FREM1

FRAS1 related extracellular matrix 1, the group of C-type lectin domain containing

Basic information

Region (hg38): 9:14737152-14910995

Previous symbols: [ "C9orf154" ]

Links

ENSG00000164946NCBI:158326OMIM:608944HGNC:23399Uniprot:Q5H8C1AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • trigonocephaly 2 (Disputed Evidence), mode of inheritance: AD
  • trigonocephaly 2 (Limited), mode of inheritance: AD
  • oculotrichoanal syndrome (Moderate), mode of inheritance: AR
  • oculotrichoanal syndrome (Supportive), mode of inheritance: AR
  • isolated trigonocephaly (Supportive), mode of inheritance: AD
  • renal agenesis, unilateral (Supportive), mode of inheritance: AD
  • BNAR syndrome (Supportive), mode of inheritance: AR
  • BNAR syndrome (Strong), mode of inheritance: AR
  • oculotrichoanal syndrome (Strong), mode of inheritance: AR
  • trigonocephaly 2 (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Bifid nose with or without anorectal and renal anomalies; Trigonocephaly 2; Manitoba oculotrichoanal syndromeAD/ARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingCraniofacial; Dermatologic; Gastrointestinal; Musculoskeletal; Ophthalmologic; Renal1554017; 11332973; 11822703; 17352387; 19732862; 21507892; 21931569; 23112756; 23221805

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FREM1 gene.

  • not provided (8 variants)
  • BNAR syndrome (3 variants)
  • Oculotrichoanal syndrome (2 variants)
  • FREM1-related disorder (1 variants)
  • Trigonocephaly 2;Oculotrichoanal syndrome;BNAR syndrome (1 variants)
  • Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FREM1 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
34
clinvar
136
clinvar
27
clinvar
197
missense
2
clinvar
599
clinvar
23
clinvar
20
clinvar
644
nonsense
5
clinvar
11
clinvar
16
start loss
1
clinvar
1
frameshift
6
clinvar
13
clinvar
3
clinvar
22
inframe indel
5
clinvar
1
clinvar
6
splice donor/acceptor (+/-2bp)
1
clinvar
15
clinvar
2
clinvar
18
splice region
1
24
13
6
44
non coding
35
clinvar
48
clinvar
71
clinvar
154
Total 13 41 678 207 119

Highest pathogenic variant AF is 0.0000526

Variants in FREM1

This is a list of pathogenic ClinVar variants found in the FREM1 region.

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

Position Type Phenotype Significance ClinVar
9-14737156-T-A Oculotrichoanal syndrome Uncertain significance (Jan 12, 2018)914093
9-14737167-G-A Oculotrichoanal syndrome Uncertain significance (Jan 12, 2018)366094
9-14737179-A-C Oculotrichoanal syndrome Uncertain significance (Jan 12, 2018)914094
9-14737194-C-G Oculotrichoanal syndrome Likely benign (Jan 13, 2018)914604
9-14737248-T-C Oculotrichoanal syndrome Benign (May 12, 2021)366095
9-14737256-AT-A Oculotrichoanal syndrome Uncertain significance (Jun 14, 2016)366096
9-14737341-C-A Oculotrichoanal syndrome Uncertain significance (Jan 13, 2018)366097
9-14737386-T-A Oculotrichoanal syndrome Uncertain significance (Jan 12, 2018)366098
9-14737408-G-A Oculotrichoanal syndrome Benign/Likely benign (Dec 20, 2024)366099
9-14737424-T-C Uncertain significance (Jul 21, 2022)1721840
9-14737454-T-A Uncertain significance (Jun 09, 2022)1968765
9-14737454-TG-T BNAR syndrome;Oculotrichoanal syndrome;Trigonocephaly 2 Uncertain significance (Feb 09, 2024)3596945
9-14737462-C-T FREM1-related disorder Benign (Oct 31, 2024)2711736
9-14737463-C-T BNAR syndrome;Oculotrichoanal syndrome;Trigonocephaly 2 Uncertain significance (Jun 18, 2024)3596947
9-14737467-G-C BNAR syndrome;Oculotrichoanal syndrome;Trigonocephaly 2 Uncertain significance (Feb 28, 2024)3596948
9-14737471-T-C Oculotrichoanal syndrome Conflicting classifications of pathogenicity (Oct 29, 2024)366100
9-14737480-A-C Likely benign (Sep 04, 2024)3714761
9-14737482-C-T Oculotrichoanal syndrome • Trigonocephaly 2;Oculotrichoanal syndrome;BNAR syndrome Uncertain significance (Jun 13, 2024)366101
9-14737490-T-C Inborn genetic diseases Uncertain significance (Mar 06, 2023)2462540
9-14737505-C-T Uncertain significance (Nov 10, 2022)1937588
9-14737506-G-A BNAR syndrome;Oculotrichoanal syndrome;Trigonocephaly 2 • Inborn genetic diseases Uncertain significance (Dec 23, 2024)1406788
9-14737506-G-C BNAR syndrome;Oculotrichoanal syndrome;Trigonocephaly 2 Uncertain significance (Apr 08, 2024)3596949
9-14737508-T-G not specified • Oculotrichoanal syndrome Benign (Feb 03, 2025)262545
9-14737518-C-T Uncertain significance (Dec 23, 2021)2055469
9-14737523-C-T BNAR syndrome;Oculotrichoanal syndrome;Trigonocephaly 2 Uncertain significance (May 21, 2024)3596950

