Intellectual disability, autosomal recessive 65

Summary

Intellectual disability, autosomal recessive 65 (MONDO:0020850) is a disease caused by KDM5B (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: KDM5B (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 91

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual disability, autosomal recessive 65
Mondo ID	MONDO:0020850
OMIM	618109
DOID	DOID:0081226
UMLS	C4748219
MedGen	1648401
GARD	0022578
Is cancer (heuristic)	no

Also known as: intellectual disability, autosomal recessive 65 · mental retardation, autosomal recessive 65 · MRT65

Data availability: 91 ClinVar variants · 2 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 65

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, intellectual disability, autosomal recessive 47, 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 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

91 retrieved; paginated sample, class counts are floors:

33 uncertain significance, 27 likely pathogenic, 12 pathogenic, 7 conflicting classifications of pathogenicity, 5 benign, 5 pathogenic/likely pathogenic, 2 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
1699572	NM_006618.5(KDM5B):c.1321C>T (p.Arg441Ter)	KDM5B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1803645	NM_006618.5(KDM5B):c.1708C>T (p.Arg570Ter)	KDM5B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1804411	NM_006618.5(KDM5B):c.3139C>T (p.Arg1047Ter)	KDM5B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1992395	NM_006618.5(KDM5B):c.453_454del (p.Trp152fs)	KDM5B	Pathogenic	criteria provided, single submitter
2500707	NM_006618.5(KDM5B):c.2117del (p.Cys706fs)	KDM5B	Pathogenic	criteria provided, single submitter
2576173	NM_006618.5(KDM5B):c.2265C>G (p.Tyr755Ter)	KDM5B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2584391	NM_006618.5(KDM5B):c.2830dup (p.Leu944fs)	KDM5B	Pathogenic	criteria provided, single submitter
3366608	NM_006618.5(KDM5B):c.954_957del (p.Asn319fs)	KDM5B	Pathogenic	criteria provided, single submitter
3376907	NM_006618.5(KDM5B):c.326_327del (p.Lys109fs)	KDM5B	Pathogenic	criteria provided, single submitter
4688410	NM_006618.5(KDM5B):c.4198C>T (p.Arg1400Ter)	KDM5B	Pathogenic	criteria provided, single submitter
4813831	NM_006618.5(KDM5B):c.4422T>G (p.Tyr1474Ter)	KDM5B	Pathogenic	criteria provided, single submitter
4845460	NM_006618.5(KDM5B):c.394C>T (p.Gln132Ter)	KDM5B	Pathogenic	criteria provided, single submitter
560601	c.2475-2A-G	KDM5B	Pathogenic	no assertion criteria provided
560602	NM_006618.5(KDM5B):c.787C>T (p.Pro263Ser)	KDM5B	Pathogenic	no assertion criteria provided
560603	NM_006618.5(KDM5B):c.3799del (p.Gln1267fs)	KDM5B	Pathogenic	no assertion criteria provided
560604	NM_006618.5(KDM5B):c.622dup (p.Tyr208fs)	KDM5B	Pathogenic	no assertion criteria provided
626239	NM_006618.5(KDM5B):c.895C>T (p.Arg299Ter)	KDM5B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1184541	NM_006618.5(KDM5B):c.2251C>T (p.Arg751Ter)	KDM5B	Likely pathogenic	criteria provided, single submitter
1192275	NM_006618.5(KDM5B):c.2945+1G>A	KDM5B	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2440966	NM_006618.5(KDM5B):c.418G>T (p.Glu140Ter)	KDM5B	Likely pathogenic	criteria provided, single submitter
2440970	NM_006618.5(KDM5B):c.3224del (p.Asn1075fs)	KDM5B	Likely pathogenic	criteria provided, single submitter
2444377	NM_006618.5(KDM5B):c.3635del (p.Gly1212fs)	KDM5B	Likely pathogenic	criteria provided, single submitter
2500805	NM_006618.5(KDM5B):c.998_1004del (p.Ser333fs)	KDM5B	Likely pathogenic	criteria provided, single submitter
2630485	NM_006618.5(KDM5B):c.3640C>T (p.Arg1214Ter)	KDM5B	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2687877	NM_006618.5(KDM5B):c.3309_3312del (p.Arg1103fs)	KDM5B	Likely pathogenic	criteria provided, single submitter
3065927	NM_006618.5(KDM5B):c.2589+1G>A	KDM5B	Likely pathogenic	criteria provided, single submitter
3236595	NM_006618.5(KDM5B):c.4132C>T (p.Gln1378Ter)	KDM5B	Likely pathogenic	criteria provided, single submitter
3238651	NM_006618.5(KDM5B):c.1520C>G (p.Ser507Ter)	KDM5B	Likely pathogenic	no assertion criteria provided
3393440	NM_006618.5(KDM5B):c.1701+1G>T	KDM5B	Likely pathogenic	criteria provided, single submitter
3775809	NM_006618.5(KDM5B):c.1162dup (p.Ala388fs)	KDM5B	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 2 · 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
KDM5B	Strong	Autosomal recessive	intellectual disability, autosomal recessive 65	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KDM5B	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
KDM5B	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
KDM5B	HGNC:18039	ENSG00000117139	Q9UGL1	Lysine-specific demethylase 5B	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KDM5B	Lysine-specific demethylase 5B	Histone demethylase that demethylates ‘Lys-4’ of histone H3, thereby playing a central role in histone code.

