SLC16A8

Chr 22

solute carrier family 16 member 8

Also known as: MCT3, REMP

NCBI Gene: 23539 ENSG00000100156 UniProt: O95907 OMIM: 610409

This protein functions as a retinal pigment epithelium-specific proton-coupled lactate transporter that facilitates lactate and proton transport out of the retina, maintaining pH and ion homeostasis in the outer retina. Mutations cause autosomal recessive retinal dystrophy, affecting vision and retinal function. The gene shows low constraint against loss-of-function variants.

OMIM ResearchSummary from RefSeq, UniProt

SLC16A8 is a member of a family of proton-coupled monocarboxylate transporters that mediate lactate transport across cell membranes (Yoon et al., 1999 [PubMed 10493836]).[supplied by OMIM, Apr 2010]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.28

Clinical Summary— SLC16A8

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Population Constraint (gnomAD)

Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

99 VUS of 111 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?

1.28LOEUF

pLI 0.009

Z-score 1.08

OE 0.56 (0.28–1.28)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.93Z-score

OE missense 0.84 (0.75–0.94)

221 obs / 263.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.56 (0.28–1.28)

0≤0.351.4

Missense OE?0.84 (0.75–0.94)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 4 / 7.1Missense obs/exp: 221 / 263.4Syn Z: -0.19

This gene — mechanism propensity

0.75top 25%

GOF

0.88top 5%

LOF

0.1993th %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

111 submitted variants in ClinVar

ClinVar

Classification Summary

VUS99

Likely Benign4

Benign3

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	0	99	0	99
Likely Benign	0	3	1	4
Benign	1	2	0	3
Total	1	104	1	106

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

View in ClinVar →

25 pathogenic / likely-pathogenic (of 27) ClinVar copy-number / structural variants overlap SLC16A8 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →