Categories: Pigmentation phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 600570 (gene)

Single-gene trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: unknown

Key variant known: yes

Year key variant first reported: 2025

Species summary: Montandon et al. (2025) investigated "a mono-locus trait with two recessive alleles, motley and stripe, that both cause pattern aberrations in the corn snake":
"The wild-type pattern of the corn snake . . . consists of dorsal and lateral red blotches on an orange background, whereas the ventral scales exhibit black and white checkers.
The Motley phenotype . . . is characterized by elongated dorsal blotches that tend to fuse together at the edges and reduced and less well-defined lateral blotches than the wild-type. As its name implies, this phenotype is highly variable along the body of a single individual and among Motley individuals. Yet, they are all characterized by the absence of the ventral black checkers.
In Stripe animals . . . , the dorsal and lateral blotches are replaced by four continuous red stripes, two dorsally and two laterally, that run along the entire length of the body. Stripe individuals also have uniformly white ventral scales."

Inheritance: Montandon et al. (2025): " The motley (m^m) and stripe (m^s) alleles are recessive to the wild-type one. Heterozygous Motley/Stripe individuals (m^m/m^s) have a phenotype intermediate between Motley and Stripe with dorsal blotches that tend to fuse and occasionally form stripes."

Mapping: Using mapping-by-sequencing, Montandon et al. (2025) mapped this pigmentation locus to a 4Mb region containing the Chloride Voltage-Gated Channel 2 (CLCN2) gene.

Molecular basis: Montandon et al. (2025): "the Motley phenotype is associated with the downregulation of CLCN2 in embryonic skin, while a disruptive mutation affects the Stripe CLCN2 protein.  . . .  The CLCN2 Stripe transcript includes a 397 bp insertion, between exons 5 and 6, that introduces a premature stop codon and truncates the protein to only 205 aa [omia.variant:1783] . . .  . As a result, the chloride channel core domain is shortened from twelve to two transmembrane regions and the cystathionine-beta-synthase (CBS) domain is absent". Intriguingly, "The insertion in the Stripe CLCN2 resembles in length and sequence the insertion in the OCA2 gene that we previously identified as the causal mutation for the amelanistic trait in corn snakes [OMIA:002130-94885] . . .  . It corresponds to a 5832 bp Copia LTR-retrotransposon. The CLCN2 and OCA2 retrotransposon inserts only differ by a single nucleotide substitution . . .  . It is therefore possible that this transposable element is currently active in the corn snake genome and contributes to the evolution of new traits."

Pathology: Montandon et al. (2025): "most of the symptoms observed in humans [with mutations in CLCN2], such as loss of coordination, difficulty walking, personality changes, trouble speaking, and weak muscles, do not apply to snakes".

Associated gene: