FGFR3

fibroblast growth factor receptor 3, the group of I-set domain containing|CD molecules|Receptor tyrosine kinases

Basic information

Region (hg38): 4:1793292-1808872

Previous symbols: [ "ACH" ]

Links

ENSG00000068078 ∙ NCBI:2261 ∙ OMIM:134934 ∙ HGNC:3690 ∙ Uniprot:P22607 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• LADD syndrome 1 (Definitive), mode of inheritance: AD
• Muenke syndrome (Definitive), mode of inheritance: AD
• Crouzon syndrome-acanthosis nigricans syndrome (Definitive), mode of inheritance: AD
• Achondroplasia (Definitive), mode of inheritance: AD
• thanatophoric dysplasia type 2 (Definitive), mode of inheritance: AD
• camptodactyly-tall stature-scoliosis-hearing loss syndrome (Definitive), mode of inheritance: AD
• hypochondroplasia (Definitive), mode of inheritance: AD
• thanatophoric dysplasia type 1 (Definitive), mode of inheritance: AD
• Crouzon syndrome-acanthosis nigricans syndrome (Strong), mode of inheritance: AD
• Muenke syndrome (Strong), mode of inheritance: AD
• Achondroplasia (Strong), mode of inheritance: AD
• Muenke syndrome (Strong), mode of inheritance: AD
• Crouzon syndrome-acanthosis nigricans syndrome (Strong), mode of inheritance: AD
• thanatophoric dysplasia type 1 (Strong), mode of inheritance: AD
• thanatophoric dysplasia type 2 (Strong), mode of inheritance: AD
• Achondroplasia (Definitive), mode of inheritance: AD
• camptodactyly-tall stature-scoliosis-hearing loss syndrome (Moderate), mode of inheritance: AR
• Crouzon syndrome-acanthosis nigricans syndrome (Definitive), mode of inheritance: AD
• hypochondroplasia (Strong), mode of inheritance: AD
• Muenke syndrome (Definitive), mode of inheritance: AD
• thanatophoric dysplasia type 1 (Strong), mode of inheritance: AD
• Achondroplasia (Supportive), mode of inheritance: AD
• hypochondroplasia (Supportive), mode of inheritance: AD
• thanatophoric dysplasia type 1 (Supportive), mode of inheritance: AD
• LADD syndrome (Supportive), mode of inheritance: AD
• isolated plagiocephaly (Supportive), mode of inheritance: AD
• isolated brachycephaly (Supportive), mode of inheritance: AD
• Muenke syndrome (Supportive), mode of inheritance: AD
• camptodactyly-tall stature-scoliosis-hearing loss syndrome (Supportive), mode of inheritance: AD
• severe achondroplasia-developmental delay-acanthosis nigricans syndrome (Supportive), mode of inheritance: AD
• Crouzon syndrome-acanthosis nigricans syndrome (Supportive), mode of inheritance: AD
• thanatophoric dysplasia type 2 (Supportive), mode of inheritance: AD
• Achondroplasia (Strong), mode of inheritance: AD
• camptodactyly-tall stature-scoliosis-hearing loss syndrome (Strong), mode of inheritance: AD
• camptodactyly-tall stature-scoliosis-hearing loss syndrome (Limited), mode of inheritance: AR
• Crouzon syndrome-acanthosis nigricans syndrome (Strong), mode of inheritance: AD
• hypochondroplasia (Strong), mode of inheritance: AD
• LADD syndrome 1 (Limited), mode of inheritance: AD
• Muenke syndrome (Strong), mode of inheritance: AD
• severe achondroplasia-developmental delay-acanthosis nigricans syndrome (Strong), mode of inheritance: AD
• thanatophoric dysplasia type 2 (Strong), mode of inheritance: AD
• Achondroplasia (Definitive), mode of inheritance: AD
• thanatophoric dysplasia type 2 (Definitive), mode of inheritance: AD
• hypochondroplasia (Definitive), mode of inheritance: AD
• camptodactyly-tall stature-scoliosis-hearing loss syndrome (Moderate), mode of inheritance: Semidominant
• Crouzon syndrome-acanthosis nigricans syndrome (Definitive), mode of inheritance: AD
• severe achondroplasia-developmental delay-acanthosis nigricans syndrome (Moderate), mode of inheritance: AD
• thanatophoric dysplasia type 1 (Definitive), mode of inheritance: AD
• Muenke syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Camptodactyly, tall stature, and hearing loss (CATSHL) syndrome; Crouzon syndrome with acanthosis nigricans; Lacrimoauriculodentodigital syndrome 2; Muenke syndrome	AD/AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Craniofacial; Dermatologic; Musculoskeletal; Neurologic	5783850; 4697848; 474637; 3631079; 2650599; 7968151; 8078586; 7913883; 7847369; 7670477; 7493034; 7758520; 7773297; 8589699; 7647778 ; 8585566; 8841188; 8845844; 8923856; 8834055; 8880573; 9279764; 9042914; 9842995; 9600744; 9580776; 3631079; 9279753; 3228140; 9525367; 9733026; 9585583; 9450868; 9797588; 9677066; 10360402; 10360393; 10360392; 10053006; 11055896; 11186939; 10777366; 12116251; 15517832; 16912704; 15241680; 16353253; 16501574; 16411219; 17033969 18000976; 17935505; 17764078; 18000903; 17360555; 17879967; 17895900; 18266238; 18000903; 19449410; 20301540; 20624921; 9842995; 20301588; 19215249; 21204234; 20301331; 20301628; 21403557; 21403567; 22038757; 21971908; 22085076; 22446440; 22565872; 23044018; 23378035; 24168007; 24864036
Certain variants in FGFR3 (such as result in CATSHL or Muenke syndrome) can result in congenital hearing loss, and thecondition may not be recognized early

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FGFR3 gene.

• not provided (722 variants)
• not specified (106 variants)
• Inborn genetic diseases (44 variants)
• 14 conditions (26 variants)
• Hypochondroplasia (25 variants)
• Connective tissue disorder (24 variants)
• FGFR3-related condition (20 variants)
• Thanatophoric dysplasia type 1 (16 variants)
• Achondroplasia (16 variants)
• Carcinoma (6 variants)
• See cases (6 variants)
• Urinary bladder carcinoma (5 variants)
• Sarcoma (4 variants)
• Craniosynostosis syndrome (4 variants)
• Transitional cell carcinoma of the bladder (3 variants)
• Malignant tumor of urinary bladder (3 variants)
• Craniosynostosis, nonspecific (3 variants)
• Cervical cancer (3 variants)
• Short stature (3 variants)
• Camptodactyly-tall stature-scoliosis-hearing loss syndrome (3 variants)
• Thanatophoric dysplasia (3 variants)
• Epidermal nevus (3 variants)
• Squamous cell lung carcinoma (3 variants)
• Crouzon syndrome-acanthosis nigricans syndrome (2 variants)
• FGFR3-related chondrodysplasia (2 variants)
• Seborrheic keratosis (2 variants)
• Muenke syndrome (2 variants)
• Multiple myeloma (2 variants)
• Neurodevelopmental delay (2 variants)
• Thanatophoric dysplasia, type 2 (2 variants)
• FGFR3-related disorder (2 variants)
• Myeloproliferative disorder (2 variants)
• Squamous cell carcinoma of the head and neck (2 variants)
• Papillary renal cell carcinoma, sporadic (2 variants)
• 7 conditions (1 variants)
• Diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype (1 variants)
• Achondroplasia;Hypochondroplasia (1 variants)
• Lung adenocarcinoma (1 variants)
• Lacrimoauriculodentodigital syndrome 2 (1 variants)
• Pituitary stalk interruption syndrome (1 variants)
• Acanthosis nigricans (1 variants)
• Levy-Hollister syndrome (1 variants)
• Spermatocytic seminoma (1 variants)
• - (1 variants)
• Severe achondroplasia-developmental delay-acanthosis nigricans syndrome (1 variants)
• FGFR3-Related Disorders (1 variants)
• SEVERE ACHONDRODYSPLASIA WITH DEVELOPMENTAL DELAY AND ACANTHOSIS NIGRICANS (1 variants)
• Classic Hodgkin lymphoma (1 variants)
• Global developmental delay (1 variants)
• Hypochondroplasia;Thanatophoric dysplasia type 1;Achondroplasia;Muenke syndrome;Crouzon syndrome-acanthosis nigricans syndrome (1 variants)
• Skeletal dysplasia;Genu varum;Craniosynostosis syndrome;Short stature (1 variants)
• Abnormality of the nervous system (1 variants)
• Thanatophoric dysplasia type 1;Thanatophoric dysplasia, type 2 (1 variants)
• 9 conditions (1 variants)
• Hepatoblastoma (1 variants)
• Saethre-Chotzen syndrome (1 variants)
• 13 conditions (1 variants)
• Anophthalmia-microphthalmia syndrome (1 variants)
• Skeletal dysplasia with acanthosis nigricans (1 variants)
• Achondroplasia;Hypochondroplasia;Camptodactyly-tall stature-scoliosis-hearing loss syndrome;Crouzon syndrome-acanthosis nigricans syndrome;Levy-Hollister syndrome (1 variants)
• Autism spectrum disorder (1 variants)
• Hamartoma (1 variants)
• Neoplasm of ovary (1 variants)
• FGFR3-related disoder (1 variants)
• Larsen syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FGFR3 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			7	141	16	164
missense	20	16	263	44	1	344
nonsense	1		1	2		4
start loss			1			1
frameshift			9			9
inframe indel			4			4
splice donor/acceptor (+/-2bp)			3			3
splice region			11	30	9	50
non coding	1		3	107	36	147
Total	22	16	291	294	53

Highest pathogenic variant AF is 0.00000657

Variants in FGFR3

This is a list of pathogenic ClinVar variants found in the FGFR3 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-1793594-C-A			Benign (Jun 14, 2018)
4-1793606-C-T			Benign (Jun 30, 2018)
4-1793652-G-A			Likely benign (Aug 19, 2018)
4-1793812-GCTGCCTTC-G			Benign (Nov 13, 2017)
4-1793824-C-T			Likely benign (Jul 21, 2020)
4-1793830-T-C		not specified	Benign (Jun 25, 2020)
4-1793937-G-A			Uncertain significance (Oct 14, 2021)
4-1793937-G-T			Uncertain significance (Sep 16, 2018)
4-1793940-C-T			Likely benign (Jun 03, 2022)
4-1793941-G-A		Inborn genetic diseases	Uncertain significance (Jun 29, 2023)
4-1793947-G-C			Uncertain significance (Jun 09, 2022)
4-1793948-C-T			Uncertain significance (Nov 07, 2022)
4-1793949-C-A			Likely benign (Aug 10, 2023)
4-1793951-G-A			Uncertain significance (Nov 22, 2022)
4-1793955-C-T		not specified	Likely benign (Apr 13, 2022)
4-1793962-C-T			Uncertain significance (Aug 09, 2022)
4-1793964-C-T			Likely benign (Aug 04, 2023)
4-1793973-C-G			Likely benign (Nov 23, 2021)
4-1793974-G-A			Uncertain significance (Mar 28, 2022)
4-1793977-G-A			Uncertain significance (May 18, 2023)
4-1793977-G-T			Uncertain significance (Nov 04, 2019)
4-1793984-TGGCCGGCGC-T			Uncertain significance (Jul 26, 2023)
4-1793986-G-A			Uncertain significance (Nov 18, 2023)
4-1793996-C-A		not specified	not provided (Sep 19, 2013)
4-1793999-C-T		Inborn genetic diseases	Uncertain significance (Feb 06, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FGFR3	protein_coding	protein_coding	ENST00000340107	17	15566

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000164	1.00	125514	0	36	125550	0.000143

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.26	458	540	0.848	0.0000388	5114
Missense in Polyphen		158	239.3	0.66025		2226
Synonymous	-3.39	324	255	1.27	0.0000206	1680
Loss of Function	3.48	15	38.2	0.392	0.00000200	405

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000162	0.000158
Ashkenazi Jewish	0.00	0.00
East Asian	0.000368	0.000326
Finnish	0.0000478	0.0000462
European (Non-Finnish)	0.000130	0.000123
Middle Eastern	0.000368	0.000326
South Asian	0.000298	0.000294
Other	0.000353	0.000326

dbNSFP

Source: dbNSFP

• 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 and apoptosis. Plays an essential role in the regulation of chondrocyte differentiation, proliferation and apoptosis, and is required for normal skeleton development. Regulates both osteogenesis and postnatal bone mineralization by osteoblasts. Promotes apoptosis in chondrocytes, but can also promote cancer cell proliferation. Required for normal development of the inner ear. Phosphorylates PLCG1, CBL and FRS2. 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. Plays a role in the regulation of vitamin D metabolism. Mutations that lead to constitutive kinase activation or impair normal FGFR3 maturation, internalization and degradation lead to aberrant signaling. Over-expressed or constitutively activated FGFR3 promotes activation of PTPN11/SHP2, STAT1, STAT5A and STAT5B. Secreted isoform 3 retains its capacity to bind FGF1 and FGF2 and hence may interfere with FGF signaling. {ECO:0000269|PubMed:10611230, ECO:0000269|PubMed:11294897, ECO:0000269|PubMed:11703096, ECO:0000269|PubMed:14534538, ECO:0000269|PubMed:16410555, ECO:0000269|PubMed:16597617, ECO:0000269|PubMed:17145761, ECO:0000269|PubMed:17311277, ECO:0000269|PubMed:17509076, ECO:0000269|PubMed:17561467, ECO:0000269|PubMed:19088846, ECO:0000269|PubMed:19286672, ECO:0000269|PubMed:8663044}.
• Disease: DISEASE: Achondroplasia (ACH) [MIM:100800]: A frequent form of short-limb dwarfism. It is characterized by a long, narrow trunk, short extremities, particularly in the proximal (rhizomelic) segments, a large head with frontal bossing, hypoplasia of the midface and a trident configuration of the hands. ACH is an autosomal dominant disease. {ECO:0000269|PubMed:10611230, ECO:0000269|PubMed:12297284, ECO:0000269|PubMed:7758520, ECO:0000269|PubMed:7847369, ECO:0000269|PubMed:8078586, ECO:0000269|PubMed:8599935}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Crouzon syndrome with acanthosis nigricans (CAN) [MIM:612247]: Classic Crouzon disease which is caused by mutations in the FGFR2 gene is characterized by craniosynostosis (premature fusion of the skull sutures), and facial hypoplasia. Crouzon syndrome with acanthosis nigricans (a skin disorder characterized by pigmentation anomalies), CAN, is considered to be an independent disorder from classic Crouzon syndrome. CAN is characterized by additional more severe physical manifestation, such as Chiari malformation, hydrocephalus, and atresia or stenosis of the choanas, and is caused by a specific mutation (Ala-391 to Glu) in the transmembrane domain of FGFR3. It is proposed to have an autosomal dominant mode of inheritance. {ECO:0000269|PubMed:17935505, ECO:0000269|PubMed:7493034}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Thanatophoric dysplasia 1 (TD1) [MIM:187600]: A neonatal lethal skeletal dysplasia. Affected individuals manifest severe shortening of the limbs with macrocephaly, narrow thorax, short ribs, and curved femurs. {ECO:0000269|PubMed:10360402, ECO:0000269|PubMed:10671061, ECO:0000269|PubMed:7773297, ECO:0000269|PubMed:8589699, ECO:0000269|PubMed:8845844, ECO:0000269|PubMed:9790257}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Thanatophoric dysplasia 2 (TD2) [MIM:187601]: A neonatal lethal skeletal dysplasia causing severe shortening of the limbs, narrow thorax and short ribs. Patients with thanatophoric dysplasia type 2 have straight femurs and cloverleaf skull. {ECO:0000269|PubMed:12297284, ECO:0000269|PubMed:7773297, ECO:0000269|PubMed:8754806}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Hypochondroplasia (HCH) [MIM:146000]: Autosomal dominant disease and is characterized by disproportionate short stature. It resembles achondroplasia, but with a less severe phenotype. {ECO:0000269|PubMed:10215410, ECO:0000269|PubMed:10777366, ECO:0000269|PubMed:11055896, ECO:0000269|PubMed:12707965, ECO:0000269|PubMed:7670477, ECO:0000269|PubMed:9452043}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Bladder cancer (BLC) [MIM:109800]: A malignancy originating in tissues of the urinary bladder. It often presents with multiple tumors appearing at different times and at different sites in the bladder. Most bladder cancers are transitional cell carcinomas that begin in cells that normally make up the inner lining of the bladder. Other types of bladder cancer include squamous cell carcinoma (cancer that begins in thin, flat cells) and adenocarcinoma (cancer that begins in cells that make and release mucus and other fluids). Bladder cancer is a complex disorder with both genetic and environmental influences. {ECO:0000269|PubMed:10471491, ECO:0000269|PubMed:11314002}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. Somatic mutations can constitutively activate FGFR3.; DISEASE: Cervical cancer (CERCA) [MIM:603956]: A malignant neoplasm of the cervix, typically originating from a dysplastic or premalignant lesion previously present at the active squamocolumnar junction. The transformation from mild dysplastic to invasive carcinoma generally occurs slowly within several years, although the rate of this process varies widely. Carcinoma in situ is particularly known to precede invasive cervical cancer in most cases. Cervical cancer is strongly associated with infection by oncogenic types of human papillomavirus. {ECO:0000269|PubMed:10471491}. Note=The gene represented in this entry is involved in disease pathogenesis.; DISEASE: Camptodactyly, tall stature, and hearing loss syndrome (CATSHLS) [MIM:610474]: An autosomal dominant syndrome characterized by permanent and irreducible flexion of one or more fingers of the hand and/or feet, tall stature, scoliosis and/or a pectus excavatum, and hearing loss. Affected individuals have developmental delay and/or mental retardation, and several of these have microcephaly. Radiographic findings included tall vertebral bodies with irregular borders and broad femoral metaphyses with long tubular shafts. On audiological exam, each tested member have bilateral sensorineural hearing loss and absent otoacoustic emissions. The hearing loss was congenital or developed in early infancy, progressed variably in early childhood, and range from mild to severe. Computed tomography and magnetic resonance imaging reveal that the brain, middle ear, and inner ear are structurally normal. {ECO:0000269|PubMed:17033969}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Multiple myeloma (MM) [MIM:254500]: A malignant tumor of plasma cells usually arising in the bone marrow and characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones proteinuria and anemia. Complications of multiple myeloma are bone pain, hypercalcemia, renal failure and spinal cord compression. The aberrant antibodies that are produced lead to impaired humoral immunity and patients have a high prevalence of infection. Amyloidosis may develop in some patients. Multiple myeloma is part of a spectrum of diseases ranging from monoclonal gammopathy of unknown significance (MGUS) to plasma cell leukemia. {ECO:0000269|PubMed:11529856, ECO:0000269|PubMed:9207791}. Note=The gene represented in this entry may be involved in disease pathogenesis. A chromosomal aberration involving FGFR3 is found in multiple myeloma. Translocation t(4;14)(p16.3;q32.3) with the IgH locus.; 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}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Keratinocytic non-epidermolytic nevus (KNEN) [MIM:162900]: Epidermal nevi of the common, non-organoid and non- epidermolytic type are benign skin lesions and may vary in their extent from a single (usually linear) lesion to widespread and systematized involvement. They may be present at birth or develop early during childhood. {ECO:0000269|PubMed:16841094}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Muenke syndrome (MNKS) [MIM:602849]: A condition characterized by premature closure of coronal suture of skull during development (coronal craniosynostosis), which affects the shape of the head and face. It may be uni- or bilateral. When bilateral, it is characterized by a skull with a small antero- posterior diameter (brachycephaly), often with a decrease in the depth of the orbits and hypoplasia of the maxillae. Unilateral closure of the coronal sutures leads to flattening of the orbit on the involved side (plagiocephaly). The intellect is normal. In addition to coronal craniosynostosis some affected individuals show skeletal abnormalities of hands and feet, sensorineural hearing loss, mental retardation and respiratory insufficiency. {ECO:0000269|PubMed:11746040, ECO:0000269|PubMed:9042914, ECO:0000269|PubMed:9950359}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Keratosis, seborrheic (KERSEB) [MIM:182000]: A common benign skin tumor. Seborrheic keratoses usually begin with the appearance of one or more sharply defined, light brown, flat macules. The lesions may be sparse or numerous. As they initially grow, they develop a velvety to finely verrucous surface, followed by an uneven warty surface with multiple plugged follicles and a dull or lackluster appearance. {ECO:0000269|PubMed:15772091}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Testicular germ cell tumor (TGCT) [MIM:273300]: A common malignancy in males representing 95% of all testicular neoplasms. TGCTs have various pathologic subtypes including: unclassified intratubular germ cell neoplasia, seminoma (including cases with syncytiotrophoblastic cells), spermatocytic seminoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma, and teratoma. {ECO:0000269|PubMed:19855393}. Note=The gene represented in this entry may be involved in disease pathogenesis.; DISEASE: Achondroplasia, severe, with developmental delay and acanthosis nigricans (SADDAN) [MIM:616482]: A severe form of achondroplasia associated with developmental delay and acanthosis nigricans. Patients manifest short-limb dwarfism, with a long, narrow trunk, short extremities, particularly in the proximal (rhizomelic) segments, a large head with frontal bossing, hypoplasia of the midface and a trident configuration of the hands. Acanthosis nigricans is a skin condition characterized by brown-pigmented, velvety verrucosities in body folds and creases. {ECO:0000269|PubMed:10053006}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);Central carbon metabolism in cancer - Homo sapiens (human);Bladder cancer - Homo sapiens (human);Endocytosis - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);MicroRNAs in cancer - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Vemurafenib Pathway, Pharmacodynamics;update your name in edit mode;VEGF Signaling Pathway;Neural Crest Differentiation;Bladder Cancer;NOTCH1 regulation of human endothelial cell calcification;MAPK Signaling Pathway;ESC Pluripotency Pathways;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;Endometrial cancer;PI3K-Akt Signaling Pathway;Ras Signaling;Endochondral Ossification;Regulation of Actin Cytoskeleton;FGFR3b ligand binding and activation;FGFR3c ligand binding and activation;FRS-mediated FGFR3 signaling;SHC-mediated cascade:FGFR3;PI-3K cascade:FGFR3;Downstream signaling of activated FGFR3;Disease;Negative regulation of FGFR3 signaling;Signaling by FGFR3;Signal Transduction;Signaling by FGFR;FGFR3 ligand binding and activation;t(4;14) translocations of FGFR3;FGFR3 mutant receptor activation;PI3K Cascade;IRS-mediated signalling;Insulin receptor signalling cascade;Signaling by Insulin receptor;FGF;Fibroblast growth factor-1;IL-7 signaling;Signaling by activated point mutants of FGFR3;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;PIP3 activates AKT signaling;JAK STAT pathway and regulation;EPO signaling;PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling;Negative regulation of the PI3K/AKT network;Signaling by FGFR3 point mutants in cancer;Signaling by FGFR3 fusions in cancer;Signaling by FGFR3 in disease;Signaling by FGFR in disease;Constitutive Signaling by Aberrant PI3K in Cancer;PI3K/AKT Signaling in Cancer;IRS-related events triggered by IGF1R;IGF1R signaling cascade;Signaling by Receptor Tyrosine Kinases;VEGF;Intracellular signaling by second messengers;Diseases of signal transduction;Syndecan-1-mediated signaling events;Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R);FGF signaling pathway;Syndecan-2-mediated signaling events;Syndecan-3-mediated signaling events;Phospholipase C-mediated cascade; FGFR3 (Consensus)

Recessive Scores

• pRec: 0.785

Intolerance Scores

• loftool: 0.0225
• rvis_EVS: -2.05
• rvis_percentile_EVS: 1.64

Haploinsufficiency Scores

• pHI: 0.846
• hipred: Y
• hipred_score: 0.747
• ghis: 0.642

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.837

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Fgfr3
• Phenotype: respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); neoplasm; hematopoietic 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; digestive/alimentary 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); hearing/vestibular/ear phenotype; skeleton phenotype; renal/urinary system phenotype; immune system phenotype; homeostasis/metabolism phenotype; cellular 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

Zebrafish Information Network

• Gene name: fgfr3
• Affected structure: hematopoietic stem cell differentiation
• Phenotype tag: abnormal
• Phenotype quality: decreased occurrence

Gene ontology

• Biological process: MAPK cascade;skeletal system development;endochondral ossification;chondrocyte differentiation;endochondral bone growth;transmembrane receptor protein tyrosine kinase signaling pathway;cell-cell signaling;positive regulation of cell population proliferation;fibroblast growth factor receptor signaling pathway;positive regulation of phospholipase activity;peptidyl-tyrosine phosphorylation;bone mineralization;chondrocyte proliferation;phosphatidylinositol-3-phosphate biosynthetic process;positive regulation of tyrosine phosphorylation of STAT protein;positive regulation of MAPK cascade;positive regulation of phosphatidylinositol 3-kinase activity;protein autophosphorylation;phosphatidylinositol phosphorylation;negative regulation of developmental growth;positive regulation of protein kinase B signaling;bone morphogenesis;positive regulation of ERK1 and ERK2 cascade;bone maturation;fibroblast growth factor receptor apoptotic signaling pathway
• Cellular component: extracellular region;nucleus;endoplasmic reticulum;Golgi apparatus;plasma membrane;integral component of plasma membrane;focal adhesion;cell surface;transport vesicle;receptor complex
• 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;ATP binding;1-phosphatidylinositol-3-kinase activity;fibroblast growth factor binding;identical protein binding;phosphatidylinositol-4,5-bisphosphate 3-kinase activity