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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KDM5B	Transcription factor	no	1.14.11.67	ARID_dom, Znf_PHD, JmjC_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
left testis	1
male germ cell	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KDM5B	272	ubiquitous	marker	sperm, male germ cell, left testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KDM5B	3,722

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KDM5B	Q9UGL1	56

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. 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
TFAP2 (AP-2) family regulates transcription of cell cycle factors	1	2284.0×	0.005	KDM5B
Maternal to zygotic transition (MZT)	1	713.8×	0.006	KDM5B
Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors	1	634.4×	0.006	KDM5B
HDMs demethylate histones	1	228.4×	0.012	KDM5B
Chromatin modifications during the maternal to zygotic transition (MZT)	1	163.1×	0.013	KDM5B
Chromatin organization	1	81.6×	0.022	KDM5B
Chromatin modifying enzymes	1	72.3×	0.022	KDM5B
RNA Polymerase II Transcription	1	22.5×	0.061	KDM5B
Gene expression (Transcription)	1	17.8×	0.068	KDM5B
Generic Transcription Pathway	1	15.1×	0.069	KDM5B
Developmental Biology	1	14.5×	0.069	KDM5B

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
regulation of estradiol secretion	1	16852.0×	9e-04	KDM5B
mammary duct terminal end bud growth	1	5617.3×	0.001	KDM5B
positive regulation of mammary gland epithelial cell proliferation	1	2808.7×	0.001	KDM5B
response to fungicide	1	2808.7×	0.001	KDM5B
uterus morphogenesis	1	2808.7×	0.001	KDM5B
branching involved in mammary gland duct morphogenesis	1	1404.3×	0.002	KDM5B
lens fiber cell differentiation	1	1053.2×	0.002	KDM5B
cellular response to fibroblast growth factor stimulus	1	543.6×	0.004	KDM5B
rhythmic process	1	251.5×	0.007	KDM5B
post-embryonic development	1	205.5×	0.008	KDM5B
single fertilization	1	183.2×	0.008	KDM5B
cellular response to leukemia inhibitory factor	1	159.0×	0.008	KDM5B
chromatin remodeling	1	73.0×	0.017	KDM5B
positive regulation of gene expression	1	38.7×	0.030	KDM5B
regulation of DNA-templated transcription	1	31.6×	0.032	KDM5B
negative regulation of DNA-templated transcription	1	31.6×	0.032	KDM5B

Therapeutics

Drug target analysis

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

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
KDM5B	2	3

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CAFFEIC ACID	3	KDM5B
EBSELEN	3	KDM5B

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
KDM5B	146	Binding:146

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
KDM5B	1.14.11.67	[histone H3]-trimethyl-L-lysine4 demethylase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
KDM5B	146

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

2 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.

Compound	Max phase	Cohort target (bioactivity)
CAFFEIC ACID	3	KDM5B
EBSELEN	3	KDM5B

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	1	KDM5B
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 0.