FGFR2
protein-codingfibroblast growth factor receptor 2, the group of Receptor tyrosine kinases|CD molecules|I-set domain containing
Gene summary
The protein encoded by this gene is a member of the fibroblast growth factor receptor family, where amino acid sequence is highly conserved between members and throughout evolution. FGFR family members differ from one another in their ligand affinities and tissue distribution. A full-length representative protein consists of an extracellular region, composed of three immunoglobulin-like domains, a single hydrophobic membrane-spanning segment and a cytoplasmic tyrosine kinase domain. The extracellular portion of the protein interacts with fibroblast growth factors, setting in motion a cascade of downstream signals, ultimately influencing mitogenesis and differentiation. This particular family member is a high-affinity receptor for acidic, basic and/or keratinocyte growth factor, depending on the isoform. Mutations in this gene are associated with Crouzon syndrome, Pfeiffer syndrome, Craniosynostosis, Apert syndrome, Jackson-Weiss syndrome, Beare-Stevenson cutis gyrata syndrome, Saethre-Chotzen syndrome, and syndromic craniosynostosis. Multiple alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Jan 2009]
- KGFR
- BEK
- CFD1
- JWS
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~120.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0600018
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0007043
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0007405
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0007412
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0007400
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0008803
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0007041
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0007412
Submitter: ClinGen
FGFR2 was first reported in relation to autosomal dominant Beare-Stevenson cutis gyrata syndrome in 1996 (Przylepa et al., PMID: 8696350). Beare-Stevenson cutis gyrata syndrome is characterized by cloverleaf skull deformity and deep skin folds on the scalp, palms, soles, and other areas of the body. The mechanism of pathogenicity appears to be GOF. Two GOF missense variants in FGFR2 are associated with Beare-Stevenson cutis gyrata syndrome and have been reported in 17 probands in 13 publications (PMIDs: 8696350, 19610084, 18247426, 9545103, 12000365, 12145519, 16531735, 17449949, 21397175, 32158469, 21479481, 25706251, 12900900). Due to the lethal phenotypes and high penetrance, and the confirmed autosomal dominant inheritance, all cases are assumed de novo and were scored accordingly. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. This gene-disease association is also supported by a mouse model that recapitulates the cloverleaf skull deforminity and skin phenotyupes (PMID: 22585574). In summary, FGFR2 is definitively associated with autosomal dominant Beare-Stevenson cutis gyrata syndrome. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Craniofacial Malformations Gene Curation Expert Panel on 3/17/2022. Gene Clinical Validity Standard Operating Procedures (SOP) – Version 8.
Inheritance Pattern: AD
Disease ID:MONDO:0007872
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0012307
Submitter: Genomics England PanelApp
Inheritance Pattern: AD
Disease ID:MONDO:0007042
Submitter: Genomics England PanelApp
Inheritance Pattern: AD
Disease ID:MONDO:0007405
Submitter: ClinGen
FGFR2 has been repeatedly described in association with autosomal dominant Crouzon Syndrome which is characterized by craniosynostosis and facial abnormalities with a lack of major hand and feet abnormalities (Reardon et al. 1994; PMID: 7987400). This curation includes 15 variants (missense, in-frame indel, and splice variants) reported in 19 probands in 7 publications (PMIDs: 7987400, 7874170, 7773284, 7655462, 8528214, 8528214). Variants in this gene segregated with disease in 4 families (PMIDs: 29848297, 7987400). More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. This gene-disease association is also supported by experimental evidence including an animal model, and an assay showing increased binding activity of variant FGFR2 receptor protein (PMIDs: 15316116, 9539778). In summary, FGFR2 is definitively associated with autosomal dominant Crouzon Syndrome. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Craniofacial Malformations Gene Curation Expert Panel on 9/16/2021. Gene Clinical Validity Standard Operating Procedures (SOP) – Version 8.
Inheritance Pattern: AD
Disease ID:MONDO:0007041
Submitter: ClinGen
FGFR2 has been repeatedly described in association with autosomal dominant Apert Syndrome which is characterized by craniofacial anomalies and syndactyly of the hands and feet. FGFR2-related Apert Syndrome is primarily caused by two gain-of-function missense variants, the p.Ser252Trp variant which leads to more severe craniofacial phenotypes, and the p.Pro253Arg variant which leads to more severe syndactyly (Wilkie et al. 1995; PMID: 7719344). These two missense variants, an indel, and an Alu insertion have been reported in at least 15 probands from 9 publications (PMIDs: 33585639, 9002682, 9973282, 28316926, 10658283, 9452027, 29483804, 21943124, 18726952). This gene-disease association is also supported by experimental evidence including an animal model, and an assay showing increased binding of variant FGFR2 with FGF ligands (PMIDs: 23495236, 11390973). In summary, FGFR2 is definitively associated with autosomal dominant Apert Syndrome. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Craniofacial Malformations Gene Curation Expert Panel on 8/19/2021. Gene Clinical Validity Standard Operating Procedures (SOP) – Version 8.
Inheritance Pattern: AD
Disease ID:MONDO:0013815
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0007405
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0007043
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0007043
Submitter: ClinGen
FGFR2 has been repeatedly described in association with autosomal dominant Pfeiffer Syndrome which is characterized by broad and medially deviated thumbs and great toes, proptosis, syndactyly in some cases, and cloverleaf skull in more severe cases. At least 12 variants (missense and splice) have been reported in 24 probands in 10 publications (PMIDs: 7719333, 7719345, 8841188, 9150725, 9475591, 9475590, 10712195, 15996217, 34182859, 15305355). More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. This gene-disease association is also supported by experimental evidence including two studies of one mouse model (PMIDs: 15316116, 31064775). In summary, FGFR2 is definitively associated with autosomal dominant Pfeiffer Syndrome. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Craniofacial Malformations Gene Curation Expert Panel on 12/16/2021. Gene Clinical Validity Standard Operating Procedures (SOP) – Version 8.
Inheritance Pattern: AD
Disease ID:MONDO:0007412
Submitter: Genomics England PanelApp
Inheritance Pattern: AD
Disease ID:MONDO:0007041
Submitter: Genomics England PanelApp
Inheritance Pattern: AD
Disease ID:MONDO:0013815
Submitter: ClinGen
*FGFR2* was first reported in relation to autosomal dominant FGFR2-related bent bone dysplasia in 2012 (Merill et al., PMID: 22387015). 2 variants (missense) that have been reported in 13 probands in 5 publications (PMIDs:22387015, 24300289, 26446305, 26573129,27240702) are included in this curation. The mechanism of pathogenicity appears to be gain of function. This gene-disease association is also supported by functional alteration and animal model evidence. (PMIDs: 24908667,28595297, 30620790 ). In summary,*FGFR2* is definitively associated with autosomal dominant FGFR2-related bent bone dysplasia . This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Craniofacial Malformations Gene Expert Panel on the meeting date May 19, 2022 (SOP Version 8)
Inheritance Pattern: AD
Disease ID:MONDO:0019661
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0019660
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0019659
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0007400
Submitter: Genomics England PanelApp
Inheritance Pattern: AD
Disease ID:MONDO:0007405
Submitter: Genomics England PanelApp
Inheritance Pattern: AD
Disease ID:MONDO:0007043
Submitter: Genomics England PanelApp
Inheritance Pattern: AD
Disease ID:MONDO:0007400
Submitter: G2P
Inheritance Pattern: AD
Disease ID:MONDO:0007043
Submitter: G2P
Inheritance Pattern: AD
Disease ID:MONDO:0007405
Submitter: G2P
Inheritance Pattern: AD
Disease ID:MONDO:0007041
Submitter: G2P
Inheritance Pattern: AD
Disease ID:MONDO:0007412
Submitter: G2P
Inheritance Pattern: AD
Disease ID:MONDO:0007872
Submitter: ClinGen
*FGFR2* was first reported in relation to autosomal dominant LADD syndrome in 2006 (Rohmann E et al., PMID: 22387015). 6 variants (missense, deletion) that have been reported in 8 probands in 3 publications and 2 ClinVar entries (PMIDs:16501574,28043400, 32715658,1 SCV000781492.1 (VCV000547379.1), SCV000781491.1 (VCV000547378.1)) are included in this curation. The mechanism of pathogenicity appears to be dominant negative. This gene-disease association is also supported by functional alteration and animal model evidence. (PMIDs: 30253032,18056630, 17682060). In summary, there is limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship. This classification was approved by the ClinGen Craniofacial Malformations Gene Expert Panel on the meeting date June 16, 2022 (SOP Version 8)
Inheritance Pattern: AD
Disease ID:MONDO:0100302
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0007043
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0013815
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0020667
Submitter: Genomics England PanelApp
Inheritance Pattern: AD
Disease ID:MONDO:0100302
Submitter: G2P
Inheritance Pattern: AD
Disease ID:MONDO:0007405
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0013815
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0012307
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0020667
Submitter: G2P
Inheritance Pattern: AD
Disease ID:MONDO:0100302
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0007412
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0007041
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Audiologic/Otolaryngologic; Craniofacial; Dental; Dermatologic; Musculoskeletal; Neurologic
Intervention: Audiologic/Otolaryngologic
Rationale: Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development
Comments: FGFR2-related craniosynostosis can include deafness, and may be clinically recognizable, including by outer ear malformations
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to FGFR2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000141.5. 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 | 2 | 21 | 142 | 3 | 168 | |
| missense | 52 | 59 | 308 | 27 | 3 | 449 |
| nonsense | 2 | 7 | 9 | |||
| start loss | 1 | 1 | ||||
| frameshift | 1 | 5 | 6 | |||
| splice donor/acceptor (+/-2bp) | 8 | 4 | 10 | 22 | ||
| Total | 63 | 65 | 352 | 169 | 6 | 655 |
Highest pathogenic variant AF is 0.000016728707
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000132.3 | 17 | MANE Select | |
| Ensembl | ENSP00000351276.6 | 17 | MANE Select | |
| RefSeq | NP_001138385.1 | 17 | Standard | |
| RefSeq | NP_001138386.1 | 15 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| fgfr2 | Danio rerio | Structure: intestine Quality: has fewer parts of type abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- PI3K-Akt signaling pathway - Homo sapiens (human)
- Gastric cancer - Homo sapiens (human)
- Central carbon metabolism in cancer - Homo sapiens (human)
- Endocytosis - Homo sapiens (human)
- Regulation of actin cytoskeleton - Homo sapiens (human)
Biological Process
- negative regulation of transcription by RNA polymerase II
- MAPK cascade
- angiogenesis
- ureteric bud development
- in utero embryonic development
Molecular Function
- protein tyrosine kinase activity
- transmembrane receptor protein tyrosine kinase activity
- fibroblast growth factor-activated receptor activity
- Ras guanyl-nucleotide exchange factor activity
- protein binding
Cellular Component
- nucleus
- nucleoplasm
- cytoplasm
- Golgi apparatus
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000457416
- Coding exons
- 17
- Length
- 120125
- Individuals with no LoFs
- 125738
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 10
- Defined
- 125748
- p
- 0.0000398
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.40 | 323 | 469 | 0.688 | 0.0000281 | 5404 |
| Missense (PolyPhen) | 130 | 206.49 | 0.62957 | 2412 | ||
| Synonymous | -1.17 | 205 | 185 | 1.11 | 0.0000126 | 1591 |
| Loss of Function | 5.29 | 6 | 43.8 | 0.137 | 0.00000248 | 499 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.00023 | 0.00023 | rare |
| European (Non-Finnish) | 0.000026 | 0.000026 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosis, and in the regulation of embryonic development. Required for normal embryonic patterning, trophoblast function, limb bud development, lung morphogenesis, osteogenesis and skin development. Plays an essential role in the regulation of osteoblast differentiation, proliferation and apoptosis, and is required for normal skeleton development. Promotes cell proliferation in keratinocytes and immature osteoblasts, but promotes apoptosis in differentiated osteoblasts. Phosphorylates PLCG1, FRS2 and PAK4. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. FGFR2 signaling is down-regulated by ubiquitination, internalization and degradation. Mutations that lead to constitutive kinase activation or impair normal FGFR2 maturation, internalization and degradation lead to aberrant signaling. Over-expressed FGFR2 promotes activation of STAT1. {ECO:0000269|PubMed:12529371, ECO:0000269|PubMed:15190072, ECO:0000269|PubMed:15629145, ECO:0000269|PubMed:16384934, ECO:0000269|PubMed:16597617, ECO:0000269|PubMed:17311277, ECO:0000269|PubMed:17623664, ECO:0000269|PubMed:18374639, ECO:0000269|PubMed:19103595, ECO:0000269|PubMed:19387476, ECO:0000269|PubMed:19410646, ECO:0000269|PubMed:21596750, ECO:0000269|PubMed:8663044}.;
- Disease
- DISEASE: Crouzon syndrome (CS) [MIM:123500]: An autosomal dominant syndrome characterized by craniosynostosis, hypertelorism, exophthalmos and external strabismus, parrot-beaked nose, short upper lip, hypoplastic maxilla, and a relative mandibular prognathism. {ECO:0000269|PubMed:10574673, ECO:0000269|PubMed:11173845, ECO:0000269|PubMed:11380921, ECO:0000269|PubMed:11781872, ECO:0000269|PubMed:17803937, ECO:0000269|PubMed:7581378, ECO:0000269|PubMed:7655462, ECO:0000269|PubMed:7874170, ECO:0000269|PubMed:7987400, ECO:0000269|PubMed:8528214, ECO:0000269|PubMed:8644708, ECO:0000269|PubMed:8946174, ECO:0000269|PubMed:8956050, ECO:0000269|PubMed:9152842, ECO:0000269|PubMed:9521581, ECO:0000269|PubMed:9677057, ECO:0000269|Ref.10}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Jackson-Weiss syndrome (JWS) [MIM:123150]: An autosomal dominant craniosynostosis syndrome characterized by craniofacial abnormalities and abnormality of the feet: broad great toes with medial deviation and tarsal-metatarsal coalescence. {ECO:0000269|PubMed:7874170, ECO:0000269|PubMed:8528214, ECO:0000269|PubMed:8644708, ECO:0000269|PubMed:9385368, ECO:0000269|PubMed:9677057}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Apert syndrome (APRS) [MIM:101200]: A syndrome characterized by facio-cranio-synostosis, osseous and membranous syndactyly of the four extremities, and midface hypoplasia. The craniosynostosis is bicoronal and results in acrocephaly of brachysphenocephalic type. Syndactyly of the fingers and toes may be total (mitten hands and sock feet) or partial affecting the second, third, and fourth digits. Intellectual deficit is frequent and often severe, usually being associated with cerebral malformations. {ECO:0000269|PubMed:11390973, ECO:0000269|PubMed:11781872, ECO:0000269|PubMed:15190072, ECO:0000269|PubMed:7668257, ECO:0000269|PubMed:7719344, ECO:0000269|PubMed:9002682, ECO:0000269|PubMed:9452027, ECO:0000269|PubMed:9677057}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Pfeiffer syndrome (PS) [MIM:101600]: A syndrome characterized by the association of craniosynostosis, broad and deviated thumbs and big toes, and partial syndactyly of the fingers and toes. Three subtypes are known: mild autosomal dominant form (type 1); cloverleaf skull, elbow ankylosis, early death, sporadic (type 2); craniosynostosis, early demise, sporadic (type 3). {ECO:0000269|PubMed:10394936, ECO:0000269|PubMed:10945669, ECO:0000269|PubMed:11173845, ECO:0000269|PubMed:11781872, ECO:0000269|PubMed:16844695, ECO:0000269|PubMed:17803937, ECO:0000269|PubMed:7719333, ECO:0000269|PubMed:7719345, ECO:0000269|PubMed:8644708, ECO:0000269|PubMed:9002682, ECO:0000269|PubMed:9150725, ECO:0000269|PubMed:9693549, ECO:0000269|PubMed:9719378}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Beare-Stevenson cutis gyrata syndrome (BSTVS) [MIM:123790]: An autosomal dominant disease characterized by craniofacial anomalies, particularly craniosynostosis, and ear defects, cutis gyrata, acanthosis nigricans, anogenital anomalies, skin tags, and prominent umbilical stump. The skin furrows have a corrugated appearance and are widespread. Cutis gyrata variably affects the scalp, forehead, face, preauricular area, neck, trunk, hands, and feet. {ECO:0000269|PubMed:12000365, ECO:0000269|PubMed:8696350}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Familial scaphocephaly syndrome (FSPC) [MIM:609579]: An autosomal dominant craniosynostosis syndrome characterized by scaphocephaly, macrocephaly, hypertelorism, maxillary retrusion, and mild intellectual disability. Scaphocephaly is the most common of the craniosynostosis conditions and is characterized by a long, narrow head. It is due to premature fusion of the sagittal suture or from external deformation. {ECO:0000269|PubMed:16061565, ECO:0000269|PubMed:17803937}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Lacrimo-auriculo-dento-digital syndrome (LADDS) [MIM:149730]: An autosomal dominant ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. Lacrimo-auriculo-dento-digital syndrome is characterized by aplastic/hypoplastic lacrimal and salivary glands and ducts, cup-shaped ears, hearing loss, hypodontia and enamel hypoplasia, and distal limb segments anomalies. In addition to these cardinal features, facial dysmorphism, malformations of the kidney and respiratory system and abnormal genitalia have been reported. Craniosynostosis and severe syndactyly are not observed. {ECO:0000269|PubMed:16501574, ECO:0000269|PubMed:18056630}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Antley-Bixler syndrome, without genital anomalies or disordered steroidogenesis (ABS2) [MIM:207410]: A rare syndrome characterized by craniosynostosis, radiohumeral synostosis present from the perinatal period, midface hypoplasia, choanal stenosis or atresia, femoral bowing and multiple joint contractures. Arachnodactyly and/or camptodactyly have also been reported. {ECO:0000269|PubMed:10633130}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Bent bone dysplasia syndrome (BBDS) [MIM:614592]: A perinatal lethal skeletal dysplasia characterized by poor mineralization of the calvarium, craniosynostosis, dysmorphic facial features, prenatal teeth, hypoplastic pubis and clavicles, osteopenia, and bent long bones. Dysmorphic facial features included low-set ears, hypertelorism, midface hypoplasia, prematurely erupted fetal teeth, and micrognathia. {ECO:0000269|PubMed:22387015}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Saethre-Chotzen syndrome (SCS) [MIM:101400]: A craniosynostosis syndrome characterized by coronal synostosis, brachycephaly, low frontal hairline, facial asymmetry, hypertelorism, broad halluces, and clinodactyly. {ECO:0000269|PubMed:9585583}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.763
Intolerance Scores
- LoFtool
- 0.00179
- RVIS EVS
- -1.5
- RVIS percentile EVS
- 3.57
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- H
- Indispensability pred.
- E
- Indispensability score
- 0.956
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |