FREM2

FRAS1 related extracellular matrix 2

Basic information

Region (hg38): 13:38687077-38887131

Links

ENSG00000150893

∙ NCBI:341640 ∙ OMIM:608945 ∙ HGNC:25396 ∙ Uniprot:Q5SZK8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

Fraser syndrome 2 (Moderate), mode of inheritance: AR
Fraser syndrome (Supportive), mode of inheritance: AR
renal agenesis, unilateral (Supportive), mode of inheritance: AD
Fraser syndrome 1 (Strong), mode of inheritance: AR
Fraser syndrome 2 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Fraser syndrome 2; Cryptophthalmos, unilateral or bilateral, isolated	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	Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic; Renal	15838507; 18203166; 18000968; 18671281; 30802441

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FREM2 gene.

not_provided (1475 variants)
Fraser_syndrome_2 (687 variants)
Isolated_cryptophthalmia (531 variants)
Inborn_genetic_diseases (439 variants)
FREM2-related_disorder (129 variants)
not_specified (55 variants)
Fraser_syndrome_1 (17 variants)
Congenital_anomaly_of_kidney_and_urinary_tract (4 variants)
Congenital_diaphragmatic_hernia (3 variants)
Microcephaly (2 variants)
Cryptophthalmia (1 variants)
Toe_syndactyly (1 variants)
Abnormality_of_the_anus (1 variants)
Schizophrenia (1 variants)
Finger_syndactyly (1 variants)
Ambiguous_genitalia (1 variants)
Prostate_cancer (1 variants)
Childhood-onset_schizophrenia (1 variants)
Unilateral_renal_agenesis (1 variants)
Epidermolysis_bullosa_simplex_with_nail_dystrophy (1 variants)
Cryptotia (1 variants)
Renal_hypoplasia/aplasia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FREM2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000207361.6. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			14 clinvar	826 clinvar	11 clinvar	851
missense	1 clinvar	4 clinvar	888 clinvar	75 clinvar	17 clinvar	985
nonsense	30 clinvar	17 clinvar	2 clinvar			49
start loss			1			1
frameshift	44 clinvar	23 clinvar	2 clinvar			69
splice donor/acceptor (+/-2bp)	1 clinvar	9 clinvar	1 clinvar			11
Total	76	53	908	901	28

Highest pathogenic variant AF is 0.0000558332

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FREM2	protein_coding	protein_coding	ENST00000280481	24	198809

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.60e-11	1.00	125616	0	132	125748	0.000525

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.859	1835	1.73e+3	1.06	0.0000950	20721
Missense in Polyphen		393	459.66	0.85498		5544
Synonymous	-1.48	727	678	1.07	0.0000376	6524
Loss of Function	6.05	38	105	0.363	0.00000603	1236

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000879	0.000879
Ashkenazi Jewish	0.000298	0.000298
East Asian	0.000109	0.000109
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000689	0.000686
Middle Eastern	0.000109	0.000109
South Asian	0.000523	0.000523
Other	0.000492	0.000489

dbNSFP

Source: dbNSFP

Function: FUNCTION: Extracellular matrix protein required for maintenance of the integrity of the skin epithelium and for maintenance of renal epithelia. May be required for epidermal adhesion. {ECO:0000269|PubMed:15838507}.;
Disease: DISEASE: Fraser syndrome 2 (FRASRS2) [MIM:617666]: A form of Fraser syndrome, an autosomal recessive disorder characterized by cryptophthalmos, cutaneous syndactyly, and urogenital abnormalities including renal agenesis or hypoplasia. Additional features include abnormalities of the larynx, ear malformations, and facial abnormalities. {ECO:0000269|PubMed:15838507}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.112

Intolerance Scores

loftool: 0.708
rvis_EVS: -0.63
rvis_percentile_EVS: 16.77

Haploinsufficiency Scores

pHI: 0.413
hipred: Y
hipred_score: 0.604
ghis: 0.479

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.838

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

Gene name: Frem2
Phenotype: pigmentation phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; respiratory system phenotype; embryo phenotype; skeleton phenotype; renal/urinary system phenotype; vision/eye phenotype; muscle 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); hearing/vestibular/ear phenotype; limbs/digits/tail phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); craniofacial phenotype;

Zebrafish Information Network

Gene name: frem2b
Affected structure: blood island
Phenotype tag: abnormal
Phenotype quality: blistered

Gene ontology

Biological process: eye development;morphogenesis of an epithelium;cell communication;cell adhesion;heart development;embryonic digit morphogenesis;inner ear development
Cellular component: basement membrane;plasma membrane;integral component of membrane;extracellular exosome
Molecular function: metal ion binding