SLC39A14

Chr 8ADAR

solute carrier family 39 member 14

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

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).

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAD/ARLOEUF 0.552 OMIM phenotypes
Clinical SummarySLC39A14
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.
📖
GeneReview available — SLC39A14
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.55LOEUF
pLI 0.150
Z-score 2.97
OE 0.26 (0.140.55)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.92Z-score
OE missense 0.68 (0.600.77)
194 obs / 285.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.26 (0.140.55)
00.351.4
Missense OE0.68 (0.600.77)
00.61.4
Synonymous OE0.93
01.21.6
LoF obs/exp: 5 / 19.0Missense obs/exp: 194 / 285.1Syn Z: 0.62
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveSLC39A14-related early onset dystonia parkinsonismLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7229th %ile
GOF
0.75top 25%
LOF
0.2969th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SLC39A14 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →