Nestor-Guillermo progeria syndrome

Summary

Nestor-Guillermo progeria syndrome (MONDO:0013523) is a disease with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 2
• ClinVar variants: 27

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		2	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	Nestor-Guillermo progeria syndrome
Mondo ID	MONDO:0013523
OMIM	614008
Orphanet	280576
DOID	DOID:0081334
UMLS	C3151446
MedGen	462796
GARD	0011008
Is cancer (heuristic)	no

Also known as: BANF1-related neurodevelopmental syndrome · Nestor-Guillermo progeria syndrome · NGPS · PSCOO

Data availability: 27 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › Nestor-Guillermo progeria syndrome

Related subtypes (218): immunodeficiency-centromeric instability-facial anomalies syndrome, hypercalcemia, infantile, Ochoa syndrome, autosomal recessive Ehlers-Danlos syndrome, vascular type, hydrolethalus syndrome, 3-M syndrome, isolated hyperchlorhidrosis, dacryocystitis-osteopoikilosis syndrome, Hutchinson-Gilford progeria syndrome, achalasia microcephaly syndrome, acrorenal syndrome, autosomal recessive, beta-ketothiolase deficiency, autosomal recessive Alport syndrome, Alstrom syndrome, microphthalmia with limb anomalies, camptodactyly-arthropathy-coxa vara-pericarditis syndrome, Behr syndrome, bifid nose, autosomal recessive, Bloom syndrome, Bowen-Conradi syndrome, camptodactyly with fibrous tissue hyperplasia and skeletal dysplasia, heart defects-limb shortening syndrome, autosomal recessive palmoplantar keratoderma and congenital alopecia, COFS syndrome, craniometaphyseal dysplasia, autosomal recessive, Fraser syndrome, cystic fibrosis, polycystic lipomembranous osteodysplasia with sclerosing leukoencephaly, persistent hyperplastic primary vitreous, autosomal recessive, Donnai-Barrow syndrome, Schöpf-Schulz-Passarge syndrome, cleft lip/palate-ectodermal dysplasia syndrome, Ellis-van Creveld syndrome, Wolcott-Rallison syndrome, autosomal recessive faciodigitogenital syndrome, acromesomelic dysplasia 2B, brittle cornea syndrome, triple-A syndrome, autosomal recessive humeroradial synostosis, multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome, hydrocephalus, nonsyndromic, autosomal recessive 1, autosomal recessive hydrocephalus due to congenital stenosis of aqueduct of Sylvius, hypertelorism, microtia, facial clefting syndrome, hypoparathyroidism-retardation-dysmorphism syndrome, Vici syndrome, Johanson-Blizzard syndrome, autosomal recessive Kenny-Caffey syndrome, Papillon-Lefevre disease, Haim-Munk syndrome, Laurence-Moon syndrome, Donohue syndrome, lipase deficiency, combined, autosomal recessive familial Mediterranean fever, thiamine-responsive megaloblastic anemia syndrome, cartilage-hair hypoplasia, Nijmegen breakage syndrome, pseudo-TORCH syndrome, Galloway-Mowat syndrome, mulibrey nanism, myotonia congenita, autosomal recessive, Schwartz-Jampel syndrome, proteosome-associated autoinflammatory syndrome, Netherton syndrome, Niemann-Pick disease type A, oculodentodigital dysplasia, autosomal recessive, odonto-onycho-dermal dysplasia, autosomal recessive omodysplasia, osteoporosis-pseudoglioma syndrome, Shwachman-Diamond syndrome, phenylketonuria, Bjornstad syndrome, Laron syndrome, autosomal recessive polycystic kidney disease, autosomal recessive inherited pseudoxanthoma elasticum, autosomal recessive multiple pterygium syndrome, rapadilino syndrome, short-rib thoracic dysplasia 9 with or without polydactyly, autosomal recessive Robinow syndrome, Sjogren-Larsson syndrome, scapuloperoneal spinal muscular atrophy, autosomal recessive, spondyloepiphyseal dysplasia tarda, autosomal recessive, inherited threoninemia, Pendred syndrome, autosomal recessive spondylocostal dysostosis, Werner syndrome, ABCD syndrome, Naxos disease, autosomal recessive amelia, human HOXA1 syndromes, sickle cell disease, autosomal recessive proximal renal tubular acidosis, hyper-IgM syndrome type 2, temtamy preaxial brachydactyly syndrome, TH-deficient dopa-responsive dystonia, craniosynostosis syndrome, autosomal recessive, Niemann-Pick disease type B, skin fragility-woolly hair-palmoplantar keratoderma syndrome, CoQ-responsive OXPHOS deficiency, familial adenomatous polyposis 2, Pierson syndrome, palmoplantar keratoderma-XX sex reversal-predisposition to squamous cell carcinoma syndrome, cardiomyopathy-hypotonia-lactic acidosis syndrome, PHARC syndrome, Kahrizi syndrome, cutis laxa with severe pulmonary, gastrointestinal and urinary anomalies, congenital prothrombin deficiency, immunodeficiency 31B, dyskeratosis congenita, autosomal recessive 2, dyskeratosis congenita, autosomal recessive 3, leukoencephalopathy with calcifications and cysts, mitochondrial pyruvate carrier deficiency, branched-chain keto acid