Genes in panel

STRs in panel

Prev Next

Regions in panel

Prev Next

Intellectual disability
Gene: KDM5B

KDM5B (lysine demethylase 5B)
EnsemblGeneIds (GRCh38): ENSG00000117139
EnsemblGeneIds (GRCh37): ENSG00000117139
OMIM: 605393, Gene2Phenotype
KDM5B is in 2 panels

9 reviews

Arina Puzriakova (Genomics England Curator)

The mode of inheritance of this gene has been updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Created: 12 Mar 2026, 1:33 p.m. | Last Modified: 12 Mar 2026, 1:33 p.m.

Panel Version: 9.299

Tagged for GMS review to determine whether the MOI should be changed to biallelic only, in line with Tracy Lester's review.

Some de novo LOF variants have been reported for the AD condition, but some have also been inherited from unaffected/mildly affected parents and detected in unaffected siblings, suggestive of reduced penetrance. KDM5B is tolerant to LOF variants (pLI score = 0) and the phenotype does not represent a specific distinguishable disorder (other than ID, there were no consistent phenotypes or distinctive features shared between individuals) so it could be possible that the enrichment seen in ID patients reflects normal variation in KDM5B, and other genes are responsible for patient phenotypes (although there is no data to support this). Heterozygous knockout mice appear normal and fertile, while homozygous Kdm5b-null mice had partial lethality with fully penetrant vertebral patterning defect and behavioural issues.
Created: 30 Jun 2025, 9:07 a.m. | Last Modified: 30 Jun 2025, 9:07 a.m.

Panel Version: 9.28

Created: 30 Jun 2025, 9:07 a.m.
Last Modified: 30 Jun 2025, 9:07 a.m.
Panel version: 9.299

Tracy Lester (Genetics laboratory, Oxford UK)

Green List (high evidence)

There is currently insufficient evidence that this gene is associated with an autosomal dominant disorder. Although several de novo LOF variants have been reported the gene is not constrained for LOF variants, and lack of segregation and reduced penetrance has been reported. Until there is definitive evidence for this gene acting as an AD I think it should only be on panelapp in a recessive context.
Created: 1 Apr 2025, 12:15 p.m. | Last Modified: 1 Apr 2025, 12:15 p.m.

Panel Version: 8.235

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Intellectual disability; developmental delay

Created: 1 Apr 2025, 12:15 p.m.
Last Modified: 1 Apr 2025, 12:15 p.m.
Panel version: 8.235

Ivone Leong (Genomics England Curator)

Comment on mode of inheritance: Changed mode of inheritance from Monoallelic to Both monoallelic and biallelic based on evidence provided by expert review.
Created: 27 Feb 2019, 2:38 p.m.

Comment on publications: PMID: 30217758 reports on 2 de novo splice variants found in 3 patients from 2 unrelated families who have ID and ASD. One variant was found in a boy with mild ID and autism traits. In vitro studies found that this variant reduced KDM5B mRNA production. The sister of this affected patient did not have carry this splice variant but she also presented with mild ID and epilepsy. The authors suggest that a variant in another gene may be linked to these phenotypes and that KDM5B haploinsufficiency cannot explain the ID/ASD phenotype.

The other variant was found in a pair of monozygotic twins who both presented with global developmental delay, poor language and ASD. In vitro studies of this second variant showed that it causes the production of an abnormal transcript which is degraded by nonsense-mediated decay.
Created: 27 Feb 2019, 2:28 p.m.

Created: 27 Feb 2019, 2:28 p.m.

Panel version: 2.779

Konstantinos Varvagiannis (Other)

Green List (high evidence)

Initially reported in a publication with participation of DDD study (PMID: 29276005) it is further demonstrated in a recent DDD article (PMID: 30409806) that BOTH biallelic as well as monoallelic variants are associated with intellectual disability.

In the latter publication 4 individuals with ID and biallelic mutations in KDM5B are reported. 3 of these patients had biallelic loss-of-function (LoF) variants while a fourth one was compound heterozygous for a splice variant and a large deletion disrupting KDM5B.

KDM5B seems to be tolerant to LoF variants (pLI of 5x10-5 - in gnomAD o/e ratio for LoF variants : 0.45) while some LoF variants were transmitted by - most commonly - unaffected parents.

The authors found no evidence for :
- A parent-of-origin bias suggestive of imprinting.
- Possibility of de novo variants occuring as second hits and/or missed second variants in the dominant cases (as they comment this may have been the case for only 2 individuals).
- Certain LoF variants escaping nonsense mediated decay.
- Modifying variants in other genes.

Overall incomplete penetrance for heterozygous LoF variants and complete for biallelic LoF variants is favored as a plausible mechanism.

In the article it is not clear whether the individuals with biallelic variants present with more severe intellectual disability. Based on the initial article (PMID: 29276005) reporting on 3 of the (4 total) DDD participants published in the latter study, this seems to be unlikely (1 with severe and 2 with moderate ID).

As a result the mode of inheritance should probably be modified.
Created: 18 Nov 2018, 11:44 a.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Publications

Created: 18 Nov 2018, 11:44 a.m.

Panel version: 2.535

BRIDGE consortium (NIHRBR-RD)

Green List (high evidence)

This is a pertinent gene from the NIHR BioResource - Rare Diseases Study (NIHRBR-RD) BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene is on the SPEED_NEURO_20170705 gene list. Evidences used for SPEED NEURO gene list: in_ddg2p_2_4_2017;in_ddg2p_2_4_2017_conf . Main mutation mechanism : NA
Created: 27 Jul 2017, 7:03 p.m.

Mode of inheritance
Unknown

Publications

25529582

Created: 2 Aug 2017, 7:42 p.m.

Panel version: 1.354

Caroline Wright (Genomics England Curator)

Comment when marking as ready: New DDD gene
Created: 15 Feb 2016, 1:25 p.m.

Created: 15 Feb 2016, 1:25 p.m.

Panel version: 0.302

Richard Scott (Genomics England Curator)

Green List (high evidence)

Comment when marking as ready: New gene on G2P list
Created: 29 Jan 2016, 1:29 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Created: 29 Jan 2016, 1:17 p.m.

Panel version: 0.10

Ellen McDonagh (Genomics England Curator)

Supporting functional evidence...
- PMID: 26077434; a review "Disrupted intricacy of histone H3K4 methylation in neurodevelopmental disorders"
- PMID: 21369698; The Histone Demethylase Jarid1b Ensures Faithful Mouse Development by Protecting Developmental Genes from Aberrant H3K4me3. Jarid1b knockout embryos have several neural defects including disorganized cranial nerves, defects in eye development, and increased incidences of exencephaly.
Created: 26 Nov 2015, 10:48 a.m.

Family members KDM5A (rated red) and KDM5C (rated green) are on the current ID gene panel.
Created: 26 Nov 2015, 10:25 a.m.

Created: 26 Nov 2015, 10:25 a.m.

Panel version: 0

Maria Bitner-Glindzicz (UCL)

Green List (high evidence)

2 papers in literature; >4 patients with truncating mutations and similar phenotypes
Created: 25 Nov 2015, 10:44 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Neurodevelopmental delay and autistic spectrum disorder

Publications

PMCID: PMC4313871
PMID: 24307393

Created: 25 Nov 2015, 10:44 p.m.

Panel version: 0

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

NHS GMS
Victorian Clinical Genetics Services
Expert Review Green

Phenotypes

Intellectual developmental disorder, autosomal recessive 65, OMIM:618109

OMIM

605393

Clinvar variants

Variants in KDM5B

Penetrance

Complete

Publications

Panels with this gene