MFRP

Summary

MFRP (membrane frizzled-related protein, HGNC:18121) is a protein-coding gene on chromosome 11q23.3, encoding Membrane frizzled-related protein (Q9BY79). May play a role in eye development.

This gene encodes a member of the frizzled-related protein family. The encoded protein plays an important role in eye development and mutations in this gene have been associated with nanophthalmos, posterior microphthalmia, retinitis pigmentosa, foveoschisis, and optic disc drusen. The protein is encoded by a bicistronic transcript which also encodes C1q and tumor necrosis factor related protein 5 (C1QTNF5).

Source: NCBI Gene 83552 — RefSeq curated summary.

At a glance

• Gene–disease (curated): nanophthalmos 2 (Definitive, GenCC) — +2 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 22 total — 1 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 50
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_031433

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18121
Approved symbol	MFRP
Name	membrane frizzled-related protein
Location	11q23.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ30570, rd6, NNO2, C1QTNF5
Ensembl gene	ENSG00000235718
Ensembl biotype	protein_coding
OMIM	606227
Entrez	83552

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000360167, ENST00000449574, ENST00000526059, ENST00000529147, ENST00000619721, ENST00000634542

RefSeq mRNA: 1 — MANE Select: NM_031433 NM_031433

CCDS: CCDS8421

Canonical transcript exons

ENST00000619721 — 15 exons

Exon	Start	End
ENSE00003459013	119344874	119345004
ENSE00003473098	119340184	119340440
ENSE00003475980	119340695	119341772
ENSE00003544798	119342873	119343003
ENSE00003549514	119346460	119346705
ENSE00003570689	119344315	119344391
ENSE00003578983	119346272	119346374
ENSE00003579943	119343816	119343964
ENSE00003594772	119338942	119339848
ENSE00003600579	119346046	119346159
ENSE00003601370	119345773	119345928
ENSE00003684883	119344632	119344757
ENSE00003788256	119345420	119345633
ENSE00003788812	119341857	119341984
ENSE00003791297	119342596	119342727

Expression profiles

Bgee: expression breadth broad, 29 present calls, max score 74.00.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2910 / max 168.9791, expressed in 21 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
122707	0.3890	25
122706	0.2776	21
122708	0.2176	20
122709	0.0714	14
122710	0.0145	6
122705	0.0134	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	74.00	gold quality
stromal cell of endometrium	CL:0002255	49.72	gold quality
sural nerve	UBERON:0015488	47.00	gold quality
skeletal muscle tissue	UBERON:0001134	46.63	gold quality
apex of heart	UBERON:0002098	45.64	gold quality
calcaneal tendon	UBERON:0003701	44.33	silver quality
Ammon’s horn	UBERON:0001954	43.65	gold quality
placenta	UBERON:0001987	42.97	silver quality
colonic epithelium	UBERON:0000397	42.47	gold quality
muscle tissue	UBERON:0002385	42.16	gold quality
ventricular zone	UBERON:0003053	41.98	gold quality
granulocyte	CL:0000094	40.68	gold quality
hindlimb stylopod muscle	UBERON:0004252	40.50	silver quality
corpus callosum	UBERON:0002336	40.41	gold quality
bone marrow cell	CL:0002092	39.85	gold quality
substantia nigra	UBERON:0002038	39.36	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	37.66	gold quality
tonsil	UBERON:0002372	37.50	gold quality
lower esophagus mucosa	UBERON:0035834	37.15	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
hypothalamus	UBERON:0001898	36.27	gold quality
lymph node	UBERON:0000029	35.70	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
urinary bladder	UBERON:0001255	34.98	gold quality
right coronary artery	UBERON:0001625	34.89	gold quality
bone marrow	UBERON:0002371	34.71	gold quality
tibial artery	UBERON:0007610	34.21	silver quality
popliteal artery	UBERON:0002250	34.15	silver quality
right adrenal gland cortex	UBERON:0035827	34.13	silver quality
right adrenal gland	UBERON:0001233	34.09	silver quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-135922	yes	15.81
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

65 targeting MFRP, 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-3120-5P	100.00	65.56	965
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-4716-3P	99.69	66.73	1022
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-653-5P	99.46	67.35	1300
HSA-MIR-6165	99.44	67.12	1389
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-3125	99.14	68.49	2269
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-6830-5P	99.01	68.73	1884

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 32)

• Describes the role of CTRP5 in disease, in addition to the bicistronic nature of CTRP5 and MFRP, which is confirmed by RT-PCR. (PMID:12944416)
• Extreme hyperopia (Nanophthalmos) is the result of null mutations in MFRP. (PMID:15976030)
• Mutation of the membrane-type frizzled-related protein gene is associated with inherited retinal degenerations (PMID:16352475)
• Defects in MFRP could be responsible for syndromic forms of microphthalmos/retinal degeneration. This gene is necessary for photoreceptor maintenance. (PMID:17167404)
• These results indicate that the MFRP gene may not play a role in regulating ocular axial length in these phenotypes. (PMID:18334955)
• Patients without MFRP gene function exhibit no correction of refractive error during childhood, which suggests that this gene is essential for emmetropization, a complex process by which vision regulates axial growth of the eye. (PMID:18363166)
• The novel frameshift mutation identified in the family described here validates MFRP as the gene responsible for this particular disease, which characteristically involves structures located at the posterior segment of the eye. (PMID:18554571)
• These results do not support a significant role for CHX10 or MFRP mutations in primary angle closure glaucoma. (PMID:18648522)
• Significant associations between angle-closure glaucoma and sequence variants in the MFRP gene, was analyzed. (PMID:18781223)
• MFRP is less likely to play a major role in physiologic high hyperopia. (PMID:19169412)
• This is the first demonstration of compound heterozygosity for MFRP mutations. (PMID:19753314)
• Three novel MFRP mutations that expand the phenotypic data available on patients with MFRP mutations, are reported. (PMID:20361016)
• In both previous reports of PMPRS, mutations in membrane type frizzled-related protein (MFRP) gene (located at 11q23) was demonstrated to be present (PMID:21416382)
• Posterior microphthalmos can be caused by nonsense compound heterozygous mutations in the MFRP gene. (PMID:22565643)
• Homozygous autosomal recessive retinitis pigmentosa-causing mutations have been found in three Indian families. These included a single base deletion in MFRP. (PMID:22605927)
• MFRP gene shows tendency to be associated with primary angle closure glaucoma in both the Australian and Nepalese cohorts. (PMID:22933837)
• Corneal diameter decreases with decreasing axial length, suggesting posterior microphthalmos and nanophthalmos represent a spectrum of high hyperopia rather than distinct phenotypes. In the Saudi population PRSS56 mutations are the major cause. (PMID:23127749)
• nanophthalmos and high hyperopia but without electrophysiological evidence of retinal dystrophy has also been associated with MFRP mutations. (PMID:23143909)
• Among five single nucleotide polymorphism(SNP)s tested, only MFRP rs3814762 and heat shock protein (HSP)70 rs1043618 show nominal association with primary angle closure. (PMID:23378726)
• The current study expands our knowledge of the mutation spectrum of MFRP and its associated phenotypes. To our knowledge, this is the first report of MFRP mutations in a Chinese cohort. (PMID:26583794)
• We report the MFRP-related ocular phenotype in three siblings with glycogen storage disease type 1b. Molecular genetic studies identified novel mutations in the MFRP and SLC37A4 genes. (PMID:28511025)
• MFRP mutation is associated with posterior microphthalmos, retinitis pigmentosa, and foveoschisis. (PMID:31264930)
• This is the first trio-based whole-genome sequencing (WGS), study for nanophthalmos, revealing the potential role of de novo mutations (DNMs) in MYRF and rare inherited genetic variants in PRSS56 and MFRP. (PMID:31266062)
• The majority of autosomal recessive nanophthalmos and posterior microphthalmia can be attributed to biallelic sequence and structural variants in MFRP and PRSS56. (PMID:31992737)
• Novel mutations in MFRP and PRSS56 are associated with posterior microphthalmos. (PMID:32118495)
• A novel MFRP gene variant in a family with posterior microphthalmos, retinitis pigmentosa, foveoschisis, and foveal hypoplasia. (PMID:32703043)
• Genotype-phenotype spectrum in isolated and syndromic nanophthalmos. (PMID:32996714)
• Novel TMEM98, MFRP, PRSS56 variants in a large United States high hyperopia and nanophthalmos cohort. (PMID:33203948)
• Membrane Frizzled-Related Protein-Related Disease Mimicking Idiopathic Intracranial Hypertension. (PMID:36255095)
• Pathogenic variants of MFRP and PRSS56 genes are major causes of nanophthalmos in Japanese patients. (PMID:37501562)
• Posterior microphthalmos with retinal involvement related to MFRP gene: a report of 10 Brazilian patients. (PMID:38557281)
• Comprehensive genetic analysis uncovers the mutational spectrum of MFRP and its genotype-phenotype correlation in a large cohort of Chinese microphthalmia patients. (PMID:38848879)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	mfrp	ENSDARG00000087814
mus_musculus	Mfrp	ENSMUSG00000034739
rattus_norvegicus	Mfrp	ENSRNOG00000039107

