Fetal akinesia deformation sequence 4

Summary

Fetal akinesia deformation sequence 4 (MONDO:0100104) is a disease caused by NUP88 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: NUP88 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 18

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	fetal akinesia deformation sequence 4
Mondo ID	MONDO:0100104
OMIM	618393
DOID	DOID:0111379
UMLS	C4760578
MedGen	1675450
GARD	0016497
Is cancer (heuristic)	no

Also known as: FADS4

Data availability: 18 ClinVar variants · 2 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 4

Related subtypes (4): fetal akinesia syndrome, X-linked, fetal akinesia deformation sequence 1, fetal akinesia deformation sequence 2, fetal akinesia deformation sequence 3

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

18 retrieved; paginated sample, class counts are floors:

8 benign, 6 uncertain significance, 3 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
625468	NM_002532.6(NUP88):c.1300G>T (p.Asp434Tyr)	NUP88	Pathogenic	no assertion criteria provided
625469	NM_002532.6(NUP88):c.1525C>T (p.Arg509Ter)	NUP88	Pathogenic	no assertion criteria provided
625470	NM_002532.6(NUP88):c.1899_1901del (p.Glu634del)	NUP88	Pathogenic	no assertion criteria provided
4845740	NM_002532.6(NUP88):c.322_323del (p.Leu108fs)	NUP88	Likely pathogenic	criteria provided, single submitter
2434473	NM_002532.6(NUP88):c.585C>T (p.Asn195=)	LOC126862474	Uncertain significance	criteria provided, multiple submitters, no conflicts
1029454	NM_002532.6(NUP88):c.1510C>T (p.Pro504Ser)	NUP88	Uncertain significance	criteria provided, single submitter
2434474	NM_002532.6(NUP88):c.16G>A (p.Gly6Arg)	NUP88	Uncertain significance	criteria provided, multiple submitters, no conflicts
2442042	NM_002532.6(NUP88):c.1117C>T (p.Leu373Phe)	NUP88	Uncertain significance	criteria provided, multiple submitters, no conflicts
3203262	NM_002532.6(NUP88):c.614C>T (p.Pro205Leu)	NUP88	Uncertain significance	criteria provided, multiple submitters, no conflicts
4079470	NM_002532.6(NUP88):c.1501G>C (p.Ala501Pro)	NUP88	Uncertain significance	criteria provided, single submitter
1327052	NM_002532.6(NUP88):c.468-38G>T	LOC126862474	Benign	criteria provided, multiple submitters, no conflicts
1327042	NM_002532.6(NUP88):c.2172T>C (p.His724=)	NUP88	Benign	criteria provided, multiple submitters, no conflicts
1327043	NM_002532.6(NUP88):c.2157A>G (p.Lys719=)	NUP88	Benign	criteria provided, multiple submitters, no conflicts
1327047	NM_002532.6(NUP88):c.1916+25T>G	NUP88	Benign	criteria provided, multiple submitters, no conflicts
1327048	NM_002532.6(NUP88):c.1916+3C>T	NUP88	Benign	criteria provided, multiple submitters, no conflicts
1327049	NM_002532.6(NUP88):c.1836-38G>T	NUP88	Benign	criteria provided, multiple submitters, no conflicts
1327050	NM_002532.6(NUP88):c.1389A>T (p.Pro463=)	NUP88	Benign	criteria provided, multiple submitters, no conflicts
1327051	NM_002532.6(NUP88):c.1292-19G>A	NUP88	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
NUP88	Strong	Autosomal recessive	fetal akinesia deformation sequence 4	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NUP88	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
NUP88	HGNC:8067	ENSG00000108559	Q99567	Nuclear pore complex protein Nup88	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NUP88	Nuclear pore complex protein Nup88	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)
NUP88	Other/Unknown	no		Nucleoporin_Nup88, NUP88/NUP82

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
right testis	1
testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NUP88	290	ubiquitous	marker	right testis, left testis, testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NUP88	1,600

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NUP88	Q99567	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 30. 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
IPs transport between nucleus and cytosol	1	380.7×	0.006	NUP88
IP3 and IP4 transport between cytosol and nucleus	1	380.7×	0.006	NUP88
IP6 and IP7 transport between cytosol and nucleus	1	380.7×	0.006	NUP88
Transport of Ribonucleoproteins into the Host Nucleus	1	356.9×	0.006	NUP88
Regulation of Glucokinase by Glucokinase Regulatory Protein	1	356.9×	0.006	NUP88
Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC)	1	356.9×	0.006	NUP88
NEP/NS2 Interacts with the Cellular Export Machinery	1	346.1×	0.006	NUP88
Nuclear import of Rev protein	1	335.9×	0.006	NUP88
Vpr-mediated nuclear import of PICs	1	335.9×	0.006	NUP88
Transport of the SLBP independent Mature mRNA	1	326.3×	0.006	NUP88
SUMOylation of SUMOylation proteins	1	326.3×	0.006	NUP88
Transport of the SLBP Dependant Mature mRNA	1	317.2×	0.006	NUP88
Rev-mediated nuclear export of HIV RNA	1	317.2×	0.006	NUP88
Nuclear Pore Complex (NPC) Disassembly	1	308.6×	0.006	NUP88
SUMOylation of ubiquitinylation proteins	1	292.8×	0.006	NUP88
NS1 Mediated Effects on Host Pathways	1	285.5×	0.006	NUP88
Transport of Mature mRNA Derived from an Intronless Transcript	1	271.9×	0.006	NUP88
Viral Messenger RNA Synthesis	1	259.6×	0.006	NUP88
SUMOylation of DNA replication proteins	1	248.3×	0.006	NUP88
SUMOylation of RNA binding proteins	1	237.9×	0.006	NUP88
snRNP Assembly	1	211.5×	0.007	NUP88
tRNA processing in the nucleus	1	196.9×	0.007	NUP88
SUMOylation of chromatin organization proteins	1	158.6×	0.008	NUP88
Transport of Mature mRNA derived from an Intron-Containing Transcript	1	152.3×	0.008	NUP88
ISG15 antiviral mechanism	1	150.3×	0.008	NUP88
SUMOylation of DNA damage response and repair proteins	1	146.4×	0.008	NUP88
Regulation of HSF1-mediated heat shock response	1	139.3×	0.008	NUP88
HCMV Late Events	1	98.5×	0.011	NUP88
SARS-CoV-2 activates/modulates innate and adaptive immune responses	1	89.2×	0.012	NUP88
HCMV Early Events	1	81.0×	0.012	NUP88

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
ribosomal large subunit export from nucleus	1	2407.4×	0.001	NUP88
ribosomal small subunit export from nucleus	1	2106.5×	0.001	NUP88
nucleocytoplasmic transport	1	391.9×	0.004	NUP88
mRNA export from nucleus	1	295.6×	0.004	NUP88
protein import into nucleus	1	144.0×	0.007	NUP88

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
NUP88	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	NUP88

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)
NUP88	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.