Details of Disease

General Information of Disease (ID: DIS14IG3)

Disease Name Cleft lip/palate
Synonyms cleft lip and palate; cleft lip-alveolus-palate syndrome; alveolar cleft lip and palate; FLP
Definition Cleft lip and palate is a fissure type embryopathy extending across the upper lip, nasal base, alveolar ridge and the hard and soft palate.
Disease Hierarchy
DISQCXZX: Disorder of development or morphogenesis
DIST1HG6: Orofacial cleft
DIS14IG3: Cleft lip/palate
Disease Identifiers
MONDO ID
MONDO_0016044
UMLS CUI
C0158646
MedGen ID
57640
Orphanet ID
199306
SNOMED CT ID
66948001

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)
This Disease Is Related to 9 DTT Molecule(s)
Gene Name DTT ID Evidence Level Mode of Inheritance REF
BMP4 TTD3BSX Strong Genetic Variation [1]
CDH1 TTLAWO6 Strong Genetic Variation [2]
FGF10 TTNPEFX Strong Biomarker [3]
FGF8 TTIUF3J Strong Altered Expression [3]
MTR TTUTO39 Strong Genetic Variation [4]
NECTIN4 TTPO9EG Strong Genetic Variation [5]
PHF8 TT81PFE Strong Genetic Variation [6]
RPE65 TTBOH16 Definitive Genetic Variation [7]
TGFB3 TTWOMY8 Definitive Genetic Variation [8]
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⏷ Show the Full List of 9 DTT(s)
This Disease Is Related to 1 DME Molecule(s)
Gene Name DME ID Evidence Level Mode of Inheritance REF
NAT1 DE7OAB3 Strong Genetic Variation [9]
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This Disease Is Related to 42 DOT Molecule(s)
Gene Name DOT ID Evidence Level Mode of Inheritance REF
ARHGAP29 OT8JH4TY Limited SusceptibilityMutation [10]
CHD7 OTHNIZWZ Limited Genetic Variation [11]
DLG1 OTCRZYWT Limited SusceptibilityMutation [12]
GABRB3 OT80C3D4 moderate Biomarker [13]
ADAMTS20 OTU0EKLN Strong Genetic Variation [14]
B3GLCT OTXH6KOQ Strong Genetic Variation [15]
BHMT OTYB6PXZ Strong Genetic Variation [16]
BHMT2 OTWYGLDU Strong Biomarker [17]
CLPTM1 OT14QP7N Strong Genetic Variation [18]
CLPTM1L OTDJWQXI Strong Biomarker [19]
CPO OTOIG8C9 Strong Biomarker [20]
DLX1 OT7BH057 Strong Biomarker [21]
DLX4 OTLWVCN4 Strong GermlineCausalMutation [22]
DNAJC5 OTCZDXAL Strong Biomarker [23]
FOXE1 OT5IR5IT Strong Genetic Variation [24]
GRHL3 OT1V4ZEH Strong Genetic Variation [25]
GTPBP4 OT6ZHAWC Strong Biomarker [26]
IFT88 OTDR3VBD Strong Biomarker [27]
KLF17 OT5NWVP7 Strong Biomarker [28]
MAFB OTH2N3T8 Strong Genetic Variation [29]
MID1 OTWN1PGU Strong Genetic Variation [30]
MSX1 OT5U41ZP Strong Genetic Variation [31]
NECTIN1 OTTE5ZR6 Strong Genetic Variation [32]
NHLH1 OTXN5B9R Strong Biomarker [33]
PAX7 OTDMQRPO Strong Biomarker [26]
PGAP2 OTUW3SAX Strong Genetic Variation [34]
POMT1 OTGQSHL5 Strong Biomarker [35]
PRSS35 OT09H6WH Strong Biomarker [36]
RAB34 OTHKTSA0 Strong Genetic Variation [37]
RAD51C OTUD6SY5 Strong Genetic Variation [38]
RIC1 OT3X4606 Strong Genetic Variation [39]
RYK OTZ3WWZH Strong Genetic Variation [40]
SAE1 OT18HFX5 Strong Biomarker [41]
SHTN1 OTB07MOG Strong Biomarker [26]
SNAP91 OTE3EXWZ Strong Biomarker [36]
STOM OTC8R6EH Strong Genetic Variation [42]
SYNJ2 OTLRHXP1 Strong Genetic Variation [18]
TBX22 OTT1RM26 Strong Genetic Variation [43]
TINAGL1 OTZZO56M Strong Biomarker [44]
TP63 OT0WOOKQ Strong Genetic Variation [7]
CKAP4 OTDUC9ME Definitive Genetic Variation [7]
SUMO1 OTJFD4P5 Definitive Genetic Variation [45]
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⏷ Show the Full List of 42 DOT(s)

References

1 BMP2 and BMP4 variations and risk of non-syndromic cleft lip and palate.Arch Oral Biol. 2016 Dec;72:134-137. doi: 10.1016/j.archoralbio.2016.08.019. Epub 2016 Aug 24.
2 Cleft lip/palate and hereditary diffuse gastric cancer: report of a family harboring a CDH1 c.687??G?A germline mutation and review of the literature.Fam Cancer. 2019 Apr;18(2):253-260. doi: 10.1007/s10689-018-0111-5.
3 Molecular pathology of the fibroblast growth factor family.Hum Mutat. 2009 Sep;30(9):1245-55. doi: 10.1002/humu.21067.
4 Polymorphisms in genes MTHFR, MTR and MTRR are not risk factors for cleft lip/palate in South Brazil.Braz J Med Biol Res. 2007 Jun;40(6):787-91. doi: 10.1590/s0100-879x2006005000112.
5 Nectin-4 mutations causing ectodermal dysplasia with syndactyly perturb the rac1 pathway and the kinetics of adherens junction formation.J Invest Dermatol. 2014 Aug;134(8):2146-2153. doi: 10.1038/jid.2014.119. Epub 2014 Feb 27.
6 Phf8 loss confers resistance to depression-like and anxiety-like behaviors in mice.Nat Commun. 2017 May 9;8:15142. doi: 10.1038/ncomms15142.
7 Single-cell RNA-seq identifies a reversible mesodermal activation in abnormally specified epithelia of p63 EEC syndrome.Proc Natl Acad Sci U S A. 2019 Aug 27;116(35):17361-17370. doi: 10.1073/pnas.1908180116. Epub 2019 Aug 14.
8 Evidence for transforming growth factor-beta 3 gene polymorphism in non-syndromic cleft lip and palate patients from Indian sub-continent.Med Oral Patol Oral Cir Bucal. 2012 Mar 1;17(2):e197-200. doi: 10.4317/medoral.17453.
9 Association of NAT1 and NAT2 genes with nonsyndromic cleft lip and palate.Mol Med Rep. 2013 Jul;8(1):211-6. doi: 10.3892/mmr.2013.1467. Epub 2013 May 9.
10 Impact of rare variants in ARHGAP29 to the etiology of oral clefts: role of loss-of-function vs missense variants.Clin Genet. 2017 May;91(5):683-689. doi: 10.1111/cge.12823. Epub 2016 Jul 26.
11 Molecular genetic and clinical delineation of 22 patients with congenital hypogonadotropic hypogonadism.J Pediatr Endocrinol Metab. 2017 Oct 26;30(10):1111-1118. doi: 10.1515/jpem-2017-0035.
12 Common variants in DLG1 locus are associated with non-syndromic cleft lip with or without cleft palate.Clin Genet. 2018 Apr;93(4):784-793. doi: 10.1111/cge.13141. Epub 2018 Feb 11.
13 Patterns of some extracellular matrix gene expression are similar in cells from cleft lip-palate patients and in human palatal fibroblasts exposed to diazepam in culture. Toxicology. 2009 Mar 4;257(1-2):10-6. doi: 10.1016/j.tox.2008.12.002. Epub 2008 Dec 9.
