Lysine demethylase 6B is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that in humans is encoded by the KDM6B (JMJD3)

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

Regulation during differentiation

KDM6B was found to be expressional increased during cardiac and endothelial differentiation of murine embryonic stem cells.

Small molecule inhibition

A small molecule inhibitor (GSK-J1) has been developed to inhibit the jumonji domain of KDM6 histone

demethylase Demethylases are enzymes that remove methyl (CH3) groups from nucleic acids, proteins (particularly histones), and other molecules. Demethylases are important epigenetics, epigenetic proteins, as they are responsible for transcriptional regulation ...

family to modulate

proinflammatory Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', ''d ...

response in

macrophages Macrophages (; abbreviated MPhi, φ, MΦ or MP) are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that ...

Role in pathology

Mutations of the KDM6B gene may cause neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities, which was first described in 2019 by Stolerman et al. Standard laboratory

exome sequencing Exome sequencing, also known as whole exome sequencing (WES), is a genomic technique for sequencing all of the protein-coding regions of genes in a genome (known as the exome). It consists of two steps: the first step is to select only the subs ...

can be used to identify the KDM6B gene variant.

Clinical picture

A 2019 study on symptoms from KDM6B variations reported: * Delays in speech and motor development * Dysmorphic facial features including coarse features, a prominent forehead, broad mouth, large and prominent ears, a round face,

prognathism Prognathism is a positional relationship of the mandible or maxilla to the skeletal base where either of the jaws protrudes beyond a predetermined imaginary line in the coronal plane of the skull. In the case of ''mandibular'' prognathism (nev ...

, and epicanthal fold * Musculoskeletal features including somewhat widened and thickened hands and fingers, joint hypermobility,

clinodactyly Clinodactyly is a medical term describing the curvature of a digit (a finger or toe) in the plane of the palm, most commonly the fifth finger (the "little finger") towards the adjacent fourth finger (the "ring finger"). It is a fairly common i ...

of the fifth fingers, and toe

syndactyly Syndactyly is a condition wherein two or more digits are fused together. It occurs normally in some mammals, but is an unusual condition in humans. The term is . Classification Syndactyly can be simple or complex. * In simple syndactyly, adja ...

* Neuromuscular

hypotonia Hypotonia is a state of low muscle tone (the amount of tension or resistance to stretch in a muscle), often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but it is a potential manifestation of many different dis ...

* Intellectual disability *

Autism Autism, also known as autism spectrum disorder (ASD), is a neurodevelopmental disorder characterized by differences or difficulties in social communication and interaction, a preference for predictability and routine, sensory processing d ...

spectrum disorder A further 2023 international study reported on the following clinical features among individuals with (likely) pathogenic KDM6B variants:

Epidemiology

For patients reporting intellectual disability and/or developmental delay, approximately 0.12% have de novo alterations in the KDM6B gene.

Related conditions

Overlapping phenotypic features for patients between

KDM6A Lysine-specific demethylase 6A also known as Ubiquitously transcribed tetratricopeptide repeat, X chromosome (UTX), is a protein which in humans is encoded by the ''KDM6A'' gene. It belongs to the 2-oxoglutarate (2OG)-dependent dioxygenase supe ...

associated with

Kabuki syndrome Kabuki syndrome (previously known as Kabuki-makeup syndrome (KMS) or Niikawa–Kuroki syndrome) is a rare birth defect, congenital disorder of genetics, genetic origin. It affects multiple parts of the body, with varying symptoms and severity, alth ...

and KDM6B variations include prominent ears, abnormal dentition, congenital heart disease, feeding difficulties, cryptorchidism, joint hyper-mobility, developmental delay, hypotonia, and behavioral difficulties.

Ongoing research

According to a study published in 2022, pathologic mutations of KDM6B were found in five patients with cerebral folate deficiency.