Details of Disease

General Information of Disease (ID: DISV3XW6)

• Disease Name: Cleft lip
• Synonyms: cheiloschisis; cleft lip (disease); labium leporinum; cleft lip; complete unilateral cleft lip; cleft lip, unilateral, complete; hare lip
• Definition: A congenital abnormality consisting of one or more clefts (splits) in the upper lip, which may be accompanied by a cleft palate; it is the result of the failure of the embryonic parts of the lip to fuse.
• Disease Hierarchy:
  DIST1HG6: Orofacial cleft
  DISV3XW6: Cleft lip
• Disease Identifiers:
  MONDO ID: MONDO_0004747
  UMLS CUI: C4321245
  MedGen ID: 1370297
  HPO ID: HP:0410030

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 9 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
TGFB3	TTWOMY8	Limited	Biomarker	[1]
EPHB3	TT5LM7U	Strong	Biomarker	[2]
F13A1	TTXI2RA	Strong	Biomarker	[3]
HHAT	TT1VNCG	Strong	Genetic Variation	[4]
NEK2	TT3VZ24	Strong	Biomarker	[5]
NR1D1	TTAD1O8	Strong	Biomarker	[6]
PDGFC	TTOABM9	Strong	Genetic Variation	[7]
PHF8	TT81PFE	Strong	Altered Expression	[8]
TGFA	TTTLQFR	Strong	Genetic Variation	[9]

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC31A1	DTP8L4F	Strong	Genetic Variation	[10]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
FPGS	DECWT2V	Strong	Biomarker	[11]

This Disease Is Related to 16 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
CRNKL1	OTWBQNGU	moderate	Biomarker	[12]
FOXE1	OT5IR5IT	moderate	Genetic Variation	[13]
COL21A1	OT7GS82E	Strong	Genetic Variation	[14]
CRISPLD2	OTVSFHTL	Strong	Genetic Variation	[15]
MSX1	OT5U41ZP	Strong	Biomarker	[1]
PAX9	OT25J0F7	Strong	Genetic Variation	[16]
RPL5	OTM8EBRI	Strong	Genetic Variation	[17]
RYK	OTZ3WWZH	Strong	Genetic Variation	[2]
SMC1A	OT9ZMRK9	Strong	Genetic Variation	[18]
TACC1	OTGX20TE	Strong	Genetic Variation	[5]
TBCA	OTCCWMGK	Strong	Genetic Variation	[19]
TBX22	OTT1RM26	Strong	Genetic Variation	[20]
TOX3	OTC9NR4W	Strong	Genetic Variation	[14]
TP63	OT0WOOKQ	Strong	CausalMutation	[21]
TTF2	OT5LJOWM	Strong	Genetic Variation	[22]
NECTIN1	OTTE5ZR6	Definitive	Genetic Variation	[23]

References

• [1] TGF3, MSX1, and MMP3 as Candidates for NSCLP in an Indian Population.Cleft Palate Craniofac J. 2019 Mar;56(3):363-372. doi: 10.1177/1055665618775727. Epub 2018 May 8.
• [2] 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.
• [3] Is there a genetic relationship between epilepsy and birth defects?.Neurology. 1992 Apr;42(4 Suppl 5):63-7.
• [4] Disrupting hedgehog and WNT signaling interactions promotes cleft lip pathogenesis.J Clin Invest. 2014 Apr;124(4):1660-71. doi: 10.1172/JCI72688. Epub 2014 Mar 3.
• [5] Molecular contribution to cleft palate production in cleft lip mice.Congenit Anom (Kyoto). 2014 May;54(2):94-9. doi: 10.1111/cga.12038.
• [6] Application of transmission disequilibrium tests to nonsyndromic oral clefts: including candidate genes and environmental exposures in the models.Am J Med Genet. 1997 Dec 19;73(3):337-44. doi: 10.1002/(sici)1096-8628(19971219)73:3<337::aid-ajmg21>3.0.co;2-j.
• [7] Maternal transmission effect of a PDGF-C SNP on nonsyndromic cleft lip with or without palate from a Chinese population.PLoS One. 2012;7(9):e46477. doi: 10.1371/journal.pone.0046477. Epub 2012 Sep 28.
• [8] PHF8, a gene associated with cleft lip/palate and mental retardation, encodes for an Nepsilon-dimethyl lysine demethylase.Hum Mol Genet. 2010 Jan 15;19(2):217-22. doi: 10.1093/hmg/ddp480. Epub 2009 Oct 19.
• [9] Transforming Growth Factor Alpha Taq I Polymorphisms and Nonsyndromic Cleft Lip and/or Palate Risk: A Meta-Analysis.Cleft Palate Craniofac J. 2018 Jul;55(6):814-820. doi: 10.1597/16-008. Epub 2018 Feb 22.
• [10] Searching for genes for cleft lip and/or palate based on breakpoint analysis of a balanced translocation t(9;17)(q32;q12).Cleft Palate Craniofac J. 2009 Sep;46(5):532-40. doi: 10.1597/08-047.1. Epub 2009 Feb 2.
• [11] FPGS gene is a novel causative gene for cleft lip in China.Med Hypotheses. 2011 Mar;76(3):371-3. doi: 10.1016/j.mehy.2010.10.043. Epub 2010 Nov 19.
• [12] 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.
• [13] FOXE1 polymorphisms and non-syndromic orofacial cleft susceptibility in a Chinese Han population.Oral Dis. 2016 May;22(4):274-9. doi: 10.1111/odi.12435. Epub 2016 Jan 20.
• [14] Two novel genes TOX3 and COL21A1 in large extended Malay families with nonsyndromic cleft lip and/or palate.Mol Genet Genomic Med. 2019 May;7(5):e635. doi: 10.1002/mgg3.635. Epub 2019 Mar 28.
• [15] 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.
• [16] SNPs and interaction analyses of IRF6, MSX1 and PAX9 genes in patients with nonsyndromic cleft lip with or without palate.Mol Med Rep. 2013 Oct;8(4):1228-34. doi: 10.3892/mmr.2013.1617. Epub 2013 Aug 6.
• [17] Molecular pathogenesis in Diamond-Blackfan anemia.Int J Hematol. 2010 Oct;92(3):413-8. doi: 10.1007/s12185-010-0693-7. Epub 2010 Sep 30.
• [18] 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.
• [19] Psychosocial Adjustments Among Adolescents With Craniofacial Conditions and the Influence of Social Factors: A Multi-Informant Study.Cleft Palate Craniofac J. 2020 May;57(5):624-636. doi: 10.1177/1055665619888308. Epub 2019 Nov 26.
• [20] Cleft lip with cleft palate, ankyloglossia, and hypodontia are associated with TBX22 mutations.J Dent Res. 2011 Apr;90(4):450-5. doi: 10.1177/0022034510391052. Epub 2011 Jan 19.
• [21] Molecular basis of EEC (ectrodactyly, ectodermal dysplasia, clefting) syndrome: five new mutations in the DNA-binding domain of the TP63 gene and genotype-phenotype correlation.Br J Dermatol. 2010 Jan;162(1):201-7. doi: 10.1111/j.1365-2133.2009.09496.x. Epub 2009 Nov 9.
• [22] 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.
• [23] Mutation analysis of PVRL1 in patients with non-syndromic cleft of the lip and/or palate in Guangdong.Genet Mol Res. 2015 Apr 15;14(2):3400-8. doi: 10.4238/2015.April.15.3.