Mary Shelley's Frankenstein was published just a year after Northanger Abbey, in the midst of gothic romance fever. It immediately distanced itself from the rest of the genre though in almost every way. It's themes are deeper, it's narrative structure is more compelling, it's characters are more complicated, and it avoids (or at least seriously tweaks) the standard gothic romance conventions.
In fact, at first look it's hard to spot any similarities at all between Frankenstein and books like The Castle of Otranto or The Mysteries of Udolpho. The most obvious connections are simply kindred tones and settings. There's an undeniable sense of gloom and dread over Frankenstein. And of course a strong supernatural angle and a crumbling building or two. But there's no dashing young hero out to rescue an innocent beauty from a sinister count. Shelley's not that interested in the typical plot.
Those elements are present in Frankenstein, but Shelley subverts them. Elizabeth is the heroine, but she's murdered instead of rescued. Not the first time that's happened in a gothic romance, but Shelley twists further by making Victor Frankenstein play a dual role as both would-be protector to Elizabeth and the architect of her doom. The Monster is also a paradox in that he's a willful murderer, but also extremely sympathetic. The lines between hero and villain - if there even are such things in the novel - are very blurry.