Ogden syndrome

Summary

Ogden syndrome (MONDO:0010457) is a disease caused by NAA10 (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: NAA10 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 44
• Phenotypes (HPO): 41

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		8	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

41 HPO clinical features (Orphanet curated; top 41 by frequency):

HPO ID	Term	Frequency
HP:0000270	Delayed cranial suture closure	Frequent (30-79%)
HP:0000473	Torticollis	Frequent (30-79%)
HP:0001262	Excessive daytime somnolence	Frequent (30-79%)
HP:0001263	Global developmental delay	Frequent (30-79%)
HP:0001290	Generalized hypotonia	Frequent (30-79%)
HP:0002059	Cerebral atrophy	Frequent (30-79%)
HP:0002213	Fine hair	Frequent (30-79%)
HP:0002650	Scoliosis	Frequent (30-79%)
HP:0008897	Postnatal growth retardation	Frequent (30-79%)
HP:0010055	Broad hallux	Frequent (30-79%)
HP:0100840	Aplasia/Hypoplasia of the eyebrow	Frequent (30-79%)
HP:0000023	Inguinal hernia	Occasional (5-29%)
HP:0000028	Cryptorchidism	Occasional (5-29%)
HP:0000280	Coarse facial features	Occasional (5-29%)
HP:0000290	Abnormality of the forehead	Occasional (5-29%)
HP:0000308	Microretrognathia	Occasional (5-29%)
HP:0000341	Narrow forehead	Occasional (5-29%)
HP:0000369	Low-set ears	Occasional (5-29%)
HP:0000400	Macrotia	Occasional (5-29%)
HP:0000430	Underdeveloped nasal alae	Occasional (5-29%)
HP:0000494	Downslanted palpebral fissures	Occasional (5-29%)
HP:0000520	Proptosis	Occasional (5-29%)
HP:0000708	Atypical behavior	Occasional (5-29%)
HP:0000729	Autistic behavior	Occasional (5-29%)
HP:0000973	Cutis laxa	Occasional (5-29%)
HP:0001254	Lethargy	Occasional (5-29%)
HP:0001276	Hypertonia	Occasional (5-29%)
HP:0001629	Ventricular septal defect	Occasional (5-29%)
HP:0002000	Short columella	Occasional (5-29%)
HP:0002007	Frontal bossing	Occasional (5-29%)
HP:0002119	Ventriculomegaly	Occasional (5-29%)
HP:0002194	Delayed gross motor development	Occasional (5-29%)
HP:0002362	Shuffling gait	Occasional (5-29%)
HP:0002457	Abnormal head movements	Occasional (5-29%)
HP:0002705	High, narrow palate	Occasional (5-29%)
HP:0004415	Pulmonary artery stenosis	Occasional (5-29%)
HP:0009931	Enlarged naris	Occasional (5-29%)
HP:0010803	Everted upper lip vermilion	Occasional (5-29%)
HP:0011675	Arrhythmia	Occasional (5-29%)
HP:0025104	Capillary malformation	Occasional (5-29%)
HP:0030149	Cardiogenic shock	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Ogden syndrome
Mondo ID	MONDO:0010457
MeSH	C536107
OMIM	300855
Orphanet	276432
DOID	DOID:0050781
NCIT	C188215
UMLS	C3275447
MedGen	477078
GARD	0017281
Is cancer (heuristic)	no

Also known as: Acetyl-CoA:arylamine n-acetyltransferase · arylamine n-acetyltransferase 1 · N acetyltransferase 1 deficiency · N acetyltransferase deficiency · N-terminal acetyltransferase deficiency · NAT1 deficiency · Ogden syndrome · Ogden syndrome, X-linked recessive, X-linked dominant · OGDNS · premature ageing appearance-developmental delay-cardiac arrhythmia syndrome · premature aging appearance-developmental delay-cardiac arrhythmia syndrome

Data availability: 44 ClinVar variants · 4 GenCC gene-disease records · 1 cell line.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › disorder of development or morphogenesis › Ogden syndrome

