KDM6A

Protein identityUniProt · HPA

UniProt accession

O15550

Gene

KDM6A

Ensembl

ENSG00000147050

Chromosome

X

Canonical length

1401 aa

Protein class

Cancer-related genes, Disease related genes, Enzymes, Human disease related genes, Potential drug targets, Predicted intracellular proteins

Subcellular location

Nucleoplasm,Nucleoli,Nucleoli rim

OverviewNCBI Gene

This gene is located on the X chromosome and is the corresponding locus to a Y-linked gene which encodes a tetratricopeptide repeat (TPR) protein. The encoded protein of this gene contains a JmjC-domain and catalyzes the demethylation of tri/dimethylated histone H3. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Apr 2014]

Canonical amino-acid sequenceUniProt

1401 residues, UniProt reviewed canonical sequence.

>O15550|KDM6A
     1  MKSCGVSLAT AAAAAAAFGD EEKKMAAGKA SGESEEASPS LTAEEREALG GLDSRLFGFV
    61  RFHEDGARTK ALLGKAVRCY ESLILKAEGK VESDFFCQLG HFNLLLEDYP KALSAYQRYY
   121  SLQSDYWKNA AFLYGLGLVY FHYNAFQWAI KAFQEVLYVD PSFCRAKEIH LRLGLMFKVN
   181  TDYESSLKHF QLALVDCNPC TLSNAEIQFH IAHLYETQRK YHSAKEAYEQ LLQTENLSAQ
   241  VKATVLQQLG WMHHTVDLLG DKATKESYAI QYLQKSLEAD PNSGQSWYFL GRCYSSIGKV
   301  QDAFISYRQS IDKSEASADT WCSIGVLYQQ QNQPMDALQA YICAVQLDHG HAAAWMDLGT
   361  LYESCNQPQD AIKCYLNATR SKSCSNTSAL AARIKYLQAQ LCNLPQGSLQ NKTKLLPSIE
   421  EAWSLPIPAE LTSRQGAMNT AQQNTSDNWS GGHAVSHPPV QQQAHSWCLT PQKLQHLEQL
   481  RANRNNLNPA QKLMLEQLES QFVLMQQHQM RPTGVAQVRS TGIPNGPTAD SSLPTNSVSG
   541  QQPQLALTRV PSVSQPGVRP ACPGQPLANG PFSAGHVPCS TSRTLGSTDT ILIGNNHITG
   601  SGSNGNVPYL QRNALTLPHN RTNLTSSAEE PWKNQLSNST QGLHKGQSSH SAGPNGERPL
   661  SSTGPSQHLQ AAGSGIQNQN GHPTLPSNSV TQGAALNHLS SHTATSGGQQ GITLTKESKP
   721  SGNILTVPET SRHTGETPNS TASVEGLPNH VHQMTADAVC SPSHGDSKSP GLLSSDNPQL
   781  SALLMGKANN NVGTGTCDKV NNIHPAVHTK TDNSVASSPS SAISTATPSP KSTEQTTTNS
   841  VTSLNSPHSG LHTINGEGME ESQSPMKTDL LLVNHKPSPQ IIPSMSVSIY PSSAEVLKAC
   901  RNLGKNGLSN SSILLDKCPP PRPPSSPYPP LPKDKLNPPT PSIYLENKRD AFFPPLHQFC
   961  TNPNNPVTVI RGLAGALKLD LGLFSTKTLV EANNEHMVEV RTQLLQPADE NWDPTGTKKI
  1021  WHCESNRSHT TIAKYAQYQA SSFQESLREE NEKRSHHKDH SDSESTSSDN SGRRRKGPFK
  1081  TIKFGTNIDL SDDKKWKLQL HELTKLPAFV RVVSAGNLLS HVGHTILGMN TVQLYMKVPG
  1141  SRTPGHQENN NFCSVNINIG PGDCEWFVVP EGYWGVLNDF CEKNNLNFLM GSWWPNLEDL
  1201  YEANVPVYRF IQRPGDLVWI NAGTVHWVQA IGWCNNIAWN VGPLTACQYK LAVERYEWNK
  1261  LQSVKSIVPM VHLSWNMARN IKVSDPKLFE MIKYCLLRTL KQCQTLREAL IAAGKEIIWH
  1321  GRTKEEPAHY CSICEVEVFD LLFVTNESNS RKTYIVHCQD CARKTSGNLE NFVVLEQYKM
  1381  EDLMQVYDQF TLAPPLPSAS S

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against KDM6A can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.4

Highest tissue expression

18 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about KDM6A.

Disease | AllUniProt

Conditions KDM6A is implicated in, by any mechanism.

• Kabuki syndrome 2 (KABUK2) MIM:300867

Disease | GeneticClinVar

178 pathogenic / likely-pathogenic of 1,575 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Kabuki syndrome 2
• Malignant tumor of urinary bladder
• Inborn genetic diseases
• Nonpapillary renal cell carcinoma
• Kabuki syndrome 1

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.16

gnomAD pLI

1

gnomAD missense Z

2.95

DepMap mean gene effect

0.09

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• chromatin remodeling
• heart development
• regulation of gene expression

Molecular functions

• chromatin DNA binding
• histone demethylase activity
• histone H3K27me2/H3K27me3 demethylase activity
• metal ion binding
• RNA polymerase II cis-regulatory region sequence-specific DNA binding

Cellular components

• histone methyltransferase complex
• MLL3/4 complex
• nucleoplasm
• nucleus

Protein domainsUniProt · Pfam · InterPro

• JmjC domain
• Tetratricopeptide-like helical domain superfamily
• Tetratricopeptide repeat
• Lysine-specific demethylase 6, GATA-like domain superfamily
• Lysine-specific demethylase 6A/B-like, GATA-like
• Lysine-specific demethylase 6A/B-like, C-terminal helical domain
• Transcriptional Corepressor and Histone Demethylase
• JmjC domain, hydroxylase
• Tetratricopeptide repeat
• Lysine-specific demethylase 6/UTY, C-terminal helical domain
• KDM6, GATA-like

KeywordsUniProt

• Chromatin regulator
• Dioxygenase
• Intellectual disability
• Iron
• Metal-binding
• Methylation
• Nucleus
• Oxidoreductase
• Phosphoprotein
• Repeat
• TPR repeat
• Zinc

InteractionsUniProt · HPA

Protein binding partners of KDM6A in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• PROSER1
• SMARCA4
• SUPT6H
• TLE1
• SOX2
• WDR5