Intellectual developmental disorder, autosomal recessive 72

Summary

Intellectual developmental disorder, autosomal recessive 72 (MONDO:0032860) is a disease caused by METTL5 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: METTL5 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 14

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual developmental disorder, autosomal recessive 72
Mondo ID	MONDO:0032860
OMIM	618665
DOID	DOID:0080765
UMLS	C5231452
MedGen	1684805
GARD	0025761
Is cancer (heuristic)	no

Also known as: MRT72

Data availability: 14 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 recessive non-syndromic intellectual disability › intellectual developmental disorder, autosomal recessive 72

Related subtypes (67): intellectual disability, autosomal recessive 1, intellectual disability, autosomal recessive 2, intellectual disability, autosomal recessive 3, intellectual disability, autosomal recessive 12, intellectual disability, autosomal recessive 5, intellectual disability, autosomal recessive 6, intellectual disability, autosomal recessive 7, intellectual disability, autosomal recessive 9, intellectual disability, autosomal recessive 10, intellectual disability, autosomal recessive 11, intellectual disability, autosomal recessive 4, intellectual disability, autosomal recessive 13, intellectual disability, autosomal recessive 14, Rafiq syndrome, intellectual disability, autosomal recessive 16, intellectual disability, autosomal recessive 18, intellectual disability, autosomal recessive 31, intellectual disability, autosomal recessive 29, intellectual disability, autosomal recessive 27, intellectual disability, autosomal recessive 33, intellectual disability, autosomal recessive 30, intellectual disability, autosomal recessive 19, intellectual disability, autosomal recessive 23, intellectual disability, autosomal recessive 24, intellectual disability, autosomal recessive 25, intellectual disability, autosomal recessive 28, intellectual disability, autosomal recessive 34, intellectual disability, autosomal recessive 42, intellectual disability, autosomal recessive 43, intellectual disability, autosomal recessive 44, intellectual disability, autosomal recessive 45, intellectual disability, autosomal recessive 46, intellectual disability, autosomal recessive 47, Al-Raqad syndrome, intellectual disability, autosomal recessive 50, intellectual disability, autosomal recessive 51, intellectual disability, autosomal recessive 52, intellectual disability, autosomal recessive 54, intellectual disability, autosomal recessive 56, intellectual developmental disorder, autosomal recessive 74, intellectual disability, autosomal recessive 57, intellectual disability, autosomal recessive 58, intellectual disability, autosomal recessive 59, pontocerebellar hypoplasia type 1, intellectual disability, autosomal recessive 64, intellectual disability, autosomal recessive 65, intellectual developmental disorder, autosomal recessive 73, intellectual developmental disorder, autosomal recessive 75, with neuropsychiatric features and variant lissencephaly, intellectual disability, autosomal recessive 61, intellectual developmental disorder, autosomal recessive 76, intellectual developmental disorder, autosomal recessive 77, intellectual disability, autosomal recessive 66, intellectual developmental disorder, autosomal recessive 67, intellectual developmental disorder, autosomal recessive 68, intellectual developmental disorder, autosomal recessive 69, intellectual developmental disorder, autosomal recessive 70, intellectual developmental disorder, autosomal recessive 71, glycosylphosphatidylinositol biosynthesis defect 16, intellectual disability, autosomal recessive 60, intellectual disability, autosomal recessive 63, adenosine kinase deficiency, intellectual developmental disorder, autosomal recessive 78, intellectual developmental disorder, autosomal recessive 79, intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly, intellectual developmental disorder, autosomal recessive 81, intellectual developmental disorder, autosomal recessive 82, intellectual developmental disorder, autosomal recessive 83

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

14 retrieved; paginated sample, class counts are floors:

4 pathogenic, 3 uncertain significance, 3 likely pathogenic, 2 conflicting classifications of pathogenicity, 2 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1685946	NM_014168.4(METTL5):c.591+2T>G	METTL5	Pathogenic	criteria provided, single submitter
3064180	NM_014168.4(METTL5):c.224+1G>A	METTL5	Pathogenic	criteria provided, single submitter
3391100	NM_014168.4(METTL5):c.542-1G>T	METTL5	Pathogenic	criteria provided, single submitter
689363	NM_014168.4(METTL5):c.571_572del (p.Lys191fs)	METTL5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
689379	NM_014168.4(METTL5):c.344_345del (p.Arg115fs)	METTL5	Pathogenic	criteria provided, multiple submitters, no conflicts
917596	NM_014168.4(METTL5):c.541+1G>C	METTL5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1804912	NM_014168.4(METTL5):c.406+1_406+2insATACAAATTC	METTL5	Likely pathogenic	criteria provided, single submitter
3065390	NM_014168.4(METTL5):c.225-1G>T	METTL5	Likely pathogenic	criteria provided, single submitter
3393292	NM_014168.4(METTL5):c.196dup (p.Ser66fs)	METTL5	Likely pathogenic	criteria provided, single submitter
1327662	NM_014168.4(METTL5):c.224+5G>A	METTL5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
983495	NM_014168.4(METTL5):c.362A>G (p.Asp121Gly)	METTL5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1236168	NM_014168.4(METTL5):c.406+5G>A	METTL5	Uncertain significance	criteria provided, single submitter
1298336	NM_014168.4(METTL5):c.43C>T (p.Gln15Ter)	METTL5	Uncertain significance	criteria provided, single submitter
3779847	NM_014168.4(METTL5):c.141T>A (p.Tyr47Ter)	METTL5	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
METTL5	Strong	Autosomal recessive	intellectual developmental disorder, autosomal recessive 72	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
METTL5	Orphanet:2512	Autosomal recessive primary microcephaly

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
METTL5	HGNC:25006	ENSG00000138382	Q9NRN9	rRNA N(6)-adenosine-methyltransferase METTL5	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
METTL5	rRNA N(6)-adenosine-methyltransferase METTL5	Catalytic subunit of a heterodimer with TRMT112, which specifically methylates the 6th position of adenine in position 1832 of 18S rRNA.

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)
METTL5	Other/Unknown	no		DNA_methylase_N6_adenine_CS, Small_mtfrase_dom, SAM-dependent_MTases_sf

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
biceps brachii	1
parotid gland	1
skeletal muscle tissue of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
METTL5	292	ubiquitous	marker	parotid gland, skeletal muscle tissue of biceps brachii, biceps brachii

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
METTL5	1,166

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
METTL5	Q9NRN9	3

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
rRNA methylation	1	1404.3×	0.003	METTL5
stem cell differentiation	1	300.9×	0.006	METTL5
positive regulation of translation	1	227.7×	0.006	METTL5
rRNA processing	1	141.6×	0.007	METTL5

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
METTL5	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
METTL5	1	Binding:1

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	METTL5

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)
METTL5	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.