FREM3

protein-coding

FRAS1 related extracellular matrix 3

Gene summary

This gene encodes an integral membrane protein containing numerous CSPG (chondroitin sulfate proteoglycan element) repeats and Calx-beta domains. The protein belongs to the family of FRAS1/FREM extracellular matrix proteins and may play a role cell adhesion. [provided by RefSeq, Feb 2017]

MANE transcript

NM_001168235.2

Inheritance

—

ClinVar variants

U:328B:29

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.67

Max pathogenic AF

—

Genomic locus

chr4:143,577,302-143,700,675

External References & Databases

Ensembl (ENSG00000183090)

Transcript & Mutation Effects

hg38 • Region Span ~123.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FREM3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 346

not providedTotal: 11

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001168235.2. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	7 clinvar	1 clinvar	9
missense			326 clinvar	20 clinvar	1 clinvar	347
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	328	27	2	357

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001168235.2	RefSeq	NP_001161707.1	8	MANE Select
ENST00000329798.5	Ensembl	ENSP00000332886.5	8	MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

cell communication
cell adhesion

Molecular Function

metal ion binding

Cellular Component

basement membrane
extracellular space
integral component of membrane
collagen-containing extracellular matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000329798
Coding exons: 8
Length: 123374
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.97	843	1.12e+3	0.751	0.0000565	13988
Missense (PolyPhen)		156	241.06	0.64714		3203
Synonymous	4.42	335	455	0.736	0.0000240	4404
Loss of Function	2.31	39	58.0	0.672	0.00000298	707

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Extracellular matrix protein which may play a role in cell adhesion. {ECO:0000250}.;

Recessive Scores

pRec: 0.0987

Intolerance Scores

RVIS EVS: 4.07
RVIS percentile EVS: 99.68

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.103

Gene Damage Prediction

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