FLVCR1

Chr 1

FLVCR choline and heme transporter 1

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

NCBI Gene: 28982 ENSG00000162769 UniProt: Q9Y5Y0

The protein functions as a transporter that mediates uptake of choline and ethanolamine for phospholipid biosynthesis and exports heme from cells to prevent toxicity. Mutations cause autosomal recessive neurodevelopmental disorder with microcephaly, absent speech, and hypotonia, as well as retinopathy-sensory neuropathy syndrome. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.668), and clinical manifestations primarily affect the nervous system with early neurodevelopmental impacts.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.67

Clinical Summary— FLVCR1

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Gene-Disease Validity (ClinGen)

FLVCR1-related retinopathy with or without ataxia · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

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

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ClinVar Variants

64 unique Pathogenic / Likely Pathogenic· 308 VUS of 614 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — FLVCR1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.67LOEUF

pLI 0.001

Z-score 2.77

OE 0.38 (0.23–0.67)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.85Z-score

OE missense 0.86 (0.77–0.95)

243 obs / 283.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.38 (0.23–0.67)

0≤0.351.4

Missense OE?0.86 (0.77–0.95)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 9 / 23.5Missense obs/exp: 243 / 283.3Syn Z: -0.19

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveFLVCR1-related ataxia, posterior column, with retinitis pigmentosaLOFAR

This gene — mechanism propensity

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

0.7034th %ile

GOF

0.77top 25%

LOF

0.2485th %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

614 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic34

Likely Pathogenic30

VUS308

Likely Benign158

Benign48

Conflicting19

Pathogenic

Likely Pathogenic

308

VUS

158

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	21	9	4	0	34
Likely Pathogenic	17	10	2	1	30
VUS	3	221	69	15	308
Likely Benign	0	1	53	104	158
Benign	0	3	43	2	48
Conflicting	—				19
Total	41	244	171	122	597

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

View in ClinVar →

17 pathogenic / likely-pathogenic (of 25) ClinVar copy-number / structural variants overlap FLVCR1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →