A Rare Case of Human Diphallia Associated with Hypospadias

Table 1

Selected genetic variants associated with present diphallia case.

Gene	Protein Function
Development and morphogenesis
BMP4	Bone morphogenetic protein 4. Cartilage and bone formation. Tooth development, limb formation. Embryonic mammary development. Prostate gland, ureteric bud morphogenesis.
CFAP53	Cilia- and flagella-associated protein 53. Beating of primary cilia. Organ laterality during embryogenesis.
DNAH5	Dynein heavy chain 5, axonemal. Cilium assembly, cilium movement, determination of left/right asymmetry, heart development.
IFT172	Intraflagellar transport protein 172 homolog. Maintenance and formation of cilia. Hedgehog signaling. Dorsal/ventral pattern formation, left/right axis specification, limb, bone, brain development.
KMT2C	Histone-lysine N-methyltransferase 2C. Histone methyltransferase. Leukemogenesis and developmental disorder.
SOX6	Transcription factor SOX-6. Plays a key role in several developmental processes, including neurogenesis and skeleton formation.
TBX6	T-box transcription factor TBX6. Neural development. Morphology and motility of nodal cilia.
UBE3A	Ubiquitin-protein ligase E3A. Development. Androgen receptor signaling. Prostate gland growth.
Signal transduction
ADGRA2	Adhesion G protein-coupled receptor A2. Functions as a WNT7-specific coactivator of canonical Wnt signaling.
APC	Adenomatous polyposis coli protein. Participates in Wnt signaling as a negative regulator.
CCAR2	Cell cycle and apoptosis regulator protein 2. Positively regulates the beta-catenin pathway (canonical Wnt signaling pathway) and is required for MCC-mediated repression of the beta-catenin pathway.
RYR2	Ryanodine receptor 2. Calcium, BMP signaling.
Cell differentiation, organization, division, proliferation, growth, migration, death
CDK15	Cyclin-dependent kinase 15. Anti-apoptotic protein.
CYFIP2	Cytoplasmic FMR1-interacting protein 2. T-cell adhesion, apoptosis.
DAPK1	Death-associated protein kinase 1. Cell survival, apoptosis, autophagy.
DRAM1	DNA damage-regulated autophagy modulator protein 1.
HSP90AB1	Heat shock protein HSP 90-beta. Cell cycle control. Epigenetic modifier regulation.
MADD	MAP kinase-activating death domain protein. Cell proliferation, survival, death.
NFKB1	Nuclear factor NF-kappa-B p105 subunit. Cell growth, differentiation.
PAK2	Serine/threonine-protein kinase PAK 2. Cell motility, cell cycle progression, apoptosis or proliferation.
TNFAIP8L2	Tumor necrosis factor alpha-induced protein 8-like protein 2. Promotes Fas-induced apoptosis.
TP53BP2	Apoptosis-stimulating of p53 protein 2. Regulates apoptosis and cell growth. Impedes cell cycle progression at G2/M.
WWC1	Protein KIBRA. Cell proliferation, apoptosis.
Hormones and hormonal regulation
NCOA6	Nuclear receptor coactivator 6. Androgen receptor coactivator.
TMF1	TATA element modulatory factor. Androgen receptor coactivator.
UBE3A	Ubiquitin-protein ligase E3A. Androgen receptor coactivator.