Details of Disease

General Information of Disease (ID: DIS6G5TF)

Disease Name Cleft palate
Synonyms palatoschisis; uranostaphyloschisis
Definition Cleft palate is a fissure type embryopathy that affects the soft and hard palate to varying degrees.
Disease Hierarchy
DIST1HG6: Orofacial cleft
DIS7GG31: Developmental defect during embryogenesis
DIS6G5TF: Cleft palate
Disease Identifiers
MONDO ID
MONDO_0016064
UMLS CUI
C2981150
MedGen ID
756015
HPO ID
HP:0000175
Orphanet ID
2014
SNOMED CT ID
63567004

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)
This Disease Is Related to 13 DTT Molecule(s)
Gene Name DTT ID Evidence Level Mode of Inheritance REF
CDKN1C TTBSUAR Strong Biomarker [1]
EPHA4 TTG84D3 Strong Genetic Variation [2]
EPHB3 TT5LM7U Strong Biomarker [3]
F13A1 TTXI2RA Strong Biomarker [4]
FAF1 TTSKL3G Strong Biomarker [5]
GMNN TT390KA Strong Genetic Variation [6]
GREM1 TTOUZN5 Strong Genetic Variation [7]
JAG2 TTOJY1B Strong Genetic Variation [8]
KAT6B TTH4VJL Strong Biomarker [9]
LRRC32 TT0FAYT Strong Genetic Variation [10]
PHF8 TT81PFE Strong Genetic Variation [11]
SLC2A9 TTIF3GB Strong Biomarker [12]
TGFB3 TTWOMY8 Strong Genetic Variation [13]
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⏷ Show the Full List of 13 DTT(s)
This Disease Is Related to 1 DTP Molecule(s)
Gene Name DTP ID Evidence Level Mode of Inheritance REF
SLC32A1 DTXQYLR Strong Biomarker [14]
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This Disease Is Related to 68 DOT Molecule(s)
Gene Name DOT ID Evidence Level Mode of Inheritance REF
DLX5 OTEEFBEU Limited Genetic Variation [15]
FOXF2 OTV20NGX Limited Biomarker [16]
GABRB3 OT80C3D4 Limited Genetic Variation [17]
GOLGB1 OT2S0GK8 Limited Genetic Variation [18]
HAND2 OTCXYW4Y Limited Genetic Variation [19]
MN1 OTVQR4R9 Limited Biomarker [20]
NEDD4L OT1B19RU Limited Genetic Variation [21]
NHLH1 OTXN5B9R Limited Genetic Variation [22]
OSR2 OTYG371T Limited Genetic Variation [23]
SOX11 OT4LG7LA Limited Genetic Variation [24]
AXIN2 OTRMGQNU moderate Altered Expression [25]
CKAP4 OTDUC9ME moderate Altered Expression [26]
CRISPLD2 OTVSFHTL moderate Genetic Variation [27]
LEF1 OTWS5I5H moderate Biomarker [28]
MEIS2 OTG4ADLM moderate Genetic Variation [29]
PAX9 OT25J0F7 moderate Biomarker [30]
ADAMTS20 OTU0EKLN Strong Biomarker [31]
ADAMTS9 OTV3Q0DS Strong Biomarker [31]
AMIGO2 OTPAIT1O Strong Biomarker [32]
BHMT OTYB6PXZ Strong Genetic Variation [33]
BRWD3 OT3BM9B0 Strong Genetic Variation [34]
CANT1 OT1TPWQR Strong Genetic Variation [35]
CILK1 OTWOYEYP Strong Biomarker [36]
COL11A1 OTB0DRMS Strong Genetic Variation [37]
CRNKL1 OTWBQNGU Strong Biomarker [38]
DDX59 OTHJANS0 Strong Genetic Variation [39]
DLX6 OT0FIJHY Strong Genetic Variation [15]
EVC2 OTY0M5SD Strong Genetic Variation [40]
FGD1 OTV3T64P Strong Genetic Variation [11]
FGF16 OT6BHWZP Strong Posttranslational Modification [41]
FOXE1 OT5IR5IT Strong Biomarker [42]
GAS1 OTKJXG52 Strong Biomarker [43]
GTPBP4 OT6ZHAWC Strong Genetic Variation [44]
HOXA2 OT6G6ZIK Strong Genetic Variation [45]
IFT88 OTDR3VBD Strong Genetic Variation [46]
ITM2A OT590V63 Strong Genetic Variation [34]
JARID2 OT14UM8H Strong Genetic Variation [47]
KIF21A OT511XD9 Strong Genetic Variation [48]
KIF3A OTMUBSSK Strong Altered Expression [49]
KIF7 OT1J6NAW Strong Genetic Variation [50]
LOXL3 OTLLY1QI Strong Genetic Variation [51]
LRMDA OTIPNKTU Strong Biomarker [9]
MEOX2 OTKZCJCB Strong Genetic Variation [52]
MSX1 OT5U41ZP Strong Genetic Variation [53]
MYF5 OTTVO2S5 Strong Biomarker [54]
NECTIN1 OTTE5ZR6 Strong Genetic Variation [55]
NXF2 OTJS5KTH Strong Biomarker [56]
NXF3 OTI0RW72 Strong Biomarker [56]
PDS5B OT3U3X8Z Strong Biomarker [57]
POU3F4 OTKF5AF7 Strong Biomarker [34]
RBFOX2 OTXY1WVH Strong Altered Expression [58]
RBM10 OTES2MES Strong Genetic Variation [59]
RPL5 OTM8EBRI Strong Genetic Variation [60]
RYK OTZ3WWZH Strong Genetic Variation [3]
SAG OTDNS3ZQ Strong Biomarker [61]
SATB2 OT2W80XC Strong Biomarker [62]
SHOC2 OTUNQ2CT Strong Genetic Variation [63]
SIX2 OTYOVGSC Strong Genetic Variation [64]
SMC1A OT9ZMRK9 Strong Biomarker [65]
SMOC1 OTJG2JQY Strong Genetic Variation [66]
STX2 OTO2IDDR Strong Biomarker [67]
TBX1 OTQLBPRA Strong Biomarker [68]
TBX22 OTT1RM26 Strong Posttranslational Modification [41]
TCOF1 OT4BOYTM Strong Biomarker [69]
TNS1 OTZ8S1PL Strong Biomarker [70]
TTF2 OT5LJOWM Strong Genetic Variation [71]
GRHL3 OT1V4ZEH Definitive Biomarker [72]
SC5D OT41KMW4 Definitive Altered Expression [73]
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⏷ Show the Full List of 68 DOT(s)

References

1 Mutations of the Imprinted CDKN1C Gene as a Cause of the Overgrowth Beckwith-Wiedemann Syndrome: Clinical Spectrum and Functional Characterization. Hum Mutat. 2015 Sep;36(9):894-902. doi: 10.1002/humu.22824. Epub 2015 Aug 6.
2 De novo 2q36.1q36.3 interstitial deletion involving the PAX3 and EPHA4 genes in a fetus with spina bifida and cleft palate.Birth Defects Res A Clin Mol Teratol. 2014 Jun;100(6):507-11. doi: 10.1002/bdra.23246. Epub 2014 Apr 18.
3 A mutation in RYK is a genetic factor for nonsyndromic cleft lip and palate.Cleft Palate Craniofac J. 2006 May;43(3):310-6. doi: 10.1597/04-145.1.
4 Is there a genetic relationship between epilepsy and birth defects?.Neurology. 1992 Apr;42(4 Suppl 5):63-7.
5 FAF1, a gene that is disrupted in cleft palate and has conserved function in zebrafish.Am J Hum Genet. 2011 Feb 11;88(2):150-61. doi: 10.1016/j.ajhg.2011.01.003. Epub 2011 Feb 3.
6 De Novo GMNN Mutations Cause Autosomal-Dominant Primordial Dwarfism Associated with Meier-Gorlin Syndrome. Am J Hum Genet. 2015 Dec 3;97(6):904-13. doi: 10.1016/j.ajhg.2015.11.006.
7 Novel GREM1 Variations in Sub-Saharan African Patients With Cleft Lip and/or Cleft Palate.Cleft Palate Craniofac J. 2018 May;55(5):736-742. doi: 10.1177/1055665618754948. Epub 2018 Feb 28.
