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 (1511 variants)
• Fraser_syndrome_2 (690 variants)
• Isolated_cryptophthalmia (532 variants)
• Inborn_genetic_diseases (494 variants)
• FREM2-related_disorder (129 variants)
• not_specified (61 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			16	839	11	866
missense	1	5	934	78	17	1035
nonsense	32	17	3			52
start loss			1			1
frameshift	49	24	2			75
splice donor/acceptor (+/-2bp)	1	9	1			11
Total	83	55	957	917	28

Highest pathogenic variant AF is 0.000055833207

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
		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

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

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