Intellectual disability, autosomal dominant 11

Summary

Intellectual disability, autosomal dominant 11 (MONDO:0013658) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 16

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual disability, autosomal dominant 11
Mondo ID	MONDO:0013658
OMIM	614257
DOID	DOID:0070041
UMLS	C3280285
MedGen	481915
GARD	0016461
Is cancer (heuristic)	no

Also known as: autosomal dominant intellectual disability 11 · autosomal dominant non-syndromic intellectual disability caused by mutation in EPB41L1 · EPB41L1 autosomal dominant non-syndromic intellectual disability · intellectual developmental disorder, autosomal dominant 11 · intellectual disability, autosomal dominant 11 · intellectual disability, autosomal dominant type 11 · mental retardation, autosomal dominant 11 · mental retardation, autosomal dominant type 11 · MRD11

Data availability: 16 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › intellectual disability, autosomal dominant › intellectual disability, autosomal dominant 11

Related subtypes (28): intellectual disability, autosomal dominant 1, intellectual disability, autosomal dominant 3, intellectual disability, autosomal dominant 4, intellectual disability, autosomal dominant 5, intellectual disability, autosomal dominant 6, intellectual disability, autosomal dominant 2, neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant, intellectual disability, autosomal dominant 9, intellectual disability, autosomal dominant 10, intellectual disability, autosomal dominant 24, intellectual disability, autosomal dominant 38, intellectual disability, autosomal dominant 39, intellectual disability, autosomal dominant 40, intellectual disability, autosomal dominant 42, autosomal dominant non-syndromic intellectual disability, intellectual developmental disorder, autosomal dominant 65, intellectual developmental disorder, autosomal dominant 69, intellectual developmental disorder, autosomal dominant 66, intellectual developmental disorder, autosomal dominant 64, intellectual developmental disorder, autosomal dominant 67, intellectual developmental disorder, autosomal dominant 68, autosomal dominant syndromic intellectual disability, intellectual developmental disorder, autosomal dominant 70, intellectual developmental disorder, autosomal dominant 71, with behavioral abnormalities, intellectual developmental disorder, autosomal dominant 72, intellectual developmental disorder, autosomal dominant 74, intellectual developmental disorder, autosomal dominant 75, intellectual developmental disorder, autosomal dominant 76

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

16 retrieved; paginated sample, class counts are floors:

14 uncertain significance, 1 conflicting classifications of pathogenicity, 1 no classifications from unflagged records

ClinVar	Variant (HGVS)	Gene	Classification	Review
210946	NM_012156.2(EPB41L1):c.1661C>A (p.Ala554Asp)	EPB41L1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1027767	NM_012156.2(EPB41L1):c.1892G>T (p.Ser631Ile)	EPB41L1	Uncertain significance	criteria provided, single submitter
1301595	NM_001258329.1(EPB41L1):c.-15+11729G>A	EPB41L1	Uncertain significance	criteria provided, single submitter
1341873	NM_012156.2(EPB41L1):c.130T>C (p.Ser44Pro)	EPB41L1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1707595	NM_012156.2(EPB41L1):c.1982T>C (p.Leu661Pro)	EPB41L1	Uncertain significance	criteria provided, single submitter
1803745	NM_012156.2(EPB41L1):c.1807C>T (p.Arg603Cys)	EPB41L1	Uncertain significance	criteria provided, single submitter
1805753	NM_001258330.1(EPB41L1):c.17G>A (p.Arg6Lys)	EPB41L1	Uncertain significance	criteria provided, single submitter
30281	NM_012156.2(EPB41L1):c.2560C>T (p.Pro854Ser)	EPB41L1	no classifications from unflagged records	no classifications from unflagged records
3238826	NM_012156.2(EPB41L1):c.1026+4A>G	EPB41L1	Uncertain significance	criteria provided, single submitter
3764749	NM_012156.2(EPB41L1):c.2557C>T (p.His853Tyr)	EPB41L1	Uncertain significance	no assertion criteria provided
3766939	NM_012156.2(EPB41L1):c.858C>A (p.Asp286Glu)	EPB41L1	Uncertain significance	criteria provided, single submitter
3901993	NM_012156.2(EPB41L1):c.2500G>A (p.Glu834Lys)	EPB41L1	Uncertain significance	criteria provided, single submitter
4292855	NM_012156.2(EPB41L1):c.674G>A (p.Gly225Asp)	EPB41L1	Uncertain significance	criteria provided, single submitter
4846788	NM_012156.2(EPB41L1):c.862C>T (p.His288Tyr)	EPB41L1	Uncertain significance	criteria provided, single submitter
561007	NM_012156.2(EPB41L1):c.1844G>C (p.Ser615Thr)	EPB41L1	Uncertain significance	criteria provided, single submitter
931461	NM_012156.2(EPB41L1):c.2207T>C (p.Val736Ala)	EPB41L1	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
EPB41L1	Supportive	Autosomal dominant	autosomal dominant non-syndromic intellectual disability	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
EPB41L1	Orphanet:178469	Autosomal dominant 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
EPB41L1	HGNC:3378	ENSG00000088367	Q9H4G0	Band 4.1-like protein 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
EPB41L1	Band 4.1-like protein 1	May function to confer stability and plasticity to neuronal membrane via multiple interactions, including the spectrin-actin-based cytoskeleton, integral membrane channels and membrane-associated guanylate kinases.

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)
EPB41L1	Other/Unknown	no		FERM_domain, Ez/rad/moesin-like, SAB_dom

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
adrenal tissue	1
substantia nigra pars compacta	1
superior vestibular nucleus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
EPB41L1	278	ubiquitous	marker	superior vestibular nucleus, substantia nigra pars compacta, adrenal tissue

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EPB41L1	1,437

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
EPB41L1	Q9H4G0	62.40

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
Trafficking of AMPA receptors	1	543.8×	0.006	EPB41L1
Sensory processing of sound by outer hair cells of the cochlea	1	203.9×	0.006	EPB41L1
Neurexins and neuroligins	1	196.9×	0.006	EPB41L1
Sensory processing of sound by inner hair cells of the cochlea	1	163.1×	0.006	EPB41L1

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
cortical actin cytoskeleton organization	1	601.9×	0.002	EPB41L1
actomyosin structure organization	1	561.7×	0.002	EPB41L1

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
EPB41L1	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	EPB41L1

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)
EPB41L1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.