SLC22A14

Chr 3

solute carrier family 22 member 14

Also known as: OCTL2, OCTL4, ORCTL4

The protein functions as a riboflavin transporter at the inner mitochondrial membrane, particularly in spermatozoa, where it facilitates riboflavin uptake essential for energy generation and sperm motility. Mutations cause male infertility due to defects in sperm motility and flagellar structure, following an autosomal recessive inheritance pattern. This gene is not highly constrained against loss-of-function variants, consistent with its specialized role in male reproductive function.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.26
Clinical SummarySLC22A14
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.26LOEUF
pLI 0.000
Z-score 0.57
OE 0.88 (0.621.26)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.14Z-score
OE missense 0.98 (0.891.07)
325 obs / 332.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.88 (0.621.26)
00.351.4
Missense OE0.98 (0.891.07)
00.61.4
Synonymous OE1.04
01.21.6
LoF obs/exp: 21 / 24.0Missense obs/exp: 325 / 332.2Syn Z: -0.35
DN
0.80top 25%
GOF
0.7029th %ile
LOF
0.1993th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SLC22A14 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