Details of Disease

General Information of Disease (ID: DIS48CCP)

Disease Name Hypospadias
Synonyms hypospadias familial; familial hypospadias; hypospadias (disease); hypospadias
Definition Hypospadias is the displacement of the urethral meatus on the ventrum of the penis. This abnormality is associated with a varyingly bent, twisted penis and opened dorsal prepuce.
Disease Hierarchy
DISQCXZX: Disorder of development or morphogenesis
DISYKSRF: Genetic disease
DIS7W23Z: Reproductive system disorder
DIS48CCP: Hypospadias
Disease Identifiers
MONDO ID
MONDO_0005345
MESH ID
D007021
UMLS CUI
C0848558
MedGen ID
163083
HPO ID
HP:0000047
SNOMED CT ID
416010008

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)
This Disease Is Related to 16 DTT Molecule(s)
Gene Name DTT ID Evidence Level Mode of Inheritance REF
BMP7 TTKOBRA Limited Autosomal dominant [1]
BMP7 TTKOBRA Limited Genetic Variation [2]
ADK TTL732K Strong Genetic Variation [3]
ATF3 TTCE793 Strong Biomarker [4]
CYP11A1 TTSYVO6 Strong Biomarker [5]
CYP17A1 TTRA5BZ Strong Genetic Variation [6]
FGFR2 TTGJVQM Strong Biomarker [7]
FKBP4 TTHY0FT Strong Biomarker [8]
GREM1 TTOUZN5 Strong Genetic Variation [3]
HAAO TTWON83 Strong Genetic Variation [9]
HOXA13 TTN26OM Strong Biomarker [10]
HSD17B13 TTDJYZR Strong Genetic Variation [11]
KCNMA1 TTE87WJ Strong Genetic Variation [3]
MAP3K1 TTW8TJI Strong Genetic Variation [12]
MMP11 TTZW4MV Strong Altered Expression [13]
WT1 TTZ8UT4 Strong Biomarker [14]
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⏷ Show the Full List of 16 DTT(s)
This Disease Is Related to 3 DME Molecule(s)
Gene Name DME ID Evidence Level Mode of Inheritance REF
HSD17B3 DEX8J7E Limited Genetic Variation [15]
HSD3B2 DEN0GVQ moderate Genetic Variation [16]
HSD17B7 DEDMWFX Strong Genetic Variation [11]
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This Disease Is Related to 38 DOT Molecule(s)
Gene Name DOT ID Evidence Level Mode of Inheritance REF
BMP7 OTYATP2K Limited Autosomal dominant [1]
DGKK OTHIMF7L Limited Genetic Variation [17]
ARNT2 OTAQD3YV Strong Genetic Variation [13]
BNC2 OTU22H9Z Strong Genetic Variation [18]
CCDC59 OT2U776E Strong Genetic Variation [3]
CD207 OTI9RUDN Strong Biomarker [19]
DENND2B OT7UH61B Strong Genetic Variation [3]
DHRS11 OTU3J0ZL Strong Genetic Variation [11]
DNAH6 OTUZNWKV Strong Genetic Variation [3]
DOCK11 OTFSTN6A Strong Genetic Variation [20]
EEFSEC OTJ4KKOO Strong Genetic Variation [3]
EMX2 OT0V8OYK Strong Genetic Variation [21]
EXOC3 OT8N3306 Strong Genetic Variation [3]
EYA1 OTHU807A Strong Genetic Variation [22]
FLAD1 OTY8R02L Strong Genetic Variation [23]
GLI3 OTKDOE94 Strong Biomarker [10]
HHIP OT77RQYS Strong Biomarker [24]
HOXA3 OTIX5XFB Strong Genetic Variation [3]
HOXA4 OTNVTQDT Strong Genetic Variation [3]
HOXB6 OT3TFQ0U Strong Genetic Variation [25]
HOXD13 OTWSC8TF Strong Biomarker [10]
INSL3 OT7KUNTE Strong Biomarker [26]
IRX6 OTL79R2K Strong Genetic Variation [9]
LAMA5 OTIIXE4M Strong Biomarker [27]
MAFB OTH2N3T8 Strong Biomarker [4]
MAMLD1 OT9EVMQY Strong Biomarker [28]
MID1 OTWN1PGU Strong Genetic Variation [29]
MYBPH OTQJBPUR Strong Biomarker [30]
MYH11 OTVNVWY3 Strong Posttranslational Modification [31]
PHACTR2 OTWMX2A8 Strong Genetic Variation [3]
PIP OTH719AH Strong Altered Expression [32]
PROK2 OT70IFEZ Strong Biomarker [33]
RNF128 OTJO86CJ Strong Biomarker [3]
SF1 OTLEDM2S Strong Genetic Variation [34]
SOX9 OTVDJFGN Strong Biomarker [35]
TAX1BP1 OTGJMGJ9 Strong Genetic Variation [3]
TMEM70 OTLTKYXG Strong Genetic Variation [36]
TPPP OTCFMSUF Strong Biomarker [37]
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⏷ Show the Full List of 38 DOT(s)

References

1 Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
2 Hypospadias and genes related to genital tubercle and early urethral development.J Urol. 2013 Nov;190(5):1884-92. doi: 10.1016/j.juro.2013.05.061. Epub 2013 May 30.
3 Genome-wide association analyses identify variants in developmental genes associated with hypospadias.Nat Genet. 2014 Sep;46(9):957-63. doi: 10.1038/ng.3063. Epub 2014 Aug 10.
4 Regulation of masculinization: androgen signalling for external genitalia development.Nat Rev Urol. 2018 Jun;15(6):358-368. doi: 10.1038/s41585-018-0008-y.
5 A novel homozygous mutation in CYP11A1 gene is associated with late-onset adrenal insufficiency and hypospadias in a 46,XY patient.J Clin Endocrinol Metab. 2009 Mar;94(3):936-9. doi: 10.1210/jc.2008-1118. Epub 2008 Dec 30.
6 Interaction between CYP1A1/CYP17A1 polymorphisms and parental risk factors in the risk of hypospadias in a Chinese population.Sci Rep. 2019 Mar 11;9(1):4123. doi: 10.1038/s41598-019-40755-8.
7 FGF8, FGF10 and FGF receptor 2 in foreskin of children with hypospadias: an analysis of immunohistochemical expression patterns and gene transcription.J Pediatr Urol. 2020 Feb;16(1):41.e1-41.e10. doi: 10.1016/j.jpurol.2019.10.007. Epub 2019 Oct 18.
8 Fkbp52 regulates androgen receptor transactivation activity and male urethra morphogenesis.J Biol Chem. 2010 Sep 3;285(36):27776-84. doi: 10.1074/jbc.M110.156091. Epub 2010 Jul 6.
9 Single Nucleotide Polymorphisms of HAAO and IRX6 Genes as Risk Factors for Hypospadias.J Urol. 2019 Feb;201(2):386-392. doi: 10.1016/j.juro.2018.07.050.
10 Maternal exposure to di-n-butyl phthalate (DBP) induces combined anorectal and urogenital malformations in male rat offspring.Reprod Toxicol. 2016 Jun;61:169-76. doi: 10.1016/j.reprotox.2016.04.007. Epub 2016 Apr 11.
11 Genetic polymorphisms of 17 -hydroxysteroid dehydrogenase 3 and the risk of hypospadias.J Sex Med. 2010 Aug;7(8):2729-38. doi: 10.1111/j.1743-6109.2009.01641.x. Epub 2010 Jan 6.
12 Molecular diagnostics of disorders of sexual development: an Indian survey and systems biology perspective.Syst Biol Reprod Med. 2019 Apr;65(2):105-120. doi: 10.1080/19396368.2018.1549619. Epub 2018 Dec 14.
13 Individual variation of the genetic response to bisphenol a in human foreskin fibroblast cells derived from cryptorchidism and hypospadias patients.PLoS One. 2012;7(12):e52756. doi: 10.1371/journal.pone.0052756. Epub 2012 Dec 28.
14 The Wilms' tumour 1 gene as a factor in non-syndromic hypospadias: evidence and controversy.Pathology. 2018 Jun;50(4):377-381. doi: 10.1016/j.pathol.2017.12.341. Epub 2018 May 7.
15 46,XY Disorder of Sex Development due to 17-Beta Hydroxysteroid Dehydrogenase Type 3 Deficiency in an Infant of Greek Origin.J Clin Res Pediatr Endocrinol. 2018 Mar 1;10(1):74-78. doi: 10.4274/jcrpe.4829. Epub 2017 Jul 24.
16 Molecular basis of non-syndromic hypospadias: systematic mutation screening and genome-wide copy-number analysis of 62 patients.Hum Reprod. 2015 Mar;30(3):499-506. doi: 10.1093/humrep/deu364. Epub 2015 Jan 20.
17 Association between diacylglycerol kinase kappa variants and hypospadias susceptibility in a Han Chinese population.Asian J Androl. 2018 Jan-Feb;20(1):85-89. doi: 10.4103/aja.aja_13_17.
18 Human balanced translocation and mouse gene inactivation implicate Basonuclin 2 in distal urethral development.Eur J Hum Genet. 2011 May;19(5):540-6. doi: 10.1038/ejhg.2010.245. Epub 2011 Feb 2.
19 Langerhans cells in hypospadias: an analysis of Langerin (CD207) and HLA-DR on epidermal sheets and full thickness skin sections.BMC Urol. 2019 Nov 12;19(1):114. doi: 10.1186/s12894-019-0551-8.
20 Characterization of two novel homozygous missense mutations involving codon 6 and 259 of type II 3beta-hydroxysteroid dehydrogenase (3betaHSD) gene causing, respectively, nonsalt-wasting and salt-wasting 3betaHSD deficiency disorder.J Clin Endocrinol Metab. 2000 Apr;85(4):1678-85. doi: 10.1210/jcem.85.4.6539.
21 Severe sex differentiation disorder in a boy with a 3.8 Mb 10q25.3-q26.12 microdeletion encompassing EMX2.Am J Med Genet A. 2014 Oct;164A(10):2618-22. doi: 10.1002/ajmg.a.36662. Epub 2014 Jun 26.
22 Six1 and Eya1 are critical regulators of peri-cloacal mesenchymal progenitors during genitourinary tract development.Dev Biol. 2011 Dec 1;360(1):186-94. doi: 10.1016/j.ydbio.2011.09.020. Epub 2011 Sep 24.
23 Post-mortem detection of FLAD1 mutations in 2 Turkish siblings with hypotonia in early infancy.Neuromuscul Disord. 2018 Sep;28(9):787-790. doi: 10.1016/j.nmd.2018.05.009. Epub 2018 May 31.
24 Di-n-butyl phthalate induced autophagy of uroepithelial cells via inhibition of hedgehog signaling in newborn male hypospadias rats.Toxicology. 2019 Dec 1;428:152300. doi: 10.1016/j.tox.2019.152300. Epub 2019 Sep 27.
25 Mutation screening of BMP4, BMP7, HOXA4 and HOXB6 genes in Chinese patients with hypospadias.Eur J Hum Genet. 2007 Jan;15(1):23-8. doi: 10.1038/sj.ejhg.5201722. Epub 2006 Sep 27.
26 Phthalate-Induced Fetal Leydig Cell Dysfunction Mediates Male Reproductive Tract Anomalies.Front Pharmacol. 2019 Nov 6;10:1309. doi: 10.3389/fphar.2019.01309. eCollection 2019.
27 Requirement for basement membrane laminin 5 during urethral and external genital development.Mech Dev. 2016 Aug;141:62-69. doi: 10.1016/j.mod.2016.05.004. Epub 2016 May 18.
28 Family History is Underestimated in Children with Isolated Hypospadias: A French Multicenter Report of 88 Families.J Urol. 2018 Oct;200(4):890-894. doi: 10.1016/j.juro.2018.04.072. Epub 2018 Apr 30.
29 Complex rearrangement of the exon 6 genomic region among Opitz G/BBB Syndrome MID1 alterations.Eur J Med Genet. 2013 Aug;56(8):404-10. doi: 10.1016/j.ejmg.2013.05.009. Epub 2013 Jun 19.
30 Genome-wide DNA methylation profiling of CpG islands in hypospadias.J Urol. 2012 Oct;188(4 Suppl):1450-5. doi: 10.1016/j.juro.2012.03.047. Epub 2012 Aug 17.
31 Exploring disease-specific methylated CpGs in human male genital abnormalities by using methylated-site display-amplified fragment length polymorphism (MSD-AFLP).J Reprod Dev. 2019 Dec 18;65(6):491-497. doi: 10.1262/jrd.2019-069. Epub 2019 Aug 29.
32 Association of prolactin-induced protein with preputial development of hypospadias.BJU Int. 2012 Mar;109(6):926-32. doi: 10.1111/j.1464-410X.2011.10467.x. Epub 2011 Aug 25.
33 Variants in congenital hypogonadotrophic hypogonadism genes identified in an Indonesian cohort of 46,XY under-virilised boys.Hum Genomics. 2017 Feb 16;11(1):1. doi: 10.1186/s40246-017-0098-2.
34 Mutation analysis of the SRD5A2, AR and SF-1 genes in 52 Chinese boys with hypospadias.J Pediatr Endocrinol Metab. 2013;26(9-10):887-93. doi: 10.1515/jpem-2012-0316.
35 MiR-145-modulated SOX9-mediated hypospadias through acting on mitogen-activated protein kinase signaling pathway.J Cell Physiol. 2019 Jul;234(7):10397-10410. doi: 10.1002/jcp.27708. Epub 2018 Nov 22.
36 Mitochondrial encephalocardio-myopathy with early neonatal onset due to TMEM70 mutation.Arch Dis Child. 2010 Apr;95(4):296-301. doi: 10.1136/adc.2009.168096.
37 Cri-du-chat (5p-) syndrome presenting with cerebellar hypoplasia and hypospadias: prenatal diagnosis and aCGH characterization using uncultured amniocytes.Gene. 2013 Jul 25;524(2):407-11. doi: 10.1016/j.gene.2013.03.003. Epub 2013 Mar 14.