14 Genome-wide association studies in dogs and humans identify ADAMTS20 as a risk variant for cleft lip and palate.PLoS Genet. 2015 Mar 23;11(3):e1005059. doi: 10.1371/journal.pgen.1005059. eCollection 2015 Mar.
15 Hydrocephalus, agenesis of the corpus callosum, and cleft lip/palate represent frequent associations in fetuses with Peters' plus syndrome and B3GALTL mutations. Fetal PPS phenotypes, expanded by Dandy Walker cyst and encephalocele.Prenat Diagn. 2013 Jan;33(1):75-80. doi: 10.1002/pd.4012. Epub 2012 Nov 13.
16 BHMT gene polymorphisms as risk factors for cleft lip and cleft palate in a Chinese population.Biomed Environ Sci. 2011 Apr;24(2):89-93. doi: 10.3967/0895-3988.2011.02.001.
17 Are the betaine-homocysteine methyltransferase (BHMT and BHMT2) genes risk factors for spina bifida and orofacial clefts?.Am J Med Genet A. 2005 Jun 15;135(3):274-7. doi: 10.1002/ajmg.a.30739.
18 Identification of inactivating mutations in the JAK1, SYNJ2, and CLPTM1 genes in prostate cancer cells using inhibition of nonsense-mediated decay and microarray analysis.Cancer Genet Cytogenet. 2005 Sep;161(2):97-103. doi: 10.1016/j.cancergencyto.2005.02.006.
19 CLPTM1L/CRR9 ectodomain interaction with GRP78 at the cell surface signals for survival and chemoresistance upon ER stress in pancreatic adenocarcinoma cells.Int J Cancer. 2019 Mar 15;144(6):1367-1378. doi: 10.1002/ijc.32012. Epub 2019 Jan 3.
20 A comparison of DNA methylation in newborn blood samples from infants with and without orofacial clefts.Clin Epigenetics. 2019 Mar 4;11(1):40. doi: 10.1186/s13148-019-0638-9.
21 DLX1 and MMP3 contribute to oral clefts with and without positive family history of cancer.Arch Oral Biol. 2015 Feb;60(2):223-8. doi: 10.1016/j.archoralbio.2014.10.002. Epub 2014 Oct 22.
22 DLX4 is associated with orofacial clefting and abnormal jaw development. Hum Mol Genet. 2015 Aug 1;24(15):4340-52. doi: 10.1093/hmg/ddv167. Epub 2015 May 7.
23 A Comparative Study of Oral Microbiota in Infants with Complete Cleft Lip and Palate or Cleft Soft Palate.Biomed Res Int. 2017;2017:1460243. doi: 10.1155/2017/1460243. Epub 2017 Mar 14.
24 Association between FOXE1 and non-syndromic orofacial clefts in a northeastern Chinese population.Br J Oral Maxillofac Surg. 2015 Oct;53(8):705-10. doi: 10.1016/j.bjoms.2015.05.021. Epub 2015 Jun 19.
25 Disrupted IRF6-NME1/2 Complexes as a Cause of Cleft Lip/Palate.J Dent Res. 2017 Oct;96(11):1330-1338. doi: 10.1177/0022034517723615. Epub 2017 Aug 2.
26 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.
27 Intraflagellar transport 88 (IFT88) is crucial for craniofacial development in mice and is a candidate gene for human cleft lip and palate.Hum Mol Genet. 2017 Mar 1;26(5):860-872. doi: 10.1093/hmg/ddx002.
28 Irf6 directly regulates Klf17 in zebrafish periderm and Klf4 in murine oral epithelium, and dominant-negative KLF4 variants are present in patients with cleft lip and palate.Hum Mol Genet. 2016 Feb 15;25(4):766-76. doi: 10.1093/hmg/ddv614. Epub 2015 Dec 21.
