KDM6B
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesKDM6B, JMJD3, lysine demethylase 6B, NEDCFSA
External IDsOMIM: 611577 MGI: 2448492 HomoloGene: 18945 GeneCards: KDM6B
Orthologs
SpeciesHumanMouse
Entrez

23135

216850

Ensembl

ENSG00000132510

ENSMUSG00000018476

UniProt

O15054

Q5NCY0

RefSeq (mRNA)

NM_001080424
NM_001348716

NM_001017426

RefSeq (protein)

NP_001073893
NP_001335645

NP_001017426

Location (UCSC)Chr 17: 7.83 – 7.85 MbChr 11: 69.4 – 69.41 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Lysine demethylase 6B is a protein that in humans is encoded by the KDM6B gene.[5]

Regulation during differentiation

KDM6B was found to be expressional increased during cardiac and endothelial differentiation of murine embryonic stem cells.[6]

Small molecule inhibition

A small molecule inhibitor (GSK-J1) has been developed to inhibit the jumonji domain of KDM6 histone demethylase family to modulate proinflammatory response in macrophages.[7]

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.[8]

Standard laboratory exome sequencing can be used to identify the KDM6B gene variant.

Clinical picture

A 2019 study[8] 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, and epicanthal fold
  • Musculoskeletal features including somewhat widened and thickened hands and fingers, joint hypermobility, clinodactyly of the fifth fingers, and toe syndactyly
  • Neuromuscular hypotonia
  • Intellectual disability
  • Autism spectrum disorder

Epidemiology

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

Overlapping phenotypic features for patients between KDM6A associated with Kabuki syndrome 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.[9]

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000132510 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000018476 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "Entrez Gene: Lysine demethylase 6B". Retrieved 2016-04-09.
  6. Boeckel JN, Derlet A, Glaser SF, Luczak A, Lucas T, Heumüller AW, et al. (July 2016). "JMJD8 Regulates Angiogenic Sprouting and Cellular Metabolism by Interacting With Pyruvate Kinase M2 in Endothelial Cells". Arteriosclerosis, Thrombosis, and Vascular Biology. 36 (7): 1425–33. doi:10.1161/ATVBAHA.116.307695. PMID 27199445.
  7. Kruidenier L, Chung CW, Cheng Z, Liddle J, Che K, Joberty G, et al. (August 2012). "A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response". Nature. 488 (7411): 404–8. Bibcode:2012Natur.488..404K. doi:10.1038/nature11262. PMC 4691848. PMID 22842901.
  8. 1 2 Stolerman ES, Francisco E, Stallworth JL, Jones JR, Monaghan KG, Keller-Ramey J, et al. (July 2019). "Genetic variants in the KDM6B gene are associated with neurodevelopmental delays and dysmorphic features". American Journal of Medical Genetics. Part A. 179 (7): 1276–1286. doi:10.1002/ajmg.a.61173. PMID 31124279. S2CID 163167304.
  9. Han X, Cao X, Cabrera RM, Pimienta Ramirez PA, Zhang C, Ramaekers VT, Finnell RH, Lei Y (December 2022). "KDM6B Variants May Contribute to the Pathophysiology of Human Cerebral Folate Deficiency". Biology. 12 (1): 74. doi:10.3390/biology12010074. PMC 9855468. PMID 36671766.

Further reading

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