001	NUP155
protein localization to nuclear inner membrane	1	4213.0×	0.001	NUP155
atrial cardiac muscle cell action potential	1	1685.2×	0.002	NUP155
miRNA processing	1	1053.2×	0.002	NUP155
nuclear envelope organization	1	991.3×	0.002	NUP155
RNA export from nucleus	1	936.2×	0.002	NUP155
nucleocytoplasmic transport	1	391.9×	0.003	NUP155
mRNA export from nucleus	1	295.6×	0.004	NUP155
protein import into nucleus	1	144.0×	0.007	NUP155

Therapeutics

Drug target analysis

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

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
NUP155	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	NUP155

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
NUP155	9	Binding:9

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

1 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.

Compound	Max phase	Cohort target (bioactivity)
MOLIBRESIB	2	NUP155

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	1	NUP155
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.