SLC39A14

Chr 8ADAR

solute carrier family 39 member 14

Also known as: HCIN, HMNDYT2, LZT-Hs4, NET34, ZIP14, cig19

NCBI Gene: 23516 ENSG00000104635 UniProt: Q15043 OMIM: 608736

This protein is a divalent metal transporter that mediates cellular uptake of manganese, zinc, and iron, functioning as a critical regulator of systemic metal homeostasis including manganese transport across the blood-brain barrier and intestinal absorption. Mutations cause hypermanganesemia with dystonia 2 and hyperostosis cranialis interna, both involving early-onset movement disorders with abnormal metal accumulation. The gene shows both autosomal dominant and autosomal recessive inheritance patterns and is moderately constrained against loss-of-function variants (LOEUF 0.554).

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the the SLC39A family of divalent metal transporters that mediates the cellular uptake of manganese, zinc, iron, and cadmium. The encoded protein contains eight transmembrane domains, a histidine-rich motif, and a metalloprotease motif, and is expressed on the plasma membrane and the endocytic vesicle membrane. It is an important transporter of nontransferrin-bound iron and a critical regulator of manganese homeostasis. Naturally occurring mutations in this gene are associated with neurodegeneration with brain iron accumulation and early-onset parkinsonism-dystonia with hypermanganesemia. [provided by RefSeq, May 2017]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Hyperostosis cranalis internaMIM #144755

Hypermanganesemia with dystonia 2MIM #617013

UniProtHyperostosis cranialis interna

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.55

LOEUF

LOF

Mechanism· G2P

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GeneReview available — SLC39A14