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
FREM1protein_codingprotein_codingENST00000422223 36176330
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
1.57e-522.53e-712446712111246790.000851
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-3.5114851.15e+31.290.000059714317
Missense in Polyphen346286.771.20653704
Synonymous-5.005754411.300.00002464182
Loss of Function0.6088389.20.9310.000004281126

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.002440.00234
Ashkenazi Jewish0.0003010.000298
East Asian0.0005720.000556
Finnish0.0007040.000696
European (Non-Finnish)0.0007170.000699
Middle Eastern0.0005720.000556
South Asian0.001680.00160
Other0.0005010.000495

dbNSFP

Source: dbNSFP

Function
FUNCTION: Extracellular matrix protein that plays a role in epidermal differentiation and is required for epidermal adhesion during embryonic development. {ECO:0000250}.;
Disease
DISEASE: Bifid nose, with or without anorectal and renal anomalies (BNAR) [MIM:608980]: A disease characterized by the presence of a bifid nose usually associated with renal agenesis and anorectal malformations. A bifid nose is a congenital deformity due to failure of the paired nasal processes to fuse to a single midline organ during early gestation. {ECO:0000269|PubMed:19732862}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Manitoba oculotrichoanal syndrome (MOTA) [MIM:248450]: A rare condition defined by eyelid colobomas, cryptophthalmos, and anophthalmia/microphthalmia, an aberrant hairline, a bifid or broad nasal tip, and gastrointestinal anomalies such as omphalocele and anal stenosis. {ECO:0000269|PubMed:21507892, ECO:0000269|PubMed:28111185}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Trigonocephaly 2 (TRIGNO2) [MIM:614485]: A keel-shaped deformation of the forehead, caused by premature fusion of the metopic sutures. It results in a triangular shape of the head. {ECO:0000269|PubMed:21931569}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.102

Intolerance Scores

loftool
0.995
rvis_EVS
-0.63
rvis_percentile_EVS
17.04

Haploinsufficiency Scores

pHI
0.100
hipred
hipred_score
ghis
0.471

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.548

Gene Damage Prediction

AllRecessiveDominant
MendelianHighMediumHigh
Primary ImmunodeficiencyHighHighHigh
CancerHighHighHigh

Mouse Genome Informatics

Gene name
Frem1
Phenotype
liver/biliary system phenotype; respiratory system phenotype; reproductive system phenotype; normal phenotype; 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); vision/eye phenotype; limbs/digits/tail 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); digestive/alimentary phenotype; skeleton phenotype; renal/urinary system phenotype; endocrine/exocrine gland 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); growth/size/body region phenotype; craniofacial phenotype; muscle phenotype;

Zebrafish Information Network

Gene name
frem1a
Affected structure
dorsal fin
Phenotype tag
abnormal
Phenotype quality
has fewer parts of type

Gene ontology

Biological process
cell communication;cell-matrix adhesion;craniofacial suture morphogenesis
Cellular component
basement membrane;integral component of membrane
Molecular function
carbohydrate binding;metal ion binding