FGF13

Summary

FGF13 (fibroblast growth factor 13, HGNC:3670) is a protein-coding gene on chromosome Xq26.3-q27.1, encoding Fibroblast growth factor 13 (Q92913). Microtubule-binding protein which directly binds tubulin and is involved in both polymerization and stabilization of microtubules. In precision oncology, FGF2 EXPRESSION is associated with resistance to Quizartinib in Acute Myeloid Leukemia (CIViC Level D).

The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth, and invasion. This gene is located in a region on chromosome X, which is associated with Borjeson-Forssman-Lehmann syndrome (BFLS), making it a possible candidate gene for familial cases of the BFLS, and for other syndromal and nonspecific forms of X-linked cognitive disability mapping to this region. Alternative splicing of this gene at the 5’ end results in several transcript variants encoding different isoforms with different N-termini.

Source: NCBI Gene 2258 — RefSeq curated summary.

At a glance

• Gene–disease (curated): developmental and epileptic encephalopathy, 90 (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 126 total — 5 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 49
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• MANE Select transcript: NM_004114

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3670
Approved symbol	FGF13
Name	fibroblast growth factor 13
Location	Xq26.3-q27.1
Locus type	gene with protein product
Status	Approved
Aliases	FHF2, FGF2, FLJ30672
Ensembl gene	ENSG00000129682
Ensembl biotype	protein_coding
OMIM	300070
Entrez	2258

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 9 protein_coding

ENST00000305414, ENST00000315930, ENST00000421460, ENST00000436198, ENST00000441825, ENST00000448673, ENST00000455663, ENST00000626909, ENST00000875444

RefSeq mRNA: 6 — MANE Select: NM_004114 NM_001139498, NM_001139500, NM_001139501, NM_001139502, NM_004114, NM_033642

CCDS: CCDS14664, CCDS14665, CCDS55511, CCDS55512, CCDS55513

Canonical transcript exons

ENST00000315930 — 5 exons

Exon	Start	End
ENSE00001124987	138710817	138711717
ENSE00003765119	138614727	138632986
ENSE00003805811	138702984	138703087
ENSE00003810423	138635457	138635655
ENSE00003811014	138708818	138708928

Expression profiles

Bgee: expression breadth ubiquitous, 268 present calls, max score 98.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.8799 / max 317.5898, expressed in 982 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
200704	3.7832	760
200692	2.2638	357
200691	0.5963	192
200707	0.3873	161
200700	0.3743	214
200690	0.3257	185
200694	0.2347	69
200708	0.2334	34
200706	0.2132	85
200701	0.1929	79

Top tissues by expression

294 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	98.61	gold quality
dorsal root ganglion	UBERON:0000044	98.07	gold quality
cortical plate	UBERON:0005343	97.90	gold quality
CA1 field of hippocampus	UBERON:0003881	96.54	gold quality
substantia nigra pars reticulata	UBERON:0001966	96.37	gold quality
orbitofrontal cortex	UBERON:0004167	95.84	gold quality
trigeminal ganglion	UBERON:0001675	95.69	gold quality
Ammon’s horn	UBERON:0001954	94.97	gold quality
middle temporal gyrus	UBERON:0002771	94.97	gold quality
blood vessel layer	UBERON:0004797	94.55	gold quality
Brodmann (1909) area 46	UBERON:0006483	94.50	gold quality
postcentral gyrus	UBERON:0002581	94.29	gold quality
parietal lobe	UBERON:0001872	94.28	gold quality
superior frontal gyrus	UBERON:0002661	94.22	gold quality
nucleus accumbens	UBERON:0001882	94.20	gold quality
ganglionic eminence	UBERON:0004023	93.80	gold quality
lateral nuclear group of thalamus	UBERON:0002736	93.75	gold quality
amygdala	UBERON:0001876	93.68	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	93.54	gold quality
prefrontal cortex	UBERON:0000451	93.49	gold quality
temporal lobe	UBERON:0001871	93.38	gold quality
Brodmann (1909) area 23	UBERON:0013554	93.36	gold quality
entorhinal cortex	UBERON:0002728	93.20	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	93.00	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	92.82	gold quality
substantia nigra pars compacta	UBERON:0001965	92.71	gold quality
biceps brachii	UBERON:0001507	92.50	gold quality
cerebral cortex	UBERON:0000956	92.46	gold quality
superior vestibular nucleus	UBERON:0007227	92.43	gold quality
hypothalamus	UBERON:0001898	92.36	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	1996.38
E-HCAD-25	yes	1498.56
E-GEOD-81383	yes	343.61
E-CURD-119	yes	50.95
E-ANND-3	yes	7.12
E-MTAB-7249	no	521.71
E-MTAB-7606	no	35.62

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EGR1, GLI2

miRNA regulators (miRDB)

114 targeting FGF13, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-8068	99.98	73.85	2376
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-4753-3P	99.90	71.03	3786

Literature-anchored findings (GeneRIF, showing 34)

• interactions with perlecans (PMID:11847221)
• identification of a domain controlling angiogenic properties (PMID:12496262)
• FHF2B is an interacting partner of Na(v)1.6. The preferential expression of FHF2B in sensory neurons may provide a basis for physiological differences in sodium currents that have been reported at the nodes of Ranvier in sensory versus motor axons. (PMID:15282281)
• X-chromosome deletions may be a cause of WS with larger deletions being lethal to males and that FGF13 mutations may be a cause of Wildervanck Syndrome (WS). (PMID:23373430)
• FGF13 has a role in hair follicle growth and in the hair cycle as shown in a family with X-linked congenital generalized hypertrichosis (PMID:23603273)
• Upregulated expression of FGF13/FHF2 mediates resistance to platinum drugs in cervical cancer cells (PMID:24113164)
• The findings of this study reveal a novel cause of this syndrome and underscore the powerful role of FGF13 in control of neuronal excitability. (PMID:26063919)
• for PCa patients after RP, FGF13 serves as a potential novel prognostic marker that improves prediction of BCR-free survival, in particular if combined with other clinical parameters. (PMID:26891277)
• These data showed the diversity of the roles of the FGF13 N-termini in NaV1.5 channel modulation and suggested the importance of isoform-specific regulation (PMID:27246624)
• Study screened the coding and splice site regions of the FGF13 gene in a sample of 45 unrelated probands where genetic epilepsy with febrile seizures plus segregated in an X-linked pattern; subsequently identified a de novo FGF13 missense variant in an additional patient with febrile seizures and facial edema. Results suggest that FGF13 is not a common cause of genetic epilepsy with febrile seizures plus. (PMID:27810516)
• Autism-related protein MeCP2 regulates FGF13 expression and emotional behaviors (PMID:27916441)
• We propose that, in cells in which activated oncogenes drive excessive protein synthesis, FGF13 may favor survival by maintaining translation rates at a level compatible with the protein quality-control capacity of the cell. Thus, FGF13 may serve as an enabler, allowing cancer cells to evade proteostasis stress triggered by oncogene activation. (PMID:27994142)
• the FGF13/Nav1.7 complex is essential for sustaining the transmission of noxious heat signals (PMID:28162808)
• identified two novel native phosphorylation sites in the C terminus of NaV1.5 that impair FGF13-dependent regulation of channel inactivation and may contribute to CaMKIIdeltac-dependent arrhythmogenic disorders in failing hearts. (PMID:28882890)
• High FGF13 expression is associated with glioma cell invasion. (PMID:29059154)
• FGF13 was downregulated in human placentae with early-onset preeclampsia. FGF13 played an important role in maintaining placental trophoblast permeability via the modulation of E-cadherin. (PMID:29405966)
• The present study reported the presence of FGF13 in the follicular fluid of women undergoing IVF/ICSI. Moreover, the relationships between FF-FGF13 and FF-TT, ovarian morphology and oocyte developmental competence imply that FF-FGF13 might be involved in the pathophysiological process of polycystic ovary syndrome. (PMID:30257687)
• The knockdown of FGF13 was able to mimic the inhibitory effects of miR-10b on the progression of colorectal cancer (CRC) cells. (PMID:30720165)
• Genetic polymorphisms in FGF3, FGF10, and FGF13 genes were associated with temporomandibular disorders in a population with dentofacial deformities (PMID:31574782)
• FGF13 promotes metastasis of triple-negative breast cancer. (PMID:31957002)
• FGF13 interaction with SHCBP1 activates AKT-GSK3alpha/beta signaling and promotes the proliferation of A549 cells. (PMID:33064958)
• Missense variants in the N-terminal domain of the A isoform of FHF2/FGF13 cause an X-linked developmental and epileptic encephalopathy. (PMID:33245860)
• Increased expression of fibroblast growth factor 13 in cortical lesions of the focal cortical dysplasia. (PMID:33285262)
• FGF10 and FGF13 genetic variation and tooth-size discrepancies. (PMID:33492380)
• lncRNA LINC00963 downregulation regulates colorectal cancer tumorigenesis and progression via the miR10b/FGF13 axis. (PMID:33495804)
• Expression and cellular distribution of FGF13 in cortical tubers of the tuberous sclerosis complex. (PMID:33582188)
• 5’-UTR SNP of FGF13 causes translational defect and intellectual disability. (PMID:34184986)
• FGF13 enhances resistance to platinum drugs by regulating hCTR1 and ATP7A via a microtubule-stabilizing effect. (PMID:34533854)
• Further evidence of affected females with a heterozygous variant in FGF13 causing X-linked developmental and epileptic encephalopathy 90. (PMID:34871784)
• FGF13 suppresses acute myeloid leukemia by regulating bone marrow niches. (PMID:36053411)
• The inhibitory role of microRNA-141-3p in human cutaneous melanoma growth and metastasis through the fibroblast growth factor 13-mediated mitogen-activated protein kinase axis. (PMID:36988403)
• A Heterozygous Variant of FGF13 Caused X-Linked Developmental and Epileptic Encephalopathy 90 in a Chinese Family. (PMID:37536293)
• FGF13A interacts with NPM1 and UBF and inhibits the invasion of bladder cancer cells. (PMID:37603967)
• FGF13 enhances the function of TRPV1 by stabilizing microtubules and regulates acute and chronic itch. (PMID:38733310)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	fgf13a	ENSDARG00000035056
danio_rerio	fgf13b	ENSDARG00000056633
mus_musculus	Fgf13	ENSMUSG00000031137
rattus_norvegicus	Fgf13	ENSRNOG00000042753

Paralogs (21): FGF10 (ENSG00000070193), FGF22 (ENSG00000070388), FGF4 (ENSG00000075388), FGF20 (ENSG00000078579), FGF14 (ENSG00000102466), FGF9 (ENSG00000102678), FGF21 (ENSG00000105550), FGF8 (ENSG00000107831), FGF6 (ENSG00000111241), FGF1 (ENSG00000113578), FGF12 (ENSG00000114279), FGF23 (ENSG00000118972), FGF5 (ENSG00000138675), FGF2 (ENSG00000138685), FGF7 (ENSG00000140285), FGF18 (ENSG00000156427), FGF17 (ENSG00000158815), FGF11 (ENSG00000161958), FGF19 (ENSG00000162344), FGF3 (ENSG00000186895), FGF16 (ENSG00000196468)

Protein

Protein identifiers

Fibroblast growth factor 13 — Q92913 (reviewed: Q92913)

Alternative names: Fibroblast growth factor homologous factor 2

All UniProt accessions (5): Q92913, A0A0C4DG13, A8K1P5, B1AJW0, B1B1H9

UniProt curated annotations — full annotation on UniProt →

Function. Microtubule-binding protein which directly binds tubulin and is involved in both polymerization and stabilization of microtubules. Through its action on microtubules, may participate in the refinement of axons by negatively regulating axonal and leading processes branching. Plays a crucial role in neuron polarization and migration in the cerebral cortex and the hippocampus. Regulates voltage-gated sodium channel transport and function. May also play a role in MAPK signaling. Required for the development of axonal initial segment-targeting inhibitory GABAergic synapses made by chandelier neurons.

Subunit / interactions. Interacts with SCN8A; regulates SCN8A activity. Interacts with SCN1A; may regulate SCN1A activity. Interacts with SCN5A; the interaction is direct and may regulate SNC5A density at membranes and function. May also interact with SCN2A and SCN11A. Interacts with MAPK8IP2; may regulate the MAPK8IP2 scaffolding activity.

Subcellular location. Nucleus Cytoplasm. Nucleus Cell projection. Filopodium. Cell projection. Growth cone. Dendrite. Cell membrane. Sarcolemma. Cytoplasm.

Tissue specificity. Ubiquitously expressed. Predominantly expressed in the nervous system.

Post-translational modifications. May be phosphorylated.

Disease relevance. Developmental and epileptic encephalopathy 90 (DEE90) [MIM:301058] A form of epileptic encephalopathy, a heterogeneous group of early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE90 is an X-linked form characterized by onset of refractory seizures in the first days or months of life. The disease is caused by variants affecting the gene represented in this entry. Intellectual developmental disorder, X-linked 110 (XLID110) [MIM:301095] A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the heparin-binding growth factors family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q92913-1	1, FGF13A, 1A, hFHF-2(1S), FGF13S	yes
Q92913-2	2, FGF13B, 1B, hFHF-2(1U), FGF13U, FHF2B
Q92913-3	3, hFHF-2(1Y+1V), FGF13YV
Q92913-4	4, hFHF-2(1Z+1Y), FGF13V
Q92913-5	5, hFHF-2(1X+1W+1V), FGF13Y

RefSeq proteins (6): NP_001132970, NP_001132972, NP_001132973, NP_001132974, NP_004105, NP_378668 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002209	Fibroblast_GF_fam	Family
IPR008996	IL1/FGF	Homologous_superfamily

Pfam: PF00167

UniProt features (37 total): strand 12, sequence variant 5, region of interest 4, splice variant 4, turn 4, helix 4, chain 1, mutagenesis site 1, compositionally biased region 1, modified residue 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
3HBW	X-RAY DIFFRACTION	1.9
4DCK	X-RAY DIFFRACTION	2.2
4JPZ	X-RAY DIFFRACTION	3.02

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92913-F1	80.27	0.59

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 208

Mutagenesis-validated functional residues (1):

Position	Phenotype
207	loss of interaction with scn1a.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5576892	Phase 0 - rapid depolarisation

MSigDB gene sets: 1260 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, GOBP_POSITIVE_REGULATION_OF_EPITHELIAL_CELL_DIFFERENTIATION, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, GOBP_MEMORY, VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOBP_HINDBRAIN_DEVELOPMENT, REACTOME_SIGNALING_BY_INSULIN_RECEPTOR, GOBP_RESPONSE_TO_ETHANOL, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_LENS_FIBER_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, MODULE_516, GOBP_EPITHELIUM_DEVELOPMENT

GO Biological Process (21): MAPK cascade (GO:0000165), neuron migration (GO:0001764), sodium ion transport (GO:0006814), negative regulation of microtubule depolymerization (GO:0007026), signal transduction (GO:0007165), cell-cell signaling (GO:0007267), nervous system development (GO:0007399), learning (GO:0007612), memory (GO:0007613), hippocampus development (GO:0021766), cerebral cortex cell migration (GO:0021795), neurogenesis (GO:0022008), establishment of neuroblast polarity (GO:0045200), microtubule polymerization (GO:0046785), negative regulation of collateral sprouting (GO:0048671), branching morphogenesis of a nerve (GO:0048755), protein localization to plasma membrane (GO:0072659), regulation of cardiac muscle cell action potential involved in regulation of contraction (GO:0098909), inhibitory synapse assembly (GO:1904862), positive regulation of voltage-gated sodium channel activity (GO:1905152), learning or memory (GO:0007611)

GO Molecular Function (6): microtubule binding (GO:0008017), growth factor activity (GO:0008083), sodium channel regulator activity (GO:0017080), transmembrane transporter binding (GO:0044325), beta-tubulin binding (GO:0048487), protein binding (GO:0005515)

GO Cellular Component (15): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), microtubule (GO:0005874), plasma membrane (GO:0005886), intercalated disc (GO:0014704), lateral plasma membrane (GO:0016328), filopodium (GO:0030175), axon (GO:0030424), dendrite (GO:0030425), growth cone (GO:0030426), sarcolemma (GO:0042383), neuron projection (GO:0043005), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Cardiac conduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cell communication	2
signaling	2
learning or memory	2
nervous system development	2
tubulin binding	2
plasma membrane	2
neuron projection	2
intracellular signaling cassette	1
cell migration	1
generation of neurons	1
metal ion transport	1
microtubule depolymerization	1
negative regulation of microtubule polymerization or depolymerization	1
regulation of microtubule depolymerization	1
negative regulation of protein depolymerization	1
negative regulation of supramolecular fiber organization	1
cellular process	1
regulation of cellular process	1
cellular response to stimulus	1
system development	1
pallium development	1
limbic system development	1
anatomical structure development	1
cerebral cortex development	1
telencephalon cell migration	1
cell differentiation	1
establishment of cell polarity	1
establishment or maintenance of neuroblast polarity	1
microtubule nucleation	1
microtubule polymerization or depolymerization	1
protein polymerization	1
supramolecular fiber organization	1
negative regulation of cell growth	1
negative regulation of developmental growth	1
collateral sprouting	1
regulation of collateral sprouting	1
negative regulation of axonogenesis	1
morphogenesis of a branching structure	1
protein localization to membrane	1

Protein interactions and networks

STRING

3628 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FGF13	FGFR1	P11362	998
FGF13	FGFR3	P22607	997
FGF13	FGFR2	P18443	996
FGF13	FGFR4	P22455	989
FGF13	EGF	P01133	975
FGF13	CX3CL1	P78423	968
FGF13	HSPG2	P98160	966
FGF13	CCL11	P50877	960
FGF13	CSF2	P04141	953
FGF13	FGFBP1	Q14512	952
FGF13	CSF3	P09919	951
FGF13	KDR	P35968	949
FGF13	SCN5A	Q14524	949
FGF13	FGF1	P05230	925
FGF13	FLT3LG	P49771	906

IntAct

13 interactions, top by confidence:

A	B	Type	Score
FGF13	PLEKHF2	psi-mi:“MI:0915”(physical association)	0.560
MAPK8IP2	FGF13	psi-mi:“MI:0915”(physical association)	0.550
FGF13	MARK3	psi-mi:“MI:0914”(association)	0.530
SCN2A	IGLL5	psi-mi:“MI:0914”(association)	0.350
NOLC1	FGF13	psi-mi:“MI:0914”(association)	0.350
SCHIP1	VWA8	psi-mi:“MI:0914”(association)	0.350
FGF13	MPHOSPH10	psi-mi:“MI:0914”(association)	0.350
GZMH	IPO13	psi-mi:“MI:0914”(association)	0.350
FGF13	CLEC3B	psi-mi:“MI:0915”(physical association)	0.000
PLEKHF2	FGF13	psi-mi:“MI:0915”(physical association)	0.000
PRNP	FGF13	psi-mi:“MI:0407”(direct interaction)	0.000

BioGRID (122): FGF13 (Reconstituted Complex), FGF13 (Two-hybrid), FGF13 (Affinity Capture-RNA), FGF13 (Biochemical Activity), PLEKHF2 (Two-hybrid), FGF13 (Affinity Capture-Western), FGF13 (Positive Genetic), RPL5 (Affinity Capture-MS), RPL3 (Affinity Capture-MS), CHD1 (Affinity Capture-MS), CHD3 (Affinity Capture-MS), ZNF768 (Affinity Capture-MS), URB1 (Affinity Capture-MS), RPS18 (Affinity Capture-MS), RPS24 (Affinity Capture-MS)

ESM2 similar proteins: A6P7H6, O35622, O57341, O76093, O88182, O89101, P03968, P03969, P12226, P13109, P15655, P19596, P20003, P21781, P36363, P37237, P41444, P48798, P48800, P48808, P61150, P61328, P61329, P70377, P70378, P70379, P79150, Q02195, Q0VCA0, Q5D0X0, Q5MK86, Q5MPA9, Q5RAY8, Q5RDS9, Q60487, Q6DTM3, Q6GLR6, Q6PGN3, Q6SJP8, Q7M303

Diamond homologs: A0MTF4, A6P7H6, M3X9S6, O15520, O35565, O43320, O54769, P03968, P03969, P05230, P05524, P08620, P09038, P10767, P11403, P11487, P12034, P12226, P13109, P15655, P15656, P19596, P20002, P20003, P21658, P21781, P31371, P34004, P36363, P36364, P36386, P48798, P48799, P48800, P48801, P48802, P48803, P48804, P48805, P48806

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
FGF13	“down-regulates activity”	SCN8A	binding
FGF13	“down-regulates activity”	SCN5A	binding
FGF13	“down-regulates activity”	SCN1A	binding
FGF13	“down-regulates activity”	SCN9A	binding
FGF13	“down-regulates activity”	SCN2A	binding
FGF13	“down-regulates activity”	SCN4A	binding
FGF13	“down-regulates activity”	SCN11A	binding
FGF13	“down-regulates activity”	SCN10A	binding
FGF13	“down-regulates activity”	SCN3A	binding

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

126 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	2
Uncertain significance	50
Likely benign	6
Benign	1

