MCID: ORF002
MIFTS: 43

Orofacial Cleft

Categories: Fetal diseases, Genetic diseases, Rare diseases

Aliases & Classifications for Orofacial Cleft

MalaCards integrated aliases for Orofacial Cleft:

Name: Orofacial Cleft 12 29 6 15
Cleft, Orofacial 39

Classifications:



External Ids:

Disease Ontology 12 DOID:0050567

Summaries for Orofacial Cleft

Disease Ontology : 12 A physical disorder that is characterized by cleft lip and/or cleft palate that result in feeding, speech and hearing problems caused by failures during development.

MalaCards based summary : Orofacial Cleft, also known as cleft, orofacial, is related to orofacial cleft 1 and orofacial cleft 4. An important gene associated with Orofacial Cleft is OFC1 (Orofacial Cleft 1), and among its related pathways/superpathways are Embryonic and Induced Pluripotent Stem Cell Differentiation Pathways and Lineage-specific Markers and TP53 Network. The drugs leucovorin and Folic acid have been mentioned in the context of this disorder. Affiliated tissues include heart, bone and pituitary, and related phenotypes are craniofacial and digestive/alimentary

Related Diseases for Orofacial Cleft

Diseases in the Orofacial Cleft family:

Orofacial Cleft 1 Orofacial Cleft 11
Orofacial Cleft 3 Orofacial Cleft 2
Orofacial Cleft 4 Orofacial Cleft 6
Orofacial Cleft 5 Orofacial Cleft 9
Orofacial Cleft 12 Orofacial Cleft 10
Orofacial Cleft 13 Orofacial Cleft 14
Orofacial Cleft 15 Orofacial Cleft 8

Diseases related to Orofacial Cleft via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 216)
# Related Disease Score Top Affiliating Genes
1 orofacial cleft 1 35.3 OFCC1 OFC1
2 orofacial cleft 4 35.2 TP63 SUMO1 OFC4
3 orofacial cleft 10 35.2 SUMO1 IRF6
4 cleft lip/palate-ectodermal dysplasia syndrome 34.8 NECTIN1 IRF6 FOXE1
5 cleft lip 34.4 VAX1 TP63 SUMO1 OFC1 NECTIN1 MSX1
6 cleft palate, isolated 34.3 VAX1 TP63 SUMO1 NECTIN1 MSX1 IRF6
7 van der woude syndrome 1 33.9 VAX1 TP63 NECTIN1 MSX1 IRF6 FOXE1
8 popliteal pterygium syndrome 33.6 VAX1 NECTIN1 MSX1 IRF6 FOXE1
9 rapp-hodgkin syndrome 33.0 TP63 IRF6
10 cleft lip with or without cleft palate 32.8 SUMO1 OFC1 NECTIN1 MSX1 IRF6 BMP4
11 cleft lip/palate 32.8 TP63 NECTIN1 MSX1 IRF6 DLX4 BMP4
12 isolated cleft lip 32.4 TP63 NECTIN1 MSX1 IRF6 FOXE1
13 tooth agenesis 31.7 TP63 SUMO1 NECTIN1 MSX1 IRF6 BMP4
14 cleft lip and alveolus 31.5 TP63 NECTIN1 MSX1 IRF6
15 chromosome 2q35 duplication syndrome 31.2 TP63 NECTIN1 MSX1 IRF6 GREM1 BMP4
16 ankyloglossia with or without tooth anomalies 30.9 MSX1 IRF6
17 ankyloblepharon-ectodermal defects-cleft lip/palate 30.7 TP63 IRF6
18 orofacial cleft 6 12.8
19 orofacial cleft 5 12.8
20 orofacial cleft 15 12.8
21 orofacial cleft 11 12.7
22 orofacial cleft 2 12.7
23 orofacial cleft 8 12.7
24 orofacial cleft 12 12.6
25 orofacial cleft 9 12.6
26 orofacial cleft 13 12.6
27 orofacial cleft 3 12.6
28 orofacial cleft 14 12.6
29 orofacial clefting syndrome 12.5
30 tooth agenesis, selective, 1 12.3
31 microphthalmia, syndromic 11 11.6
32 split-hand/foot malformation 1 11.6
33 ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 1 11.6
34 microphthalmia, syndromic 6 11.5
35 split-hand/foot malformation 6 11.4
36 split-hand/foot malformation 3 11.4
37 split-hand/foot malformation 4 11.4
38 otofaciocervical syndrome 1 11.3
39 otofaciocervical syndrome 2 11.3
40 coloboma, ocular, with or without hearing impairment, cleft lip/palate, and/or mental retardation 11.2
41 hemifacial microsomia with radial defects 11.2
42 split-hand/foot malformation 1 with sensorineural hearing loss, autosomal recessive 11.2
43 facial clefting, oblique, 1 11.2
44 split-hand/foot malformation 5 11.2
45 split hand-foot malformation 11.2
46 physical disorder 10.8 VAX1 MSX1 IRF6 BMP4
47 syngnathia 10.8 MSX1 IRF6 BMP4
48 hypothyroidism, thyroidal or athyroidal, with spiky hair and cleft palate 10.8 MSX1 IRF6 FOXE1
49 hard palate cancer 10.8 MSX1 IRF6 BMP4
50 tooth size 10.8 MSX1 BMP4

Graphical network of the top 20 diseases related to Orofacial Cleft:



Diseases related to Orofacial Cleft

Symptoms & Phenotypes for Orofacial Cleft

MGI Mouse Phenotypes related to Orofacial Cleft:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 craniofacial MP:0005382 9.61 BMP4 FOXE1 IRF6 MSX1 NECTIN1 OFCC1
2 digestive/alimentary MP:0005381 9.17 BMP4 FOXE1 IRF6 MSX1 SUMO1 TP63

Drugs & Therapeutics for Orofacial Cleft

Drugs for Orofacial Cleft (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 11)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
leucovorin Approved 58-05-9 6006 143
2
Folic acid Approved, Nutraceutical, Vet_approved 59-30-3 6037
3 Anti-Inflammatory Agents
4 Diflucortolone valerate
5 Hormone Antagonists
6 Diflucortolone
7 Hormones
8 glucocorticoids
9 Vitamin B Complex
10 Vitamin B9
11 Folate

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Risk Association of Orofacial Cleft and Glucocorticoids Exposure During Pregnancy: a Meta-analysis Completed NCT03788863 Diflucortolone valerate (BAY866146)
2 Unilateral Cleft Repair in One Surgery With Pure Primary Healing Completed NCT04108416
3 Identification of Genetic Factors Implicated in Orofacial Cleft Using Whole Exome Sequencing GENEPIC Recruiting NCT03065686
4 Three-dimensional Development of the Palate in Bilateral Orofacial Cleft Newborns One Year After Early Neonatal Cheiloplasty: Classic and Geometric Morphometric Evaluation Recruiting NCT03839290
5 Genetic Analysis of Neural Tube and Orofacial Cleft Defects in the Irish Population Terminated NCT00341068

Search NIH Clinical Center for Orofacial Cleft

Genetic Tests for Orofacial Cleft

Genetic tests related to Orofacial Cleft:

# Genetic test Affiliating Genes
1 Orofacial Cleft 29

Anatomical Context for Orofacial Cleft

MalaCards organs/tissues related to Orofacial Cleft:

40
Heart, Bone, Pituitary, Whole Blood, Kidney, B Lymphoblasts, Eye

Publications for Orofacial Cleft

Articles related to Orofacial Cleft:

(show top 50) (show all 350)
# Title Authors PMID Year
1
Body Mass Index and Association With Caries in School-Aged Children With Orofacial Cleft: A Case-Control Study. 61
31450975 2020
2
A retrospective nationwide study of the dental caries experience of New Zealand children with orofacial cleft. 61
31596004 2020
3
Whole genome sequencing of orofacial cleft trios from the Gabriella Miller Kids First Pediatric Research Consortium identifies a new locus on chromosome 21. 61
31848685 2020
4
Analysis of zebrafish periderm enhancers facilitates identification of a regulatory variant near human KRT8/18. 61
32031521 2020
5
Feeding problems and gastrointestinal diseases in Down syndrome. 61
31784293 2020
6
Morphological variability in unrepaired bilateral clefts with and without cleft palate evaluated with geometric morphometrics. 61
31792971 2019
7
Epidemiological characteristic of Orofacial clefts and its associated congenital anomalies: retrospective study. 61
31870360 2019
8
Neurophysiological changes and chronic pain in cleft patients. 61
31711995 2019
9
Nonlinear gene expression-phenotype relationships contribute to variation and clefting in the A/WySn mouse. 61
31469941 2019
10
Prenatal diagnosis of foetal hydrocephalus and suspected X-linked recessive inheritance of cleft lip in a Chihuahua. 61
31902834 2019
11
Paramedian Orofacial Cleft. 61
31679595 2019
12
Holoprosencephaly, orofacial cleft, and frontonaso-orbital encephaloceles: Genetic evaluation of a possible new syndrome. 61
31353810 2019
13
The impact of cleft lip and/or palate on parental quality of life: A pilot study. 61
31369974 2019
14
Interferon regulatory factor 6 is required for proper wound healing in vivo. 61
31724286 2019
15
The functional variant of NTN1 contributes to the risk of nonsyndromic cleft lip with or without cleft palate. 61
31780810 2019
16
Frequencies of Different Types of Cleft Lip, Cleft Lip with Palate and Cleft Palate in Bangladeshi Children. 61
31599248 2019
17
A novel mutation (c.1010G>T; p.R337L) in TP63 as a cause of split-hand/foot malformation with hypodontia. 61
31420900 2019
18
Genetic factors define CPO and CLO subtypes of nonsyndromicorofacial cleft. 61
31609978 2019
19
Health Information Seeking Through Social Media and Search Engines by Parents of Children With Orofacial Cleft in Nigeria. 61
31665894 2019
20
Deregulated Adhesion Program in Palatal Keratinocytes of Orofacial Cleft Patients. 61
31652793 2019
21
Reconstruction of a Unilateral Alveolar Cleft Using a Customized Allogenic Bone Block and Subsequent Dental Implant Placement in an Adult Patient. 61
31276656 2019
22
Coordination of the Fetal Medicine Institute and the Cleft and Craniofacial Center: Application to Early Management of Infants With Cleft Lip and Palate. 61
31524754 2019
23
miRNAs as biomarkers of orofacial clefts: A systematic review. 61
31479540 2019
24
Can contamination of the environment by dioxins cause craniofacial defects? 61
31169026 2019
25
A systematic genetic analysis and visualization of phenotypic heterogeneity among orofacial cleft GWAS signals. 61
31172578 2019
26
Nasolabial outcomes in a nationwide study of orofacial cleft in New Zealand. 61
30849215 2019
27
Surgical, Speech, and Audiologic Outcomes in Patients With Orofacial Cleft and Van der Woude Syndrome. 61
31299749 2019
28
Five decades of orofacial cleft management and research in Brazil. 61
30297262 2019
29
Response to comments on "Orofacial cleft management by short-term surgical missions in South America: literature review". 61
30318114 2019
30
Re: "Orofacial cleft management by short-term surgical missions in South America: literature review". 61
30935819 2019
31
Oral Health-Related Quality of Life and Dental Caries Status in Children With Orofacial Cleft: An Indian Outlook. 61
31198331 2019
32
Efficacy of Periconceptional High-Dose Folic Acid in Isolated Orofacial Cleft Prevention: A Systematic Review. 61
31602129 2019
33
Patient-Perceived Barriers to Accessing Cleft Care at a Tertiary Referral Center in São Paulo, Brazil. 61
30153749 2019
34
Two novel genes TOX3 and COL21A1 in large extended Malay families with nonsyndromic cleft lip and/or palate. 61
30924295 2019
35
Social impact of cleft lip repair on married adults: an uncommon finding from a semi-urban African settlement. 61
30850222 2019
36
A Comparison of Early Versus Late Prenatal Magnetic Resonance Imaging in the Diagnosis of Cleft Palate. 61
30855394 2019
37
Orthodontic-Surgical Approach for Treating Skeletal Class III Malocclusion With Severe Maxillary Deficiency in Isolated Cleft Palate. 61
29787302 2019
38
Maternal folic acid supplementation reduces the severity of cleft palate in Tgf-β3 null mutant mice. 61
30683931 2019
39
Proportion of Orofacial Clefts Attributable to Recognized Risk Factors. 61
29727221 2019
40
Molecular Screening of VAX1 Gene Polymorphisms Uncovered the Genetic Heterogeneity of Nonsyndromic Orofacial Cleft Among Saudi Arabian Patients. 61
30633559 2019
41
Cleft Palate with or without Cleft Lip: The Role of Retronasal Triangle View and Maxillary Gap at 11-14 Weeks. 61
30852571 2019
42
Copy number variation analysis of twin pairs discordant for cleft lip with or without cleft palate. 61
31663445 2019
43
First trimester ondansetron exposure and risk of structural birth defects. 61
30385129 2019
44
GESTATIONAL DIABETES MELLITUS AND THE DEVELOPMENT OF CLEFT LIP / PALATE IN NEWBORNS. 61
31149070 2019
45
Nonsyndromic orofacial clefts among Jews and non-Jews born in 13 hospitals in Israel during 1993-2005. 61
29956842 2018
46
Identification of paternal uniparental disomy on chromosome 22 and a de novo deletion on chromosome 18 in individuals with orofacial clefts. 61
30141273 2018
47
Malthus Mysterious Orofacial Cleft Correction. 61
29537879 2018
48
Orofacial cleft management by short-term surgical missions in South America: literature review. 61
29945819 2018
49
A score-based method for quality control of fetal hard palate assessment during routine second-trimester ultrasound examination. 61
29964326 2018
50
Candida species biotypes in the oral cavity of infants and children with orofacial clefts under surgical rehabilitation. 61
30138757 2018

Variations for Orofacial Cleft

ClinVar genetic disease variations for Orofacial Cleft:

6 (show all 23) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 BMP4 NM_001202.6(BMP4):c.*143A>TSNV Uncertain significance 313347 rs750395429 14:54416607-54416607 14:53949889-53949889
2 BMP4 NM_001202.6(BMP4):c.*251C>TSNV Uncertain significance 313336 rs573118445 14:54416499-54416499 14:53949781-53949781
3 BMP4 NM_001202.6(BMP4):c.*150deldeletion Uncertain significance 313337 rs878985651 14:54416600-54416600 14:53949882-53949882
4 BMP4 NM_001202.6(BMP4):c.*148_*149insAATinsertion Uncertain significance 313342 rs796563569 14:54416601-54416602 14:53949883-53949884
5 BMP4 NM_001202.6(BMP4):c.*148_*149insTinsertion Uncertain significance 313341 rs796563569 14:54416601-54416602 14:53949883-53949884
6 BMP4 NM_001202.6(BMP4):c.*35C>GSNV Uncertain significance 313350 rs886050540 14:54416715-54416715 14:53949997-53949997
7 BMP4 NM_001202.6(BMP4):c.-342G>ASNV Uncertain significance 313356 rs778139957 14:54423477-54423477 14:53956759-53956759
8 BMP4 NM_001202.6(BMP4):c.*272A>GSNV Uncertain significance 313335 rs568281464 14:54416478-54416478 14:53949760-53949760
9 BMP4 NM_001202.6(BMP4):c.*149G>ASNV Uncertain significance 313345 rs74495140 14:54416601-54416601 14:53949883-53949883
10 BMP4 NM_001202.6(BMP4):c.*148_*149deldeletion Uncertain significance 313338 rs140085940 14:54416601-54416602 14:53949883-53949884
11 BMP4 NM_001202.6(BMP4):c.*146_*148dupduplication Uncertain significance 313344 rs1555339771 14:54416601-54416602 14:53949883-53949884
12 BMP4 NM_001202.6(BMP4):c.370+12C>TSNV Uncertain significance 313351 rs368426865 14:54418559-54418559 14:53951841-53951841
13 BMP4 NM_001202.6(BMP4):c.288A>G (p.Glu96=)SNV Uncertain significance 313352 rs886050541 14:54418653-54418653 14:53951935-53951935
14 BMP4 NM_001202.6(BMP4):c.224A>G (p.Lys75Arg)SNV Uncertain significance 313353 rs777501416 14:54418717-54418717 14:53951999-53951999
15 BMP4 NM_001202.6(BMP4):c.215A>G (p.Gln72Arg)SNV Uncertain significance 313354 rs771047931 14:54418726-54418726 14:53952008-53952008
16 BMP4 NM_001202.6(BMP4):c.*148_*149insATinsertion Uncertain significance 313339 rs796563569 14:54416601-54416602 14:53949883-53949884
17 BMP4 NM_001202.6(BMP4):c.*148_*149insAGinsertion Uncertain significance 313343 rs796563569 14:54416601-54416602 14:53949883-53949884
18 BMP4 NM_001202.6(BMP4):c.*145_*149deldeletion Uncertain significance 313340 rs886050539 14:54416601-54416605 14:53949883-53949887
19 BMP4 NM_001202.6(BMP4):c.*131A>TSNV Uncertain significance 313348 rs76149166 14:54416619-54416619 14:53949901-53949901
20 BMP4 NM_001202.6(BMP4):c.-146T>CSNV Likely benign 313355 rs73267467 14:54423281-54423281 14:53956563-53956563
21 BMP4 NM_001202.6(BMP4):c.*148A>TSNV Likely benign 313346 rs76335800 14:54416602-54416602 14:53949884-53949884
22 BMP4 NM_001202.6(BMP4):c.*88C>TSNV Likely benign 313349 rs74054236 14:54416662-54416662 14:53949944-53949944
23 BMP4 NM_001202.6(BMP4):c.455T>C (p.Val152Ala)SNV Benign/Likely benign 197190 rs17563 14:54417522-54417522 14:53950804-53950804

Expression for Orofacial Cleft

Search GEO for disease gene expression data for Orofacial Cleft.

Pathways for Orofacial Cleft

Pathways related to Orofacial Cleft according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.05 TP63 MSX1 IRF6 BMP4
2
Show member pathways
10.5 TP63 SUMO1
3 9.86 TP63 IRF6

GO Terms for Orofacial Cleft

Cellular components related to Orofacial Cleft according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nuclear chromatin GO:0000790 9.1 VAX1 TP63 MSX1 IRF6 FOXE1 DLX4

Biological processes related to Orofacial Cleft according to GeneCards Suite gene sharing:

(show all 22)
# Name GO ID Score Top Affiliating Genes
1 regulation of transcription, DNA-templated GO:0006355 10.1 VAX1 TP63 SUMO1 MSX1 IRF6 FOXE1
2 positive regulation of transcription by RNA polymerase II GO:0045944 10.07 TP63 MSX1 IRF6 GREM1 DLX4 BMP4
3 cell differentiation GO:0030154 9.99 VAX1 TP63 IRF6 FOXE1 DLX4 BMP4
4 positive regulation of transcription, DNA-templated GO:0045893 9.93 TP63 IRF6 GREM1 FOXE1 BMP4
5 negative regulation of transcription, DNA-templated GO:0045892 9.85 TP63 SUMO1 MSX1 GREM1 FOXE1 BMP4
6 negative regulation of transcription by RNA polymerase II GO:0000122 9.8 VAX1 TP63 SUMO1 MSX1 FOXE1 DLX4
7 odontogenesis of dentin-containing tooth GO:0042475 9.63 TP63 MSX1 BMP4
8 pituitary gland development GO:0021983 9.61 MSX1 BMP4
9 hair follicle morphogenesis GO:0031069 9.6 TP63 FOXE1
10 proximal/distal pattern formation GO:0009954 9.58 TP63 GREM1
11 camera-type eye morphogenesis GO:0048593 9.58 NECTIN1 BMP4
12 embryonic morphogenesis GO:0048598 9.57 MSX1 BMP4
13 negative regulation of chondrocyte differentiation GO:0032331 9.55 GREM1 BMP4
14 anatomical structure formation involved in morphogenesis GO:0048646 9.52 TP63 BMP4
15 epithelial to mesenchymal transition involved in endocardial cushion formation GO:0003198 9.49 MSX1 BMP4
16 cranial skeletal system development GO:1904888 9.48 TP63 FOXE1
17 mesenchymal to epithelial transition involved in metanephros morphogenesis GO:0003337 9.43 GREM1 BMP4
18 BMP signaling pathway involved in heart development GO:0061312 9.4 MSX1 BMP4
19 embryonic hindlimb morphogenesis GO:0035116 9.33 TP63 MSX1 BMP4
20 cloacal septation GO:0060197 9.32 TP63 BMP4
21 embryonic limb morphogenesis GO:0030326 9.26 TP63 MSX1 GREM1 BMP4
22 roof of mouth development GO:0060021 9.02 VAX1 SUMO1 MSX1 IRF6 FOXE1

Molecular functions related to Orofacial Cleft according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 DNA-binding transcription factor activity, RNA polymerase II-specific GO:0000981 9.43 VAX1 TP63 MSX1 IRF6 FOXE1 DLX4
2 sequence-specific DNA binding GO:0043565 9.1 VAX1 TP63 MSX1 IRF6 FOXE1 DLX4

Sources for Orofacial Cleft

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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