intellectual disability, X-linked 103

Summary

intellectual disability, X-linked 103 (MONDO:0010508) is a disease caused by KLHL15 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: KLHL15 (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 disability, X-linked 103
Mondo ID	MONDO:0010508
OMIM	300982
DOID	DOID:0112020
UMLS	C4310818
MedGen	934785
GARD	0024734
Is cancer (heuristic)	no

Also known as: intellectual developmental disorder, X-linked 103, X-linked recessive · intellectual disability, X-linked 103 · intellectual disability, X-linked type 103 · KLHL15 non-syndromic X-linked intellectual disability · mental retardation, X-linked 103 · mental retardation, X-linked type 103 · MRX103 · non-syndromic X-linked intellectual disability caused by mutation in KLHL15

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 › non-syndromic X-linked intellectual disability › intellectual disability, X-linked 103

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 104, 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

14 retrieved; paginated sample, class counts are floors:

12 uncertain significance, 2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
254657	NC_000023.10:g.24020361_24042839del	KLHL15	Pathogenic	no assertion criteria provided
254658	NM_030624.3(KLHL15):c.1179del (p.Tyr394fs)	KLHL15	Pathogenic	no assertion criteria provided
1028386	NM_030624.3(KLHL15):c.710A>T (p.Lys237Met)	KLHL15	Uncertain significance	criteria provided, single submitter
1028387	NM_030624.3(KLHL15):c.820C>T (p.Arg274Cys)	KLHL15	Uncertain significance	criteria provided, single submitter
1334900	NM_030624.3(KLHL15):c.26G>A (p.Cys9Tyr)	KLHL15	Uncertain significance	no assertion criteria provided
1801338	NM_030624.3(KLHL15):c.91C>T (p.Leu31Phe)	KLHL15	Uncertain significance	criteria provided, single submitter
1992386	NM_030624.3(KLHL15):c.523C>G (p.Leu175Val)	KLHL15	Uncertain significance	criteria provided, single submitter
2441635	NM_030624.3(KLHL15):c.1406A>G (p.Glu469Gly)	KLHL15	Uncertain significance	criteria provided, single submitter
3066102	NM_030624.3(KLHL15):c.1493_1494del (p.Val498fs)	KLHL15	Uncertain significance	criteria provided, single submitter
3362658	NM_030624.3(KLHL15):c.1543T>C (p.Tyr515His)	KLHL15	Uncertain significance	criteria provided, single submitter
3382908	NM_030624.3(KLHL15):c.1000G>A (p.Gly334Arg)	KLHL15	Uncertain significance	criteria provided, single submitter
4279780	NM_030624.3(KLHL15):c.1693C>G (p.Pro565Ala)	KLHL15	Uncertain significance	criteria provided, single submitter
828195	NM_030624.3(KLHL15):c.391G>A (p.Glu131Lys)	KLHL15	Uncertain significance	criteria provided, single submitter
976080	NM_030624.3(KLHL15):c.217C>G (p.His73Asp)	KLHL15	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 0 · 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
KLHL15	Strong	X-linked	intellectual disability, X-linked 103	4

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
KLHL15	HGNC:29347	ENSG00000174010	Q96M94	Kelch-like protein 15	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KLHL15	Kelch-like protein 15	Substrate-specific adapter for CUL3 E3 ubiquitin-protein ligase complex.

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)
KLHL15	Other/Unknown	no		BTB/POZ_dom, Kelch_1, SKP1/BTB/POZ_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
adrenal tissue	1
endothelial cell	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KLHL15	235		marker	adrenal tissue, secondary oocyte, endothelial cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KLHL15	1,164

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
KLHL15	Q96M94	91.35

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
nuclear protein quality control by the ubiquitin-proteasome system	1	4213.0×	9e-04	KLHL15
negative regulation of double-strand break repair via homologous recombination	1	624.1×	0.003	KLHL15
ubiquitin-dependent protein catabolic process	1	74.2×	0.018	KLHL15
protein ubiquitination	1	41.4×	0.024	KLHL15

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
KLHL15	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	KLHL15

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)
KLHL15	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.