FLVCR1

Summary

FLVCR1 (FLVCR choline and heme transporter 1, HGNC:24682) is a protein-coding gene on chromosome 1q32.3, encoding Choline/ethanolamine transporter FLVCR1 (Q9Y5Y0). Uniporter that mediates the transport of extracellular choline and ethanolamine into cells, thereby playing a key role in phospholipid biosynthesis.

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.

Source: NCBI Gene 28982 — RefSeq curated summary.

At a glance

• Gene–disease (curated): FLVCR1-related retinopathy with or without ataxia (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 6
• Clinical variants (ClinVar): 609 total — 34 pathogenic, 17 likely-pathogenic
• Phenotypes (HPO): 113
• MANE Select transcript: NM_014053

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24682
Approved symbol	FLVCR1
Name	FLVCR choline and heme transporter 1
Location	1q32.3
Locus type	gene with protein product
Status	Approved
Aliases	FLVCR, MFSD7B, PCA, SLC49A1
Ensembl gene	ENSG00000162769
Ensembl biotype	protein_coding
OMIM	609144
Entrez	28982

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 6 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000366971, ENST00000419102, ENST00000474693, ENST00000483790, ENST00000579295, ENST00000867613, ENST00000930967, ENST00000930968, ENST00000971333

RefSeq mRNA: 1 — MANE Select: NM_014053 NM_014053

CCDS: CCDS1510

Canonical transcript exons

ENST00000366971 — 10 exons

Exon	Start	End
ENSE00001068430	212887891	212888001
ENSE00001068434	212863725	212863869
ENSE00001443144	212858275	212859190
ENSE00001629822	212895216	212899363
ENSE00003529134	212872678	212872818
ENSE00003543077	212888489	212888594
ENSE00003559288	212885293	212885396
ENSE00003583473	212889146	212889257
ENSE00003596929	212894986	212895053
ENSE00003605605	212883371	212883438

Expression profiles

Bgee: expression breadth ubiquitous, 240 present calls, max score 98.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.7436 / max 327.2458, expressed in 1621 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
8491	6.7673	1516
8492	0.9927	530
8490	0.9836	569

Top tissues by expression

252 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	98.88	gold quality
ileal mucosa	UBERON:0000331	98.39	gold quality
epithelial cell of pancreas	CL:0000083	95.34	gold quality
corpus epididymis	UBERON:0004359	93.28	gold quality
adrenal tissue	UBERON:0018303	90.60	gold quality
bronchial epithelial cell	CL:0002328	90.46	gold quality
buccal mucosa cell	CL:0002336	89.88	gold quality
duodenum	UBERON:0002114	89.80	gold quality
bronchus	UBERON:0002185	89.52	gold quality
germinal epithelium of ovary	UBERON:0001304	88.24	gold quality
oviduct epithelium	UBERON:0004804	87.84	gold quality
pylorus	UBERON:0001166	87.21	gold quality
pigmented layer of retina	UBERON:0001782	86.90	gold quality
tibia	UBERON:0000979	86.87	gold quality
trabecular bone tissue	UBERON:0002483	86.77	gold quality
pancreatic ductal cell	CL:0002079	86.74	gold quality
colonic mucosa	UBERON:0000317	86.53	gold quality
caput epididymis	UBERON:0004358	86.21	gold quality
seminal vesicle	UBERON:0000998	86.15	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.10	gold quality
calcaneal tendon	UBERON:0003701	85.74	gold quality
ventricular zone	UBERON:0003053	85.36	gold quality
mucosa of sigmoid colon	UBERON:0004993	85.27	gold quality
visceral pleura	UBERON:0002401	84.78	gold quality
islet of Langerhans	UBERON:0000006	84.54	gold quality
cerebellar vermis	UBERON:0004720	84.51	gold quality
jejunum	UBERON:0002115	84.29	gold quality
Brodmann (1909) area 23	UBERON:0013554	83.57	gold quality
sural nerve	UBERON:0015488	83.27	gold quality
bone marrow cell	CL:0002092	83.05	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.54

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EPAS1, ETS1

miRNA regulators (miRDB)

123 targeting FLVCR1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-10527-5P	99.91	72.28	3754

Literature-anchored findings (GeneRIF, showing 29)

• the FLVCR gene on 1q31 is not involved in Diamond-Blackfan anemia in families studied (PMID:15996880)
• results suggest that multiple FLVCR1 regions are critical for mediating efficient feline leukemia virus subgroup C (FeLV-C) infection and that these regions are distinct from the FeLV-C envelope binding site (PMID:16439531)
• Alternative splicing of FLVCR1 transcripts and subsequent FLVCR1 insufficiency is an additional contributing factor to the erythropoietic defect observed in Diamond-Blackfan anemia. (PMID:18815190)
• hemopexin directly interacts with FLVCR (PMID:20610401)
• These results suggest that aberrant FLVCR1 causes a selective degeneration of a subpopulation of neurons in the retina and the posterior columns of the spinal cord via dysregulation of heme or iron homeostasis. (PMID:21070897)
• Posterior column ataxia with retinitis pigmentosa is caused by mutations in FLVCR1. (PMID:21267618)
• relative protein expression of 2 heme transporters, Feline Leukemia Virus, Subgroup C, Receptor 1 (FLVCR1) and Breast Cancer Resistance Protein, was assessed in placental tissue in relation to maternal/neonatal iron status and placental iron concentration (PMID:21593354)
• Study identified sequence variants in the known disease-causing genes SLC6A3 and FLVCR1, and present evidence to strongly support the pathogenicity of variants identified in TUBGCP6, BRAT1, SNIP1, CRADD, and HARS. (PMID:22279524)
• FLVCR1 mutants failed to fold properly in the ER, were rapidly degraded in the lysosomes, and therefore, could not export heme out of cells. Thus, accumulation of heme in FLVCR1-mutant cells could cause cellular toxicity. (PMID:22483575)
• FLVCR1b regulates erythropoiesis by controlling mitochondrial heme efflux, whereas FLVCR1a expression is required to prevent hemorrhages and edema. (PMID:23187127)
• both HIF2alpha and ETS1 are involved in the transcriptional regulation of Flvcr1a and that HIF2alpha is absolutely required for Flvcr1a induction upon hypoxia (PMID:24576667)
• Flvcr1 regulates differentiation of erythroid progenitors by controlling intracellular heme accumulation. (PMID:25795718)
• RPS19-downregulated erythroleukemia cells show reduced FLVCR1a and FLVCR1b mRNA levels associated with heme overload. (PMID:26058344)
• Data shows that FLVCR1a participates in the control of intestinal mucosa homeostasis by exporting the excess of de novo synthesized heme from intestinal cells. (PMID:26067085)
• Using fibroblasts and lymphoblastoid cell lines from patients with sensory neurodegeneration, we here show that the FLVCR1-mutations reduce heme export activity, enhance oxidative stress and increase sensitivity to programmed cell death. Our data link heme metabolism to sensory neuron maintenance and suggest that intracellular heme overload causes early-onset degeneration of pain-sensing neurons in humans (PMID:27923065)
• Altogether, these findings showed a direct association between FLVCR1 mRNA levels and hyperglycemia, suggesting that increased adipose tissue heme exportation might disrupt, or is the consequence of, impaired systemic glucose metabolism during the progression to type 2 diabetes. (PMID:28706239)
• Mutation in FLVCR1 gene is associated with Posterior column ataxia with retinitis pigmentosa coexisting with sensory-autonomic neuropathy and leukemia. (PMID:28766925)
• Here, we describe a patient with non-syndromic retinitis pigmentosa homozygous for a splice-site variant in FLVCR1 (c.1092 + 5G>A) without evidence of posterior column ataxia or cerebellar degeneration. (PMID:29192808)
• findings suggested that FLVCR1-AS1/miR-573/E2F3 axis was an important signaling pathway in mediating tumorigenesis and progression of NSCLC (PMID:30309647)
• We describe clinical and retinal imaging features in the one of the largest cohorts of affected patients in the literature. Given the availability of genetic testing for this phenotype, testing for FLVCR1 mutations should be considered in pediatric and adult patients with sensory ataxia and retinitis pigmentosa. (PMID:30444160)
• Mutations in FLVCR1 can present with the clinical picture of a non-syndromic autosomal recessive RP (in this case RP without PCA), RP with mild cerebellar signs, but also PCARP. (PMID:30656474)
• FLVCR1 p.Tyr341Cys mutation was observed homozygously in seven Retinitis Pigmentosa affected Irish patients across four pedigrees. (PMID:31884612)
• Isolated juvenile macular dystrophy without posterior column ataxia associated with FLVCR1 mutation. (PMID:34433355)
• Extending the phenotype of posterior column ataxia with retinitis pigmentosa caused by variants in FLVCR1. (PMID:34931442)
• Mfsd7b facilitates choline transport and missense mutations affect choline transport function. (PMID:38055060)
• Structural basis of lipid head group entry to the Kennedy pathway by FLVCR1. (PMID:38693265)
• Molecular mechanism of choline and ethanolamine transport in humans. (PMID:38778100)
• Dysregulation of FLVCR1a-dependent mitochondrial calcium handling in neural progenitors causes congenital hydrocephalus. (PMID:39019006)
• Apoptotic metabolites ameliorate bone aging phenotypes via TCOF1/FLVCR1-mediated mitochondrial homeostasis. (PMID:39237990)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	flvcr1	ENSDARG00000031587
mus_musculus	Flvcr1	ENSMUSG00000066595
rattus_norvegicus	Flvcr1	ENSRNOG00000049633
drosophila_melanogaster	HisT	FBGN0033196
caenorhabditis_elegans	C09D4.1	WBGENE00015632

Paralogs (4): FLVCR2 (ENSG00000119686), SLC49A4 (ENSG00000138463), SLC49A3 (ENSG00000169026), CFAP276 (ENSG00000179902)

Protein

Protein identifiers

Choline/ethanolamine transporter FLVCR1 — Q9Y5Y0 (reviewed: Q9Y5Y0)

Alternative names: Feline leukemia virus subgroup C receptor-related protein 1, Heme transporter FLVCR1

All UniProt accessions (2): Q9Y5Y0, H7C3Z2

UniProt curated annotations — full annotation on UniProt →

Function. Uniporter that mediates the transport of extracellular choline and ethanolamine into cells, thereby playing a key role in phospholipid biosynthesis. Choline and ethanolamine are the precursors of phosphatidylcholine and phosphatidylethanolamine, respectively, the two most abundant phospholipids. Transport is not coupled with proton transport and is exclusively driven by the choline (or ethanolamine) gradient across the plasma membrane. Also acts as a heme b transporter that mediates heme efflux from the cytoplasm to the extracellular compartment. Uniporter that mediates the transport of extracellular choline and ethanolamine into cells. Choline and ethanolamine are the precursors of phosphatidylcholine and phosphatidylethanolamine, respectively, the two most abundant phospholipids. Transport is not coupled with proton transport and is exclusively driven by the choline (or ethanolamine) gradient across the plasma membrane. Also acts as a heme b transporter that mediates heme efflux from the cytoplasm to the extracellular compartment. Heme export depends on the presence of HPX and is required to maintain intracellular free heme balance, protecting cells from heme toxicity. Heme export provides protection from heme or ferrous iron toxicities in liver, brain, sensory neurons and during erythropoiesis, a process in which heme synthesis intensifies. Possibly export coproporphyrin and protoporphyrin IX, which are both intermediate products in the heme biosynthetic pathway. Does not export bilirubin. The molecular mechanism of heme transport, whether electrogenic, electroneutral or coupled to other ions, remains to be elucidated. Heme b transporter that promotes heme efflux from the mitochondrion to the cytoplasm. Essential for erythroid differentiation. (Microbial infection) Confers susceptibility to feline leukemia virus subgroup C (FeLV-C) infection in vitro.

Subcellular location. Cell membrane Mitochondrion membrane.

Tissue specificity. Found all hematopoietic tissues including peripheral blood lymphocytes. Some expression is found in pancreas and kidney.

Post-translational modifications. N-Glycosylated.

Disease relevance. Retinopathy-sensory neuropathy syndrome (RETSNS) [MIM:609033] An autosomal recessive neurodegenerative syndrome beginning in infancy with areflexia and retinitis pigmentosa. Nyctalopia (night blindness) and peripheral visual field loss are usually evident during late childhood or teenage years, with subsequent progressive constriction of the visual fields and loss of central retinal function over time. A sensory ataxia caused by degeneration of the posterior columns of the spinal cord results in a loss of proprioceptive sensation that is clinically evident in the second decade of life and gradually progresses. Scoliosis, camptodactyly, achalasia, gastrointestinal dysmotility, and a sensory peripheral neuropathy are variable features of the disease. Affected individuals have no clinical or radiological evidence of cerebral or cerebellar involvement. Some patients have pain insensitivity and commonly manifest self-injury, ulcers and amputations. The disease is caused by variants affecting the gene represented in this entry. Defective neuronal heme transmembrane export due to FLVCR1 mutations may abrogate the neuroprotective effects of neuroglobin and initiate an apoptotic cascade that results in the selective degeneration of photoreceptors in the neurosensory retina and sensory neurons in the posterior spinal cord. Neurodevelopmental disorder with microcephaly, absent speech, and hypotonia (NEDMISH) [MIM:621060] A severe, autosomal recessive disorder characterized by profound global developmental delay, impaired intellectual development, absent speech, microcephaly, brain malformations, epilepsy, spasticity, and premature death. Brain malformations range from mild brain volume reduction to hydranencephaly. Additional features may include cortical visual impairment, sensory neuropathy, limb and digital malformations, and macrocytic anemia. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. Has a probable mitochondrial transit peptide at positions 1-38.

Similarity. Belongs to the major facilitator superfamily. Feline leukemia virus subgroup C receptor (TC 2.A.1.28.1) family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y5Y0-1	1, FLVCR1a	yes
Q9Y5Y0-2	2, FLVCR1b, mitochondrial

RefSeq proteins (1): NP_054772* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011701	MFS	Family
IPR020846	MFS_dom	Domain
IPR036259	MFS_trans_sf	Homologous_superfamily
IPR049680	FLVCR1-2_SLC49-like	Family

Pfam: PF07690

Catalyzed reactions (Rhea), 3 shown:

• ethanolamine(in) = ethanolamine(out) (RHEA:32747)
• choline(out) = choline(in) (RHEA:32751)
• heme b(in) = heme b(out) (RHEA:75443)

UniProt features (86 total): sequence variant 22, helix 18, topological domain 13, transmembrane region 12, mutagenesis site 8, binding site 3, region of interest 2, modified residue 2, turn 2, chain 1, glycosylation site 1, splice variant 1, strand 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
8UC0	ELECTRON MICROSCOPY	2.42
8UBX	ELECTRON MICROSCOPY	2.5
8UBW	ELECTRON MICROSCOPY	2.59
8QCT	ELECTRON MICROSCOPY	2.6
8UBY	ELECTRON MICROSCOPY	2.67
8QCS	ELECTRON MICROSCOPY	2.9
8R8T	ELECTRON MICROSCOPY	2.9
8UBZ	ELECTRON MICROSCOPY	3.02

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y5Y0-F1	78.49	0.54

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (3): 214; 471; 471

Post-translational modifications (2): 56, 536

Glycosylation sites (1): 265

Mutagenesis-validated functional residues (8):

Position	Phenotype
125	reduced transport of choline and ethanolamine.
151	no effect on choline transmembrane transporter activity. no effect on ethanolamine transmembrane transporter activity.
153	reduced transport of choline and ethanolamine.
214	reduced transport of choline and nearly abolished transport of ethanolamine.
245	slightly reduced transport of choline and ethanolamine.
349	reduced transport of choline and ethanolamine.
443	decreased choline and ethanolamine transmembrane transporter activity.
471	slightly reduced transport of choline and ethanolamine.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-189451	Heme biosynthesis
R-HSA-917937	Iron uptake and transport

MSigDB gene sets: 307 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_BODY_MORPHOGENESIS, GOBP_MYELOID_CELL_HOMEOSTASIS, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_MYELOID_CELL_DEVELOPMENT, GOBP_IRON_COORDINATION_ENTITY_TRANSPORT, GOBP_EMBRYONIC_DIGIT_MORPHOGENESIS, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_TRANSITION_METAL_ION_TRANSPORT, GOBP_EMBRYONIC_SKELETAL_SYSTEM_DEVELOPMENT, REACTOME_METABOLISM_OF_PORPHYRINS, GOBP_EMBRYONIC_SKELETAL_SYSTEM_MORPHOGENESIS, GOBP_ERYTHROCYTE_HOMEOSTASIS

GO Biological Process (20): blood vessel development (GO:0001568), in utero embryonic development (GO:0001701), heme biosynthetic process (GO:0006783), mitochondrial transport (GO:0006839), intracellular iron ion homeostasis (GO:0006879), phospholipid biosynthetic process (GO:0008654), choline transport (GO:0015871), heme transport (GO:0015886), erythrocyte differentiation (GO:0030218), multicellular organism growth (GO:0035264), embryonic digit morphogenesis (GO:0042733), erythrocyte maturation (GO:0043249), regulation of organ growth (GO:0046620), spleen development (GO:0048536), embryonic skeletal system morphogenesis (GO:0048704), head morphogenesis (GO:0060323), heme export (GO:0097037), ethanolamine transport (GO:0034229), limb morphogenesis (GO:0035108), transmembrane transport (GO:0055085)

GO Molecular Function (6): choline transmembrane transporter activity (GO:0015220), heme transmembrane transporter activity (GO:0015232), heme binding (GO:0020037), ethanolamine transmembrane transporter activity (GO:0034228), protein binding (GO:0005515), transmembrane transporter activity (GO:0022857)

GO Cellular Component (5): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), plasma membrane (GO:0005886), membrane (GO:0016020), mitochondrial membrane (GO:0031966)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Metabolism of porphyrins	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nitrogen compound transport	2
heme transport	2
transmembrane transporter activity	2
vasculature development	1
anatomical structure development	1
chordate embryonic development	1
porphyrin-containing compound biosynthetic process	1
heme metabolic process	1
pigment biosynthetic process	1
intracellular transport	1
intracellular monoatomic cation homeostasis	1
inorganic ion homeostasis	1
phospholipid metabolic process	1
lipid biosynthetic process	1
organophosphate biosynthetic process	1
iron coordination entity transport	1
myeloid cell differentiation	1
erythrocyte homeostasis	1
multicellular organismal process	1
developmental growth	1
embryonic limb morphogenesis	1
embryonic morphogenesis	1
cell maturation	1
erythrocyte development	1
organ growth	1
regulation of developmental growth	1
regulation of multicellular organismal process	1
hematopoietic or lymphoid organ development	1
embryonic organ morphogenesis	1
skeletal system morphogenesis	1
embryonic skeletal system development	1
anatomical structure morphogenesis	1
body morphogenesis	1
head development	1
amine transport	1
organic hydroxy compound transport	1
appendage morphogenesis	1
limb development	1
transport	1
cellular process	1

Protein interactions and networks

STRING

958 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FLVCR1	HPX	P02790	827
FLVCR1	SLC48A1	Q6P1K1	724
FLVCR1	SLC46A1	Q96NT5	717
FLVCR1	ABCB10	Q9NRK6	649
FLVCR1	STEAP3	Q658P3	617
FLVCR1	FECH	P22830	615
FLVCR1	ABCB6	Q9NP58	609
FLVCR1	ALAS1	P13196	600
FLVCR1	CPOX	P36551	578
FLVCR1	SLC25A37	Q9NYZ2	578
FLVCR1	SLC40A1	Q9NP59	571
FLVCR1	PPOX	P50336	543
FLVCR1	SLC11A2	P49281	541
FLVCR1	ABCB7	O75027	529
FLVCR1	CYBRD1	Q53TN4	527

IntAct

200 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
IL2RG	REEP6	psi-mi:“MI:0914”(association)	0.710
TMEM9B	DNAJC13	psi-mi:“MI:0914”(association)	0.640
SLC20A1	LIN7A	psi-mi:“MI:0914”(association)	0.640
CD27	TCAF2	psi-mi:“MI:0914”(association)	0.640
FAM234B	ABCD4	psi-mi:“MI:0914”(association)	0.620
SLC7A1	TMEM223	psi-mi:“MI:0914”(association)	0.530
XKRX	FAM234B	psi-mi:“MI:0914”(association)	0.530
ADGRG5	KLRG2	psi-mi:“MI:0914”(association)	0.530
GYPB	TCAF2	psi-mi:“MI:0914”(association)	0.530
TEX29	TOR1A	psi-mi:“MI:0914”(association)	0.530
NT5E	SCAMP1	psi-mi:“MI:0914”(association)	0.530
SLC15A4	PGRMC1	psi-mi:“MI:0914”(association)	0.530
TMEM9	ESYT2	psi-mi:“MI:0914”(association)	0.530
VAMP5	NBAS	psi-mi:“MI:0914”(association)	0.530
SLC22A9	GPR89A	psi-mi:“MI:0914”(association)	0.530
PTGIR	TMEM63A	psi-mi:“MI:0914”(association)	0.530
SLC22A16	APBA3	psi-mi:“MI:0914”(association)	0.530
OPALIN	BTAF1	psi-mi:“MI:0914”(association)	0.530
ANKH	FAM234B	psi-mi:“MI:0914”(association)	0.530
FLVCR1	TNFRSF10B	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480

BioGRID (190): FLVCR1 (Affinity Capture-MS), FLVCR1 (Affinity Capture-MS), FLVCR1 (Affinity Capture-MS), FLVCR1 (Affinity Capture-MS), FLVCR1 (Affinity Capture-MS), FLVCR1 (Affinity Capture-MS), FLVCR1 (Affinity Capture-MS), FLVCR1 (Affinity Capture-MS), FLVCR1 (Affinity Capture-MS), FLVCR1 (Proximity Label-MS), FLVCR1 (Proximity Label-MS), FLVCR1 (Affinity Capture-MS), FLVCR1 (Affinity Capture-MS), FLVCR1 (Affinity Capture-MS), FLVCR1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4ILB2, A0A8M9Q308, A1A4N1, A2CER7, A5D7V7, A8WGF7, B0S5Y3, B2RXV4, B5X4H8, O00400, O00476, O01735, O23596, P30638, P36836, P46029, P60815, Q11073, Q16348, Q28722, Q28FF3, Q503P5, Q5F4B8, Q5RBM3, Q5XGK0, Q63424, Q6AYY8, Q6DDL7, Q6DIT7, Q6GMG6, Q6PB15, Q7Z3Q1, Q84XI3, Q86WB7, Q91X85, Q944P0, Q99808, Q99J27, Q9BZD2, Q9C8X2

Diamond homologs: A0A0R4ILB2, A0A8M9Q308, B2RXV4, O01735, P60815, Q91X85, Q9ES43, Q9N1F2, Q9UPI3, Q9Y5Y0, Q28FF3, Q501I9, Q66H95, Q6GNV7, Q8BFQ6, Q96SL1, Q11073, Q503P5, Q6UXD7, Q8CE47

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 175 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ras activation upon Ca2+ influx through NMDA receptor	8	41.1×	2e-09
Unblocking of NMDA receptors, glutamate binding and activation	5	24.5×	9e-05
Negative regulation of NMDA receptor-mediated neuronal transmission	5	24.5×	9e-05
Assembly and cell surface presentation of NMDA receptors	10	22.9×	2e-09
Dopamine Neurotransmitter Release Cycle	5	22.4×	1e-04
Long-term potentiation	5	21.4×	1e-04
Neurotransmitter release cycle	5	19.8×	2e-04
Neurexins and neuroligins	11	19.5×	2e-09

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	10	36.3×	8e-11
protein localization to synapse	6	28.7×	9e-06
receptor clustering	7	27.3×	2e-06
regulation of postsynaptic membrane neurotransmitter receptor levels	7	21.7×	9e-06
cell-cell adhesion	11	7.0×	8e-05
exocytosis	7	6.6×	6e-03
protein-containing complex assembly	9	6.4×	1e-03
protein transport	16	4.4×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

609 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	34
Likely pathogenic	17
Uncertain significance	306
Likely benign	155
Benign	48

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1069108	NM_014053.4(FLVCR1):c.1291dup (p.Thr431fs)	Pathogenic
1069681	NC_000001.10:g.(?213058615)(213058758_?)del	Pathogenic
1071648	NM_014053.4(FLVCR1):c.1488dup (p.Leu497fs)	Pathogenic
1377362	NM_014053.4(FLVCR1):c.28del (p.Ala10fs)	Pathogenic
1415512	NM_014053.4(FLVCR1):c.561_656del (p.Ala188_Gly219del)	Pathogenic
1451205	NM_014053.4(FLVCR1):c.835del (p.Tyr279fs)	Pathogenic
1456300	NM_014053.4(FLVCR1):c.126del (p.Ala44fs)	Pathogenic
1456369	NC_000001.10:g.(?213061213)(213062619_?)del	Pathogenic
1457358	NM_014053.4(FLVCR1):c.947del (p.Pro316fs)	Pathogenic
18418	NM_014053.4(FLVCR1):c.361A>G (p.Asn121Asp)	Pathogenic
18419	NM_014053.4(FLVCR1):c.721G>A (p.Ala241Thr)	Pathogenic
1962180	NM_014053.4(FLVCR1):c.154del (p.Ala52fs)	Pathogenic
2007153	NM_014053.4(FLVCR1):c.238del (p.Arg80fs)	Pathogenic
2425886	NC_000001.10:g.(?213046000)(213046180_?)del	Pathogenic
2425887	NC_000001.10:g.(?213031795)(213037231_?)del	Pathogenic
2770146	NM_014053.4(FLVCR1):c.1194C>A (p.Tyr398Ter)	Pathogenic
3010005	NM_014053.4(FLVCR1):c.1427del (p.Leu476fs)	Pathogenic
30775	NM_014053.4(FLVCR1):c.1477G>C (p.Gly493Arg)	Pathogenic
3377003	NM_014053.4(FLVCR1):c.441_445del (p.Trp148fs)	Pathogenic
3383430	NM_014053.4(FLVCR1):c.1193dup (p.Tyr398Ter)	Pathogenic
3600271	NM_014053.4(FLVCR1):c.610del (p.Met204fs)	Pathogenic
3600274	NM_014053.4(FLVCR1):c.1390G>A (p.Gly464Ser)	Pathogenic
3600275	NM_014053.4(FLVCR1):c.1328T>G (p.Leu443Arg)	Pathogenic
3600279	NM_014053.4(FLVCR1):c.382T>A (p.Tyr128Asn)	Pathogenic
3721315	NM_014053.4(FLVCR1):c.160dup (p.Arg54fs)	Pathogenic
3725377	NM_014053.4(FLVCR1):c.440_447del (p.Asp147fs)	Pathogenic
379610	NM_014053.4(FLVCR1):c.1093-1G>A	Pathogenic
4074396	NM_014053.4(FLVCR1):c.899dup (p.Arg301fs)	Pathogenic
450232	NM_014053.4(FLVCR1):c.1377dup (p.Gly460fs)	Pathogenic
4730270	NM_014053.4(FLVCR1):c.370C>T (p.Gln124Ter)	Pathogenic

SpliceAI

2129 predictions. Top by Δscore:

Variant	Effect	Δscore
1:212872668:A:AG	acceptor_gain	1.0000
1:212872669:T:G	acceptor_gain	1.0000
1:212872670:A:AG	acceptor_gain	1.0000
1:212872671:T:G	acceptor_gain	1.0000
1:212872675:CA:C	acceptor_loss	1.0000
1:212872676:A:AG	acceptor_gain	1.0000
1:212872677:G:GT	acceptor_gain	1.0000
1:212872677:GC:G	acceptor_gain	1.0000
1:212872677:GCC:G	acceptor_gain	1.0000
1:212872815:TATGG:T	donor_loss	1.0000
1:212872816:ATGGT:A	donor_loss	1.0000
1:212872817:TGGTA:T	donor_loss	1.0000
1:212872819:G:GG	donor_gain	1.0000
1:212872819:GT:G	donor_loss	1.0000
1:212872820:T:G	donor_loss	1.0000
1:212885397:G:GG	donor_gain	1.0000
1:212887751:T:A	acceptor_gain	1.0000
1:212895051:GCT:G	donor_gain	1.0000
1:212895054:G:GG	donor_gain	1.0000
1:212895350:GAGAT:G	donor_gain	1.0000
1:212895352:GAT:G	donor_gain	1.0000
1:212863723:A:AG	acceptor_gain	0.9900
1:212863723:AGCTT:A	acceptor_gain	0.9900
1:212863724:G:GG	acceptor_gain	0.9900
1:212863724:GCTTG:G	acceptor_gain	0.9900
1:212864516:G:GT	donor_gain	0.9900
1:212864517:A:T	donor_gain	0.9900
1:212870169:G:GG	donor_gain	0.9900
1:212872663:C:CA	acceptor_gain	0.9900
1:212872665:T:TA	acceptor_gain	0.9900

AlphaMissense

3551 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:212859137:T:C	F229L	0.999
1:212859139:T:A	F229L	0.999
1:212859139:T:G	F229L	0.999
1:212863735:C:A	A250E	0.999
1:212858825:T:A	W125R	0.998
1:212858825:T:C	W125R	0.998
1:212859126:C:A	A225D	0.998
1:212859134:T:A	W228R	0.998
1:212859134:T:C	W228R	0.998
1:212859168:C:A	A239D	0.998
1:212863729:G:A	G248E	0.998
1:212863740:G:C	G252R	0.998
1:212863741:G:A	G252D	0.998
1:212883383:G:A	G346D	0.998
1:212885350:G:C	G384R	0.998
1:212885351:G:A	G384D	0.998
1:212889153:G:A	G474E	0.998
1:212859162:C:A	A237D	0.997
1:212863728:G:A	G248R	0.997
1:212863728:G:C	G248R	0.997
1:212863743:T:C	F253L	0.997
1:212863745:T:A	F253L	0.997
1:212863745:T:G	F253L	0.997
1:212883371:G:A	G342D	0.997
1:212883382:G:C	G346R	0.997
1:212885341:G:A	G381R	0.997
1:212885341:G:C	G381R	0.997
1:212885375:T:C	L392P	0.997
1:212888578:T:C	L466P	0.997
1:212889152:G:A	G474R	0.997

dbSNP variants (sampled 300 via entrez): RS1000082915 (1:212884406 A>G), RS1000330964 (1:212866110 A>G), RS1000485115 (1:212873036 A>G), RS1000543404 (1:212873200 C>T), RS1000663131 (1:212867572 G>A), RS1000726024 (1:212859490 G>A), RS1000814885 (1:212873326 GAAAGA>G), RS1000865057 (1:212884971 A>G), RS1000914773 (1:212873387 G>C), RS1000921427 (1:212878031 C>G), RS1000963358 (1:212860279 A>G), RS1001075184 (1:212859825 T>G), RS1001077425 (1:212897357 C>T), RS1001135817 (1:212870853 A>C,G), RS1001138006 (1:212896913 T>C)

Disease associations

OMIM: gene MIM:609144 | disease phenotypes: MIM:609033, MIM:268000, MIM:621060, MIM:208500, MIM:248200, MIM:162400

GenCC curated gene-disease

Disease	Classification	Inheritance
posterior column ataxia-retinitis pigmentosa syndrome	Definitive	Autosomal recessive
FLVCR1-related retinopathy with or without ataxia	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
FLVCR1-related retinopathy with or without ataxia	Definitive	AR

Mondo (10): posterior column ataxia-retinitis pigmentosa syndrome (MONDO:0012177), retinitis pigmentosa (MONDO:0019200), neurodevelopmental disorder with microcephaly, absent speech, and hypotonia (MONDO:0976126), inherited retinal dystrophy (MONDO:0019118), sensory peripheral neuropathy (MONDO:0002321), Jeune syndrome (MONDO:0018770), short rib-polydactyly syndrome (MONDO:0015461), Stargardt disease (MONDO:0019353), hereditary sensory and autonomic neuropathy (MONDO:0015364), FLVCR1-related retinopathy with or without ataxia (MONDO:0100449)

Orphanet (7): Posterior column ataxia-retinitis pigmentosa syndrome (Orphanet:88628), Retinitis pigmentosa (Orphanet:791), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Jeune syndrome (Orphanet:474), Short rib-polydactyly syndrome (Orphanet:1505), Stargardt disease (Orphanet:827), Hereditary sensory and autonomic neuropathy (Orphanet:140471)

HPO phenotypes

113 total (30 of 113 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000011	Neurogenic bladder
HP:0000020	Urinary incontinence
HP:0000028	Cryptorchidism
HP:0000104	Renal agenesis
HP:0000105	Enlarged kidney
HP:0000175	Cleft palate
HP:0000218	High palate
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000272	Malar flattening
HP:0000347	Micrognathia
HP:0000369	Low-set ears
HP:0000431	Wide nasal bridge
HP:0000470	Short neck
HP:0000510	Rod-cone dystrophy
HP:0000518	Cataract
HP:0000550	Undetectable electroretinogram
HP:0000572	Visual loss
HP:0000580	Pigmentary retinopathy
HP:0000618	Blindness
HP:0000648	Optic atrophy
HP:0000662	Nyctalopia
HP:0000729	Autistic behavior
HP:0000742	Self-mutilation
HP:0000763	Sensory neuropathy
HP:0000821	Hypothyroidism
HP:0000879	Short sternum
HP:0001059	Pterygium

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST007800_23	Asthma (childhood onset)	3.000000e-10
GCST010083_4	Hemoglobin levels	1.000000e-12
GCST90002383_347	Hematocrit	4.000000e-09
GCST90002384_25	Hemoglobin	7.000000e-10
GCST90002385_104	High light scatter reticulocyte count	1.000000e-10
GCST90002386_390	High light scatter reticulocyte percentage of red cells	5.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004509	hemoglobin measurement
EFO:0004348	hematocrit
EFO:0007986	reticulocyte count

MeSH disease descriptors (7)

Descriptor	Name	Tree numbers
D009477	Hereditary Sensory and Autonomic Neuropathies	C10.500.250; C10.574.500.493; C10.668.829.800.175; C16.131.666.310; C16.320.400.415
D058499	Retinal Dystrophies	C11.768.585.658
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684
D012779	Short Rib-Polydactyly Syndrome	C05.116.099.708.857; C05.660.585.600.750; C16.131.077.850; C16.131.621.585.600.750
D000080362	Stargardt Disease	C11.270.872; C11.768.585.439.339; C16.320.290.724
C537571	Jeune syndrome (supp.)
C536343	Posterior column ataxia with retinitis pigmentosa (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — SLC49 family of FLVCR-related heme transporters

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression, increases expression	3
FR900359	decreases phosphorylation	1
ethylbenzene	decreases expression, increases methylation, affects cotreatment	1
alpha phellandrene	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	decreases expression	1
ICG 001	decreases expression	1
jinfukang	decreases expression	1
Sunitinib	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Air Pollutants, Occupational	decreases expression, increases methylation	1
Atrazine	increases expression	1
Caffeine	decreases phosphorylation	1
Doxorubicin	decreases expression	1
Lead	affects splicing	1
Tobacco Smoke Pollution	decreases expression	1
Toluene	affects cotreatment, decreases expression, increases methylation	1
Valproic Acid	increases expression	1
Xylenes	decreases expression, increases methylation, affects cotreatment	1
Cyclosporine	decreases expression	1
Aflatoxin B1	decreases expression, increases methylation	1
Aflatoxin M1	decreases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	increases expression	1
Vitamin K 3	affects expression	1
Particulate Matter	decreases expression, increases abundance	1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D4FZ	HCT116-FLVCR1-KO-c10	Cancer cell line	Male
CVCL_D4G0	HCT116-FLVCR1-KO-c2	Cancer cell line	Male
CVCL_SN77	HAP1 FLVCR1 (-) 1	Cancer cell line	Male
CVCL_SN78	HAP1 FLVCR1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

235 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00717080	PHASE4	COMPLETED	The Role of Capsular Tension Ring (CTR) in Anterior Capsular Contraction
NCT00000114	PHASE3	COMPLETED	Randomized Trial of Vitamin A and Vitamin E Supplementation for Retinitis Pigmentosa
NCT00000116	PHASE3	COMPLETED	Randomized Trial of DHA for Retinitis Pigmentosa Patients Receiving Vitamin A
NCT00346333	PHASE3	COMPLETED	Clinical Trial of Lutein for Patients With Retinitis Pigmentosa Receiving Vitamin A
NCT01786395	PHASE3	TERMINATED	Phase III Efficacy and Safety Clinical Study of UF-021 for Treatment of Retinitis Pigmentosa
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT04636853	PHASE3	COMPLETED	CB-PRP in Retinitis Pigmentosa and Dry Age-related Macular Degeneration
NCT05537220	PHASE3	ACTIVE_NOT_RECRUITING	Oral N-acetylcysteine for Retinitis Pigmentosa
NCT05800301	PHASE3	COMPLETED	Management of Retinitis Pigmentosa Via Combination of Wharton’s Jelly-derived Mesenchymal Stem Cells and Magnovision
NCT05926583	PHASE3	ACTIVE_NOT_RECRUITING	A Study of AAV5-hRKp.RPGR for the Treatment of Japanese Participants With X-linked Retinitis Pigmentosa
NCT06388200	PHASE3	ACTIVE_NOT_RECRUITING	A Phase 3 Study Of OCU400 Gene Therapy for the Treatment Of Retinitis Pigmentosa
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT07290530	PHASE3	NOT_YET_RECRUITING	24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome
NCT00100230	PHASE2	COMPLETED	DHA and X-Linked Retinitis Pigmentosa
NCT00447980	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Participants With Early Stage Retinitis Pigmentosa
NCT00447993	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Patients With Late Stage Retinitis Pigmentosa
NCT01233609	PHASE2	COMPLETED	Trial of Oral Valproic Acid for Retinitis Pigmentosa
NCT01399515	PHASE2	COMPLETED	Efficacy and Safety of Oral Valproic Acid for Retinitis Pigmentosa
NCT01530659	PHASE2	COMPLETED	Retinal Imaging in CNTF -Releasing Encapsulated Cell Implant Treated Patients for Early-stage Retinitis Pigmentosa
NCT01560715	PHASE2	COMPLETED	Autologous Bone Marrow-Derived Stem Cells Transplantation For Retinitis Pigmentosa
NCT02609165	PHASE2	COMPLETED	Nerve Growth Factor Eye Drops Treatment in Patients With Retinitis Pigmentosa and Cystoid Macular Edema
NCT02661711	PHASE2	COMPLETED	Aflibercept for Macular Oedema With Underlying Retinitis Pigmentosa (AMOUR) Study
NCT02804360	PHASE2	UNKNOWN	Intravitreal Dexamethasone Implant in Retinitis Pigmentosa-related Macular Edema- a Retrospective Study
NCT02837640	PHASE2	UNKNOWN	Studying a Potential Protective Effect of L-Dopa on Retinitis Pigmentosa
NCT03073733	PHASE2	COMPLETED	Safety and Efficacy of Intravitreal Injection of Human Retinal Progenitor Cells in Adults With Retinitis Pigmentosa
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04356716	PHASE2	COMPLETED	Sildenafil for Treatment of Choroidal Ischemia
NCT04604899	PHASE2	COMPLETED	Safety of Repeat Intravitreal Injection of Human Retinal Progenitor Cells (jCell) in Adult Subjects With Retinitis Pigmentosa
NCT04763369	PHASE2	UNKNOWN	Investigation of Therapeutic Efficacy and Safety of UMSCs for the Management of Retinitis Pigmentosa (RP)
NCT04864496	PHASE2	UNKNOWN	Effects of Treatment With N- Acetylcysteine on Visual Outcomes in Patients With Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT05085964	PHASE2	TERMINATED	An Open-Label Extension Study to Evaluate Safety & Tolerability of QR-421a in Subjects With Retinitis Pigmentosa
NCT05392179	PHASE2	COMPLETED	A Study in Subjects With Retinitis Pigmentosa
NCT06627179	PHASE2	RECRUITING	Study to Evaluate Ultevursen in Subjects With Retinitis Pigmentosa (RP) Due to Mutations in Exon 13 of the USH2A Gene
NCT06628947	PHASE2	RECRUITING	A Phase II Study of Intravitreal KIO-301 in Patients With Late-stage Retinitis Pigmentosa
NCT06912633	PHASE2	RECRUITING	Safety of a Single, Intravitreal Injection of 6.0M jCell (Famzeretcel) in Retinitis Pigmentosa (RP)
NCT00063765	PHASE1	COMPLETED	Evaluation of Safety of Ciliary Neurotrophic Factor Implants in the Eye
NCT00065455	PHASE1	COMPLETED	Investigating the Effect of Vitamin A Supplementation on Retinitis Pigmentosa
NCT00458575	PHASE1	TERMINATED	A Study to Evaluate the Safety of CNTO 2476 in Patients With Advanced Retinitis Pigmentosa
NCT01068561	PHASE1	COMPLETED	Autologous Bone Marrow-Derived Stem Cells Transplantation For Retinitis Pigmentosa