intellectual disability, X-linked 100

Summary

intellectual disability, X-linked 100 (MONDO:0010488) is a disease caused by KIF4A (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: KIF4A (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 30

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual disability, X-linked 100
Mondo ID	MONDO:0010488
OMIM	300923
DOID	DOID:0112040
UMLS	C3890167
MedGen	855516
GARD	0024729
Is cancer (heuristic)	no

Also known as: intellectual developmental disorder, X-linked 100, X-linked recessive · intellectual disability, X-linked 100 · intellectual disability, X-linked type 100 · KIF4A non-syndromic X-linked intellectual disability · mental retardation, X-linked 100 · mental retardation, X-linked type 100 · MRX100 · non-syndromic X-linked intellectual disability caused by mutation in KIF4A

Data availability: 30 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 100

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 101, intellectual disability, X-linked 102, intellectual disability, X-linked 61, intellectual disability, X-linked 103, 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

30 retrieved; paginated sample, class counts are floors:

18 uncertain significance, 5 benign, 4 pathogenic, 2 likely pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
140729	NM_012310.5(KIF4A):c.1489-8_1490delinsATAATGAAAG	KIF4A	Pathogenic	no assertion criteria provided
2575210	NM_012310.5(KIF4A):c.1674+1G>A	KIF4A	Pathogenic	no assertion criteria provided
2575211	NM_012310.5(KIF4A):c.1616T>C (p.Leu539Pro)	KIF4A	Pathogenic	no assertion criteria provided
2575212	NM_012310.5(KIF4A):c.763G>A (p.Asp255Asn)	KIF4A	Pathogenic	no assertion criteria provided
3770236	NM_012310.5(KIF4A):c.1778+21T>C	KIF4A	Likely pathogenic	criteria provided, single submitter
632604	NM_012310.5(KIF4A):c.794G>T (p.Arg265Leu)	KIF4A	Likely pathogenic	no assertion criteria provided
1029186	NM_012310.5(KIF4A):c.1123G>A (p.Gly375Arg)	KIF4A	Uncertain significance	criteria provided, single submitter
1030246	NM_012310.5(KIF4A):c.2113G>A (p.Glu705Lys)	KIF4A	Uncertain significance	criteria provided, multiple submitters, no conflicts
1030247	NM_012310.5(KIF4A):c.2734A>G (p.Ile912Val)	KIF4A	Uncertain significance	criteria provided, single submitter
1341888	NM_012310.5(KIF4A):c.1072-8T>G	KIF4A	Uncertain significance	criteria provided, single submitter
1684508	NM_012310.5(KIF4A):c.1015A>G (p.Lys339Glu)	KIF4A	Uncertain significance	criteria provided, single submitter
1703169	NM_012310.5(KIF4A):c.1939C>T (p.Arg647Trp)	KIF4A	Uncertain significance	criteria provided, single submitter
1806559	NM_012310.5(KIF4A):c.911A>G (p.Asn304Ser)	KIF4A	Uncertain significance	criteria provided, multiple submitters, no conflicts
2433152	NM_012310.5(KIF4A):c.1921C>T (p.Arg641Trp)	KIF4A	Uncertain significance	criteria provided, multiple submitters, no conflicts
2442138	NM_012310.5(KIF4A):c.2111C>T (p.Thr704Met)	KIF4A	Uncertain significance	criteria provided, single submitter
3056938	NM_012310.5(KIF4A):c.1955G>A (p.Arg652His)	KIF4A	Uncertain significance	criteria provided, multiple submitters, no conflicts
3242151	NM_012310.5(KIF4A):c.2243G>A (p.Gly748Glu)	KIF4A	Uncertain significance	criteria provided, single submitter
3254800	NM_012310.5(KIF4A):c.2365G>A (p.Glu789Lys)	KIF4A	Uncertain significance	criteria provided, single submitter
3891485	NM_012310.5(KIF4A):c.3082T>C (p.Ser1028Pro)	KIF4A	Uncertain significance	criteria provided, single submitter
4279781	NM_012310.5(KIF4A):c.2560T>G (p.Trp854Gly)	KIF4A	Uncertain significance	criteria provided, single submitter
4294383	NM_012310.5(KIF4A):c.1210C>T (p.Arg404Cys)	KIF4A	Uncertain significance	criteria provided, single submitter
4531345	NM_012310.5(KIF4A):c.47G>C (p.Cys16Ser)	KIF4A	Uncertain significance	criteria provided, single submitter
560295	NM_012310.5(KIF4A):c.1745T>A (p.Leu582His)	KIF4A	Uncertain significance	criteria provided, single submitter
804023	NM_012310.5(KIF4A):c.1525G>A (p.Asp509Asn)	KIF4A	Uncertain significance	criteria provided, multiple submitters, no conflicts
1300073	NM_012310.5(KIF4A):c.27C>T (p.Pro9=)	KIF4A	Benign	criteria provided, multiple submitters, no conflicts
1300074	NM_012310.5(KIF4A):c.969A>G (p.Thr323=)	KIF4A	Benign	criteria provided, multiple submitters, no conflicts
1300075	NM_012310.5(KIF4A):c.987T>C (p.Tyr329=)	KIF4A	Benign	criteria provided, multiple submitters, no conflicts
1300076	NM_012310.5(KIF4A):c.3073-4C>T	KIF4A	Benign	criteria provided, multiple submitters, no conflicts
1300077	NM_012310.5(KIF4A):c.3372+11G>T	KIF4A	Benign	criteria provided, multiple submitters, no conflicts
790242	NM_012310.5(KIF4A):c.2059C>T (p.Leu687=)	KIF4A	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · 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
KIF4A	Strong	X-linked	intellectual disability, X-linked 100	6

