intellectual disability, X-linked 104

Summary

intellectual disability, X-linked 104 (MONDO:0010509) is a disease caused by FRMPD4 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: FRMPD4 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 82

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual disability, X-linked 104
Mondo ID	MONDO:0010509
OMIM	300983
DOID	DOID:0112018
UMLS	C4310817
MedGen	934784
GARD	0022696
Is cancer (heuristic)	no

Also known as: FRMPD4 non-syndromic X-linked intellectual disability · intellectual developmental disorder, X-linked 104 · intellectual disability, X-linked 104 · intellectual disability, X-linked type 104 · mental retardation, X-linked 104 · mental retardation, X-linked type 104 · MRX104 · non-syndromic X-linked intellectual disability caused by mutation in FRMPD4

Data availability: 82 ClinVar variants · 5 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 › non-syndromic X-linked intellectual disability › intellectual disability, X-linked 104

Related subtypes (51): intellectual disability, X-linked 23, intellectual disability, X-linked 20, intellectual disability, X-linked 14, intellectual disability, X-linked 50, intellectual disability, X-linked 21, intellectual disability, X-linked 58, intellectual disability, X-linked 72, intellectual disability, X-linked 53, intellectual disability, X-linked 73, intellectual disability, X-linked 42, intellectual disability, X-linked 63, intellectual disability, X-linked, with or without seizures, ARX-related, intellectual disability, X-linked 2, intellectual disability, X-linked 81, intellectual disability, X-linked 46, intellectual disability, X-linked 77, intellectual disability, X-linked 45, intellectual disability, X-linked 84, intellectual disability, X-linked 82, intellectual disability, X-linked 30, intellectual disability, X-linked 91, intellectual disability, X-linked 93, chromosome Xp11.22 duplication syndrome, intellectual disability, X-linked 95, intellectual disability, X-linked 96, intellectual disability, X-linked 97, intellectual disability, X-linked 19, intellectual disability, X-linked 89, intellectual disability, X-linked 41, intellectual disability, X-linked 90, intellectual disability, X-linked 92, intellectual disability, X-linked 88, intellectual disability, X-linked 99, intellectual disability, X-linked 100, intellectual disability, X-linked 101, intellectual disability, X-linked 102, intellectual disability, X-linked 61, intellectual disability, X-linked 103, intellectual disability, X-linked 105, intellectual disability, X-linked 1, methylmalonic acidemia with homocystinuria, type cblX, FRAXE intellectual disability, intellectual disability, X-linked 9, intellectual developmental disorder, X-linked 108, intellectual disability, X-linked 106, intellectual disability, X-linked 107, intellectual developmental disorder, X-linked 110, intellectual developmental disorder, X-linked 111, intellectual developmental disorder, X-linked 112, intellectual developmental disorder, X-linked 113, intellectual developmental disorder, X-linked 114

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

82 retrieved; paginated sample, class counts are floors:

57 uncertain significance, 11 likely pathogenic, 5 conflicting classifications of pathogenicity, 5 pathogenic, 3 benign/likely benign, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
254682	NM_001368397.1(FRMPD4):c.1851del (p.Cys618fs)	FRMPD4	Pathogenic	no assertion criteria provided
2580164	NM_001368397.1(FRMPD4):c.1411G>T (p.Glu471Ter)	FRMPD4	Pathogenic	criteria provided, single submitter
3895974	NC_000023.10:g.(12157132_12516798)_(12704324_12708313)del	FRMPD4	Pathogenic	criteria provided, single submitter
599279	NC_000023.10:g.12515801_12581900del	FRMPD4	Pathogenic	no assertion criteria provided
599280	NM_001368397.1(FRMPD4):c.856C>T (p.Arg286Ter)	FRMPD4	Pathogenic	criteria provided, single submitter
1320187	NM_001368397.1(FRMPD4):c.1151C>A (p.Ser384Ter)	FRMPD4	Likely pathogenic	criteria provided, single submitter
1709267	NM_001368397.1(FRMPD4):c.561del (p.Asn187fs)	FRMPD4	Likely pathogenic	criteria provided, single submitter
2444249	NM_001368397.1(FRMPD4):c.3258del (p.Arg1087fs)	FRMPD4	Likely pathogenic	criteria provided, single submitter
2505507	NM_001368397.1(FRMPD4):c.3024dup (p.Asp1009Ter)	FRMPD4	Likely pathogenic	criteria provided, single submitter
254683	NM_001368397.1(FRMPD4):c.1657T>C (p.Cys553Arg)	FRMPD4	Likely pathogenic	criteria provided, single submitter
3062128	NM_001368397.1(FRMPD4):c.1071-1G>A	FRMPD4	Likely pathogenic	criteria provided, single submitter
3235747	NM_001368397.1(FRMPD4):c.2800del (p.Arg934fs)	FRMPD4	Likely pathogenic	criteria provided, single submitter
3236780	NM_001368397.1(FRMPD4):c.1335T>A (p.Tyr445Ter)	FRMPD4	Likely pathogenic	criteria provided, single submitter
3338501	NM_001368397.1(FRMPD4):c.1927C>T (p.Gln643Ter)	FRMPD4	Likely pathogenic	criteria provided, single submitter
3777257	NM_001368397.1(FRMPD4):c.3144dup (p.Gln1049fs)	FRMPD4	Likely pathogenic	criteria provided, single submitter
976150	NM_001368397.1(FRMPD4):c.1298del (p.Lys433fs)	FRMPD4	Likely pathogenic	criteria provided, single submitter
1342428	NM_001368397.1(FRMPD4):c.2917G>C (p.Ala973Pro)	FRMPD4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3064463	NM_001368397.1(FRMPD4):c.3710C>T (p.Ser1237Leu)	FRMPD4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3892610	NM_001368397.1(FRMPD4):c.4858G>A (p.Val1620Ile)	FRMPD4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
752101	NM_001368397.1(FRMPD4):c.2003C>A (p.Thr668Asn)	FRMPD4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
931648	NM_001368397.1(FRMPD4):c.1925C>T (p.Ala642Val)	FRMPD4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1031296	NM_001368397.1(FRMPD4):c.1472C>G (p.Pro491Arg)	FRMPD4	Uncertain significance	criteria provided, single submitter
1031297	NM_001368397.1(FRMPD4):c.1937C>T (p.Pro646Leu)	FRMPD4	Uncertain significance	criteria provided, single submitter
1031298	NM_001368397.1(FRMPD4):c.3281A>T (p.Tyr1094Phe)	FRMPD4	Uncertain significance	criteria provided, multiple submitters, no conflicts
1031299	NM_001368397.1(FRMPD4):c.422+9C>T	FRMPD4	Uncertain significance	criteria provided, single submitter
1032633	NM_001368397.1(FRMPD4):c.2183C>T (p.Ala728Val)	FRMPD4	Uncertain significance	criteria provided, multiple submitters, no conflicts
1032634	NM_001368397.1(FRMPD4):c.3040C>A (p.Leu1014Met)	FRMPD4	Uncertain significance	criteria provided, multiple submitters, no conflicts
1032635	NM_001368397.1(FRMPD4):c.3312A>G (p.Lys1104=)	FRMPD4	Uncertain significance	criteria provided, single submitter
1098565	NM_001368397.1(FRMPD4):c.2425G>A (p.Ala809Thr)	FRMPD4	Uncertain significance	criteria provided, single submitter
1299614	NM_001368397.1(FRMPD4):c.476A>G (p.Lys159Arg)	FRMPD4	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · 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
FRMPD4	Strong	X-linked	intellectual disability, X-linked 104	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FRMPD4	Orphanet:777	X-linked 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
FRMPD4	HGNC:29007	ENSG00000169933	Q14CM0	FERM and PDZ domain-containing protein 4	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FRMPD4	FERM and PDZ domain-containing protein 4	Positive regulator of dendritic spine morphogenesis and density.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FRMPD4	Scaffold/PPI	no		FERM_domain, WW_dom, PDZ

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 23	1
endothelial cell	1
middle temporal gyrus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FRMPD4	117	broad	marker	middle temporal gyrus, endothelial cell, Brodmann (1909) area 23

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FRMPD4	2,222

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FRMPD4	Q14CM0	5

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 synapse structural plasticity	1	5617.3×	2e-04	FRMPD4

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
FRMPD4	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	FRMPD4

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)
FRMPD4	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.