8 MTHFR and MSX1 contribute to the risk of nonsyndromic cleft lip/palate.Eur J Oral Sci. 2010 Jun;118(3):213-20. doi: 10.1111/j.1600-0722.2010.00729.x.
9 De Novo 1.77-Mb Microdeletion of 10q22.2q22.3 in a Girl With Developmental Delay, Speech Delay, Congenital Cleft Palate, and Bilateral Hearing Impairment.Cleft Palate Craniofac J. 2017 May;54(3):343-350. doi: 10.1597/15-171. Epub 2016 Mar 31.
10 Homozygous stop-gain variant in LRRC32, encoding a TGF receptor, associated with cleft palate, proliferative retinopathy, and developmental delay.Eur J Hum Genet. 2019 Aug;27(8):1315-1319. doi: 10.1038/s41431-019-0380-y. Epub 2019 Apr 11.
11 A complex Xp11.22 deletion in a patient with syndromic autism: exploration of FAM120C as a positional candidate gene for autism.Am J Med Genet A. 2014 Dec;164A(12):3035-41. doi: 10.1002/ajmg.a.36752. Epub 2014 Sep 24.
12 Evidence of gene-environment interaction for two genes on chromosome 4 and environmental tobacco smoke in controlling the risk of nonsyndromic cleft palate.PLoS One. 2014 Feb 6;9(2):e88088. doi: 10.1371/journal.pone.0088088. eCollection 2014.
13 SMAD2 overexpression rescues the TGF-3 null mutant mice cleft palate by increased apoptosis.Differentiation. 2020 Jan-Feb;111:60-69. doi: 10.1016/j.diff.2019.10.001. Epub 2019 Oct 8.
14 Genetic ablation of VIAAT in glycinergic neurons causes a severe respiratory phenotype and perinatal death.Brain Struct Funct. 2015 Sep;220(5):2835-49. doi: 10.1007/s00429-014-0829-2. Epub 2014 Jul 16.
15 A LINE-1 insertion in DLX6 is responsible for cleft palate and mandibular abnormalities in a canine model of Pierre Robin sequence.PLoS Genet. 2014 Apr 3;10(4):e1004257. doi: 10.1371/journal.pgen.1004257. eCollection 2014 Apr.
16 A Shh-Foxf-Fgf18-Shh Molecular Circuit Regulating Palate Development.PLoS Genet. 2016 Jan 8;12(1):e1005769. doi: 10.1371/journal.pgen.1005769. eCollection 2016 Jan.
17 Cleft Palate as Distinguishing Feature in a Patient with GABRB3 Epileptic Encephalopathy.Neuropediatrics. 2019 Dec;50(6):378-381. doi: 10.1055/s-0039-1693143. Epub 2019 Jul 18.
18 Association between GOLGB1 tag-polymorphisms and nonsyndromic cleft palate only in the Brazilian population.Ann Hum Genet. 2018 Jul;82(4):227-231. doi: 10.1111/ahg.12242. Epub 2018 Feb 12.
19 Requirement of Hyaluronan Synthase-2 in Craniofacial and Palate Development.J Dent Res. 2019 Nov;98(12):1367-1375. doi: 10.1177/0022034519872478. Epub 2019 Sep 11.
20 Chromosome 22q12.1 microdeletions: confirmation of the MN1 gene as a candidate gene for cleft palate.Eur J Hum Genet. 2016 Jan;24(1):51-8. doi: 10.1038/ejhg.2015.65. Epub 2015 May 6.
21 Author Correction: A missense mutation in the HECT domain of NEDD4L identified in a girl with periventricular nodular heterotopia, polymicrogyria, and cleft palate.J Hum Genet. 2019 Jul;64(7):701-702. doi: 10.1038/s10038-019-0610-8.
22 Association of the WNT3 polymorphisms and non-syndromic cleft lip with or without cleft palate: evidence from a meta-analysis.Biosci Rep. 2018 Nov 23;38(6):BSR20181676. doi: 10.1042/BSR20181676. Print 2018 Dec 21.
23 Inactivation of Fgfr2 gene in mouse secondary palate mesenchymal cells leads to cleft palate.Reprod Toxicol. 2018 Apr;77:137-142. doi: 10.1016/j.reprotox.2018.03.004. Epub 2018 Mar 8.
24 Observation of Cleft Palate in an Individual with SOX11 Mutation: Indication of a Role for SOX11 in Human Palatogenesis.Cleft Palate Craniofac J. 2018 Mar;55(3):456-461. doi: 10.1177/1055665617739312. Epub 2017 Dec 14.
25 Modulating Wnt Signaling Rescues Palate Morphogenesis in Pax9 Mutant Mice.J Dent Res. 2017 Oct;96(11):1273-1281. doi: 10.1177/0022034517719865. Epub 2017 Jul 10.
26 Periderm: Life-cycle and function during orofacial and epidermal development.Semin Cell Dev Biol. 2019 Jul;91:75-83. doi: 10.1016/j.semcdb.2017.08.021. Epub 2017 Aug 10.
27 Association Between CRISPLD2 Polymorphisms and the Risk of Nonsyndromic Clefts of the Lip and/or Palate: A Meta-analysis.Cleft Palate Craniofac J. 2018 Mar;55(3):328-334. doi: 10.1177/1055665617738995. Epub 2017 Dec 14.
28 Genome-Wide mRNA-Seq Profiling Reveals that LEF1 and SMAD3 Regulate Epithelial-Mesenchymal Transition Through the Hippo Signaling Pathway During Palatal Fusion.Genet Test Mol Biomarkers. 2019 Mar;23(3):197-203. doi: 10.1089/gtmb.2018.0221. Epub 2019 Feb 15.
29 MEIS2 gene is responsible for intellectual disability, cardiac defects and a distinct facial phenotype.Eur J Med Genet. 2020 Jan;63(1):103627. doi: 10.1016/j.ejmg.2019.01.017. Epub 2019 Feb 5.
30 The Function and Regulatory Network of Pax9 Gene in Palate Development.J Dent Res. 2019 Mar;98(3):277-287. doi: 10.1177/0022034518811861. Epub 2018 Dec 24.
31 ADAMTS9 and ADAMTS20 are differentially affected by loss of B3GLCT in mouse model of Peters plus syndrome.Hum Mol Genet. 2019 Dec 15;28(24):4053-4066. doi: 10.1093/hmg/ddz225.
32 A de novo 12q13.11 microdeletion in a patient with severe mental retardation, cleft palate, and high myopia.Eur J Med Genet. 2011 Jan-Feb;54(1):94-6. doi: 10.1016/j.ejmg.2010.09.008. Epub 2010 Oct 8.
33 Accumulation of rare coding variants in genes implicated in risk of human cleft lip with or without cleft palate.Am J Med Genet A. 2019 Jul;179(7):1260-1269. doi: 10.1002/ajmg.a.61183. Epub 2019 May 7.
34 A 5.8 Mb interstitial deletion on chromosome Xq21.1 in a boy with intellectual disability, cleft palate, hearing impairment and combined growth hormone deficiency.BMC Med Genet. 2015 Sep 1;16:74. doi: 10.1186/s12881-015-0220-z.
35 IMPAD1 mutations in two Catel-Manzke like patients.Am J Med Genet A. 2012 Sep;158A(9):2183-7. doi: 10.1002/ajmg.a.35504. Epub 2012 Aug 6.
36 Activation of sonic hedgehog signaling by a Smoothened agonist restores congenital defects in mouse models of endocrine-cerebro-osteodysplasia syndrome.EBioMedicine. 2019 Nov;49:305-317. doi: 10.1016/j.ebiom.2019.10.016. Epub 2019 Oct 26.
37 Collagen XI sequence variations in nonsyndromic cleft palate, Robin sequence and micrognathia.Eur J Hum Genet. 2003 Mar;11(3):265-70. doi: 10.1038/sj.ejhg.5200950.
38 Wnt9b is the mutated gene involved in multifactorial nonsyndromic cleft lip with or without cleft palate in A/WySn mice, as confirmed by a genetic complementation test.Birth Defects Res A Clin Mol Teratol. 2006 Aug;76(8):574-9. doi: 10.1002/bdra.20302.
39 Confirmation that mutations in DDX59 cause an autosomal recessive form of oral-facial-digital syndrome: Further delineation of the DDX59 phenotype in two new families.Eur J Med Genet. 2017 Oct;60(10):527-532. doi: 10.1016/j.ejmg.2017.07.009. Epub 2017 Jul 12.
40 Association between genes on chromosome 4p16 and non-syndromic oral clefts in four populations.Eur J Hum Genet. 2010 Jun;18(6):726-32. doi: 10.1038/ejhg.2009.228. Epub 2010 Jan 20.
41 DNA hypermethylation of Fgf16 and Tbx22 associated with cleft palate during palatal fusion.J Appl Oral Sci. 2019 Oct 7;27:e20180649. doi: 10.1590/1678-7757-2018-0649. eCollection 2019.
42 A novel FOXE1 mutation (R73S) in Bamforth-Lazarus syndrome causing increased thyroidal gene expression.Thyroid. 2014 Apr;24(4):649-54. doi: 10.1089/thy.2013.0417. Epub 2014 Jan 23.
43 Gas1 is a modifier for holoprosencephaly and genetically interacts with sonic hedgehog.J Clin Invest. 2007 Jun;117(6):1575-84. doi: 10.1172/JCI32032. Epub 2007 May 24.
44 A Population-Based Study of Effects of Genetic Loci on Orofacial Clefts.J Dent Res. 2017 Oct;96(11):1322-1329. doi: 10.1177/0022034517716914. Epub 2017 Jun 29.
45 Identification of a second HOXA2 nonsense mutation in a family with autosomal dominant non-syndromic microtia and distinctive ear morphology.Clin Genet. 2017 May;91(5):774-779. doi: 10.1111/cge.12845. Epub 2016 Sep 13.
46 Association of IFT88 gene variants with nonsyndromic cleft lip with or without cleft palate.Birth Defects Res. 2019 Jul 1;111(11):659-665. doi: 10.1002/bdr2.1504. Epub 2019 Apr 5.
47 Brazilian multicenter study of association between polymorphisms in CRISPLD2 and JARID2 and non-syndromic oral clefts.J Oral Pathol Med. 2017 Mar;46(3):232-239. doi: 10.1111/jop.12470. Epub 2016 Jun 21.
48 Phenotype-genotype correlation in two patients with 12q proximal deletion.J Hum Genet. 2004;49(5):282-4. doi: 10.1007/s10038-004-0144-5.
49 The correlative hypotheses between Pitchfork and Kif3a in palate development.Med Hypotheses. 2019 May;126:23-25. doi: 10.1016/j.mehy.2019.03.005. Epub 2019 Mar 12.
50 KIF7 mutations cause fetal hydrolethalus and acrocallosal syndromes. Nat Genet. 2011 Jun;43(6):601-6. doi: 10.1038/ng.826. Epub 2011 May 8.
51 Association between a common missense variant in LOXL3 gene and the risk of non-syndromic cleft palate.Congenit Anom (Kyoto). 2018 Jul;58(4):136-140. doi: 10.1111/cga.12288. Epub 2018 Jun 11.
52 Association of MEOX2 polymorphism with nonsyndromic cleft palate only in a Vietnamese population.Congenit Anom (Kyoto). 2018 Jul;58(4):124-129. doi: 10.1111/cga.12259. Epub 2017 Nov 28.
53 Association between CDH1 and MSX1 gene polymorphisms and the risk of nonsyndromic cleft lip and/or cleft palate in a southeast Iranian population.Cleft Palate Craniofac J. 2013 Sep;50(5):e98-e104. doi: 10.1597/12-144. Epub 2012 Dec 11.
54 Altered binding of MYF-5 to FOXE1 promoter in non-syndromic and CHARGE-associated cleft palate.J Oral Pathol Med. 2009 Jan;38(1):18-23. doi: 10.1111/j.1600-0714.2008.00726.x.
55 Novel insertion mutation in the PVRL1 gene in Turkish patients with non-syndromic cleft lip with/without cleft palate.Arch Oral Biol. 2014 Mar;59(3):237-40. doi: 10.1016/j.archoralbio.2013.11.016. Epub 2013 Dec 7.
56 Respiratory failure, cleft palate and epilepsy in the mouse model of human Xq22.1 deletion syndrome.Hum Mol Genet. 2014 Jul 15;23(14):3823-9. doi: 10.1093/hmg/ddu095. Epub 2014 Feb 25.
57 Dosage effects of cohesin regulatory factor PDS5 on mammalian development: implications for cohesinopathies.PLoS One. 2009;4(5):e5232. doi: 10.1371/journal.pone.0005232. Epub 2009 May 1.
58 Neural crest-specific deletion of Rbfox2 in mice leads to craniofacial abnormalities including cleft palate.Elife. 2019 Jun 26;8:e45418. doi: 10.7554/eLife.45418.
59 Massively parallel sequencing of exons on the X chromosome identifies RBM10 as the gene that causes a syndromic form of cleft palate. Am J Hum Genet. 2010 May 14;86(5):743-8. doi: 10.1016/j.ajhg.2010.04.007. Epub 2010 May 6.
60 Ribosomal protein L5 and L11 mutations are associated with cleft palate and abnormal thumbs in Diamond-Blackfan anemia patients. Am J Hum Genet. 2008 Dec;83(6):769-80. doi: 10.1016/j.ajhg.2008.11.004.
61 Perturbed development of cranial neural crest cells in association with reduced sonic hedgehog signaling underlies the pathogenesis of retinoic-acid-induced cleft palate.Dis Model Mech. 2019 Oct 4;12(10):dmm040279. doi: 10.1242/dmm.040279.
62 SATB2-associated syndrome in patients from Japan: Linguistic profiles.Am J Med Genet A. 2019 Jun;179(6):896-899. doi: 10.1002/ajmg.a.61114. Epub 2019 Mar 7.
63 Cleft palate and hypopituitarism in a patient with Noonan-like syndrome with loose anagen hair-1.Am J Med Genet A. 2018 Sep;176(9):2024-2027. doi: 10.1002/ajmg.a.40432. Epub 2018 Sep 21.
64 Six2 regulates Pax9 expression, palatogenesis and craniofacial bone formation.Dev Biol. 2020 Feb 15;458(2):246-256. doi: 10.1016/j.ydbio.2019.11.010. Epub 2019 Nov 23.
65 Novel findings of left ventricular non-compaction cardiomyopathy, microform cleft lip and poor vision in patient with SMC1A-associated Cornelia de Lange syndrome.Am J Med Genet A. 2017 Feb;173(2):414-420. doi: 10.1002/ajmg.a.38030. Epub 2016 Nov 7.
66 Loss of the BMP antagonist, SMOC-1, causes Ophthalmo-acromelic (Waardenburg Anophthalmia) syndrome in humans and mice.PLoS Genet. 2011 Jul;7(7):e1002114. doi: 10.1371/journal.pgen.1002114. Epub 2011 Jul 7.
67 Inhibition of periderm removal in all-trans retinoic acid-induced cleft palate in mice.Exp Ther Med. 2017 Oct;14(4):3393-3398. doi: 10.3892/etm.2017.4938. Epub 2017 Aug 16.
68 Deletion of the T-box transcription factor gene, Tbx1, in mice induces differential expression of genes associated with cleft palate in humans.Arch Oral Biol. 2018 Nov;95:149-155. doi: 10.1016/j.archoralbio.2018.08.001. Epub 2018 Aug 9.
69 Excess maternal transmission of markers in TCOF1 among cleft palate case-parent trios from three populations.Am J Med Genet A. 2008 Sep 15;146A(18):2327-31. doi: 10.1002/ajmg.a.32302.
70 Analysis of candidate genes on chromosome 2 in oral cleft case-parent trios from three populations.Hum Genet. 2006 Nov;120(4):501-18. doi: 10.1007/s00439-006-0235-9. Epub 2006 Sep 5.
71 Genetic analysis of TTF-2 gene in children with congenital hypothyroidism and cleft palate, congenital hypothyroidism, or isolated cleft palate.Thyroid. 2004 Aug;14(8):584-8. doi: 10.1089/1050725041692864.
72 A systematic genetic analysis and visualization of phenotypic heterogeneity among orofacial cleft GWAS signals.Genet Epidemiol. 2019 Sep;43(6):704-716. doi: 10.1002/gepi.22214. Epub 2019 Jun 6.
73 Lathosterolosis: an inborn error of human and murine cholesterol synthesis due to lathosterol 5-desaturase deficiency. Hum Mol Genet. 2003 Jul 1;12(13):1631-41. doi: 10.1093/hmg/ddg172.