Related subtypes (189): precocious puberty, complex cortical dysplasia with other brain malformations, imperforate anus, microcephaly, demyelinating disease, hypospadias, bone development disease, primary basilar invagination, familial bicuspid aortic valve, camptodactyly of fingers, isolated congenital digital clubbing, aorta coarctation, gingival fibromatosis-progressive deafness syndrome, Eng-Strom syndrome, Morgagni-Stewart-Morel syndrome, familial partial lipodystrophy, Dunnigan type, megalodactyly, odontomatosis-aortae esophagus stenosis syndrome, otodental syndrome, oculodental syndrome, Rutherfurd type, spina bifida, steatocystoma multiplex-natal teeth syndrome, distal symphalangism, thumb deformity-alopecia-pigmentation anomaly syndrome, double uterus-hemivagina-renal agenesis syndrome, amelogenesis imperfecta type 1G, Bloom syndrome, cardiac valvular defect, developmental, isolated cerebellar hypoplasia/agenesis, cleft palate-stapes fixation-oligodontia syndrome, Jalili syndrome, craniodiaphyseal dysplasia, craniofacial dyssynostosis, deafness-oligodontia syndrome, duodenal atresia, Fowler syndrome, multiple intestinal atresia, natal teeth-intestinal pseudoobstruction-patent ductus syndrome, atresia of small intestine, mulibrey nanism, oculocerebral hypopigmentation syndrome, Cross type, familial osteodysplasia, Anderson type, pancreatic agenesis, postaxial polydactyly-dental and vertebral anomalies syndrome, familial primary pulmonary hypoplasia, renal tubular dysgenesis of genetic origin, Rothmund-Thomson syndrome, familial isolated congenital asplenia, subaortic stenosis, membranous, non-eruption of teeth-maxillary hypoplasia-genu valgum syndrome, corpus callosum agenesis-intellectual disability-coloboma-micrognathia syndrome, CK syndrome, Nance-Horan syndrome, colonic atresia, Aicardi syndrome, torticollis-keloids-cryptorchidism-renal dysplasia syndrome, 46,XY complete gonadal dysgenesis, loose anagen syndrome, lung agenesis-heart defect-thumb anomalies syndrome, Chudley-McCullough syndrome, macrocephaly-autism syndrome, DNA ligase IV deficiency, horizontal gaze palsy with progressive scoliosis, cataract - congenital heart disease - neural tube defect syndrome, autosomal recessive frontotemporal pachygyria, craniofacial dysplasia - osteopenia syndrome, porencephaly-microcephaly-bilateral congenital cataract syndrome, congenital short bowel syndrome, familial median cleft of the upper and lower lips, progeroid features-hepatocellular carcinoma predisposition syndrome, progressive microcephaly-seizures-cortical blindness-developmental delay syndrome, aneurysm of sinus of Valsalva, blepharoptosis-cleft palate-ectrodactyly-dental anomalies syndrome, medullary sponge kidney, isolated congenital syngnathia, cleft lip and alveolus, diprosopus, T-B+ severe combined immunodeficiency due to IL-7Ralpha deficiency, high anorectal malformation, intermediate anorectal malformation, low anorectal malformation, microcephaly-polymicrogyria-corpus callosum agenesis syndrome, cordiform uterus, septate uterus, bicornuate uterus, uterine hypoplasia, agenesis and aplasia of uterine body, uterine cervical aplasia and agenesis, longitudinal vaginal septum, transverse vaginal septum, axial mesodermal dysplasia spectrum, multicystic dysplastic kidney, diabetic embryopathy, congenital microgastria, isolated cleft lip, cleft lip/palate, hereditary gingival fibromatosis, congenital bronchobiliary fistula, congenital hydrocephalus, maternal hyperthermia induced birth defects, diphallia, epibulbar lipodermoid-preauricular appendage-polythelia syndrome, bronchogenic cyst, duplication of urethra, hypohidrotic ectodermal dysplasia, Lowe-Kohn-Cohen syndrome, biliary atresia with splenic malformation syndrome, congenital pulmonary airway malformation, familial intestinal malrotation-facial anomalies syndrome, megalencephaly, cephalocele, cerebral cortical dysplasia, L1 syndrome, familial omphalocele syndrome with facial dysmorphism, penoscrotal transposition, pericardial and diaphragmatic defect, hypogonadotropic hypogonadism-severe microcephaly-sensorineural hearing loss-dysmorphism syndrome, congenital deformities of limbs, familial isolated clinodactyly of fingers, congenital shoulder dislocation, congenital elbow dislocation, congenital knee dislocation, congenital patella dislocation, macrodactyly of fingers, macrodactyly of toes, upper limb hypertrophy, lower limb hypertrophy, duplication of the pituitary gland, diencephalic-mesencephalic junction dysplasia, steroid dehydrogenase deficiency-dental anomalies syndrome, congenital achiasma, tracheal agenesis, renal agenesis, hypomyelination-cerebellar atrophy-hypoplasia of the corpus callosum syndrome, isolated splenogonadal fusion, Joubert syndrome, congenital generalized hypercontractile muscle stiffness syndrome, congenital bilateral absence of vas deferens, congenital portosystemic shunt, lissencephaly spectrum disorders, Berardinelli-Seip congenital lipodystrophy, congenital primary megaureter, craniorachischisis, vaginal atresia, bronchopulmonary dysplasia, dentinogenesis imperfecta-short stature-hearing loss-intellectual disability syndrome, aniridia, atypical Werner syndrome, X-linked intellectual disability-corpus callosum agenesis-spastic quadriparesis syndrome, anterior segment dysgenesis, congenital esophageal diverticulum, renal hypoplasia, renal dysplasia, overgrowth syndrome, developmental defect during embryogenesis, acalvaria, congenital aortic valve insufficiency, congenital anomaly of superior vena cava, congenital anomaly of hepatic vein, posterior hypospadias, isolated micropenis, isolated partial vaginal agenesis, anorectal malformation, pulmonary agenesis, congenital tricuspid malformation, Noonan syndrome and Noonan-related syndrome, coronary sinus stenosis, coronary sinus atresia, cartilage development disorder, syndactyly, polydactyly, brachydactyly, neurocristopathy, congenital absence of septum pellucidum, branchial arch disease, congenital anomaly of cardiovascular system, atelencephaly, aprosencephaly, aortic valve stenosis, hereditary lethal multiple congenital anomalies/dysmorphic syndrome, congenital agenesis of the scrotum, keratinization disease, lactation disease, COACH syndrome, constitutional delay of growth and puberty, isolated congenital femoral bifurcation, congenital peritoneal encapsulation, isolated short stature, congenital high airway obstruction syndrome

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

44 retrieved; paginated sample, class counts are floors:

10 pathogenic, 10 uncertain significance, 9 conflicting classifications of pathogenicity, 8 likely pathogenic, 4 pathogenic/likely pathogenic, 2 likely benign, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1028122	NM_003491.4(NAA10):c.472-2A>C	NAA10	Pathogenic	criteria provided, single submitter
139643	NM_003491.4(NAA10):c.319G>T (p.Val107Phe)	NAA10	Pathogenic	no assertion criteria provided
139644	NM_003491.4(NAA10):c.346C>T (p.Arg116Trp)	NAA10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
208664	NM_003491.4(NAA10):c.247C>T (p.Arg83Cys)	NAA10	Pathogenic	criteria provided, multiple submitters, no conflicts
218104	NM_003491.4(NAA10):c.128A>C (p.Tyr43Ser)	NAA10	Pathogenic	no assertion criteria provided
236258	NM_003491.4(NAA10):c.384T>A (p.Phe128Leu)	NAA10	Pathogenic	criteria provided, multiple submitters, no conflicts
236259	NM_003491.4(NAA10):c.382T>A (p.Phe128Ile)	NAA10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
280237	NM_003491.4(NAA10):c.384T>G (p.Phe128Leu)	NAA10	Pathogenic	criteria provided, multiple submitters, no conflicts
29927	NM_003491.4(NAA10):c.109T>C (p.Ser37Pro)	NAA10	Pathogenic	criteria provided, multiple submitters, no conflicts
488558	NM_003491.4(NAA10):c.259G>T (p.Ala87Ser)	NAA10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
520542	NM_003491.4(NAA10):c.332T>G (p.Val111Gly)	NAA10	Pathogenic	no assertion criteria provided
561061	NM_003491.4(NAA10):c.494_495del (p.Lys165fs)	NAA10	Pathogenic	criteria provided, single submitter
804122	NM_003491.4(NAA10):c.116C>T (p.Pro39Leu)	NAA10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
973227	NM_003491.4(NAA10):c.257T>G (p.Leu86Arg)	NAA10	Pathogenic	criteria provided, single submitter
1299213	NM_003491.4(NAA10):c.376C>G (p.Leu126Val)	NAA10	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1327568	NM_003491.4(NAA10):c.469G>A (p.Glu157Lys)	NAA10	Likely pathogenic	criteria provided, single submitter
1705306	NM_003491.4(NAA10):c.128A>G (p.Tyr43Cys)	NAA10	Likely pathogenic	criteria provided, single submitter
3376962	NM_003491.4(NAA10):c.387-1G>A	NAA10	Likely pathogenic	criteria provided, single submitter
375388	NM_003491.4(NAA10):c.215T>C (p.Ile72Thr)	NAA10	Likely pathogenic	criteria provided, multiple submitters, no conflicts
431708	NM_003491.4(NAA10):c.361C>G (p.Leu121Val)	NAA10	Likely pathogenic	criteria provided, single submitter
637034	NM_003491.4(NAA10):c.115C>A (p.Pro39Thr)	NAA10	Likely pathogenic	criteria provided, single submitter
804121	NM_003491.4(NAA10):c.377T>G (p.Leu126Arg)	NAA10	Likely pathogenic	criteria provided, single submitter
1300158	NM_003491.4(NAA10):c.16G>C (p.Ala6Pro)	LOC130068840	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1326724	NM_003491.4(NAA10):c.347G>A (p.Arg116Gln)	NAA10	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1396046	NM_003491.4(NAA10):c.295A>T (p.Ile99Leu)	NAA10	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3602981	NM_003491.4(NAA10):c.263A>C (p.Gln88Pro)	NAA10	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
373777	NM_003491.4(NAA10):c.440T>C (p.Met147Thr)	NAA10	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
391316	NM_003491.4(NAA10):c.235C>T (p.Arg79Cys)	NAA10	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
843535	NM_003491.4(NAA10):c.386A>C (p.Gln129Pro)	NAA10	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
929440	NM_003491.4(NAA10):c.303C>A (p.Asn101Lys)	NAA10	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 2 · 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
NAA10	Definitive	X-linked	Ogden syndrome	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NAA10	Orphanet:276432	Ogden syndrome
NAA10	Orphanet:568	Microphthalmia, Lenz type

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
NAA10	HGNC:18704	ENSG00000102030	P41227	N-alpha-acetyltransferase 10	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NAA10	N-alpha-acetyltransferase 10	Catalytic subunit of N-terminal acetyltransferase complexes which display alpha (N-terminal) acetyltransferase activity.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NAA10	Enzyme (other)	yes	2.3.1.255	GNAT_dom, Acyl_CoA_acyltransferase, Ard1-like

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
apex of heart	1
lower esophagus muscularis layer	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NAA10	288	ubiquitous	marker	right hemisphere of cerebellum, apex of heart, lower esophagus muscularis layer

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NAA10	2,579

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NAA10	P41227	12

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
positive regulation of protein refolding	1	16852.0×	9e-05	NAA10
negative regulation of maintenance of mitotic sister chromatid cohesion, centromeric	1	16852.0×	9e-05	NAA10
protein maturation	1	163.6×	0.006	NAA10

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
NAA10	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
NAA10	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
NAA10	2.3.1.255, 2.3.1.258, 2.3.1.48	N-terminal amino-acid Nalpha-acetyltransferase NatA, N-terminal methionine Nalpha-acetyltransferase NatE, histone acetyltransferase

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	1	NAA10
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
NAA10	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.