Paralogs (35): NRXN3 (ENSG00000021645), TLL1 (ENSG00000038295), CP (ENSG00000047457), DCBLD2 (ENSG00000057019), HEPH (ENSG00000089472), TLL2 (ENSG00000095587), NRP1 (ENSG00000099250), PCOLCE (ENSG00000106333), CNTNAP3 (ENSG00000106714), CUBN (ENSG00000107611), CNTNAP1 (ENSG00000108797), NRXN2 (ENSG00000110076), MEP1A (ENSG00000112818), NRP2 (ENSG00000118257), CUZD1 (ENSG00000138161), MFGE8 (ENSG00000140545), MEP1B (ENSG00000141434), PDGFC (ENSG00000145431), CNTNAP4 (ENSG00000152910), CNTNAP3B (ENSG00000154529), CNTNAP5 (ENSG00000155052), CDCP2 (ENSG00000157211), PCOLCE2 (ENSG00000163710), EDIL3 (ENSG00000164176), NETO1 (ENSG00000166342), BMP1 (ENSG00000168487), PDGFD (ENSG00000170962), NETO2 (ENSG00000171208), CNTNAP2 (ENSG00000174469), NRXN1 (ENSG00000179915), HEPHL1 (ENSG00000181333), F8 (ENSG00000185010), ASTL (ENSG00000188886), F5 (ENSG00000198734), CNTNAP3C (ENSG00000283378)

Protein

Protein identifiers

Membrane frizzled-related protein — Q9BY79 (reviewed: Q9BY79)

Alternative names: Membrane-type frizzled-related protein

All UniProt accessions (3): Q9BY79, A0A0U1RQG2, A0A0X1KG76

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in eye development.

Subunit / interactions. Interacts with C1QTNF5.

Subcellular location. Apical cell membrane.

Tissue specificity. Specifically expressed in brain. Strongly expressed in medulla oblongata and to a lower extent in hippocampus and corpus callosum. Expressed in keratinocytes.

Disease relevance. Nanophthalmos 2 (NNO2) [MIM:609549] A form of nanophthalmos, a disorder of eye development characterized by extreme hyperopia and small functional eyes. The cornea and lens are normal in size and shape. Hyperopia occurs because insufficient growth along the visual axis places these lensing components too close to the retina. Nanophthalmic eyes show considerable thickening of both the choroidal vascular bed and scleral coat, which provide nutritive and structural support for the retina. NNO2 inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry. Microphthalmia, isolated, 5 (MCOP5) [MIM:611040] A disorder characterized by posterior microphthalmia, retinitis pigmentosa, foveoschisis and optic disk drusen. Microphthalmia is a disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues. Ocular abnormalities like opacities of the cornea and lens, scaring of the retina and choroid, and other abnormalities may also be present. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. This protein is produced by a bicistronic gene which also produces the C1QTNF5 protein from a non-overlapping reading frame.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BY79-1	1	yes
Q9BY79-2	2

