MFRP

membrane frizzled-related protein

Basic information

Region (hg38): 11:119338942-119346705

Links

ENSG00000235718 ∙ NCBI:83552 ∙ OMIM:606227 ∙ HGNC:18121 ∙ Uniprot:Q9BY79 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• isolated microphthalmia 5 (Definitive), mode of inheritance: AR
• isolated microphthalmia 5 (Strong), mode of inheritance: AR
• nanophthalmos 2 (Moderate), mode of inheritance: AR
• isolated microphthalmia 5 (Moderate), mode of inheritance: AR
• nanophthalmia (Supportive), mode of inheritance: AD
• isolated microphthalmia 5 (Supportive), mode of inheritance: AR
• nanophthalmos 2 (Definitive), mode of inheritance: AR
• isolated microphthalmia 5 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Microphthalmia, isolated 5; Nanophthalmos 2; Retinitis pigmentosa, autosomal recessive	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Ophthalmologic	1258954; 15976030; 17167404; 18554571; 19526372; 20361016; 21810984; 22565643; 22605927; 23112574
Individuals are at risk for ophthalmologic features such as retinal detachment

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MFRP gene.

• Isolated microphthalmia 5 (34 variants)
• not provided (9 variants)
• Nanophthalmos 2 (4 variants)
• Retinal dystrophy (2 variants)
• MFRP-related disorder (1 variants)
• Late-onset retinal degeneration (1 variants)
• Isolated microphthalmia 5;Nanophthalmos 2 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MFRP gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			8	115	1	124
missense		3	255	5	1	264
nonsense	10	3				13
start loss						0
frameshift	22	1	1			24
inframe indel			2			2
splice donor/acceptor (+/-2bp)	3	4				7
splice region			20	29	1	50
non coding	1	3	114	139	14	271
Total	36	14	380	259	16

Highest pathogenic variant AF is 0.000125

Variants in MFRP

This is a list of pathogenic ClinVar variants found in the MFRP region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-119338986-C-A		Late-onset retinal degeneration • Isolated microphthalmia 5	Uncertain significance (Jan 13, 2018)
11-119339080-G-A		Retinal degeneration • Isolated microphthalmia 5 • Late-onset retinal degeneration	Uncertain significance (Jan 12, 2018)
11-119339095-G-A		Isolated microphthalmia 5 • Late-onset retinal degeneration	Uncertain significance (Jan 13, 2018)
11-119339120-G-T		Late-onset retinal degeneration • Isolated microphthalmia 5	Uncertain significance (Jan 13, 2018)
11-119339173-G-T		Retinal degeneration • Late-onset retinal degeneration • Isolated microphthalmia 5	Uncertain significance (Jan 13, 2018)
11-119339269-T-A		Retinal degeneration • Isolated microphthalmia 6	Likely benign (Jun 14, 2016)
11-119339297-G-C		Retinal degeneration • Isolated microphthalmia 5 • Late-onset retinal degeneration	Benign/Likely benign (Jan 12, 2018)
11-119339330-A-G		Late-onset retinal degeneration • Isolated microphthalmia 5	Uncertain significance (Jan 13, 2018)
11-119339349-G-A			Likely benign (Nov 25, 2022)
11-119339352-G-A			Likely benign (Dec 11, 2023)
11-119339360-C-A			Uncertain significance (Apr 23, 2021)
11-119339378-C-T			Uncertain significance (Nov 29, 2022)
11-119339388-GCTGT-G			Uncertain significance (Sep 11, 2023)
11-119339410-T-A			Uncertain significance (Oct 13, 2023)
11-119339415-G-A		C1QTNF5-related disorder	Likely benign (May 10, 2023)
11-119339419-A-G		Isolated microphthalmia 5 • Retinal degeneration • Late-onset retinal degeneration	Uncertain significance (Feb 18, 2022)
11-119339421-G-A			Likely benign (Aug 15, 2022)
11-119339428-C-G			Uncertain significance (Jul 19, 2022)
11-119339433-A-G			Likely benign (Nov 19, 2022)
11-119339434-C-T			Uncertain significance (Sep 20, 2022)
11-119339435-C-G		Retinal dystrophy	Uncertain significance (Jul 17, 2018)
11-119339438-C-T			Uncertain significance (Sep 17, 2021)
11-119339450-C-G		Late-onset retinal degeneration	Likely benign (Mar 25, 2024)
11-119339462-G-A			Uncertain significance (Sep 23, 2022)
11-119339464-T-C			Uncertain significance (Sep 27, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MFRP	protein_coding	protein_coding	ENST00000555262	13	7732

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.31e-15	0.0433	124572	0	175	124747	0.000702

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.47	394	320	1.23	0.0000181	3749
Missense in Polyphen		145	111.91	1.2957		1446
Synonymous	-2.20	162	130	1.25	0.00000765	1161
Loss of Function	0.616	25	28.6	0.876	0.00000145	309

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00187	0.00185
Ashkenazi Jewish	0.00	0.00
East Asian	0.000218	0.000217
Finnish	0.0000926	0.0000924
European (Non-Finnish)	0.000983	0.000949
Middle Eastern	0.000218	0.000217
South Asian	0.000327	0.000327
Other	0.000850	0.000816

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May play a role in eye development. {ECO:0000269|PubMed:15976030}.
• Disease: DISEASE: Nanophthalmos 2 (NNO2) [MIM:609549]: Rare autosomal recessive disorder of eye development characterized by extreme hyperopia and small functional eyes. {ECO:0000269|PubMed:15976030}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:17167404}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.0969

Intolerance Scores

• loftool: 0.650
• rvis_EVS: -0.53
• rvis_percentile_EVS: 20.89

Haploinsufficiency Scores

• pHI: 0.184
• hipred: N
• hipred_score: 0.180
• ghis: 0.396

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.175

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Mfrp
• Phenotype: pigmentation phenotype; vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: mfrp
• Affected structure: retina
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• Biological process: visual perception;embryo development ending in birth or egg hatching;eye photoreceptor cell development;retina development in camera-type eye
• Cellular component: integral component of membrane;apical plasma membrane
• Molecular function: molecular_function