SLC22A31

Chr 16

solute carrier family 22 member 31

NCBI Gene: 146429 ENSG00000259803 UniProt: A6NKX4

The protein functions as an organic anion transporter that mediates cellular uptake of ions across membranes. Mutations cause autosomal recessive disorders, though specific associated phenotypes are not well-characterized in the current literature. The gene shows minimal constraint against loss-of-function variants, suggesting tolerance to complete protein loss.

ResearchSummary from RefSeq, UniProt

Predicted to enable transmembrane transporter activity. Predicted to be involved in monoatomic ion transport and transmembrane transport. Predicted to be located in membrane. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.81

Clinical Summary— SLC22A31

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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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ClinVar Variants

86 VUS of 102 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.81LOEUF

pLI 0.000

Z-score -0.71

OE 1.23 (0.81–1.81)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.19Z-score

OE missense 1.04 (0.93–1.16)

218 obs / 210.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.23 (0.81–1.81)

0≤0.351.4

Missense OE?1.04 (0.93–1.16)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 14 / 11.4Missense obs/exp: 218 / 210.2Syn Z: -0.14

This gene — mechanism propensity

0.7035th %ile

GOF

0.74top 25%

LOF

0.3163th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

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.

ClinVar Variant Classifications

102 submitted variants in ClinVar

ClinVar

Classification Summary

VUS86

Likely Benign6

Benign4

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	1	67	18	86
Likely Benign	0	3	3	6
Benign	0	4	0	4
Total	1	74	21	96

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

71 pathogenic / likely-pathogenic (of 107) ClinVar copy-number / structural variants overlap SLC22A31 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →