FGF12

fibroblast growth factor 12, the group of Fibroblast growth factor family

Basic information

Region (hg38): 3:192139389-192767764

Previous symbols: [ "FGF12B" ]

Links

ENSG00000114279 ∙ NCBI:2257 ∙ OMIM:601513 ∙ HGNC:3668 ∙ Uniprot:P61328 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• developmental and epileptic encephalopathy, 47 (Moderate), mode of inheritance: AD
• undetermined early-onset epileptic encephalopathy (Supportive), mode of inheritance: AD
• developmental and epileptic encephalopathy (Definitive), mode of inheritance: AD
• developmental and epileptic encephalopathy, 47 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Developmental and epileptic encephalopathy 47	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	27164707

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FGF12 gene.

• not provided (184 variants)
• Developmental and epileptic encephalopathy, 47 (16 variants)
• Inborn genetic diseases (4 variants)
• FGF12-related condition (2 variants)
• not specified (2 variants)
• Gestational diabetes mellitus uncontrolled (1 variants)
• Seizure (1 variants)
• Early onset epileptic encephalopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FGF12 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				30	3	33
missense	1	3	49	10	8	71
nonsense			2			2
start loss						0
frameshift			2			2
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region			2	8	8	18
non coding			2	27	34	63
Total	1	3	56	67	45

Variants in FGF12

This is a list of pathogenic ClinVar variants found in the FGF12 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-192143732-A-G			Benign (Sep 04, 2018)
3-192144014-T-C			Uncertain significance (May 21, 2023)
3-192144016-G-C			Uncertain significance (Nov 27, 2023)
3-192144040-C-A			Uncertain significance (Jul 25, 2023)
3-192144042-A-C			Uncertain significance (Jun 07, 2023)
3-192144044-T-C			Uncertain significance (Apr 18, 2022)
3-192144049-G-A			Uncertain significance (Aug 20, 2022)
3-192144064-C-T		Developmental and epileptic encephalopathy, 47	Uncertain significance (Aug 13, 2021)
3-192144071-T-A			Uncertain significance (Dec 18, 2023)
3-192144076-C-T			Uncertain significance (Jul 05, 2022)
3-192144077-G-A			Uncertain significance (Dec 06, 2023)
3-192144078-C-G			Likely benign (Nov 15, 2022)
3-192144080-C-G			Benign (Nov 15, 2023)
3-192144092-C-T			Benign (Oct 17, 2022)
3-192144100-T-G			Uncertain significance (Dec 24, 2022)
3-192144100-TG-T			Likely pathogenic (Jun 06, 2023)
3-192144105-C-T			Likely benign (Jan 19, 2024)
3-192144106-G-A			Uncertain significance (Aug 20, 2023)
3-192144124-C-A			Uncertain significance (Oct 25, 2022)
3-192144126-C-T			Benign (Jan 17, 2024)
3-192144144-C-A			Likely benign (Dec 24, 2020)
3-192144144-C-T			Likely benign (Apr 10, 2023)
3-192144401-AC-A			Benign (Mar 16, 2019)
3-192144411-G-C			Benign (Sep 04, 2018)
3-192170186-G-A			Benign (Sep 06, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FGF12	protein_coding	protein_coding	ENST00000454309	5	628370

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.623	0.376	125742	0	4	125746	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.52	91	142	0.640	0.00000718	1571
Missense in Polyphen		16	46.389	0.34491		528
Synonymous	0.453	50	54.2	0.922	0.00000279	478
Loss of Function	2.63	2	11.7	0.171	5.83e-7	141

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000290	0.0000290
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.00000928	0.00000879
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in nervous system development and function. Involved in the positive regulation of voltage-gated sodium channel activity. Promotes neuronal excitability by elevating the voltage dependence of neuronal sodium channel SCN8A fast inactivation. {ECO:0000269|PubMed:27164707}.
• Pathway: MAPK Signaling Pathway;ESC Pluripotency Pathways;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;Regulation of Actin Cytoskeleton;Phase 0 - rapid depolarisation;Cardiac conduction;Muscle contraction (Consensus)

Recessive Scores

• pRec: 0.174

Intolerance Scores

• loftool: 0.209
• rvis_EVS: -0.16
• rvis_percentile_EVS: 41.25

Haploinsufficiency Scores

• pHI: 0.908
• hipred: Y
• hipred_score: 0.697
• ghis: 0.563

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.731

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Fgf12
• 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: regulation of membrane depolarization;signal transduction;cell-cell signaling;chemical synaptic transmission;nervous system development;heart development;adult locomotory behavior;fibroblast growth factor receptor signaling pathway;regulation of signaling receptor activity;positive regulation of sodium ion transport;neuromuscular process;cardiac muscle cell action potential involved in contraction;regulation of neuronal action potential;regulation of sodium ion transmembrane transport;regulation of voltage-gated sodium channel activity;regulation of sodium ion transmembrane transporter activity;negative regulation of cation channel activity
• Cellular component: extracellular space;nucleus
• Molecular function: protein binding;growth factor activity;sodium channel regulator activity;ion channel binding