SLC17A9

Chr 20AD

solute carrier family 17 member 9

Also known as: C20orf59, POROK8, VNUT

NCBI Gene: 63910 ENSG00000101194 UniProt: Q9BYT1 OMIM: 612107

The protein is a voltage-gated ATP nucleotide transporter that controls ATP accumulation in lysosomes and secretory vesicles, regulating ATP-dependent proteins in these organelles and ATP exocytosis. Mutations cause autosomal dominant porokeratosis 8, disseminated superficial actinic type, a skin condition characterized by abnormal keratinization. The gene shows low constraint against loss-of-function variants, consistent with its specific dermatologic phenotype rather than severe developmental effects.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of a family of transmembrane proteins that are involved in the transport of small molecules. The encoded protein participates in the vesicular uptake, storage, and secretion of adenoside triphosphate (ATP) and other nucleotides. A mutation in this gene was found in individuals with autosomal dominant disseminated superficial actinic porokeratosis-8. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]

OMIM ResearchGenerating clinical summary…

MultiplemechanismADLOEUF 1.391 OMIM phenotype

Clinical Summary— SLC17A9

⚡

Population Constraint (gnomAD)

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

📋

ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 71 VUS of 114 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?

1.39LOEUF

pLI 0.000

Z-score 0.03

OE 0.99 (0.72–1.39)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.29Z-score

OE missense 0.78 (0.69–0.87)

204 obs / 262.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.99 (0.72–1.39)

0≤0.351.4

Missense OE?0.78 (0.69–0.87)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 25 / 25.1Missense obs/exp: 204 / 262.8Syn Z: -0.73

This gene — mechanism propensity

0.7327th %ile

GOF

0.6832th %ile

LOF

0.2970th %ile

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

DNprediction above median

GOFprediction 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

114 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS71

Likely Benign17

Benign9

Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	1	0	0	1
Likely Pathogenic	0	0	0	0	0
VUS	1	70	0	0	71
Likely Benign	1	7	2	7	17
Benign	2	3	3	1	9
Total	4	81	5	8	98

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

View in ClinVar →

32 pathogenic / likely-pathogenic (of 51) ClinVar copy-number / structural variants overlap SLC17A9 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →