Table 2.
Variants identified in hypospadias in humans
| Gene | Variants | Phenotype | Reference | |
|---|---|---|---|---|
| BMP pathway | BMP4 | c.619C>G (het), c.668G>A (het) c.751C>T (het) |
penoscrotal penile |
Chen et al., 2006 |
| BMP7 | c.907C>T (het) c.597G>A (het), c.1567A>G (het) c.1465T>A (het) |
glandular penile penoscrotal |
||
| WT1 | WT1 | N130N (het) A131T (het) S159S (het) |
penoscrotal or penile penile glandular |
Wang et al., 2004 |
| Homeobox | HOXA4 | c.385G>T (het) c.869C>G (het) |
penoscrotal penile |
Chen et al., 2006 |
| HOXB6 | c.367T>C (het) c.124C>A (het) |
penile scrotal |
||
| Gonad development and signalling | MAP3K1 | c.2416G>A (het) | penoscrotal | Das et al., 2013 |
| CHD7 | not specified | penoscrotal | Baxter et al., 2015 | |
| NR5A1 (SF1) | c.319C>T (het), c.103-3C>A (het), c.31G>T (het) | penoscrotal | Köhler et al., 2009 | |
| p.Arg313Cys | glandular | Allali et al., 2011 | ||
| c.184C>T, c.361delGAGACAGG, c.460G>A p.Arg62Cys (het), p.Glu121AlafsX25 (het), p.Ala154Thr (het) |
penile penile |
Tantawy et al., 2014 | ||
| W279X (het), g3314-3317delTCTC | perineal | Warman et al., 2011 | ||
| p.Y25C (het) | penoscrotal | Wu et al., 2013 | ||
| MAMLD1 | E124X (hemi), Q197X (hemi), R653X (hemi) | penoscrotal | Fukami et al., 2006 | |
| V432A (hemi), L121X (hemi) CAG 10 > 13 |
proximal coronal |
Kalfa et al., 2008a | ||
| S143X, P384L | proximal | Kalfa et al.,2012 | ||
| p.P286S, p.V432A, p.N589S, p.531ins3Q, p.Q529K | not specified | Chen Y et al., 2010 | ||
| p.K609fsX1070 | not specified | Igarashi et al., 2015 | ||
| Steroidogenesis | HSD3B2 | p.S213T (het), p.S284R (het) | proximal | Codner et al., 2004 |
| p.A10T (hom) | proximal | Kon et al., 2015 | ||
| CYP11A1 | p.R360W, p.R405X (comp het) | penoscrotal | Parajes et al., 2012 | |
| L222P (hom) | midshaft | Rubtsov et al., 2009 | ||
| AKR1C3 | p.Ala215Thr (het) | penile | Söderhäll et al., 2014 | |
| Androgen production and signalling | SRD5A2 | R246Q (hom), Q6X (hom), G203S + L224H (het), 656delT (het) | scrotal | Wang et al., 2004 |
| R227Q (hom), G203S (hom) | penile or scrotal | |||
| R227Q (het) | glandular | |||
| L113V (het), H231R (het) | proximal | Silver and Russell, 1999 | ||
| G196S (het) | midshaft | Thai et al., 2005 | ||
| AR | 1991C>T (hemi) | glandular | Wang et al., 2004 | |
| 2577C>A (hemi) | penile | |||
| 2519G>A (hemi), 2525T>C (hemi), 2564G>A (hemi) | perineal, micropenis, bifid scrotum | |||
| Q798E (hemi) | scrotal | Thai et al., 2005 | ||
| V870A (hemi) | penoscrotal | Hiort et al., 1994 | ||
| G566V (hemi) | perineal | Alléra et al., 1995 | ||
| P546S (hemi) | midshaft | Sutherland et al., 1996 | ||
| S597T (hemi) | severe | Nordenskjöld et al., 1999 | ||
| Oestrogen pathway | ATF3 | A90G (het), c.817C>T (het) | moderate | Beleza-Meireles et al., 2008 |
| C53070T, C53632A Ins53943A |
various | Kalfa et al., 2008b | ||
| L23M (het) | anterior | |||
| Others | BNC2 | p.P306A (het), p.P579L (het), p.Q152R (het), p.E240G (het) p.R283G (het) |
not detailed | Bhoj et al., 2011 |
Gene variants and mutations proposed to be pathogenic in hypospadias. Genes are grouped into signalling pathways. The cDNA or amino acid changes and the inheritance are indicated based on the original publication. The phenotype of the patient(s) carrying these variants is indicated. The references are shown for each study. hemi = Hemizygous; het = heterozygous; hom = homozygous.