Intellectual disability, autosomal recessive 57

Summary

Intellectual disability, autosomal recessive 57 (MONDO:0014962) is a disease caused by MBOAT7 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: MBOAT7 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 43

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual disability, autosomal recessive 57
Mondo ID	MONDO:0014962
OMIM	617188
DOID	DOID:0081219
UMLS	C4310673
MedGen	934640
GARD	0022575
Is cancer (heuristic)	no

Also known as: autosomal recessive non-syndromic intellectual disability caused by mutation in MBOAT7 · intellectual developmental disorder, autosomal recessive 57 · intellectual disability, autosomal recessive 57 · intellectual disability, autosomal recessive type 57 · MBOAT7 autosomal recessive non-syndromic intellectual disability · mental retardation, autosomal recessive 57 · mental retardation, autosomal recessive type 57 · MRT57

Data availability: 43 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 disability, autosomal recessive 57

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 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, intellectual developmental disorder, autosomal recessive 72, 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

43 retrieved; paginated sample, class counts are floors:

23 uncertain significance, 8 likely pathogenic, 8 pathogenic, 2 conflicting classifications of pathogenicity, 1 pathogenic/likely pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1120120	NM_024298.5(MBOAT7):c.680_690dup (p.Leu231fs)	MBOAT7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
268112	NM_024298.5(MBOAT7):c.758_778del (p.Glu253_Ala259del)	MBOAT7	Pathogenic	criteria provided, multiple submitters, no conflicts
268113	NM_024298.5(MBOAT7):c.423del (p.Leu142fs)	MBOAT7	Pathogenic	criteria provided, multiple submitters, no conflicts
268114	NM_024298.5(MBOAT7):c.854+1G>C	MBOAT7	Pathogenic	no assertion criteria provided
268115	NM_024298.5(MBOAT7):c.820_826del (p.Gly274fs)	MBOAT7	Pathogenic	no assertion criteria provided
3359225	NM_024298.5(MBOAT7):c.724C>T (p.Arg242Cys)	MBOAT7	Pathogenic	no assertion criteria provided
3775550	NM_024298.5(MBOAT7):c.-3-2del	MBOAT7	Pathogenic	criteria provided, single submitter
812079	NM_024298.5(MBOAT7):c.1135del (p.Leu379fs)	MBOAT7	Pathogenic	criteria provided, single submitter
812082	NM_024298.5(MBOAT7):c.1062C>A (p.Tyr354Ter)	MBOAT7	Pathogenic	criteria provided, multiple submitters, no conflicts
1324698	NM_024298.5(MBOAT7):c.199C>T (p.Gln67Ter)	MBOAT7	Likely pathogenic	criteria provided, single submitter
1328055	NM_024298.5(MBOAT7):c.757G>A (p.Glu253Lys)	MBOAT7	Likely pathogenic	no assertion criteria provided
1333419	NM_024298.5(MBOAT7):c.811dup (p.Arg271fs)	MBOAT7	Likely pathogenic	criteria provided, single submitter
2583119	NM_024298.5(MBOAT7):c.1290C>A (p.Tyr430Ter)	MBOAT7	Likely pathogenic	criteria provided, single submitter
268111	NM_024298.5(MBOAT7):c.126_145del (p.Leu43fs)	MBOAT7	Likely pathogenic	criteria provided, single submitter
3338607	NM_024298.5(MBOAT7):c.493+1G>T	MBOAT7	Likely pathogenic	criteria provided, single submitter
3359224	NM_024298.5(MBOAT7):c.1148_1166dup (p.Gly390fs)	MBOAT7	Likely pathogenic	no assertion criteria provided
4293725	NM_024298.5(MBOAT7):c.956_971del (p.Tyr319fs)	MBOAT7	Likely pathogenic	criteria provided, single submitter
1013401	NM_024298.5(MBOAT7):c.653G>C (p.Arg218Pro)	MBOAT7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1285426	NM_024298.5(MBOAT7):c.259C>T (p.Arg87Ter)	MBOAT7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1028295	NM_024298.5(MBOAT7):c.1031+17A>G	MBOAT7	Uncertain significance	criteria provided, single submitter
1028296	NM_024298.5(MBOAT7):c.1031G>A (p.Arg344Gln)	MBOAT7	Uncertain significance	criteria provided, multiple submitters, no conflicts
1028297	NM_024298.5(MBOAT7):c.1196A>C (p.His399Pro)	MBOAT7	Uncertain significance	criteria provided, multiple submitters, no conflicts
1028298	NM_024298.5(MBOAT7):c.849C>G (p.Pro283=)	MBOAT7	Uncertain significance	criteria provided, single submitter
1028299	NM_024298.5(MBOAT7):c.968C>T (p.Thr323Met)	MBOAT7	Uncertain significance	criteria provided, single submitter
1033618	NM_024298.5(MBOAT7):c.1229T>C (p.Met410Thr)	MBOAT7	Uncertain significance	criteria provided, multiple submitters, no conflicts
1033619	NM_024298.5(MBOAT7):c.1366A>G (p.Lys456Glu)	MBOAT7	Uncertain significance	criteria provided, multiple submitters, no conflicts
1033621	NM_024298.5(MBOAT7):c.847C>G (p.Pro283Ala)	MBOAT7	Uncertain significance	criteria provided, single submitter
1033622	NM_024298.5(MBOAT7):c.854+8G>A	MBOAT7	Uncertain significance	criteria provided, single submitter
1033623	NM_024298.5(MBOAT7):c.937G>T (p.Val313Leu)	MBOAT7	Uncertain significance	criteria provided, single submitter
1184283	NM_024298.5(MBOAT7):c.763G>A (p.Gly255Ser)	MBOAT7	Uncertain significance	criteria provided, multiple submitters, no conflicts

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
MBOAT7	Strong	Autosomal recessive	intellectual disability, autosomal recessive 57	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MBOAT7	Orphanet:88616	Autosomal recessive non-syndromic intellectual disability

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
MBOAT7	HGNC:15505	ENSG00000125505	Q96N66	Membrane-bound acylglycerophosphatidylinositol O-acyltransferase MBOAT7	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MBOAT7	Membrane-bound acylglycerophosphatidylinositol O-acyltransferase MBOAT7	Acyltransferase which catalyzes the transfer of an acyl group from an acyl-CoA to a lysophosphatidylinositol (1-acylglycerophosphatidylinositol or LPI) leading to the production of a phosphatidylinositol (1,2-diacyl-sn-glycero-3-phosphoino…

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)
MBOAT7	Enzyme (other)	yes	2.3.1.B46	MBOAT_fam, LPLAT_7/PORCN-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
blood	1
right adrenal gland	1
right adrenal gland cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MBOAT7	141	ubiquitous	marker	blood, right adrenal gland, right adrenal gland cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MBOAT7	1,217

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MBOAT7	Q96N66	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. 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
Acyl chain remodelling of PI	1	671.8×	0.007	MBOAT7
Glycerophospholipid biosynthesis	1	335.9×	0.007	MBOAT7
Phospholipid metabolism	1	200.3×	0.008	MBOAT7
Metabolism of lipids	1	31.6×	0.040	MBOAT7
Metabolism	1	11.6×	0.086	MBOAT7

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
phosphatidylinositol acyl-chain remodeling	1	2808.7×	0.001	MBOAT7
regulation of triglyceride metabolic process	1	2106.5×	0.001	MBOAT7
lipid modification	1	1872.4×	0.001	MBOAT7
layer formation in cerebral cortex	1	1123.5×	0.001	MBOAT7
phosphatidylcholine acyl-chain remodeling	1	1123.5×	0.001	MBOAT7
ventricular system development	1	842.6×	0.001	MBOAT7
phosphatidylinositol biosynthetic process	1	366.4×	0.003	MBOAT7

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
MBOAT7	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
MBOAT7	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
MBOAT7	2.3.1.B46

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	MBOAT7
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)
MBOAT7	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.