FRAS1

Fraser extracellular matrix complex subunit 1

Basic information

Region (hg38): 4:78057322-78544269

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 (1048 variants)
• Fraser syndrome 1 (626 variants)
• Inborn genetic diseases (171 variants)
• not specified (117 variants)
• FRAS1-related condition (22 variants)
• Congenital anomaly of kidney and urinary tract (5 variants)
• Renal agenesis (3 variants)
• Congenital diaphragmatic hernia (2 variants)
• Rieger anomaly (1 variants)
• Usher syndrome type 2C (1 variants)
• Anophthalmia-microphthalmia syndrome (1 variants)
• Microcephaly (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.

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			46	272	37	355
missense		2	493	31	37	563
nonsense	36	16	1			53
start loss						0
frameshift	47	9	1			57
inframe indel			2			2
splice donor/acceptor (+/-2bp)	6	27	1	2		36
splice region	2	3	23	35	8	71
non coding			70	128	55	253
Total	89	54	614	433	129

Highest pathogenic variant AF is 0.0000461

Variants in FRAS1

This is a list of pathogenic ClinVar variants found in the FRAS1 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-78057588-C-G		Fraser syndrome 1	Uncertain significance (Jan 12, 2018)
4-78057753-G-T		Fraser syndrome 1	Benign (Jan 12, 2018)
4-78057765-C-G		Fraser syndrome 1	Uncertain significance (Jan 13, 2018)
4-78057777-A-T		Fraser syndrome 1	Uncertain significance (Jan 12, 2018)
4-78057822-C-T		Fraser syndrome 1	Uncertain significance (Jan 13, 2018)
4-78057825-G-T		Fraser syndrome 1	Uncertain significance (Jan 13, 2018)
4-78057945-T-C		Fraser syndrome 1	Benign (Jan 12, 2018)
4-78057987-C-T		Fraser syndrome 1	Benign (Jan 13, 2018)
4-78057992-G-T		Fraser syndrome 1	Uncertain significance (Jul 07, 2021)
4-78058022-A-T		Fraser syndrome 1	Pathogenic/Likely pathogenic (Nov 04, 2023)
4-78058023-A-T			Uncertain significance (Jul 28, 2023)
4-78058025-G-A		Inborn genetic diseases	Uncertain significance (Dec 27, 2023)
4-78058027-G-A			Likely benign (Jan 17, 2024)
4-78058033-C-T			Likely benign (Jan 20, 2024)
4-78058036-G-A			Likely benign (Oct 06, 2023)
4-78058038-T-C			Uncertain significance (Jun 24, 2022)
4-78058039-G-A			Likely benign (Nov 22, 2023)
4-78058048-G-A		FRAS1-related disorder	Conflicting classifications of pathogenicity (Jan 27, 2024)
4-78058048-G-T			Likely benign (Dec 30, 2023)
4-78058054-G-T			Likely benign (Oct 22, 2023)
4-78058056-A-C		Fraser syndrome 1	Uncertain significance (Dec 02, 2023)
4-78058080-C-A			Uncertain significance (May 06, 2015)
4-78058081-C-T			Likely benign (Feb 04, 2023)
4-78058086-G-A			Likely pathogenic (Mar 04, 2023)
4-78058090-G-A		Fraser syndrome 1	Uncertain significance (Jan 12, 2018)

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
• 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