Intellectual disability, autosomal dominant 50

Summary

Intellectual disability, autosomal dominant 50 (MONDO:0030916) is a disease caused by NAA15 (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: NAA15 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 126

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual disability, autosomal dominant 50
Mondo ID	MONDO:0030916
OMIM	617787
DOID	DOID:0080233
UMLS	C4540470
MedGen	1616989
GARD	0025661
Is cancer (heuristic)	no

Also known as: autosomal dominant mental retardation 50 · intellectual developmental disorder, autosomal dominant 50, with behavioral abnormalities · intellectual developmental disorder, autosomal dominant 50, with behavioural abnormalities · intellectual disability, autosomal dominant 50 · mental retardation, autosomal dominant 50 · MRD50

Data availability: 126 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › neurodevelopmental disorder › intellectual disability › non-syndromic intellectual disability › autosomal dominant non-syndromic intellectual disability › intellectual disability, autosomal dominant 50

Related subtypes (25): intellectual disability, autosomal dominant 22, neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language, intellectual disability, autosomal dominant 33, intellectual disability, autosomal dominant 34, intellectual disability, autosomal dominant 41, intellectual disability, autosomal dominant 43, intellectual disability, autosomal dominant 58, intellectual disability, autosomal dominant 45, intellectual disability, autosomal dominant 46, intellectual disability, autosomal dominant 47, Clark-Baraitser syndrome, intellectual disability, autosomal dominant 51, intellectual disability, autosomal dominant 52, intellectual disability, autosomal dominant 53, intellectual disability, autosomal dominant 54, intellectual disability, autosomal dominant 55, with seizures, intellectual disability, autosomal dominant 56, intellectual developmental disorder 61, intellectual developmental disorder 59, intellectual developmental disorder 60 with seizures, intellectual developmental disorder 62, intellectual developmental disorder, autosomal dominant 63, with macrocephaly, Coffin-Siris syndrome 6, intellectual disability, autosomal dominant 57, intellectual developmental disorder, autosomal dominant 73

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

126 retrieved; paginated sample, class counts are floors:

38 likely pathogenic, 37 uncertain significance, 35 pathogenic, 7 pathogenic/likely pathogenic, 7 conflicting classifications of pathogenicity, 1 benign, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1069493	NM_057175.5(NAA15):c.1841dup (p.Asn614fs)	NAA15	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1174541	NM_057175.5(NAA15):c.908-2A>G	NAA15	Pathogenic	criteria provided, multiple submitters, no conflicts
1177057	NM_057175.5(NAA15):c.334G>A (p.Asp112Asn)	NAA15	Pathogenic	no assertion criteria provided
1177059	NM_057175.5(NAA15):c.1450T>C (p.Cys484Arg)	NAA15	Pathogenic	no assertion criteria provided
1177066	NM_057175.5(NAA15):c.2441T>C (p.Leu814Pro)	NAA15	Pathogenic	no assertion criteria provided
1218548	NM_057175.5(NAA15):c.1645C>T (p.Arg549Ter)	NAA15	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1320186	NM_057175.5(NAA15):c.1720dup (p.Thr574fs)	NAA15	Pathogenic	criteria provided, single submitter
1324774	NM_057175.5(NAA15):c.2344C>T (p.Arg782Ter)	NAA15	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1326070	NM_057175.5(NAA15):c.692-2_692-1del	NAA15	Pathogenic	criteria provided, multiple submitters, no conflicts
1327782	NM_057175.5(NAA15):c.1539+1G>A	NAA15	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1343137	NM_057175.5(NAA15):c.231dup (p.Lys78fs)	NAA15	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1344906	NM_057175.5(NAA15):c.1624_1627delinsAT (p.Leu542fs)	NAA15	Pathogenic	criteria provided, single submitter
1679219	NM_057175.5(NAA15):c.2320_2332del (p.Tyr774fs)	NAA15	Pathogenic	criteria provided, single submitter
1699231	NM_057175.5(NAA15):c.1051del (p.Thr351fs)	NAA15	Pathogenic	criteria provided, single submitter
1802607	NM_057175.5(NAA15):c.1165C>T (p.Gln389Ter)	NAA15	Pathogenic	criteria provided, multiple submitters, no conflicts
1803747	NM_057175.5(NAA15):c.1418_1421dup (p.Ala475fs)	NAA15	Pathogenic	criteria provided, single submitter
2442380	NM_057175.5(NAA15):c.908-2A>C	NAA15	Pathogenic	criteria provided, single submitter
2504072	NM_057175.5(NAA15):c.238_239insG (p.His80fs)	NAA15	Pathogenic	criteria provided, single submitter
2664796	NM_057175.5(NAA15):c.309C>G (p.Tyr103Ter)	NAA15	Pathogenic	criteria provided, single submitter
2674621	NM_057175.5(NAA15):c.1765del (p.Asp589fs)	NAA15	Pathogenic	criteria provided, single submitter
268211	NM_057175.5(NAA15):c.2322C>G (p.Tyr774Ter)	NAA15	Pathogenic	criteria provided, single submitter
3068319	NM_057175.5(NAA15):c.63T>G (p.Tyr21Ter)	NAA15	Pathogenic	no assertion criteria provided
3341040	NM_057175.5(NAA15):c.1753+1G>T	NAA15	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3359070	NM_057175.5(NAA15):c.139+1G>A	NAA15	Pathogenic	criteria provided, single submitter
3382793	NM_057175.5(NAA15):c.1881_1882insCC (p.Lys628fs)	NAA15	Pathogenic	criteria provided, single submitter
4056375	NM_057175.5(NAA15):c.1025_1029del (p.Ile342fs)	NAA15	Pathogenic	criteria provided, single submitter
446518	NM_057175.5(NAA15):c.1695T>A (p.Tyr565Ter)	NAA15	Pathogenic	no assertion criteria provided
446519	NM_057175.5(NAA15):c.2086A>T (p.Lys696Ter)	NAA15	Pathogenic	no assertion criteria provided
446520	NM_057175.4(NAA15):c.228_232del (p.Asp76Glufs)	NAA15	Pathogenic	criteria provided, multiple submitters, no conflicts
4755522	NM_057175.5(NAA15):c.2059_2060del (p.Lys687fs)	NAA15	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
NAA15	Definitive	Autosomal dominant	intellectual disability, autosomal dominant 50	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NAA15	Orphanet:528084	Non-specific syndromic intellectual disability

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
NAA15	HGNC:30782	ENSG00000164134	Q9BXJ9	N-alpha-acetyltransferase 15, NatA auxiliary subunit	gencc,clinvar
MGARP	HGNC:29969	ENSG00000137463	Q8TDB4	Protein MGARP	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NAA15	N-alpha-acetyltransferase 15, NatA auxiliary subunit	Auxillary subunit of N-terminal acetyltransferase complexes which display alpha (N-terminal) acetyltransferase (NAT) activity.
MGARP	Protein MGARP	Plays a role in the trafficking of mitochondria along microtubules.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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	6.0×	0.320
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NAA15	Enzyme (other)	yes	2.3.1.255	TPR-like_helical_dom_sf, TPR_rpt, NatA_aux_su
MGARP	Other/Unknown	no		MGARP, MGARP_N

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
adrenal tissue	2
calcaneal tendon	1
ventricular zone	1
right adrenal gland	1
right adrenal gland cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NAA15	283	ubiquitous	marker	calcaneal tendon, adrenal tissue, ventricular zone
MGARP	165	broad	marker	adrenal tissue, right adrenal gland cortex, right adrenal gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NAA15	2,017
MGARP	1,367

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NAA15	Q9BXJ9	12

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MGARP	Q8TDB4	55.28

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
cellular response to gonadotropin-releasing hormone	1	2808.7×	0.006	MGARP
negative regulation of dendrite development	1	1053.2×	0.006	MGARP
retrograde axonal transport	1	766.0×	0.006	MGARP
axonal transport of mitochondrion	1	702.2×	0.006	MGARP
cellular response to steroid hormone stimulus	1	526.6×	0.006	MGARP
regulation of mitochondrion organization	1	421.3×	0.006	MGARP
obsolete protein targeting to mitochondrion	1	290.6×	0.007	MGARP
anterograde axonal transport	1	290.6×	0.007	MGARP
axon development	1	227.7×	0.008	MGARP
cerebral cortex development	1	102.8×	0.016	MGARP
protein maturation	1	81.8×	0.018	NAA15
cellular response to hypoxia	1	60.6×	0.022	MGARP
protein stabilization	1	33.4×	0.036	NAA15
angiogenesis	1	31.2×	0.036	NAA15
cell differentiation	1	14.6×	0.070	NAA15
positive regulation of DNA-templated transcription	1	14.0×	0.070	NAA15

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
NAA15	0	0
MGARP	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
NAA15	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
NAA15	2.3.1.255, 2.3.1.258	N-terminal amino-acid Nalpha-acetyltransferase NatA, N-terminal methionine Nalpha-acetyltransferase NatE

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	1	NAA15
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	MGARP

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)
NAA15	1	—
MGARP	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.