RefSeq proteins (1): NP_113621* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000859	CUB_dom	Domain
IPR002172	LDrepeatLR_classA_rpt	Repeat
IPR020067	Frizzled_dom	Domain
IPR023415	LDLR_class-A_CS	Conserved_site
IPR035914	Sperma_CUB_dom_sf	Homologous_superfamily
IPR036055	LDL_receptor-like_sf	Homologous_superfamily
IPR036790	Frizzled_dom_sf	Homologous_superfamily

Pfam: PF00057, PF00431, PF01392

UniProt features (44 total): disulfide bond 15, sequence variant 10, domain 5, sequence conflict 3, topological domain 2, compositionally biased region 2, glycosylation site 2, splice variant 2, chain 1, transmembrane region 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BY79-F1	73.09	0.26

Functional residue map

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

Disulfide bonds (15): 144–170, 197–216, 260–272, 267–285, 279–294, 301–327, 354–377, 421–433, 428–446, 440–454, 466–528, 474–521, 512–549, 538–576, 542–564

Glycosylation sites (2): 227, 415

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 161 (showing top): GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, BENPORATH_ES_WITH_H3K27ME3, GOCC_COLLAGEN_TRIMER, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_NEUROGENESIS, CAGCTG_AP4_Q5, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_EYE_PHOTORECEPTOR_CELL_DIFFERENTIATION, GOBP_EAR_DEVELOPMENT, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, GOBP_PHOTORECEPTOR_CELL_DEVELOPMENT, GOBP_SECRETION, GOCC_APICAL_PLASMA_MEMBRANE, GOBP_PHOTORECEPTOR_CELL_DIFFERENTIATION, GOBP_SENSORY_PERCEPTION

GO Biological Process (4): visual perception (GO:0007601), embryo development ending in birth or egg hatching (GO:0009792), eye photoreceptor cell development (GO:0042462), retina development in camera-type eye (GO:0060041)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (3): membrane (GO:0016020), apical plasma membrane (GO:0016324), plasma membrane (GO:0005886)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
sensory perception of light stimulus	1
embryo development	1
eye photoreceptor cell differentiation	1
photoreceptor cell development	1
camera-type eye development	1
anatomical structure development	1
binding	1
cellular anatomical structure	1
apical part of cell	1
plasma membrane region	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

842 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MFRP	VSX2	P58304	787
MFRP	PRSS56	P0CW18	762
MFRP	RD3	Q7Z3Z2	728
MFRP	TMEM98	Q9Y2Y6	711
MFRP	PRPH2	P23942	661
MFRP	NR2E3	Q9Y5X4	660
MFRP	C1QTNF5	Q9BXJ0	636
MFRP	PDE6B	P35913	610
MFRP	TUB	P50607	573
MFRP	RPE65	Q16518	571
MFRP	PAX6	P26367	556
MFRP	PITPNM1	O00562	528
MFRP	BEST1	O76090	523
MFRP	TMEM218	A2RU14	479
MFRP	PCMTD1	Q96MG8	355

IntAct

15 interactions, top by confidence:

A	B	Type	Score
MFRP	C1QTNF5	psi-mi:“MI:0407”(direct interaction)	0.610
MFRP	C1QTNF5	psi-mi:“MI:0915”(physical association)	0.610
MFRP	C1QTNF5	psi-mi:“MI:0403”(colocalization)	0.610
C1QTNF5	MFRP	psi-mi:“MI:0915”(physical association)	0.590
MFRP	C1qtnf5	psi-mi:“MI:0915”(physical association)	0.520
C1qtnf5	MFRP	psi-mi:“MI:0915”(physical association)	0.520

BioGRID (1): MFRP (Reconstituted Complex)

ESM2 similar proteins: A0A1B0GTW7, A0A1D5NSK0, A0A1L8HYT7, A0A286YEC0, G7PWZ3, O77755, O88959, P0C0K7, P17490, P23276, P43021, P51882, P59509, P59996, P70505, Q02853, Q04912, Q04962, Q04997, Q0V8J4, Q0VAY3, Q17R55, Q3U435, Q499S5, Q4R7Z5, Q58Y75, Q62190, Q6MG64, Q76MJ5, Q7TN88, Q7Z442, Q80W65, Q8BMN4, Q8CJH3, Q8IVN8, Q8VCS0, Q91X21, Q96KR4, Q96PQ0, Q96S42

