FLVCR2

Chr 14AR

FLVCR choline and putative heme transporter 2

Also known as: C14orf58, CCT, EPV, FLVCRL14q, MFSD7C, PVHH, SLC49A2

This gene encodes a choline transporter that mediates choline uptake across the blood-brain barrier, which is critical for brain development, and also functions as a heme transporter involved in mitochondrial respiration and ATP synthesis. Mutations cause proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome, a severe developmental brain disorder affecting vascular development and resulting in fluid-filled brain cavities. The condition follows autosomal recessive inheritance and FLVCR2 is highly intolerant to loss-of-function mutations.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.931 OMIM phenotype
Clinical SummaryFLVCR2
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Gene-Disease Validity (ClinGen)
Fowler syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.93LOEUF
pLI 0.000
Z-score 1.82
OE 0.57 (0.370.93)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.06Z-score
OE missense 0.99 (0.901.09)
293 obs / 296.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.57 (0.370.93)
00.351.4
Missense OE0.99 (0.901.09)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 12 / 21.0Missense obs/exp: 293 / 296.1Syn Z: -0.05
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveFLVCR2-related proliferative vasculopathy and hydraencephaly-hydrocephaly syndromeLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.78top 25%
GOF
0.81top 10%
LOF
0.2091th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

FLVCR2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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