29 Polymorphic Variants of V-Maf Musculoaponeurotic Fibrosarcoma Oncogene Homolog B (rs13041247 and rs11696257) and Risk of Non-Syndromic Cleft Lip/Palate: Systematic Review and Meta-Analysis.Int J Environ Res Public Health. 2019 Aug 5;16(15):2792. doi: 10.3390/ijerph16152792.
30 Structural and functional observations of the P151L MID1 mutation reveal alpha4 plays a significant role in X-linked Opitz Syndrome.FEBS J. 2017 Jul;284(14):2183-2193. doi: 10.1111/febs.14121. Epub 2017 Jun 14.
31 Association between MSX1 rs12532 polymorphism with nonsyndromic unilateral complete cleft lip and palate and tooth agenesis.Arch Oral Biol. 2020 Jan;109:104556. doi: 10.1016/j.archoralbio.2019.104556. Epub 2019 Sep 17.
32 Novel homozygous mutation, c.400C>T (p.Arg134*), in the PVRL1 gene underlies cleft lip/palate-ectodermal dysplasia syndrome in an Asian patient.J Dermatol. 2015 Jul;42(7):715-9. doi: 10.1111/1346-8138.12882. Epub 2015 Apr 24.
33 The impact of nonsyndromic cleft lip with or without cleft palate on oral health-related quality of life.J Appl Oral Sci. 2018 Apr 5;26:e20170145. doi: 10.1590/1678-7757-2017-0145.
34 Glycosylphosphatidylinositol biosynthesis and remodeling are required for neural tube closure, heart development, and cranial neural crest cell survival.Elife. 2019 Jun 24;8:e45248. doi: 10.7554/eLife.45248.
35 Walker-Warburg Syndrome with POMT1 mutations can be associated with cleft lip and cleft palate.Neuromuscul Disord. 2008 Aug;18(8):675-7. doi: 10.1016/j.nmd.2008.05.014. Epub 2008 Jul 18.
36 Novel cleft susceptibility genes in chromosome 6q.J Dent Res. 2010 Sep;89(9):927-32. doi: 10.1177/0022034510370004. Epub 2010 May 28.
37 Rab34 small GTPase is required for Hedgehog signaling and an early step of ciliary vesicle formation in mouse.J Cell Sci. 2018 Nov 8;131(21):jcs213710. doi: 10.1242/jcs.213710.
38 Expanding the FANCO/RAD51C associated phenotype: Cleft lip and palate and lobar holoprosencephaly, two rare findings in Fanconi anemia.Eur J Med Genet. 2018 May;61(5):257-261. doi: 10.1016/j.ejmg.2017.12.011. Epub 2017 Dec 24.
39 Novel phenotypes and loci identified through clinical genomics approaches to pediatric cataract.Hum Genet. 2017 Feb;136(2):205-225. doi: 10.1007/s00439-016-1747-6. Epub 2016 Nov 22.
40 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.
41 Array-CGH detection of a de novo 0.8Mb deletion in 19q13.32 associated with mental retardation, cardiac malformation, cleft lip and palate, hearing loss and multiple dysmorphic features.Eur J Med Genet. 2009 Jan-Feb;52(1):62-6. doi: 10.1016/j.ejmg.2008.09.007. Epub 2008 Oct 31.
42 Follow-up association studies of chromosome region 9q and nonsyndromic cleft lip/palate.Am J Med Genet A. 2010 Jul;152A(7):1701-10. doi: 10.1002/ajmg.a.33482.
43 TBX22 mutation associated with cleft lip/palate, hypodontia, and limb anomaly.Cleft Palate Craniofac J. 2012 Mar;49(2):240-4. doi: 10.1597/10-208. Epub 2011 Mar 4.
44 Early Craniofacial Defects in Zebrafish That Have Reduced Function of a Wnt-Interacting Extracellular Matrix Protein, Tinagl1.Cleft Palate Craniofac J. 2017 Jul;54(4):381-390. doi: 10.1597/15-283. Epub 2016 May 31.
45 Sumoylation in Craniofacial Disorders.Adv Exp Med Biol. 2017;963:323-335. doi: 10.1007/978-3-319-50044-7_19.