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
KIF4A	HGNC:13339	ENSG00000090889	O95239	Chromosome-associated kinesin KIF4A	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KIF4A	Chromosome-associated kinesin KIF4A	Iron-sulfur (Fe-S) cluster binding motor protein that has a role in chromosome segregation during mitosis.

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)
KIF4A	Other/Unknown	no		Kinesin_motor_dom, Kinesin_motor_CS, P-loop_NTPase

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
oocyte	1
secondary oocyte	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KIF4A	179	broad	marker	oocyte, secondary oocyte, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KIF4A	1,982

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KIF4A	O95239	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 16. 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
Recycling pathway of L1	1	223.9×	0.025	KIF4A
Kinesins	1	178.4×	0.025	KIF4A
Golgi-to-ER retrograde transport	1	132.8×	0.025	KIF4A
L1CAM interactions	1	120.2×	0.025	KIF4A
COPI-dependent Golgi-to-ER retrograde traffic	1	110.9×	0.025	KIF4A
Intra-Golgi and retrograde Golgi-to-ER traffic	1	104.8×	0.025	KIF4A
MHC class II antigen presentation	1	89.2×	0.026	KIF4A
Factors involved in megakaryocyte development and platelet production	1	66.4×	0.030	KIF4A
Axon guidance	1	45.1×	0.035	KIF4A
Nervous system development	1	42.9×	0.035	KIF4A
Membrane Trafficking	1	37.1×	0.035	KIF4A
Hemostasis	1	36.0×	0.035	KIF4A
Vesicle-mediated transport	1	34.8×	0.035	KIF4A
Adaptive Immune System	1	29.8×	0.038	KIF4A
Developmental Biology	1	14.5×	0.074	KIF4A
Immune System	1	13.0×	0.077	KIF4A

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
spindle elongation	1	5617.3×	9e-04	KIF4A
organelle organization	1	3370.4×	9e-04	KIF4A
mitotic spindle midzone assembly	1	1532.0×	0.001	KIF4A
anterograde axonal transport	1	581.1×	0.003	KIF4A
mitotic spindle organization	1	271.8×	0.004	KIF4A
mitotic cytokinesis	1	259.3×	0.004	KIF4A

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
KIF4A	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
KIF4A	20	Binding:20

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	KIF4A

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)
KIF4A	20	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.