GeneBe

MFRP

protein-coding

membrane frizzled-related protein

Gene summary

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). [provided by RefSeq, Jun 2013]

MANE transcript

NM_031433.4

Inheritance

AR, AD

ClinVar variants

P:80U:322B:171

Top phenotype

Microphthalmia, isolated 5; Nanophthalmos 2; Retinitis pigmentosa, autosomal recessive

gnomAD constraint

pLI —, LoF o/e 0.88

Max pathogenic AF

—

Genomic locus

chr11:119,338,942-119,346,705

External References & Databases

Ensembl (ENSG00000235718)NCBI Gene (83552)OMIM (606227)HGNC:18121GenCCUniProt (Q9BY79)AlphaFoldClinVar (MFRP)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~7.8 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

isolated microphthalmia 5MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0012605

Submitter: Ambry Genetics

nanophthalmiaSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0005514

Submitter: Orphanet

nanophthalmos 2DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0012299

Submitter: G2P

isolated microphthalmia 5STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0012605

Submitter: Labcorp Genetics (formerly Invitae)

isolated microphthalmia 5STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0012605

Submitter: PanelApp Australia

nanophthalmos 2MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0012299

Submitter: Ambry Genetics

isolated microphthalmia 5SUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0012605

Submitter: Orphanet

isolated microphthalmia 5DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0012605

Submitter: G2P

Clinical Genomic Database (CGD)

Microphthalmia, isolated 5; Nanophthalmos 2; Retinitis pigmentosa, autosomal recessiveAR

Manifestation: Ophthalmologic

Intervention: General

Rationale: 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

Comments: Individuals are at risk for ophthalmologic features such as retinal detachment

Refs: 1258954; 15976030; 17167404; 18554571; 19526372; 20361016; 21810984; 22565643; 22605927; 23112574Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MFRP variants in ClinVar

14 Conditions Cataloged
Isolated microphthalmia 5Total: 601
not providedTotal: 182
Inborn genetic diseasesTotal: 100
not specifiedTotal: 97
MFRP-related disorderTotal: 55
Late-onset retinal degenerationTotal: 49
Nanophthalmos 2Total: 22
Retinal dystrophyTotal: 16

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_031433.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
11
clinvar
152
clinvar
 163
missense
3
clinvar
9
clinvar
310
clinvar
19
clinvar
 341
nonsense
8
clinvar
11
clinvar
 19
start loss
1
clinvar
 1
frameshift
20
clinvar
15
clinvar
 35
splice donor/acceptor (+/-2bp)
2
clinvar
11
clinvar
1
clinvar
 14
Total33473221710573

Highest pathogenic variant AF is 0.00021767116

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 6 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_031433.4RefSeqNP_113621.113MANE Select
ENST00000619721.6EnsemblENSP00000481824.113MANE Select
ENST00000360167.4EnsemblENSP00000353291.410Standard
ENST00000360167.5EnsemblENSP00000353291.410Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
mfrpDanio rerio

Structure: retina

Quality: decreased size

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

  • visual perception
  • embryo development ending in birth or egg hatching
  • eye photoreceptor cell development
  • retina development in camera-type eye

Molecular Function

  • molecular_function

Cellular Component

  • integral component of membrane
  • apical plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000555262
Coding exons
13
Length
7732
Individuals with no LoFs
124572
Homozygous LoFs
0
Heterozygous LoFs
175
Defined
124747
p
0.000702
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-1.473943201.230.00001813749
Missense (PolyPhen)145111.911.29571446
Synonymous-2.201621301.250.000007651161
Loss of Function0.6162528.60.8760.00000145309

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000880.00086rare
Latino/Admixed American0.000990.00098rare
Ashkenazi Jewish00.0absent
East Asian0.000220.00022rare
Finnish0.0000930.000092rare
European (Non-Finnish)0.000980.00095rare
South Asian0.000330.00033rare
Other0.000850.00082rare

dbNSFP Gene Annotations

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

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
N
Indispensability score
0.175

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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