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
144262	GRCh38/hg38 Xq21.1-28(chrX:85123740-156022206)x3	Pathogenic
1708476	NM_004114.5(FGF13):c.23C>A (p.Ser8Ter)	Pathogenic
997407	NM_004114.5(FGF13):c.31C>T (p.Arg11Cys)	Pathogenic
997408	NM_004114.5(FGF13):c.41G>C (p.Arg14Thr)	Pathogenic
997409	NM_004114.5(FGF13):c.32G>C (p.Arg11Pro)	Pathogenic
1184442	NM_004114.5(FGF13):c.14T>G (p.Ile5Ser)	Likely pathogenic
1809807	NM_004114.5(FGF13):c.5C>G (p.Ala2Gly)	Likely pathogenic

SpliceAI

1932 predictions. Top by Δscore:

Variant	Effect	Δscore
4:122827353:G:GG	donor_gain	1.0000
4:122876316:TACA:T	acceptor_loss	1.0000
4:122876318:CA:C	acceptor_loss	1.0000
4:122876319:A:AG	acceptor_gain	1.0000
4:122876319:A:AT	acceptor_loss	1.0000
4:122876320:G:GA	acceptor_gain	1.0000
4:122876320:GT:G	acceptor_gain	1.0000
4:122876320:GTC:G	acceptor_gain	1.0000
4:122876320:GTCA:G	acceptor_gain	1.0000
4:122876320:GTCAA:G	acceptor_gain	1.0000
4:122876401:G:GT	donor_gain	1.0000
4:122876420:CTTCT:C	donor_gain	1.0000
4:122876421:TTCT:T	donor_gain	1.0000
4:122876421:TTCTG:T	donor_loss	1.0000
4:122876422:TCT:T	donor_gain	1.0000
4:122876422:TCTGT:T	donor_loss	1.0000
4:122876423:CTGT:C	donor_loss	1.0000
4:122876424:TGTA:T	donor_loss	1.0000
4:122876425:G:GG	donor_gain	1.0000
4:122876425:GTAAG:G	donor_loss	1.0000
4:122876426:TAAG:T	donor_loss	1.0000
4:122876427:AA:A	donor_loss	1.0000
4:122892210:GAAAT:G	acceptor_gain	1.0000
4:122893223:CTC:C	acceptor_gain	1.0000
4:122893225:CCT:C	acceptor_loss	1.0000
4:122893227:T:C	acceptor_loss	1.0000
4:122893230:G:C	acceptor_gain	1.0000
4:122897679:C:CC	acceptor_gain	1.0000
X:138632847:TGGC:T	donor_gain	1.0000
X:138632987:C:CC	acceptor_gain	1.0000

AlphaMissense

1588 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:138635471:G:T	P196H	1.000
X:138635472:G:A	P196S	1.000
X:138635476:A:C	F194L	1.000
X:138635476:A:T	F194L	1.000
X:138635477:A:C	F194C	1.000
X:138635477:A:G	F194S	1.000
X:138635478:A:G	F194L	1.000
X:138635481:G:C	H193D	1.000
X:138635483:G:T	A192D	1.000
X:138635500:C:A	K186N	1.000
X:138635500:C:G	K186N	1.000
X:138635502:T:C	K186E	1.000
X:138635513:C:A	G182V	1.000
X:138635513:C:T	G182D	1.000
X:138635514:C:G	G182R	1.000
X:138635528:C:A	G177V	1.000
X:138635528:C:T	G177E	1.000
X:138635529:C:G	G177R	1.000
X:138635529:C:T	G177R	1.000
X:138635540:A:G	L173P	1.000
X:138635543:C:T	G172D	1.000
X:138635544:C:G	G172R	1.000
X:138635553:A:G	W169R	1.000
X:138635553:A:T	W169R	1.000
X:138635580:A:C	Y160D	1.000
X:138635592:A:G	S156P	1.000
X:138635595:A:C	Y155D	1.000
X:138635595:A:G	Y155H	1.000
X:138635600:A:T	V153E	1.000
X:138635618:A:T	V147E	1.000

dbSNP variants (sampled 300 via entrez): RS1000001563 (X:138982222 G>A), RS1000002663 (X:139039832 A>T), RS1000005691 (X:138622041 T>C), RS1000009459 (X:138617056 G>T), RS1000012469 (X:138993556 C>A,T), RS1000030690 (X:139166582 G>A), RS1000032583 (X:139043280 C>T), RS1000035882 (X:139049406 T>C), RS1000047601 (X:138814655 T>G), RS1000047856 (X:138888171 G>T), RS1000055568 (X:139114694 G>A), RS1000059740 (X:139056931 G>A), RS1000069032 (X:139117895 A>G), RS1000075797 (X:139108435 G>A), RS1000098711 (X:138621751 T>C,G)

Disease associations

OMIM: gene MIM:300070 | disease phenotypes: MIM:301058, MIM:301095

GenCC curated gene-disease

Disease	Classification	Inheritance
developmental and epileptic encephalopathy, 90	Strong	X-linked
intellectual developmental disorder, X-linked 110	Strong	X-linked
undetermined early-onset epileptic encephalopathy	Supportive	Autosomal dominant

Mondo (4): neurodevelopmental disorder (MONDO:0700092), developmental and epileptic encephalopathy, 90 (MONDO:0025353), intellectual developmental disorder, X-linked 110 (MONDO:0859086), undetermined early-onset epileptic encephalopathy (MONDO:0018614)

Orphanet (0):

HPO phenotypes

49 total (30 of 49 shown, HPO-id order):

HPO	Term
HP:0000729	Autistic behavior
HP:0000739	Anxiety
HP:0000821	Hypothyroidism
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001337	Tremor
HP:0001344	Absent speech
HP:0001419	X-linked recessive inheritance
HP:0001631	Atrial septal defect
HP:0001763	Pes planus
HP:0002019	Constipation
HP:0002027	Abdominal pain
HP:0002059	Cerebral atrophy
HP:0002067	Bradykinesia
HP:0002069	Bilateral tonic-clonic seizure
HP:0002121	Generalized non-motor (absence) seizure
HP:0002123	Generalized myoclonic seizure
HP:0002133	Status epilepticus
HP:0002197	Generalized-onset seizure
HP:0002311	Incoordination
HP:0002373	Febrile seizure (within the age range of 3 months to 6 years)
HP:0002376	Developmental regression
HP:0002384	Focal impaired awareness seizure
HP:0002509	Limb hypertonia
HP:0002521	Hypsarrhythmia
HP:0002539	Cortical dysplasia
HP:0002572	Episodic vomiting
HP:0003066	Limited knee extension
HP:0003487	Babinski sign
HP:0003593	Infantile onset

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001694_13	Response to taxane treatment (paclitaxel)	2.000000e-07
GCST007302_4	Breast cancer in BRCA2 mutation carriers	3.000000e-06

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

Clinical evidence (CIViC)

Drug × variant × indication: 1 predictive associations from 1 curated evidence items; also 1 prognostic.

Variant	Therapy	Indication	Effect	Level	CIViC
FGF2 EXPRESSION	Quizartinib	Acute Myeloid Leukemia	Resistance	CIViC D	EID1711

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1449683	Efficacy	3	fluvoxamine	Depressive Disorder
rs308395	Efficacy	3	lenalidomide;thalidomide	Multiple Myeloma

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1449683	FGF2	3	1.50	1	fluvoxamine
rs308395	FGF2	3	2.00	1	lenalidomide;thalidomide
rs1960669	FGF2		0.00	0

CTD chemical–gene interactions

45 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation	4
Aflatoxin B1	affects expression, decreases expression, decreases methylation	4
trichostatin A	decreases expression, affects cotreatment	3
Estradiol	increases expression, affects cotreatment	3
Valproic Acid	affects expression, decreases expression	3
Acetaminophen	decreases expression, increases expression	2
Tetrachlorodibenzodioxin	increases expression, affects cotreatment	2
bisphenol F	increases methylation	1
lasiocarpine	decreases expression	1
methyleugenol	decreases expression	1
propionaldehyde	increases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	affects cotreatment, increases methylation, decreases methylation	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
aflatoxin B2	increases methylation	1
bicalutamide	increases expression	1
cyanoginosin LR	decreases expression	1
octa-2,4,6-trienoic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
MRK 003	decreases expression	1
LG 100815	increases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Norethindrone Acetate	affects cotreatment, increases expression	1
Glyphosate	increases expression	1
Arsenic	affects methylation	1

Cellosaurus cell lines

2 cell lines: 2 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2X2	Abcam HEK293T FGF13 KO	Transformed cell line	Female
CVCL_D9ES	Ubigene HEK293 FGF13 KO	Transformed cell line	Female

Clinical trials (associated diseases)

202 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice