FGF12

Summary

FGF12 (fibroblast growth factor 12, HGNC:3668) is a protein-coding gene on chromosome 3q28-q29, encoding Fibroblast growth factor 12 (P61328). Involved in nervous system development and function.

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 growth factor lacks the N-terminal signal sequence present in most of the FGF family members, but it contains clusters of basic residues that have been demonstrated to act as a nuclear localization signal. When transfected into mammalian cells, this protein accumulated in the nucleus, but was not secreted. The specific function of this gene has not yet been determined.

Source: NCBI Gene 2257 — RefSeq curated summary.

At a glance

• Gene–disease (curated): genetic developmental and epileptic encephalopathy (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 20
• Clinical variants (ClinVar): 301 total — 1 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 71
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity little evidence
• MANE Select transcript: NM_004113

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3668
Approved symbol	FGF12
Name	fibroblast growth factor 12
Location	3q28-q29
Locus type	gene with protein product
Status	Approved
Aliases	FHF1
Ensembl gene	ENSG00000114279
Ensembl biotype	protein_coding
OMIM	601513
Entrez	2257

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 10 protein_coding, 3 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000418610, ENST00000430714, ENST00000440901, ENST00000445105, ENST00000448795, ENST00000450716, ENST00000454309, ENST00000491636, ENST00000682572, ENST00000682819, ENST00000683451, ENST00000683935, ENST00000684282, ENST00000684728

RefSeq mRNA: 5 — MANE Select: NM_004113 NM_001377292, NM_001377293, NM_001377294, NM_004113, NM_021032

CCDS: CCDS3301, CCDS46983, CCDS93436, CCDS93437

Canonical transcript exons

ENST00000445105 — 6 exons

Exon	Start	End
ENSE00001005526	192170458	192170656
ENSE00001407888	192139390	192144127
ENSE00001678043	192727484	192727541
ENSE00002207494	192335361	192335464
ENSE00003497617	192727181	192727323
ENSE00003532256	192360428	192360538

Expression profiles

Bgee: expression breadth ubiquitous, 204 present calls, max score 97.89.

FANTOM5 (CAGE): breadth broad, TPM avg 7.5491 / max 861.2169, expressed in 620 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
46142	6.3078	275
46124	0.3969	192
46126	0.2589	157
46125	0.2438	141
46123	0.1220	42
46141	0.0906	45
46122	0.0810	46
46121	0.0482	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right atrium auricular region	UBERON:0006631	97.89	gold quality
cardiac atrium	UBERON:0002081	97.78	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.46	gold quality
apex of heart	UBERON:0002098	97.08	gold quality
myocardium	UBERON:0002349	97.07	gold quality
pons	UBERON:0000988	96.84	gold quality
left ventricle myocardium	UBERON:0006566	96.51	gold quality
heart left ventricle	UBERON:0002084	96.49	gold quality
cardiac ventricle	UBERON:0002082	96.34	gold quality
heart right ventricle	UBERON:0002080	95.59	gold quality
right adrenal gland cortex	UBERON:0035827	95.25	gold quality
cortical plate	UBERON:0005343	94.56	gold quality
right adrenal gland	UBERON:0001233	94.15	gold quality
left adrenal gland cortex	UBERON:0035825	94.05	gold quality
left adrenal gland	UBERON:0001234	93.93	gold quality
adrenal cortex	UBERON:0001235	93.48	gold quality
middle temporal gyrus	UBERON:0002771	93.28	gold quality
heart	UBERON:0000948	93.03	gold quality
adrenal tissue	UBERON:0018303	92.88	gold quality
prefrontal cortex	UBERON:0000451	92.61	gold quality
adrenal gland	UBERON:0002369	92.31	gold quality
superior frontal gyrus	UBERON:0002661	91.09	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	90.76	gold quality
vena cava	UBERON:0004087	90.59	gold quality
postcentral gyrus	UBERON:0002581	90.56	gold quality
Brodmann (1909) area 23	UBERON:0013554	90.28	gold quality
parietal lobe	UBERON:0001872	90.21	gold quality
Brodmann (1909) area 46	UBERON:0006483	90.09	gold quality
frontal cortex	UBERON:0001870	89.92	gold quality
superior vestibular nucleus	UBERON:0007227	89.65	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-MTAB-11268	yes	4892.27
E-GEOD-93593	yes	657.70
E-HCAD-35	yes	83.81
E-HCAD-25	yes	46.36
E-MTAB-7316	yes	41.22
E-GEOD-84465	yes	23.73
E-GEOD-83139	yes	8.46
E-ANND-3	yes	8.42

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BARX2

miRNA regulators (miRDB)

253 targeting FGF12, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4789-5P	99.98	70.76	2721

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 1 (little evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 25)

• Fibroblast growth factor homologous factor 1B (FHF1B) modulated the cardiac sodium channel Nav1.5. (PMID:12401812)
• x-ray crystal structure of FHF1b (PMID:12815063)
• Data describe the biophysical characterization and folding of fibroblast growth factor homologous factor-1b (FHF-1b) in comparison with acidic fibroblast growth factor (FGF-1), and show that FHF-1 is significantly more stable than FGF-1. (PMID:18289114)
• These findings suggest that FGF12 intracellularly suppresses radiation-induced apoptosis in mast cells independently of IB2. (PMID:18525161)
• exogenous FGF12 can play a role in tissues by translocating into cells through the plasma membrane (PMID:21518765)
• PHOX2B, FGF12 and GAD2 genes are hypermethylated in colorectal neoplastic tissue (PMID:22552777)
• VAX1 rs10787760, rs6585429 and rs1871345 polymorphisms may be involved in nonsyndromic cleft lip with or without cleft palate in Brazilian patients, but there is no association with polymorphisms in FGF12, VCL, or CX43 (PMID:23679094)
• Q7R-FGF12 is a disease-associated BrS mutation. Moreover, these data suggest for the first time that FHF effects on Na(+) and Ca(2+) channels are separable. (PMID:24096171)
• Nine SNPs of the FGF12 gene were associated with Kashin-Beck disease. (PMID:26290467)
• Data indicate that SCN5A variant (Nav1.5) p.H1849R affected interaction with fibroblast growth factor homologous factor (FHFs). (PMID:26392562)
• Results demonstrate that gain-of-function FHF mutations can cause neurologic disorder, and expand the repertoire of genetic causes (FHF1) and mechanisms (altered Nav gating) underlying early-onset epileptic encephalopathies and cerebellar atrophy (PMID:27164707)
• FGF12 strongly induced the quiescent and contractile vascular smooth muscle cell phenotype and directly promoted VSMC lineage differentiation. (PMID:27470512)
• FGF12, RBFOX1, and MIR302F could be important in human heterotaxy, because they were noted in multiple cases. Further investigation into genes involved in the NODAL, BMP, and WNT body patterning pathways and into the dosage effects of FGF12, RBFOX1, and MIR302F is warranted. (PMID:27637763)
• In this study, the authors observed that rs1460922 of FGF12 was significantly associated with VT and identified that a de novo variation of FGF12 may be an important genetic risk factor for the pathogenesis of VT. (PMID:28775062)
• FGF12 has a potential role in ESCC. (PMID:29049013)
• Trio-based whole exome sequencing of the patient revealed no pathogenic single nucleotide variants causing epilepsy, but confirmed a 3q28q29 duplication involving FGF12, which encodes fibroblast growth factor 12. (PMID:31311986)
• Serum FGF21 levels were significantly elevated in Kawasaki disease (KD) patients, especially with coronary artery lesions (CALs). They were associated with levels of leukomonocytes %, CRP and albumin in KD patients. These observations indicate that high level of FGF21 may be a compensatory mechanism that plays a protective role in the antioxidant/ anti-inflammatory response during acute phase of KD. (PMID:31478099)
• FHF1 is a bona fide fibroblast growth factor that activates cellular signaling in FGFR-dependent manner. (PMID:32357892)
• Defining the phenotype of FHF1 developmental and epileptic encephalopathy. (PMID:32645220)
• A functional variant rs1464938 in the promoter of fibroblast growth factor 12 is associated with an increased risk of bladder transitional cell carcinoma. (PMID:32950810)
• Genetic diagnosis of infantile-onset epilepsy in the clinic: Application of whole-exome sequencing following epilepsy gene panel testing. (PMID:33349918)
• HMGN5 promotes invasion and migration of colorectal cancer through activating FGF/FGFR pathway. (PMID:33629303)
• Ca(2+)-saturated calmodulin binds tightly to the N-terminal domain of A-type fibroblast growth factor homologous factors. (PMID:33639159)
• Early onset epilepsy and sudden unexpected death in epilepsy with cardiac arrhythmia in mice carrying the early infantile epileptic encephalopathy 47 gain-of-function FHF1(FGF12) missense mutation. (PMID:33982289)
• Modulating effects of FGF12 variants on NaV1.2 and NaV1.6 being associated with developmental and epileptic encephalopathy and Autism spectrum disorder: A case series. (PMID:36029553)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	fgf12a	ENSDARG00000027957
danio_rerio	fgf12b	ENSDARG00000113525
mus_musculus	Fgf12	ENSMUSG00000022523
rattus_norvegicus	Fgf12	ENSRNOG00000090378

Paralogs (21): FGF10 (ENSG00000070193), FGF22 (ENSG00000070388), FGF4 (ENSG00000075388), FGF20 (ENSG00000078579), FGF14 (ENSG00000102466), FGF9 (ENSG00000102678), FGF21 (ENSG00000105550), FGF8 (ENSG00000107831), FGF6 (ENSG00000111241), FGF1 (ENSG00000113578), FGF23 (ENSG00000118972), FGF13 (ENSG00000129682), FGF5 (ENSG00000138675), FGF2 (ENSG00000138685), FGF7 (ENSG00000140285), FGF18 (ENSG00000156427), FGF17 (ENSG00000158815), FGF11 (ENSG00000161958), FGF19 (ENSG00000162344), FGF3 (ENSG00000186895), FGF16 (ENSG00000196468)

Protein

Protein identifiers

Fibroblast growth factor 12 — P61328 (reviewed: P61328)

Alternative names: Fibroblast growth factor homologous factor 1, Myocyte-activating factor

All UniProt accessions (6): P61328, A0A7U3JVY3, A0A804HIN2, C9JEN8, C9JIN3, C9JUK8

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Interacts with the C-terminal region of SCN9A.

Subcellular location. Nucleus.

Tissue specificity. Brain, eye and testis; highly expressed in embryonic retina, olfactory epithelium, olfactory bulb, and in a segmental pattern of the body wall; in adult olfactory bulb, less in cerebellum, deep cerebellar nuclei, cortex and multiple midbrain structures.

Disease relevance. Developmental and epileptic encephalopathy 47 (DEE47) [MIM:617166] A form of epileptic encephalopathy, a heterogeneous group of severe 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. The disease is caused by variants affecting the gene represented in this entry.

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

Isoforms (2)

UniProt ID	Names	Canonical?
P61328-1	1, FGF-12A	yes
P61328-2	2, FGF-12B

RefSeq proteins (5): NP_001364221, NP_001364222, NP_001364223, NP_004104, NP_066360 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002209	Fibroblast_GF_fam	Family
IPR008996	IL1/FGF	Homologous_superfamily

Pfam: PF00167

UniProt features (31 total): strand 12, turn 4, helix 4, sequence conflict 3, region of interest 2, mutagenesis site 2, chain 1, short sequence motif 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
1Q1U	X-RAY DIFFRACTION	1.7
4JQ0	X-RAY DIFFRACTION	3.84

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P61328-F1	77.91	0.54

Functional residue map

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

Mutagenesis-validated functional residues (2):

Position	Phenotype
114	gain of function, affects voltage dependence of scn8a fast inactivation.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 427 (showing top): RNGTGGGC_UNKNOWN, CREL_01, GOBP_RIBOSOME_BIOGENESIS, AP1_01, FREAC2_01, GOBP_BEHAVIOR, TGCGCANK_UNKNOWN, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, KEGG_MAPK_SIGNALING_PATHWAY, GCANCTGNY_MYOD_Q6, CMYB_01, GOBP_ADULT_BEHAVIOR, AP4_Q6, GOBP_NEUROGENESIS

GO Biological Process (14): signal transduction (GO:0007165), JNK cascade (GO:0007254), cell-cell signaling (GO:0007267), chemical synaptic transmission (GO:0007268), nervous system development (GO:0007399), heart development (GO:0007507), adult locomotory behavior (GO:0008344), positive regulation of sodium ion transport (GO:0010765), neurogenesis (GO:0022008), neuromuscular process (GO:0050905), cardiac muscle cell action potential involved in contraction (GO:0086002), regulation of neuronal action potential (GO:0098908), regulation of sodium ion transmembrane transport (GO:1902305), regulation of voltage-gated sodium channel activity (GO:1905150)

GO Molecular Function (5): growth factor activity (GO:0008083), heparin binding (GO:0008201), sodium channel regulator activity (GO:0017080), transmembrane transporter binding (GO:0044325), protein binding (GO:0005515)

GO Cellular Component (4): obsolete extracellular space (GO:0005615), nucleus (GO:0005634), cytoplasm (GO:0005737), synapse (GO:0045202)

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
cell communication	2
signaling	2
regulation of sodium ion transport	2
cellular process	1
regulation of cellular process	1
cellular response to stimulus	1
MAPK cascade	1
anterograde trans-synaptic signaling	1
system development	1
animal organ development	1
circulatory system development	1
locomotory behavior	1
adult behavior	1
sodium ion transport	1
positive regulation of monoatomic ion transport	1
nervous system development	1
cell differentiation	1
nervous system process	1
cardiac muscle cell action potential	1
cardiac muscle cell contraction	1
neuronal action potential	1
regulation of transmission of nerve impulse	1
regulation of action potential	1
sodium ion transmembrane transport	1
regulation of monoatomic cation transmembrane transport	1
voltage-gated sodium channel activity	1
regulation of sodium ion transmembrane transporter activity	1
receptor ligand activity	1
glycosaminoglycan binding	1
sulfur compound binding	1
sodium channel activity	1
ion channel regulator activity	1
protein binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1
cell junction	1

Protein interactions and networks

STRING

1534 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FGF12	MAPK8IP2	Q13387	850
FGF12	SCN5A	Q14524	745
FGF12	FGFR1	P11362	737
FGF12	FGF8	P55075	684
FGF12	CLDN16	Q9Y5I7	663
FGF12	FGFR2	P18443	644
FGF12	FGFRL1	Q8N441	633
FGF12	FGFR3	P22607	613
FGF12	RANGRF	Q9HD47	574
FGF12	SLMAP	Q14BN4	571
FGF12	APOD	P05090	566
FGF12	FGF17	O60258	515
FGF12	GPD1L	Q8N335	507
FGF12	KCNE5	Q9UJ90	506
FGF12	FGF18	O76093	496

IntAct

24 interactions, top by confidence:

A	B	Type	Score
FGF12	DCTD	psi-mi:“MI:0915”(physical association)	0.560
COIL	FGF12	psi-mi:“MI:0915”(physical association)	0.560
FGF12	IKZF1	psi-mi:“MI:0915”(physical association)	0.560
FGF12	ZNF460	psi-mi:“MI:0915”(physical association)	0.560
LZTS2	FGF12	psi-mi:“MI:0915”(physical association)	0.560
DACH1	FGF12	psi-mi:“MI:0915”(physical association)	0.560
DCTD	FGF12	psi-mi:“MI:0915”(physical association)	0.560
FGF12	COIL	psi-mi:“MI:0915”(physical association)	0.560
IKZF1	FGF12	psi-mi:“MI:0915”(physical association)	0.560
ZNF460	FGF12	psi-mi:“MI:0915”(physical association)	0.560
FGF12	LZTS2	psi-mi:“MI:0915”(physical association)	0.560
FGF12	DACH1	psi-mi:“MI:0915”(physical association)	0.560
FGF12	SRPK2	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
SRPK1	FGF12	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
FGF12	SUPT5H	psi-mi:“MI:0914”(association)	0.350
FGF12	ZMPSTE24	psi-mi:“MI:0914”(association)	0.350
	EBAG9	psi-mi:“MI:0914”(association)	0.350

BioGRID (81): FGF12 (Two-hybrid), FGF12 (Two-hybrid), COIL (Two-hybrid), IKZF1 (Two-hybrid), ZNF460 (Two-hybrid), LZTS2 (Two-hybrid), FGF12 (Reconstituted Complex), FGF12 (Two-hybrid), FGF12 (Two-hybrid), FGF12 (Biochemical Activity), FGF12 (Reconstituted Complex), FGF12 (Biochemical Activity), THAP1 (Two-hybrid), RBAK (Two-hybrid), GRIP1 (Two-hybrid)

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
FGF12	“down-regulates activity”	SCN8A	binding
FGF12	“down-regulates activity”	SCN5A	binding
FGF12	“down-regulates activity”	SCN1A	binding
FGF12	“down-regulates activity”	SCN9A	binding
FGF12	“down-regulates activity”	SCN2A	binding
FGF12	“down-regulates activity”	SCN4A	binding
FGF12	“down-regulates activity”	SCN11A	binding
FGF12	“down-regulates activity”	SCN10A	binding
FGF12	“down-regulates activity”	SCN3A	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	4
Uncertain significance	123
Likely benign	99
Benign	55

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
266034	NM_004113.6(FGF12):c.155G>A (p.Arg52His)	Pathogenic
1523399	NC_000003.11:g.(?191888227)(192126012_?)dup	Likely pathogenic
2584544	NM_004113.6(FGF12):c.341G>A (p.Gly114Glu)	Likely pathogenic
2759507	NM_004113.6(FGF12):c.14-47517G>C	Likely pathogenic
2851847	NM_004113.6(FGF12):c.454del (p.His152fs)	Likely pathogenic

SpliceAI

2265 predictions. Top by Δscore:

Variant	Effect	Δscore
3:192144124:CACA:C	acceptor_gain	1.0000
3:192144126:CA:C	acceptor_gain	1.0000
3:192170452:TCATA:T	donor_loss	1.0000
3:192170453:CATAC:C	donor_loss	1.0000
3:192170454:ATAC:A	donor_loss	1.0000
3:192170455:TACC:T	donor_loss	1.0000
3:192170457:C:T	donor_loss	1.0000
3:192170652:ACATC:A	acceptor_gain	1.0000
3:192170653:CATC:C	acceptor_gain	1.0000
3:192170653:CATCC:C	acceptor_gain	1.0000
3:192170654:ATC:A	acceptor_gain	1.0000
3:192170655:TC:T	acceptor_gain	1.0000
3:192170656:CC:C	acceptor_gain	1.0000
3:192170657:C:CC	acceptor_gain	1.0000
3:192170657:CTGTA:C	acceptor_loss	1.0000
3:192223329:CTG:C	donor_gain	1.0000
3:192223330:TGT:T	donor_gain	1.0000
3:192335353:GTAC:G	donor_loss	1.0000
3:192335354:TACT:T	donor_loss	1.0000
3:192335355:ACTT:A	donor_loss	1.0000
3:192335357:TTAC:T	donor_loss	1.0000
3:192335358:TACT:T	donor_loss	1.0000
3:192335359:A:AC	donor_gain	1.0000
3:192335359:A:T	donor_loss	1.0000
3:192335360:C:CC	donor_gain	1.0000
3:192335360:CTGA:C	donor_gain	1.0000
3:192335360:CTGAA:C	donor_gain	1.0000
3:192335460:GAGAG:G	acceptor_gain	1.0000
3:192335462:GAG:G	acceptor_gain	1.0000
3:192335463:AG:A	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000000049 (3:192291210 T>C), RS1000000953 (3:192271135 TAA>T), RS1000002628 (3:192484200 TC>T), RS1000003371 (3:192250985 T>A,C), RS1000012861 (3:192308681 A>C,G), RS1000013586 (3:192352281 T>A), RS1000013939 (3:192331622 A>G), RS1000017701 (3:192350615 A>C), RS1000025890 (3:192345149 A>G), RS1000034420 (3:192659860 T>C), RS1000036734 (3:192569401 T>C), RS1000038364 (3:192400684 T>C), RS1000047827 (3:192679153 T>C), RS1000049552 (3:192423277 T>A), RS1000058342 (3:192703559 G>GT)

Disease associations

OMIM: gene MIM:601513 | disease phenotypes: MIM:617166

GenCC curated gene-disease

Disease	Classification	Inheritance
developmental and epileptic encephalopathy, 47	Definitive	Autosomal dominant
undetermined early-onset epileptic encephalopathy	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Brugada syndrome	Disputed	AD
genetic developmental and epileptic encephalopathy	Definitive	AD

Mondo (2): developmental and epileptic encephalopathy, 47 (MONDO:0014949), undetermined early-onset epileptic encephalopathy (MONDO:0018614)

Orphanet (0):

HPO phenotypes

71 total (30 of 71 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000252	Microcephaly
HP:0000348	High forehead
HP:0000494	Downslanted palpebral fissures
HP:0000504	Abnormality of vision
HP:0000508	Ptosis
HP:0000543	Optic disc pallor
HP:0000546	Retinal degeneration
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000668	Hypodontia
HP:0000708	Atypical behavior
HP:0000713	Agitation
HP:0000717	Autism
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001265	Hyporeflexia
HP:0001268	Mental deterioration
HP:0001272	Cerebellar atrophy
HP:0001273	Abnormal corpus callosum morphology
HP:0001288	Gait disturbance
HP:0001290	Generalized hypotonia
HP:0001298	Encephalopathy
HP:0001315	Reduced tendon reflexes
HP:0001336	Myoclonus

GWAS associations

20 associations (top):

Study	Trait	p-value
GCST000274_11	Metabolite levels	4.000000e-07
GCST000908_1	Ileal carcinoids	7.000000e-06
GCST001850_25	Major depressive disorder	3.000000e-07
GCST001850_40	Major depressive disorder	6.000000e-06
GCST002049_5	Sleep quality	5.000000e-06
GCST003123_12	Severe influenza A (H1N1) infection	1.000000e-08
GCST003264_100	Post bronchodilator FEV1/FVC ratio	2.000000e-06
GCST003264_813	Post bronchodilator FEV1/FVC ratio	8.000000e-07
GCST003264_974	Post bronchodilator FEV1/FVC ratio	2.000000e-06
GCST005588_22	Idiopathic dilated cardiomyopathy	4.000000e-06
GCST005648_38	Serum metabolite concentrations in chronic kidney disease	3.000000e-08
GCST008103_184	Bipolar disorder	9.000000e-06
GCST008156_78	Hip circumference adjusted for BMI	6.000000e-06
GCST009441_1	Age-related cognitive decline (memory) (slope of z-scores)	1.000000e-06
GCST010320_111	PR interval	5.000000e-15
GCST010321_207	PR interval	1.000000e-16
GCST011692_2	Height	2.000000e-07
GCST011743_36	HDL cholesterol levels in HIV infection	6.000000e-07
GCST012367_1	Orofacial cleft x maternal periconceptional smoking interaction (1df)	1.000000e-07
GCST90006994_4	Gut microbiota relative abundance (Ruminococcus belonging to family Erysipelotrichaceae)	2.000000e-06

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:1001488	influenza A (H1N1)
EFO:0004713	FEV/FVC ratio
EFO:0009094	idiopathic dilated cardiomyopathy
EFO:0008039	BMI-adjusted hip circumference
EFO:0007710	cognitive decline measurement
EFO:0004462	PR interval
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0006527	smoking status measurement
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	decreases expression, decreases methylation, increases methylation	4
sodium arsenite	affects methylation, increases expression	3
Valproic Acid	affects expression, increases expression	3
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	2
Doxorubicin	decreases expression	2
aristolochic acid I	decreases expression	1
methylmercuric chloride	decreases expression	1
methyleugenol	decreases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
kojic acid	increases expression	1
terbufos	increases methylation	1
trichostatin A	affects cotreatment, decreases expression	1
arsenite	increases methylation	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	increases abundance, affects methylation	1
benzo(e)pyrene	affects methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
aflatoxin B2	increases methylation	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
2-ethyl-5-carboxypentyl phthalate	increases methylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Arsenic	affects expression	1
Cannabinoids	affects methylation, increases abundance	1
Chelating Agents	decreases expression, affects binding	1
Copper	affects binding, decreases expression	1

Cellosaurus cell lines

2 cell lines: 1 induced pluripotent stem cell, 1 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_C8D1	ZJSHDPi001-A	Induced pluripotent stem cell	Male
CVCL_D8GB	Ubigene H9 FGF12 KO	Embryonic stem cell	Female

Clinical trials (associated diseases)

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