SLC39A8

Chr 4AR

solute carrier family 39 member 8

Also known as: BIGM103, CDG2N, LZT-Hs6, PP3105, ZIP8

This protein functions as a divalent metal cation transporter that mediates cellular uptake of zinc, manganese, and selenium, which are essential for development, tissue homeostasis, and immune function. Mutations cause congenital disorder of glycosylation type IIn, inherited in an autosomal recessive pattern. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.465), reflecting its importance in cellular metal homeostasis across multiple organ systems including the nervous system, immune system, and hepatobiliary tract.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.471 OMIM phenotype
Clinical SummarySLC39A8
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Gene-Disease Validity (ClinGen)
Leigh syndrome · ARLimited

Limited evidence — not for standalone diagnostic reporting

Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.67) — some intolerance to loss-of-function variants.
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Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.47LOEUF
pLI 0.669
Z-score 3.10
OE 0.18 (0.080.47)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.10Z-score
OE missense 0.80 (0.710.90)
187 obs / 234.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.18 (0.080.47)
00.351.4
Missense OE0.80 (0.710.90)
00.61.4
Synonymous OE0.84
01.21.6
LoF obs/exp: 3 / 16.7Missense obs/exp: 187 / 234.3Syn Z: 1.20
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveSLC39A8-related intellectual disability with cerebellar atrophyLOFAR

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

DN
0.6162th %ile
GOF
0.6736th %ile
LOF
0.4332th %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

SLC39A8 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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