Diamond homologs: A0A0K3AWM6, B3DIG4, G5ECQ2, O00144, O19116, O42579, O57328, O57329, O60353, O70421, O75084, O93274, P18537, P58421, P97299, P97401, Q08463, Q08464, Q13467, Q14332, Q24760, Q498S8, Q5BL72, Q5RCN4, Q5RF67, Q5T4F7, Q61086, Q61088, Q61089, Q61090, Q61091, Q6FHJ7, Q7YRN1, Q80YN4, Q863H1, Q8AVJ9, Q8BKG4, Q8C4U3, Q8CHL0, Q8K480

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	10
Likely benign	1
Benign	5

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1076240	NC_000011.9:g.(?119217150)(119217243_?)del	Pathogenic
813996	NM_001278431.2(C1QTNF5):c.562C>G (p.Pro188Ala)	Likely pathogenic

SpliceAI

2344 predictions. Top by Δscore:

Variant	Effect	Δscore
11:119340693:ACCC:A	donor_gain	1.0000
11:119340693:ACCCC:A	donor_gain	1.0000
11:119340694:CCCC:C	donor_gain	1.0000
11:119340694:CCCCC:C	donor_gain	1.0000
11:119340720:T:TA	donor_gain	1.0000
11:119342871:A:AC	donor_gain	1.0000
11:119342871:ACTCT:A	donor_gain	1.0000
11:119342872:C:CC	donor_gain	1.0000
11:119342872:CT:C	donor_gain	1.0000
11:119342872:CTCTC:C	donor_gain	1.0000
11:119342875:T:A	donor_gain	1.0000
11:119343801:C:A	donor_gain	1.0000
11:119344890:AG:A	donor_gain	1.0000
11:119345003:CC:C	acceptor_gain	1.0000
11:119345004:CC:C	acceptor_gain	1.0000
11:119345005:C:CC	acceptor_gain	1.0000
11:119345772:CTGGA:C	donor_gain	1.0000
11:119345929:C:CC	acceptor_gain	1.0000
11:119346044:A:AC	donor_gain	1.0000
11:119346044:ACGGG:A	donor_gain	1.0000
11:119346045:C:CC	donor_gain	1.0000
11:119346045:CGGGC:C	donor_gain	1.0000
11:119346454:CCTTA:C	donor_loss	1.0000
11:119346455:CTTA:C	donor_loss	1.0000
11:119346456:TTAC:T	donor_loss	1.0000
11:119346457:TAC:T	donor_loss	1.0000
11:119346458:ACCTT:A	donor_loss	1.0000
11:119340693:AC:A	donor_gain	0.9900
11:119340693:ACC:A	donor_gain	0.9900
11:119340694:CC:C	donor_gain	0.9900

AlphaMissense

3788 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:119343953:C:A	W329C	0.999
11:119343953:C:G	W329C	0.999
11:119344909:A:G	F246S	0.999
11:119345545:C:A	W172C	0.999
11:119345545:C:G	W172C	0.999
11:119342897:A:C	Y411D	0.998
11:119343912:A:C	F343C	0.998
11:119343912:A:G	F343S	0.998
11:119343918:A:G	L341P	0.998
11:119344898:A:C	Y250D	0.998
11:119344909:A:C	F246C	0.998
11:119345462:T:A	D200V	0.998
11:119345590:G:C	S157R	0.998
11:119345590:G:T	S157R	0.998
11:119345592:T:G	S157R	0.998
11:119342908:A:C	F407C	0.997
11:119342908:A:G	F407S	0.997
11:119343955:A:G	W329R	0.997
11:119343955:A:T	W329R	0.997
11:119344908:G:C	F246L	0.997
11:119344908:G:T	F246L	0.997
11:119344910:A:G	F246L	0.997
11:119344942:A:C	F235C	0.997
11:119345510:A:G	L184P	0.997
11:119345547:A:G	W172R	0.997
11:119345547:A:T	W172R	0.997
11:119342907:G:C	F407L	0.996
11:119342907:G:T	F407L	0.996
11:119342909:A:G	F407L	0.996
11:119343903:A:C	F346C	0.996

dbSNP variants (sampled 300 via entrez): RS1000658864 (11:119347615 G>A), RS1000820928 (11:119345092 C>A,G), RS1001545948 (11:119348105 A>G,T), RS1001972882 (11:119345333 T>G), RS1002011614 (11:119340589 G>A), RS1002147275 (11:119340412 G>A), RS1002433949 (11:119346655 G>A,C), RS1002815720 (11:119343064 C>G,T), RS1003682914 (11:119342062 G>A), RS1003860933 (11:119340470 C>T), RS1003867368 (11:119339197 G>A,T), RS1003948702 (11:119345759 C>A), RS1004893867 (11:119339249 G>A,C,T), RS1005269543 (11:119338748 A>G), RS1005563355 (11:119342179 C>T)

Disease associations

OMIM: gene MIM:606227 | disease phenotypes: MIM:611040, MIM:605670, MIM:609549

GenCC curated gene-disease

Disease	Classification	Inheritance
nanophthalmos 2	Definitive	Autosomal recessive
isolated microphthalmia 5	Definitive	Autosomal recessive
nanophthalmia	Supportive	Autosomal dominant

Mondo (5): isolated microphthalmia 5 (MONDO:0012605), late-onset retinal degeneration (MONDO:0011579), inherited retinal dystrophy (MONDO:0019118), nanophthalmos 2 (MONDO:0012299), nanophthalmia (MONDO:0005514)

Orphanet (4): Microphthalmia-retinitis pigmentosa-foveoschisis-optic disc drusen syndrome (Orphanet:251279), Late-onset retinal degeneration (Orphanet:67042), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Nanophthalmos (Orphanet:35612)

HPO phenotypes

50 total (30 of 50 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000486	Strabismus
HP:0000488	Retinopathy
HP:0000501	Glaucoma
HP:0000518	Cataract
HP:0000533	Chorioretinal atrophy
HP:0000541	Retinal detachment
HP:0000543	Optic disc pallor
HP:0000546	Retinal degeneration
HP:0000552	Tritanomaly
HP:0000568	Microphthalmia
HP:0000572	Visual loss
HP:0000575	Scotoma
HP:0000608	Macular degeneration
HP:0000610	Abnormal choroid morphology
HP:0000613	Photophobia
HP:0000642	Red-green dyschromatopsia
HP:0000662	Nyctalopia
HP:0001089	Iris atrophy
HP:0001099	Atrophic fundus lesion
HP:0001120	Abnormality of corneal size
HP:0001141	Severely reduced visual acuity
HP:0003581	Adult onset
HP:0004328	Abnormal anterior eye segment morphology
HP:0007401	Macular atrophy
HP:0007663	Reduced visual acuity
HP:0007703	Abnormal retinal pigmentation
HP:0007722	Retinal pigment epithelial atrophy
HP:0007737	Spicular pigmentation of the retina

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006394_75	Intraocular pressure	2.000000e-08
GCST010002_199	Refractive error	3.000000e-34

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004695	intraocular pressure measurement

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D058499	Retinal Dystrophies	C11.768.585.658
C565309	Late-Onset Retinal Degeneration (supp.)
C567024	Microphthalmia, Posterior, With Retinitis Pigmentosa, Foveoschisis, And Optic Disc Drusen (supp.)
C563700	Nanophthalmos 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

3 total (human), top 3 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Arsenic	affects expression	1
Benzo(a)pyrene	increases methylation	1
Smoke	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_D6ME	IOCVi001-A	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT05902962	PHASE1	COMPLETED	SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects
NCT06319872	PHASE1	RECRUITING	The Effects of Disulfiram (Antabuse®) on Visual Acuity in Patients With Retinal Degeneration
NCT06455826	PHASE1	COMPLETED	MAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects (Wallaby)
NCT03510234	Not specified	UNKNOWN	Self-confidence Study in Patients With Argus II Artificial Retina
NCT04360291	Not specified	UNKNOWN	Impact of Visual Field Restriction on Visual Exploration
NCT04419285	Not specified	UNKNOWN	Mobility Protocol Adapted for Advanced Visually Impaired Subjects
NCT05179460	Not specified	COMPLETED	A Study of Pentosan Polysulfate Sodium and the Development of Pigmentary Maculopathy and Pigmentary Retinopathy
NCT05355415	Not specified	RECRUITING	Adaptive Optics Imaging of Outer Retinal Diseases
NCT04855045	PHASE2/PHASE3	UNKNOWN	An Open-label, Dose Escalation and Double-masked, Randomized, Controlled Trial Evaluating Safety and Tolerability of Sepofarsen in Children (<8 Years of Age) With LCA10 Caused by Mutations in the CEP290 Gene.
NCT03872479	PHASE1/PHASE2	UNKNOWN	Single Ascending Dose Study in Participants With LCA10
NCT04123626	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Safety and Tolerability of QR-1123 in Subjects With Autosomal Dominant Retinitis Pigmentosa Due to the P23H Mutation in the RHO Gene
NCT04545736	PHASE1/PHASE2	RECRUITING	Oral Metformin for Treatment of ABCA4 Retinopathy
NCT06212297	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Fellow-eye Study (FE) of LX101 in Subjects With Inherited Retinal Dystrophy
NCT06852963	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Repeat-Dose, Open-Label, Two Arm Safety and Efficacy Study of Two Doses of VP-001 Administered Intravitreally in Participants With Confirmed PRPF31 Mutation-Associated Retinal Dystrophy, Including Participants Previously Treated With VP001
NCT07177196	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Personalized Antisense Oligonucleotide Therapy for a Single Participant With PRPH2 Mutation Associated With Retinal Dystrophy
NCT07063030	EARLY_PHASE1	RECRUITING	A Study of LX107 Gene Therapy in AIPL1-IRD Patients
NCT01546181	Not specified	COMPLETED	Retinal Imaging by Adaptive Optics in Healthy Eyes and During Retinal and General Diseases
NCT01876147	Not specified	COMPLETED	Visual and Functional Assessment in Low Vision Patients
NCT01920867	Not specified	UNKNOWN	Stem Cell Ophthalmology Treatment Study
NCT02014389	Not specified	RECRUITING	Evaluation of Objective Perimetry Using Chromatic Multifocal Pupillometer
NCT02983305	Not specified	COMPLETED	Optical Head-Mounted Display Technology for Low Vision Rehabilitation
NCT03592017	Not specified	COMPLETED	Performance of Long-wavelength Autofluorescence Imaging
NCT03662386	Not specified	TERMINATED	Prospective Analysis of Genotype-phenotype Correlations Observed in a Large Cohort of Patients With Hereditary Retinal Dystrophies - GEPHIRD
NCT03691168	Not specified	UNKNOWN	Multi-center Observation of the Natural Course of Inherited Retinal Dystrophies
NCT03843840	Not specified	COMPLETED	Dual Wavelength OCT
NCT03853252	Not specified	COMPLETED	iPS Cells of Patients for Models of Retinal Dystrophies
NCT05130385	Not specified	UNKNOWN	High Resolution Optical Coherence Tomography
NCT05294978	Not specified	RECRUITING	EyeConic: Qualification for Cone-Optogenetics
NCT05573984	Not specified	ACTIVE_NOT_RECRUITING	Natural History of PRPF31 Mutation-Associated Retinal Dystrophy
NCT05793515	Not specified	COMPLETED	Mechanisms of Inherited Retinal Dystrophies Using Whole Genome Sequencing and in Vitro and in Vivo Models
NCT05820100	Not specified	COMPLETED	Observational Study to Assess the Reliability and Validity of the MLYMT and MLSDT
NCT05976139	Not specified	RECRUITING	Micropulsed Laser in Patients With Macular Oedema in Retinal Dystrophies
NCT06162585	Not specified	ACTIVE_NOT_RECRUITING	Non-Interventional Long Term Follow-up Study of Participants Previously Enrolled in the RESTORE Study
NCT06177977	Not specified	RECRUITING	SS-HH-OCT as a Novel Diagnostic Modality for Early-Onset Retinal Dystrophies (EORDs)
NCT06375239	Not specified	RECRUITING	Observational Study to Assess Endpoint Operational Feasibility & Measurement Properties in Patients with Retinal Degeneration