FLVCR1

Chr 1AR

FLVCR choline and heme transporter 1

Also known as: AXPC1, FLVCR, MFSD7B, NEDMISH, PCA, PCARP, RETSNS, SLC49A1

NCBI Gene: 28982ENSG00000162769UniProt: Q9Y5Y0

This gene encodes a member of the major facilitator superfamily of transporter proteins. The encoded protein is a heme transporter that may play a critical role in erythropoiesis by protecting developing erythroid cells from heme toxicity. This gene may play a role in posterior column ataxia with retinitis pigmentosa and the hematological disorder Diamond-Blackfan syndrome. [provided by RefSeq, Jan 2011]

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with microcephaly, absent speech, and hypotoniaMIM #621060
AR
Retinopathy-sensory neuropathy syndromeMIM #609033
AR
139
ClinVar variants
26
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— FLVCR1
🧬
Gene-Disease Validity (ClinGen)
FLVCR1-related retinopathy with or without ataxia · 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.
📋
ClinVar Variants
26 Pathogenic / Likely Pathogenic· 58 VUS of 139 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.67LOEUF
pLI 0.001
Z-score 2.77
OE 0.38 (0.23–0.67)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.85Z-score
OE missense 0.86 (0.77–0.95)
243 obs / 283.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.38 (0.23–0.67)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.86 (0.77–0.95)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.02
0≤1.21.6
LoF obs/exp: 9 / 23.5Missense obs/exp: 243 / 283.3Syn Z: -0.19

ClinVar Variant Classifications

139 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic10
VUS58
Likely Benign6
Benign40
Conflicting9
16
Pathogenic
10
Likely Pathogenic
58
VUS
6
Likely Benign
40
Benign
9
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
4
10
0
16
Likely Pathogenic
1
5
3
1
10
VUS
1
18
35
4
58
Likely Benign
0
1
5
0
6
Benign
0
3
36
1
40
Conflicting
—9
Total431896139

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

View in ClinVar →

Protein Context — Lollipop Plot

FLVCR1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

FLVCR1-related ataxia, posterior column, with retinitis pigmentosa

definitive
ARLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure
Dev. DisordersEye
G2P ↗
splice region variantframeshift variantmissense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Neurodevelopmental disorder with microcephaly, absent speech, and hypotonia

MIM #621060

Molecular basis of disorder known

Autosomal recessive

Retinopathy-sensory neuropathy syndrome

MIM #609033

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — FLVCR1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Molecular mechanism of choline and ethanolamine transport in humans.
Ri K et al.·Nature
2024Functional
Genetic landscape of congenital insensitivity to pain and hereditary sensory and autonomic neuropathies.
Lischka A et al.·Brain
2023
Dysregulation of FLVCR1a-dependent mitochondrial calcium handling in neural progenitors causes congenital hydrocephalus.
Bertino F et al.·Cell Rep Med
2024
Biallelic variation in the choline and ethanolamine transporter FLVCR1 underlies a severe developmental disorder spectrum.
Calame DG et al.·Genet Med
2025
Long non-coding RNA FLVCR1-AS1 functions as a ceRNA to aggravate cervical cancer cell growth by the miR-381-3p/MAGT1 axis.
Zhang J et al.·Arch Gynecol Obstet
2022
Clinical and imaging characteristics of posterior column ataxia with retinitis pigmentosa with a specific FLVCR1 mutation.
Lee J et al.·Ophthalmic Genet
2018
LncRNA FLVCR1-AS1 mediates miR-23a-5p/SLC7A11 axis to promote malignant behavior of cervical cancer cells.
Zhou X et al.·Bioengineered
2022
A Novel FLVCR1 Variant Implicated in Retinitis Pigmentosa.
Dockery A et al.·Adv Exp Med Biol
2019
A splice-site variant in FLVCR1 produces retinitis pigmentosa without posterior column ataxia.
Yusuf IH et al.·Ophthalmic Genet
2018Case report
HCV-related hepatocellular carcinoma: gene signatures associated with TERT promoter mutations and sex.
Bonelli P et al.·J Transl Med
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Posterior Column Ataxia with Retinitis Pigmentosa

Antisense Oligonucleotide Treatment for PCARP Disease Due to Mutation in FLVCR1

ENROLLING BY INVITATION
NCT06565572Phase EARLY_PHASE1University of Colorado, DenverStarted 2023-08-23
nL-FLVC-001

External Resources

Links to major genomics databases and tools