Seroatlas · Human Serome Atlas

KMT2D

Histone-lysine N-methyltransferase 2D

Also known as: ALR, CAGL114, KMT2D_HUMAN, MLL2, MLL4, TNRC21

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: O14686
Gene: KMT2D
Ensembl: ENSG00000167548
Chromosome: 12
Canonical length: 5537 aa
Protein class: Cancer-related genes, Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins
Subcellular location: Nucleoplasm,Plasma membrane,Cytosol

OverviewNCBI Gene

The protein encoded by this gene is a histone methyltransferase that methylates the Lys-4 position of histone H3. The encoded protein is part of a large protein complex called ASCOM, which has been shown to be a transcriptional regulator of the beta-globin and estrogen receptor genes. Mutations in this gene have been shown to be a cause of Kabuki syndrome. [provided by RefSeq, Oct 2010]

Canonical amino-acid sequenceUniProt

5537 residues, UniProt reviewed canonical sequence.

>O14686|KMT2D
     1  MDSQKLAGED KDSEPAADGP AASEDPSATE SDLPNPHVGE VSVLSSGSPR LQETPQDCSG
    61  GPVRRCALCN CGEPSLHGQR ELRRFELPFD WPRCPVVSPG GSPGPNEAVL PSEDLSQIGF
   121  PEGLTPAHLG EPGGSCWAHH WCAAWSAGVW GQEGPELCGV DKAIFSGISQ RCSHCTRLGA
   181  SIPCRSPGCP RLYHFPCATA SGSFLSMKTL QLLCPEHSEG AAYLEEARCA VCEGPGELCD
   241  LFFCTSCGHH YHGACLDTAL TARKRAGWQC PECKVCQACR KPGNDSKMLV CETCDKGYHT
   301  FCLKPPMEEL PAHSWKCKAC RVCRACGAGS AELNPNSEWF ENYSLCHRCH KAQGGQTIRS
   361  VAEQHTPVCS RFSPPEPGDT PTDEPDALYV ACQGQPKGGH VTSMQPKEPG PLQCEAKPLG
   421  KAGVQLEPQL EAPLNEEMPL LPPPEESPLS PPPEESPTSP PPEASRLSPP PEELPASPLP
   481  EALHLSRPLE ESPLSPPPEE SPLSPPPESS PFSPLEESPL SPPEESPPSP ALETPLSPPP
   541  EASPLSPPFE ESPLSPPPEE LPTSPPPEAS RLSPPPEESP MSPPPEESPM SPPPEASRLF
   601  PPFEESPLSP PPEESPLSPP PEASRLSPPP EDSPMSPPPE ESPMSPPPEV SRLSPLPVVS
   661  RLSPPPEESP LSPPPEESPT SPPPEASRLS PPPEDSPTSP PPEDSPASPP PEDSLMSLPL
   721  EESPLLPLPE EPQLCPRSEG PHLSPRPEEP HLSPRPEEPH LSPQAEEPHL SPQPEEPCLC
   781  AVPEEPHLSP QAEGPHLSPQ PEELHLSPQT EEPHLSPVPE EPCLSPQPEE SHLSPQSEEP
   841  CLSPRPEESH LSPELEKPPL SPRPEKPPEE PGQCPAPEEL PLFPPPGEPS LSPLLGEPAL
   901  SEPGEPPLSP LPEELPLSPS GEPSLSPQLM PPDPLPPPLS PIITAAAPPA LSPLGELEYP
   961  FGAKGDSDPE SPLAAPILET PISPPPEANC TDPEPVPPMI LPPSPGSPVG PASPILMEPL
  1021  PPQCSPLLQH SLVPQNSPPS QCSPPALPLS VPSPLSPIGK VVGVSDEAEL HEMETEKVSE
  1081  PECPALEPSA TSPLPSPMGD LSCPAPSPAP ALDDFSGLGE DTAPLDGIDA PGSQPEPGQT
  1141  PGSLASELKG SPVLLDPEEL APVTPMEVYP ECKQTAGQGS PCEEQEEPRA PVAPTPPTLI
  1201  KSDIVNEISN LSQGDASASF PGSEPLLGSP DPEGGGSLSM ELGVSTDVSP ARDEGSLRLC
  1261  TDSLPETDDS LLCDAGTAIS GGKAEGEKGR RRSSPARSRI KQGRSSSFPG RRRPRGGAHG
  1321  GRGRGRARLK STASSIETLV VADIDSSPSK EEEEEDDDTM QNTVVLFSNT DKFVLMQDMC
  1381  VVCGSFGRGA EGHLLACSQC SQCYHPYCVN SKITKVMLLK GWRCVECIVC EVCGQASDPS
  1441  RLLLCDDCDI SYHTYCLDPP LLTVPKGGWK CKWCVSCMQC GAASPGFHCE WQNSYTHCGP
  1501  CASLVTCPIC HAPYVEEDLL IQCRHCERWM HAGCESLFTE DDVEQAADEG FDCVSCQPYV
  1561  VKPVAPVAPP ELVPMKVKEP EPQYFRFEGV WLTETGMALL RNLTMSPLHK RRQRRGRLGL
  1621  PGEAGLEGSE PSDALGPDDK KDGDLDTDEL LKGEGGVEHM ECEIKLEGPV SPDVEPGKEE
  1681  TEESKKRKRK PYRPGIGGFM VRQRKSHTRT KKGPAAQAEV LSGDGQPDEV IPADLPAEGA
  1741  VEQSLAEGDE KKKQQRRGRK KSKLEDMFPA YLQEAFFGKE LLDLSRKALF AVGVGRPSFG
  1801  LGTPKAKGDG GSERKELPTS QKGDDGPDIA DEESRGLEGK ADTPGPEDGG VKASPVPSDP
  1861  EKPGTPGEGM LSSDLDRIST EELPKMESKD LQQLFKDVLG SEREQHLGCG TPGLEGSRTP
  1921  LQRPFLQGGL PLGNLPSSSP MDSYPGLCQS PFLDSRERGG FFSPEPGEPD SPWTGSGGTT
  1981  PSTPTTPTTE GEGDGLSYNQ RSLQRWEKDE ELGQLSTISP VLYANINFPN LKQDYPDWSS
  2041  RCKQIMKLWR KVPAADKAPY LQKAKDNRAA HRINKVQKQA ESQINKQTKV GDIARKTDRP
  2101  ALHLRIPPQP GALGSPPPAA APTIFIGSPT TPAGLSTSAD GFLKPPAGSV PGPDSPGELF
  2161  LKLPPQVPAQ VPSQDPFGLA PAYPLEPRFP TAPPTYPPYP SPTGAPAQPP MLGASSRPGA
  2221  GQPGEFHTTP PGTPRHQPST PDPFLKPRCP SLDNLAVPES PGVGGGKASE PLLSPPPFGE
  2281  SRKALEVKKE ELGASSPSYG PPNLGFVDSP SSGTHLGGLE LKTPDVFKAP LTPRASQVEP
  2341  QSPGLGLRPQ EPPPAQALAP SPPSHPDIFR PGSYTDPYAQ PPLTPRPQPP PPESCCALPP
  2401  RSLPSDPFSR VPASPQSQSS SQSPLTPRPL SAEAFCPSPV TPRFQSPDPY SRPPSRPQSR
  2461  DPFAPLHKPP RPQPPEVAFK AGSLAHTSLG AGGFPAALPA GPAGELHAKV PSGQPPNFVR
  2521  SPGTGAFVGT PSPMRFTFPQ AVGEPSLKPP VPQPGLPPPH GINSHFGPGP TLGKPQSTNY
  2581  TVATGNFHPS GSPLGPSSGS TGESYGLSPL RPPSVLPPPA PDGSLPYLSH GASQRSGITS
  2641  PVEKREDPGT GMGSSLATAE LPGTQDPGMS GLSQTELEKQ RQRQRLRELL IRQQIQRNTL
  2701  RQEKETAAAA AGAVGPPGSW GAEPSSPAFE QLSRGQTPFA GTQDKSSLVG LPPSKLSGPI
  2761  LGPGSFPSDD RLSRPPPPAT PSSMDVNSRQ LVGGSQAFYQ RAPYPGSLPL QQQQQQLWQQ
  2821  QQATAATSMR FAMSARFPST PGPELGRQAL GSPLAGISTR LPGPGEPVPG PAGPAQFIEL
  2881  RHNVQKGLGP GGTPFPGQGP PQRPRFYPVS EDPHRLAPEG LRGLAVSGLP PQKPSAPPAP
  2941  ELNNSLHPTP HTKGPTLPTG LELVNRPPSS TELGRPNPLA LEAGKLPCED PELDDDFDAH
  3001  KALEDDEELA HLGLGVDVAK GDDELGTLEN LETNDPHLDD LLNGDEFDLL AYTDPELDTG
  3061  DKKDIFNEHL RLVESANEKA EREALLRGVE PGPLGPEERP PPAADASEPR LASVLPEVKP
  3121  KVEEGGRHPS PCQFTIATPK VEPAPAANSL GLGLKPGQSM MGSRDTRMGT GPFSSSGHTA
  3181  EKASFGATGG PPAHLLTPSP LSGPGGSSLL EKFELESGAL TLPGGPAASG DELDKMESSL
  3241  VASELPLLIE DLLEHEKKEL QKKQQLSAQL QPAQQQQQQQ QQHSLLSAPG PAQAMSLPHE
  3301  GSSPSLAGSQ QQLSLGLAGA RQPGLPQPLM PTQPPAHALQ QRLAPSMAMV SNQGHMLSGQ
  3361  HGGQAGLVPQ QSSQPVLSQK PMGTMPPSMC MKPQQLAMQQ QLANSFFPDT DLDKFAAEDI
  3421  IDPIAKAKMV ALKGIKKVMA QGSIGVAPGM NRQQVSLLAQ RLSGGPSSDL QNHVAAGSGQ
  3481  ERSAGDPSQP RPNPPTFAQG VINEADQRQY EEWLFHTQQL LQMQLKVLEE QIGVHRKSRK
  3541  ALCAKQRTAK KAGREFPEAD AEKLKLVTEQ QSKIQKQLDQ VRKQQKEHTN LMAEYRNKQQ
  3601  QQQQQQQQQQ QQHSAVLALS PSQSPRLLTK LPGQLLPGHG LQPPQGPPGG QAGGLRLTPG
  3661  GMALPGQPGG PFLNTALAQQ QQQQHSGGAG SLAGPSGGFF PGNLALRSLG PDSRLLQERQ
  3721  LQLQQQRMQL AQKLQQQQQQ QQQQQHLLGQ VAIQQQQQQG PGVQTNQALG PKPQGLMPPS
  3781  SHQGLLVQQL SPQPPQGPQG MLGPAQVAVL QQQHPGALGP QGPHRQVLMT QSRVLSSPQL
  3841  AQQGQGLMGH RLVTAQQQQQ QQQHQQQGSM AGLSHLQQSL MSHSGQPKLS AQPMGSLQQL
  3901  QQQQQLQQQQ QLQQQQQQQL QQQQQLQQQQ LQQQQQQQQL QQQQQQQLQQ QQQQLQQQQQ
  3961  QQQQQFQQQQ QQQQMGLLNQ SRTLLSPQQQ QQQQVALGPG MPAKPLQHFS SPGALGPTLL
  4021  LTGKEQNTVD PAVSSEATEG PSTHQGGPLA IGTTPESMAT EPGEVKPSLS GDSQLLLVQP
  4081  QPQPQPSSLQ LQPPLRLPGQ QQQQVSLLHT AGGGSHGQLG SGSSSEASSV PHLLAQPSVS
  4141  LGDQPGSMTQ NLLGPQQPML ERPMQNNTGP QPPKPGPVLQ SGQGLPGVGI MPTVGQLRAQ
  4201  LQGVLAKNPQ LRHLSPQQQQ QLQALLMQRQ LQQSQAVRQT PPYQEPGTQT SPLQGLLGCQ
  4261  PQLGGFPGPQ TGPLQELGAG PRPQGPPRLP APPGALSTGP VLGPVHPTPP PSSPQEPKRP
  4321  SQLPSPSSQL PTEAQLPPTH PGTPKPQGPT LEPPPGRVSP AAAQLADTLF SKGLGPWDPP
  4381  DNLAETQKPE QSSLVPGHLD QVNGQVVPEA SQLSIKQEPR EEPCALGAQS VKREANGEPI
  4441  GAPGTSNHLL LAGPRSEAGH LLLQKLLRAK NVQLSTGRGS EGLRAEINGH IDSKLAGLEQ
  4501  KLQGTPSNKE DAAARKPLTP KPKRVQKASD RLVSSRKKLR KEDGVRASEA LLKQLKQELS
  4561  LLPLTEPAIT ANFSLFAPFG SGCPVNGQSQ LRGAFGSGAL PTGPDYYSQL LTKNNLSNPP
  4621  TPPSSLPPTP PPSVQQKMVN GVTPSEELGE HPKDAASARD SERALRDTSE VKSLDLLAAL
  4681  PTPPHNQTED VRMESDEDSD SPDSIVPASS PESILGEEAP RFPHLGSGRW EQEDRALSPV
  4741  IPLIPRASIP VFPDTKPYGA LGLEVPGKLP VTTWEKGKGS EVSVMLTVSA AAAKNLNGVM
  4801  VAVAELLSMK IPNSYEVLFP ESPARAGTEP KKGEAEGPGG KEKGLEGKSP DTGPDWLKQF
  4861  DAVLPGYTLK SQLDILSLLK QESPAPEPPT QHSYTYNVSN LDVRQLSAPP PEEPSPPPSP
  4921  LAPSPASPPT EPLVELPTEP LAEPPVPSPL PLASSPESAR PKPRARPPEE GEDSRPPRLK
  4981  KWKGVRWKRL RLLLTIQKGS GRQEDEREVA EFMEQLGTAL RPDKVPRDMR RCCFCHEEGD
  5041  GATDGPARLL NLDLDLWVHL NCALWSTEVY ETQGGALMNV EVALHRGLLT KCSLCQRTGA
  5101  TSSCNRMRCP NVYHFACAIR AKCMFFKDKT MLCPMHKIKG PCEQELSSFA VFRRVYIERD
  5161  EVKQIASIIQ RGERLHMFRV GGLVFHAIGQ LLPHQMADFH SATALYPVGY EATRIYWSLR
  5221  TNNRRCCYRC SIGENNGRPE FVIKVIEQGL EDLVFTDASP QAVWNRIIEP VAAMRKEADM
  5281  LRLFPEYLKG EELFGLTVHA VLRIAESLPG VESCQNYLFR YGRHPLMELP LMINPTGCAR
  5341  SEPKILTHYK RPHTLNSTSM SKAYQSTFTG ETNTPYSKQF VHSKSSQYRR LRTEWKNNVY
  5401  LARSRIQGLG LYAAKDLEKH TMVIEYIGTI IRNEVANRRE KIYEEQNRGI YMFRINNEHV
  5461  IDATLTGGPA RYINHSCAPN CVAEVVTFDK EDKIIIISSR RIPKGEELTY DYQFDFEDDQ
  5521  HKIPCHCGAW NCRKWMN

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against KMT2D 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
Highest tissue expression: 38 nTPM

Expression across tissuesHPA

Tissue

bone marrow: 38 nTPM
retina: 31 nTPM
skeletal muscle: 29 nTPM
thymus: 18 nTPM
skin: 15 nTPM
tongue: 14 nTPM

Single-cell type

neutrophils: 89 nCPM
cone photoreceptor cells: 56 nCPM
neutrophil progenitors: 53 nCPM
rod photoreceptor cells: 42 nCPM
myonuclei: 39 nCPM
adrenal cortex cells: 36 nCPM

Immune cell

NK-cell: 1.5 nTPM
neutrophil: 1.3 nTPM
basophil: 0.7 nTPM
eosinophil: 0.4 nTPM
naive CD4 T-cell: 0.4 nTPM
classical monocyte: 0.3 nTPM

Brain region

cerebral cortex: 80 nTPM
amygdala: 59 nTPM
cerebellum: 58 nTPM
thalamus: 57 nTPM
hippocampal formation: 55 nTPM
white matter: 55 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about KMT2D.

Disease | AllUniProt

Conditions KMT2D is implicated in, by any mechanism.

Kabuki syndrome 1 (KABUK1) MIM:147920
Branchial arch abnormalities, choanal atresia, athelia, hearing loss, and hypothyroidism syndrome (BCAHH) MIM:620186

Disease | GeneticClinVar

1,046 pathogenic / likely-pathogenic of 7,470 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Kabuki syndrome 1
Kabuki syndrome
Inborn genetic diseases
KMT2D-related disorder
Choanal atresia-athelia-hypothyroidism-delayed puberty-short stature syndrome

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): 0.1
gnomAD pLI: 1
gnomAD missense Z: 3.73
DepMap mean gene effect: -0.36
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

SET domain
Zinc finger, RING-type
Zinc finger, PHD-type
Post-SET domain
FY-rich, N-terminal
FY-rich, C-terminal
High mobility group box domain
Zinc finger, FYVE/PHD-type
Zinc finger, RING/FYVE/PHD-type
Zinc finger, PHD-finger
Extended PHD (ePHD) domain
High mobility group box domain superfamily
SET domain superfamily
PHD-finger
SET domain
F/Y-rich N-terminus
F/Y rich C-terminus
PHD-like zinc-binding domain
PHD-zinc-finger like domain
KMT2D, SET domain
KMT2D, ePHD1 domain
KMT2D, ePHD2 domain
KMT2D, PHD5 domain
KMT2D, PHD3 domain

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of KMT2D in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads KMT2D as an antibody target. Whether an autoantibody or antibody against KMT2D could matter depends on whether native KMT2D is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

KMT2D is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label KMT2D as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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