dehydrogenase kinase deficiency, dyskeratosis congenita, autosomal recessive 5, hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome, alacrima, achalasia, and intellectual disability syndrome, hyperlipoproteinemia, type 1D, microcephaly and chorioretinopathy 2, congenital stationary night blindness 1G, combined oxidative phosphorylation deficiency 29, hypermanganesemia with dystonia 2, growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy, gnb5-related intellectual disability-cardiac arrhythmia syndrome, autosomal recessive spastic paraplegia type 78, autosomal recessive limb-girdle muscular dystrophy, Bardet-Biedl syndrome, autosomal recessive cerebellar ataxia, neuronopathy, distal hereditary motor, autosomal recessive, UV-sensitive syndrome, Ehlers-Danlos syndrome, kyphoscoliotic type 1, Cockayne syndrome, hyperphenylalaninemia due to tetrahydrobiopterin deficiency, leukoencephalopathy-palmoplantar keratoderma syndrome, autosomal recessive hypohidrotic ectodermal dysplasia, Warburg micro syndrome, autosomal recessive primary microcephaly, autosomal recessive progressive external ophthalmoplegia, Meier-Gorlin syndrome, autosomal recessive sideroblastic anemia, autosomal recessive intermediate Charcot-Marie-Tooth disease, Perrault syndrome, autosomal recessive hypophosphatemic rickets, de Barsy syndrome, leukocyte adhesion deficiency, Senior-Loken syndrome, autosomal recessive spastic ataxia, childhood-onset autosomal recessive myopathy with external ophthalmoplegia, autosomal recessive cerebral atrophy, GM3 synthase deficiency, autosomal recessive distal renal tubular acidosis, pigmentation defects-palmoplantar keratoderma-skin carcinoma syndrome, autosomal recessive brachyolmia, Aicardi-Goutieres syndrome, homocystinuria without methylmalonic aciduria, Niemann-Pick disease type C, nephronophthisis, autosomal recessive osteopetrosis, peroxisome biogenesis disorder, congenital non-bullous ichthyosiform erythroderma, Seckel syndrome, Usher syndrome, autosomal recessive cutis laxa type 1, autosomal recessive cutis laxa type 2, hearing loss, autosomal recessive, microcephaly, growth restriction, and increased sister chromatid exchange 2, encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1, congenital vertebral-cardiac-renal anomalies syndrome, hair defect with photosensitivity and intellectual disability syndrome, autosomal recessive severe congenital neutropenia, severe combined immunodeficiency due to CARMIL2 deficiency, extraoral halitosis due to methanethiol oxidase deficiency, neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities, mitochondrial complex 2 deficiency, nuclear type 3, mitochondrial complex 2 deficiency, nuclear type 4, mismatch repair cancer syndrome, spondyloepimetaphyseal dysplasia with joint laxity, type 3, Kilquist syndrome, Duane anomaly-myopathy-scoliosis syndrome, autosomal recessive axonal charcot-marie-tooth disease due to copper metabolism defect, immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections-lymphopenia syndrome, optic atrophy-ataxia-peripheral neuropathy-global developmental delay syndrome, congenital myopathy with reduced type 2 muscle fibers, NAD(P)HX dehydratase deficiency, autosomal recessive ocular albinism, ichthyosis linearis circumflexa, eosinophil peroxidase deficiency, hyperphenylalaninemia due to DNAJC12 deficiency, autosomal recessive epidermolytic ichthyosis, Ehlers-Danlos syndrome, classic-like, 2, joint laxity, short stature, and myopia, HELIX syndrome, auditory neuropathy-optic atrophy syndrome, glycosylphosphatidylinositol biosynthesis defect 15, neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures, SCN4A-related myopathy, autosomal recessive, Uner Tan Syndrome, nephropathic cystinosis, Imerslund-Grasbeck syndrome type 1, Imerslund-Grasbeck syndrome type 2, permanent neonatal diabetes mellitus 1, growth hormone insensitivity with immune dysregulation 1, autosomal recessive, Rajab interstitial lung disease with brain calcifications 1, Roberts-SC phocomelia syndrome, neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities, RPE65-related recessive retinopathy, GUCY2D-related recessive retinopathy, autosomal recessive titinopathy, intellectual disability, autosomal recessive, ALPL-related autosomal recessive hypophosphatasia, spastic paraplegia 18b, autosomal recessive, CEP164-related ciliopathy, RP1-related recessive retinopathy, pseudohypoaldosteronism, type IB2, autosomal recessive, pseudohypoaldosteronism, type IB3, autosomal recessive, spastic paraplegia 30B, autosomal recessive, cerebral arteriopathy, autosomal recessive, with subcortical infarcts and leukoencephalopathy 1, brain small vessel disease 2B, autosomal recessive, IMPG1-related recessive retinopathy, PROM1-related recessive retinopathy

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

27 retrieved; paginated sample, class counts are floors:

16 uncertain significance, 5 likely benign, 5 benign, 1 no classifications from unflagged records

ClinVar	Variant (HGVS)	Gene	Classification	Review
30390	NM_003860.4(BANF1):c.34G>A (p.Ala12Thr)	BANF1	no classifications from unflagged records	no classifications from unflagged records
305392	NM_001143985.1(BANF1):c.-440A>G	BANF1	Uncertain significance	criteria provided, single submitter
305399	NM_001143985.1(BANF1):c.-230C>T	BANF1	Uncertain significance	criteria provided, single submitter
305402	NM_001143985.1(BANF1):c.-86G>A	BANF1	Uncertain significance	criteria provided, single submitter
305403	NM_001143985.1(BANF1):c.-35A>T	BANF1	Uncertain significance	criteria provided, single submitter
305404	NM_003860.4(BANF1):c.-70T>G	BANF1	Uncertain significance	criteria provided, single submitter
305405	NM_003860.4(BANF1):c.-62A>G	BANF1	Uncertain significance	criteria provided, single submitter
305406	NM_003860.4(BANF1):c.9C>T (p.Thr3=)	BANF1	Uncertain significance	criteria provided, single submitter
305407	NM_003860.4(BANF1):c.*64T>A	BANF1	Uncertain significance	criteria provided, single submitter
305408	NM_003860.4(BANF1):c.*120T>A	BANF1	Uncertain significance	criteria provided, single submitter
305411	NM_003860.4(BANF1):c.*209T>G	BANF1	Uncertain significance	criteria provided, single submitter
877795	NM_003860.4(BANF1):c.*143T>A	BANF1	Uncertain significance	criteria provided, single submitter
877796	NM_003860.4(BANF1):c.*182T>C	BANF1	Uncertain significance	criteria provided, single submitter
879758	NM_001143985.1(BANF1):c.-105G>A	BANF1	Uncertain significance	criteria provided, single submitter
305393	NM_001143985.1(BANF1):c.-429G>C	EIF1AD	Uncertain significance	criteria provided, single submitter
305394	NM_001143985.1(BANF1):c.-421G>A	EIF1AD	Uncertain significance	criteria provided, single submitter
879759	NM_003860.4(BANF1):c.-60C>T	LOC130006090	Uncertain significance	criteria provided, single submitter
305396	NM_001143985.1(BANF1):c.-408C>T	BANF1	Likely benign	criteria provided, single submitter
305397	NM_001143985.1(BANF1):c.-297G>A	BANF1	Likely benign	criteria provided, single submitter
305398	NM_001143985.1(BANF1):c.-254G>T	BANF1	Likely benign	criteria provided, single submitter
305400	NM_001143985.1(BANF1):c.-221T>G	BANF1	Benign	criteria provided, multiple submitters, no conflicts
305401	NM_001143985.1(BANF1):c.-192G>C	BANF1	Benign	criteria provided, multiple submitters, no conflicts
305409	NM_003860.4(BANF1):c.*128C>A	BANF1	Benign	criteria provided, multiple submitters, no conflicts
305410	NM_003860.4(BANF1):c.*177G>A	BANF1	Benign	criteria provided, multiple submitters, no conflicts
305412	NM_003860.4(BANF1):c.*273C>G	BANF1	Likely benign	criteria provided, multiple submitters, no conflicts
790644	NM_003860.4(BANF1):c.204C>T (p.Gly68=)	BANF1	Benign	criteria provided, multiple submitters, no conflicts
877794	NM_003860.4(BANF1):c.*100C>T	BANF1	Likely benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · 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
BANF1	Moderate	Autosomal recessive	Nestor-Guillermo progeria syndrome	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BANF1	Orphanet:280576	Nestor-Guillermo progeria syndrome

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BANF1	HGNC:17397	ENSG00000175334	O75531	Barrier-to-autointegration factor	gencc,clinvar
EIF1AD	HGNC:28147	ENSG00000175376	Q8N9N8	Probable RNA-binding protein EIF1AD	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BANF1	Barrier-to-autointegration factor	Non-specific DNA-binding protein that plays key roles in mitotic nuclear reassembly, chromatin organization, DNA damage response, gene expression and intrinsic immunity against foreign DNA.
EIF1AD	Probable RNA-binding protein EIF1AD	Plays a role into cellular response to oxidative stress.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BANF1	Other/Unknown	no		BAF_prot, BAF_sf, BAF
EIF1AD	Other/Unknown	no		TIF_eIF-1A, RNA-binding_domain_S1_IF1, NA-bd_OB-fold

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ganglionic eminence	1
right uterine tube	1
ventricular zone	1
amniotic fluid	1
buccal mucosa cell	1
pancreatic ductal cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BANF1	282	ubiquitous	marker	ganglionic eminence, ventricular zone, right uterine tube
EIF1AD	250	ubiquitous	marker	pancreatic ductal cell, buccal mucosa cell, amniotic fluid

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BANF1	3,376
EIF1AD	1,124

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BANF1	O75531	29
EIF1AD	Q8N9N8	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 23. Enrichment computed across 2 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
Integration of viral DNA into host genomic DNA	1	3806.7×	0.002	BANF1
Autointegration results in viral DNA circles	1	3806.7×	0.002	BANF1
Integration of provirus	1	2284.0×	0.002	BANF1
APOBEC3G mediated resistance to HIV-1 infection	1	2284.0×	0.002	BANF1
Early Phase of HIV Life Cycle	1	1631.4×	0.002	BANF1
2-LTR circle formation	1	1631.4×	0.002	BANF1
Interactions of Vpr with host cellular proteins	1	1427.5×	0.002	BANF1
Initiation of Nuclear Envelope (NE) Reformation	1	601.0×	0.005	BANF1
Nuclear Envelope Breakdown	1	456.8×	0.006	BANF1
Mitotic Prophase	1	368.4×	0.006	BANF1
Host Interactions of HIV factors	1	335.9×	0.006	BANF1
Vpr-mediated nuclear import of PICs	1	335.9×	0.006	BANF1
Nuclear Envelope (NE) Reassembly	1	292.8×	0.006	BANF1
HIV Life Cycle	1	160.8×	0.010	BANF1
HIV Infection	1	119.0×	0.013	BANF1
Mitotic Metaphase and Anaphase	1	96.8×	0.014	BANF1
Mitotic Anaphase	1	96.8×	0.014	BANF1
M Phase	1	66.0×	0.019	BANF1
Cell Cycle, Mitotic	1	48.2×	0.025	BANF1
Cell Cycle	1	36.0×	0.032	BANF1
Viral Infection Pathways	1	30.8×	0.036	BANF1
Infectious disease	1	24.8×	0.042	BANF1
Disease	1	13.1×	0.076	BANF1

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
negative regulation of protein ADP-ribosylation	1	8426.0×	0.001	BANF1
DNA integration	1	2106.5×	0.002	BANF1
mitotic nuclear membrane reassembly	1	1685.2×	0.002	BANF1
negative regulation of cGAS/STING signaling pathway	1	1053.2×	0.003	BANF1
chromosome organization	1	581.1×	0.003	BANF1
negative regulation of innate immune response	1	510.7×	0.003	BANF1
negative regulation of type I interferon production	1	495.6×	0.003	BANF1
negative regulation of viral genome replication	1	374.5×	0.004	BANF1
response to virus	1	144.0×	0.008	BANF1
response to oxidative stress	1	130.6×	0.008	BANF1
chromatin organization	1	99.1×	0.010	BANF1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BANF1	0	0
EIF1AD	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
BANF1	2	Binding:2

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	2	BANF1, EIF1AD

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
BANF1	2	—
EIF1AD	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.