Intellectual disability, autosomal recessive 47

Summary

Intellectual disability, autosomal recessive 47 (MONDO:0014524) is a disease caused by FMN2 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: FMN2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 54

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual disability, autosomal recessive 47
Mondo ID	MONDO:0014524
OMIM	616193
DOID	DOID:0081211
UMLS	C4015444
MedGen	863881
GARD	0022569
Is cancer (heuristic)	no

Also known as: autosomal recessive non-syndromic intellectual disability caused by mutation in FMN2 · FMN2 autosomal recessive non-syndromic intellectual disability · intellectual developmental disorder, autosomal recessive 47 · intellectual disability, autosomal recessive 47 · intellectual disability, autosomal recessive type 47 · mental retardation, autosomal recessive 47 · mental retardation, autosomal recessive type 47 · MRT47

Data availability: 54 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 47

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, 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, 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

54 retrieved; paginated sample, class counts are floors:

22 uncertain significance, 7 conflicting classifications of pathogenicity, 7 benign, 6 likely pathogenic, 5 likely benign, 4 pathogenic, 1 pathogenic/likely pathogenic, 1 not provided, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1028638	NM_020066.5(FMN2):c.1550del (p.Pro517fs)	FMN2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1028639	NM_020066.5(FMN2):c.1618C>T (p.Arg540Ter)	FMN2	Pathogenic	criteria provided, single submitter
162607	NM_020066.5(FMN2):c.1394dup (p.Ala466fs)	FMN2	Pathogenic	no assertion criteria provided
162608	NM_020066.5(FMN2):c.2515del (p.Thr839fs)	FMN2	Pathogenic	no assertion criteria provided
3064678	NM_020066.5(FMN2):c.2233C>T (p.Gln745Ter)	FMN2	Pathogenic	criteria provided, single submitter
1324420	NM_020066.5(FMN2):c.1861C>T (p.Arg621Ter)	FMN2	Likely pathogenic	criteria provided, single submitter
2690601	NM_020066.5(FMN2):c.874C>T (p.Gln292Ter)	FMN2	Likely pathogenic	criteria provided, single submitter
3779672	NM_020066.5(FMN2):c.2840del (p.Pro947fs)	FMN2	Likely pathogenic	criteria provided, single submitter
429780	NM_020066.5(FMN2):c.547A>T (p.Ile183Phe)	FMN2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
4813787	NM_020066.5(FMN2):c.4510G>T (p.Gly1504Ter)	FMN2	Likely pathogenic	criteria provided, single submitter
4813788	NM_020066.5(FMN2):c.4604T>A (p.Leu1535Ter)	FMN2	Likely pathogenic	criteria provided, single submitter
1033516	NM_020066.5(FMN2):c.2297G>A (p.Arg766His)	FMN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
218766	NM_020066.5(FMN2):c.2897T>C (p.Leu966Pro)	FMN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2640193	NM_020066.5(FMN2):c.3442_3507del (p.Arg1148_Pro1169del)	FMN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3064364	NM_020066.5(FMN2):c.2842_2873del (p.Leu948fs)	FMN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
435219	NM_020066.5(FMN2):c.1259A>C (p.Lys420Thr)	FMN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
435231	NM_020066.5(FMN2):c.4619C>T (p.Ser1540Leu)	FMN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
691474	NM_020066.5(FMN2):c.162del (p.Gly55fs)	FMN2	Conflicting classifications of pathogenicity	no assertion criteria provided
1028640	NM_020066.5(FMN2):c.4865T>C (p.Ile1622Thr)	FMN2	Uncertain significance	criteria provided, single submitter
1033513	NM_020066.5(FMN2):c.1244C>T (p.Thr415Ile)	FMN2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1033514	NM_020066.5(FMN2):c.2200C>T (p.Arg734Trp)	FMN2	Uncertain significance	criteria provided, single submitter
1033515	NM_020066.5(FMN2):c.2240C>T (p.Ser747Phe)	FMN2	Uncertain significance	criteria provided, single submitter
1033517	NM_020066.5(FMN2):c.2753C>T (p.Ala918Val)	FMN2	Uncertain significance	criteria provided, single submitter
1033518	NM_020066.5(FMN2):c.3131C>T (p.Pro1044Leu)	FMN2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1033928	NM_020066.5(FMN2):c.575A>T (p.Gln192Leu)	FMN2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1033929	NM_020066.5(FMN2):c.629A>G (p.Gln210Arg)	FMN2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1805480	NM_020066.5(FMN2):c.1748A>C (p.Asn583Thr)	FMN2	Uncertain significance	criteria provided, single submitter
2441527	NM_020066.5(FMN2):c.2806C>G (p.Pro936Ala)	FMN2	Uncertain significance	criteria provided, single submitter
2441528	NM_020066.5(FMN2):c.4468G>T (p.Val1490Phe)	FMN2	Uncertain significance	criteria provided, single submitter
2441529	NM_020066.5(FMN2):c.1054G>T (p.Asp352Tyr)	FMN2	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
FMN2	Strong	Autosomal recessive	intellectual disability, autosomal recessive 47	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FMN2	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
FMN2	HGNC:14074	ENSG00000155816	Q9NZ56	Formin-2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FMN2	Formin-2	Actin-binding protein that is involved in actin cytoskeleton assembly and reorganization.

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)
FMN2	Other/Unknown	no		DEP_dom, FH2_Formin, FH2_Formin_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
Brodmann (1909) area 9	1
cortical plate	1
prefrontal cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FMN2	187	broad	marker	cortical plate, prefrontal cortex, Brodmann (1909) area 9

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FMN2	1,995

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FMN2	Q9NZ56	2

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
homologous chromosome movement towards spindle pole in meiosis I anaphase	1	16852.0×	9e-04	FMN2
formin-nucleated actin cable assembly	1	5617.3×	0.001	FMN2
establishment of meiotic spindle localization	1	4213.0×	0.001	FMN2
polar body extrusion after meiotic divisions	1	3370.4×	0.001	FMN2
intracellular transport	1	1532.0×	0.002	FMN2
oogenesis	1	383.0×	0.006	FMN2
negative regulation of protein catabolic process	1	366.4×	0.006	FMN2
positive regulation of double-strand break repair	1	343.9×	0.006	FMN2
cellular response to hypoxia	1	121.2×	0.015	FMN2
vesicle-mediated transport	1	96.3×	0.017	FMN2
actin cytoskeleton organization	1	79.1×	0.018	FMN2
cell migration	1	61.5×	0.022	FMN2
DNA damage response	1	53.5×	0.023	FMN2
protein transport	1	43.9×	0.026	FMN2
intracellular signal transduction	1	38.1×	0.028	FMN2
negative regulation of apoptotic process	1	34.8×	0.029	FMN2

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FMN2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	FMN2

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)
FMN2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.