SLC30A9

Chr 4AR

solute carrier family 30 member 9

ENSG00000014824 UniProt: Q6PML9 OMIM: 604604

The protein functions as a mitochondrial proton-coupled zinc antiporter that exports zinc from mitochondria and maintains zinc homeostasis, mitochondrial morphology, and mitochondrial health. Mutations cause Birk-Landau-Perez syndrome, inherited in an autosomal recessive pattern. The gene shows tolerance to loss-of-function variants (LOEUF 0.679), suggesting complete loss of function may be required for disease manifestation.

OMIM ResearchSummary from OMIM, UniProt

Mitochondrial proton-coupled zinc ion antiporter mediating the export of zinc from the mitochondria and involved in zinc homeostasis, zinc mobilization as well as mitochondrial morphology and health (PubMed:28334855, PubMed:34397090, PubMed:34433664, PubMed:35614220). In nucleus, functions as a secondary coactivator for nuclear receptors by cooperating with p160 coactivators subtypes. Plays a role in transcriptional activation of Wnt-responsive genes (By similarity)

OMIM ResearchGenerating clinical summary…

DNmechanismARLOEUF 0.681 OMIM phenotype

Clinical Summary— SLC30A9

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Gene-Disease Validity (ClinGen)

psychomotor regression-oculomotor apraxia-movement disorder-nephropathy syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

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Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.68LOEUF

pLI 0.000

Z-score 3.11

OE 0.45 (0.31–0.68)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.85Z-score

OE missense 0.70 (0.63–0.79)

210 obs / 299.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.45 (0.31–0.68)

0≤0.351.4

Missense OE?0.70 (0.63–0.79)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 17 / 37.5Missense obs/exp: 210 / 299.9Syn Z: 0.41

This gene — mechanism propensity

0.73top 25%

GOF

0.6247th %ile

LOF

0.3067th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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