Table 5 Function of candidate genes containing SNPs in CDS region related to dermatological diseases/conditions

Malignant cutaneous melanoma cancer

OBSCN [15]

- Is a RhoGEF protein that interacts with cytoskeletal calmodulin and titin and is part of the giant sarcomeric signaling protein family of myosin light chain kinases

- Mutant human OBSCN protein (E4574K) is associated with melanoma in human.

STAB2 (or FEEL2) [16, 17]

- is a large, transmembrane receptor protein which may function in angiogenesis, lymphocyte homing, cell adhesion, or receptor scavenging.

- Somatic missense homozygous mutant human STAB2 gene (c.3862 T > G translating to p.S1288A) is associated with melanoma in skin from human leg (observed in 2 of 2 samples)

LRP2 (or megalin) [17, 18]

- Is a member of the low density lipoprotein (LDL) receptor gene family essential for brain development.

- Somatic missense heterozygous mutant human LRP2 gene (c.6284G > A translating to p.R2095Q) is associated with melanoma in skin from human leg (observed in 2 of 2 samples).

ASPM [17, 19]

- This gene is the human ortholog of the Drosophila melanogaster ’abnormal spindle’ gene (asp), which is essential for normal mitotic spindle function in embryonic neuroblasts.

- Somatic nonsense heterozygous mutant human ASPM gene (c.7174C > T translating to p.Q2392*) is associated with melanoma in skin from human leg (observed in 2 of 2 samples).

GRM5 [20]

- Is a member of G protein-coupled receptor that are widely expressed in the brain and modulate many diverse signaling pathways

- In mouse melanocytes, transgenic rat GRM5 protein (S901A mutant) affects development of melanoma in mouse.

BRCA2 [21, 22]

- At the cellular level, loss of BRCA2 function results in sensitivity to cross-linking agents, a decrease in homology-directed repair of double-stranded DNA breaks (DSBs), and defects in replication and checkpoint control

- Inherited mutations in BRCA1 and this gene, BRCA2, confer increased lifetime risk of developing breast or ovarian cancer.

- Mutant human BRCA2 gene is associated with malignant melanoma in Homo sapiens.

XIRP1 [17, 23]

- Its function is unknown, but it is upregulated in wounded skeletal muscle cells in zebrafish

- Somatic nonsense heterozygous mutant human XIRP1 gene (c.2838G > A translating to p.W946*) is associated with melanoma in skin from human leg (observed in 2 of 2 samples).

RIDDLE syndrome

RNF168 [24]

- Is an E3 ubiquitin ligase

- Mutant human RNF168 gene (deletion c.1323_1326del of ACAA and DNA duplication mutation) is associated with RIDDLE (radiosensitivity, immunodeficiency, dysmorphic features, and learning difficulties) syndrome, which a novel human immunodeficiency disorder associated with defective double strand break repair.

Schulman-Upshaw syndrome

ADAMTS13 [25]

- Is von Willebrand Factor (VWF) cleaving metalloproteinase.

- Is associated with the development of thrombotic thrombocytopenic purpura (TTP), known as the Schulman-Upshaw syndrome.

- Mutant human ADAMTS13 gene (deletion c.1783_1784delTT) is associated with congenital TTP.

Autosomal recessive cutis laxa type IIA

ATP6V0A2 [26]

- Is a subunit of the vacuolar ATPase (v-ATPase), a heteromultimeric enzyme that is essential for the acidification of diverse cellular components.

- Mutations in human ATP6V0A2 protein (p.Q765* (rs80356758), p.R63* (rs80356750), deletion, and insertion) is associated with autosomal recessive cutis laxa type IIA.

Wrinkly skin syndrome

ATP6V0A2 [26]

- Mutant human ATP6V0A2 gene (g.10132G > A) is associated with wrinkly skin syndrome

Hyperpigmentation

GRM5 [20]

- In mouse melanocytes, transgenic rat mGlur5 [GRM5] protein increases hyperpigmentation of pinna in mouse ear.

Development of blister

PLAU [27, 28]

- Is a serine protease involved in degradation of the extracellular matrix and possibly tumor cell migration and proliferation.

- Heterozygous- and heterozygous mutant mouse Plg gene in mouse affects development of blister in mouse subepidermal skin that is altered by transgenic uPAR (PLAUR) protein and transgenic uPA (product of PLAU) protein and development of blister.