FRAS1

Fraser extracellular matrix complex subunit 1

Basic information

Region (hg38): 4:78057323-78544269

Links

ENSG00000138759

∙ NCBI:80144 ∙ OMIM:607830 ∙ HGNC:19185 ∙ Uniprot:Q86XX4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

Fraser syndrome 1 (Definitive), 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 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Fraser syndrome 1	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	12766769; 16894541; 17163535; 18671281; 22029163

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FRAS1 gene.

not_provided (2318 variants)
Fraser_syndrome_1 (1051 variants)
Inborn_genetic_diseases (563 variants)
FRAS1-related_disorder (194 variants)
not_specified (98 variants)
Congenital_anomaly_of_kidney_and_urinary_tract (7 variants)
Cryptophthalmos_syndrome (5 variants)
Renal_agenesis (3 variants)
Congenital_diaphragmatic_hernia (3 variants)
Anophthalmia-microphthalmia_syndrome (1 variants)
Microcephaly (1 variants)
Rieger_anomaly (1 variants)
Myoepithelial_tumor (1 variants)
Usher_syndrome_type_2C (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FRAS1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000025074.7. 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	1 clinvar		30 clinvar	974 clinvar	20 clinvar	1025
missense	1 clinvar	6 clinvar	1117 clinvar	111 clinvar	24 clinvar	1259
nonsense	63 clinvar	36 clinvar	1 clinvar			100
start loss						0
frameshift	81 clinvar	43 clinvar	3 clinvar			127
splice donor/acceptor (+/-2bp)	7 clinvar	67 clinvar	2 clinvar	2 clinvar		78
Total	153	152	1153	1087	44

Highest pathogenic variant AF is 0.000047101756

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FRAS1	protein_coding	protein_coding	ENST00000264895	74	486700

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.08e-45	1.00	124417	1	287	124705	0.00116

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0780	2137	2.15e+3	0.995	0.000117	26340
Missense in Polyphen		533	620.43	0.85908		7652
Synonymous	-0.338	846	834	1.01	0.0000479	7670
Loss of Function	5.58	104	186	0.559	0.00000959	2301

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00222	0.00220
Ashkenazi Jewish	0.000604	0.000596
East Asian	0.00186	0.00184
Finnish	0.000419	0.000418
European (Non-Finnish)	0.00131	0.00129
Middle Eastern	0.00186	0.00184
South Asian	0.00131	0.00124
Other	0.000497	0.000495

dbNSFP

Source: dbNSFP

Disease: DISEASE: Fraser syndrome 1 (FRASRS1) [MIM:219000]: 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:12766769, ECO:0000269|PubMed:23473829}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.109

Intolerance Scores

loftool: 0.806
rvis_EVS: 4.65
rvis_percentile_EVS: 99.77

Haploinsufficiency Scores

pHI: 0.593
hipred: Y
hipred_score: 0.544
ghis: 0.412

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap
gene_indispensability_pred: N
gene_indispensability_score: 0.0989

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Fras1
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; cellular phenotype; skeleton phenotype; renal/urinary system phenotype; respiratory system 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); digestive/alimentary phenotype; limbs/digits/tail phenotype; vision/eye phenotype;

Zebrafish Information Network

Gene name: fras1
Affected structure: pharyngeal arch cartilage
Phenotype tag: abnormal
Phenotype quality: morphology

Gene ontology

Biological process: morphogenesis of an epithelium;metanephros morphogenesis;cell communication;protein transport;embryonic limb morphogenesis;skin development;roof of mouth development
Cellular component: basement membrane;plasma membrane;integral component of membrane;collagen-containing extracellular matrix
Molecular function: extracellular matrix structural constituent;metal ion binding