RNF13

Summary

RNF13 (ring finger protein 13, HGNC:10057) is a protein-coding gene on chromosome 3q25.1, encoding E3 ubiquitin-protein ligase RNF13 (O43567). E3 ubiquitin-protein ligase that regulates cell proliferation.

The protein encoded by this gene contains a RING zinc finger, a motif known to be involved in protein-protein interactions. The specific function of this gene has not yet been determined. Alternatively spliced transcript variants that encode the same protein have been reported. A pseudogene, which is also located on chromosome 3, has been defined for this gene.

Source: NCBI Gene 11342 — RefSeq curated summary.

At a glance

• Gene–disease (curated): developmental and epileptic encephalopathy, 73 (Strong, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 312 total — 3 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 53
• MANE Select transcript: NM_183381

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10057
Approved symbol	RNF13
Name	ring finger protein 13
Location	3q25.1
Locus type	gene with protein product
Status	Approved
Aliases	RZF
Ensembl gene	ENSG00000082996
Ensembl biotype	protein_coding
OMIM	609247
Entrez	11342

Gene structure

Transcript identifiers

Ensembl transcripts: 64 — 61 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000344229, ENST00000361785, ENST00000392894, ENST00000459632, ENST00000466478, ENST00000466795, ENST00000467977, ENST00000467996, ENST00000468289, ENST00000468648, ENST00000470151, ENST00000474348, ENST00000482083, ENST00000490631, ENST00000491086, ENST00000493238, ENST00000910565, ENST00000910566, ENST00000910567, ENST00000910568, ENST00000910569, ENST00000910570, ENST00000910571, ENST00000910572, ENST00000910573, ENST00000910574, ENST00000910575, ENST00000910576, ENST00000910577, ENST00000910578, ENST00000910579, ENST00000910580, ENST00000910581, ENST00000910582, ENST00000910583, ENST00000910584, ENST00000910585, ENST00000910586, ENST00000910587, ENST00000910588, ENST00000910589, ENST00000910590, ENST00000912056, ENST00000912057, ENST00000912058, ENST00000912059, ENST00000944871, ENST00000944872, ENST00000944873, ENST00000944874, ENST00000944875, ENST00000944876, ENST00000944877, ENST00000944878, ENST00000944879, ENST00000944880, ENST00000944881, ENST00000944882, ENST00000944883, ENST00000944884, ENST00000944885, ENST00000944886, ENST00000944887, ENST00000944888

RefSeq mRNA: 10 — MANE Select: NM_183381 NM_001378285, NM_001378286, NM_001378287, NM_001378288, NM_001378289, NM_001378290, NM_001378291, NM_007282, NM_183381, NM_183383

CCDS: CCDS3146, CCDS87154

Canonical transcript exons

ENST00000392894 — 10 exons

Exon	Start	End
ENSE00001708959	149960740	149962139
ENSE00001792153	149846011	149846140
ENSE00001821189	149813215	149813353
ENSE00003461684	149872029	149872154
ENSE00003479093	149960056	149960136
ENSE00003533693	149911978	149912083
ENSE00003553518	149852516	149852596
ENSE00003626014	149902072	149902162
ENSE00003690125	149921134	149921227
ENSE00003690796	149895473	149895560

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 62.3367 / max 1263.8331, expressed in 1813 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
39164	51.3452	1812
39162	7.6820	1544
39165	1.0346	315
39163	0.6421	255
39172	0.4583	117
39161	0.4201	209
39166	0.2785	131
39170	0.1457	50
39160	0.1257	46
39171	0.1105	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus callosum	UBERON:0002336	99.16	gold quality
calcaneal tendon	UBERON:0003701	98.91	gold quality
inferior vagus X ganglion	UBERON:0005363	98.72	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.65	gold quality
spinal cord	UBERON:0002240	98.59	gold quality
subthalamic nucleus	UBERON:0001906	98.42	gold quality
parotid gland	UBERON:0001831	98.33	gold quality
cranial nerve II	UBERON:0000941	98.25	gold quality
pigmented layer of retina	UBERON:0001782	98.01	gold quality
lateral globus pallidus	UBERON:0002476	97.94	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.85	gold quality
choroid plexus epithelium	UBERON:0003911	97.76	gold quality
pons	UBERON:0000988	97.52	gold quality
superior vestibular nucleus	UBERON:0007227	97.49	gold quality
globus pallidus	UBERON:0001875	97.39	gold quality
olfactory bulb	UBERON:0002264	97.33	gold quality
dorsal plus ventral thalamus	UBERON:0001897	97.30	gold quality
substantia nigra pars compacta	UBERON:0001965	97.30	gold quality
medulla oblongata	UBERON:0001896	97.26	gold quality
medial globus pallidus	UBERON:0002477	97.21	gold quality
monocyte	CL:0000576	97.20	gold quality
midbrain	UBERON:0001891	97.13	gold quality
mononuclear cell	CL:0000842	97.12	gold quality
substantia nigra	UBERON:0002038	97.11	gold quality
postcentral gyrus	UBERON:0002581	97.08	gold quality
trigeminal ganglion	UBERON:0001675	97.05	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.01	gold quality
leukocyte	CL:0000738	96.98	gold quality
dorsal root ganglion	UBERON:0000044	96.96	gold quality
ventral tegmental area	UBERON:0002691	96.72	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-13	yes	1887.39
E-MTAB-2983	no	1122.13
E-MTAB-7303	no	538.45
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

62 targeting RNF13, 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-3163	100.00	77.23	8605
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-1179	99.71	68.70	1040
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-4762-5P	99.57	68.54	1424
HSA-MIR-4753-5P	99.54	68.51	1356
HSA-MIR-543	99.52	69.03	2595
HSA-MIR-12117	99.50	67.57	868
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-3171	99.49	69.06	776
HSA-MIR-548G-3P	99.48	68.67	2159
HSA-MIR-208A-5P	99.42	70.83	1913

Literature-anchored findings (GeneRIF, showing 12)

• Mice lacking Mt1/2 have a rapid decrease in Rnf13 during acute lung injury (PMID:16166738)
• RNF13 is a novel E3 ubiquitin ligase involved in pancreatic carcinogenesis. (PMID:18794910)
• analysis of nuclear targeting of Nuclear targeting of RNF13 endosomal E3 ubiquitin ligase (PMID:20230530)
• RNF13 is a critical mediator for facilitating endoplasmic reticulum stress-induced apoptosis through the activation of the IRE1alpha-TRAF2-JNK signaling pathway. (PMID:23378536)
• Protease-activated point mutations are identified in RNF13 and RNF167. (PMID:24387786)
• results indicate that the RNF13 variants confer gain of function to the encoded protein and thereby lead to altered signaling of the ER stress response associated with severe neurodegeneration in infancy (PMID:30595371)
• MiR-32-3p Regulates Myocardial Injury Induced by Microembolism and Microvascular Obstruction by Targeting RNF13 to Regulate the Stability of Atherosclerotic Plaques. (PMID:34185281)
• Circular RNA circRNF13 inhibits proliferation and metastasis of nasopharyngeal carcinoma via SUMO2. (PMID:34465340)
• RNF13 Dileucine Motif Variants L311S and L312P Interfere with Endosomal Localization and AP-3 Complex Association. (PMID:34831286)
• Heterozygous gain of function variants in a critical region of RNF13 cause congenital microcephaly, epileptic encephalopathy, blindness, and failure to thrive. (PMID:37668308)
• E3 Ubiquitin Ligase RNF13 Suppresses TLR Lysosomal Degradation by Promoting LAMP-1 Proteasomal Degradation. (PMID:39031743)
• Cloning report of the chicken homolog (PMID:8610176)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rnf13	ENSDARG00000019438
mus_musculus	Rnf13	ENSMUSG00000036503
rattus_norvegicus	Rnf13	ENSRNOG00000029209

Paralogs (9): RNF215 (ENSG00000099999), ZNRF4 (ENSG00000105428), RNF167 (ENSG00000108523), RNF130 (ENSG00000113269), RNF128 (ENSG00000133135), RNF149 (ENSG00000163162), RNF150 (ENSG00000170153), RNF133 (ENSG00000188050), RNF148 (ENSG00000235631)

Protein

Protein identifiers

E3 ubiquitin-protein ligase RNF13 — O43567 (reviewed: O43567)

Alternative names: RING finger protein 13

All UniProt accessions (13): O43567, C9IY58, C9J383, C9J7B4, C9J8T4, C9JCY0, C9JRV0, C9JU37, C9JYN7, C9JYY4, F8WDJ5, F8WEX6, H7C5Q6

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin-protein ligase that regulates cell proliferation. Involved in apoptosis regulation. Mediates ER stress-induced activation of JNK signaling pathway and apoptosis by promoting ERN1 activation and splicing of XBP1 mRNA. Also involved in protein trafficking and localization.

Subunit / interactions. Interacts with ERN1.

Subcellular location. Endoplasmic reticulum membrane. Late endosome membrane. Lysosome membrane. Nucleus inner membrane.

Tissue specificity. Widely expressed (at protein level). In normal pancreas, expressed in islets, but not in ducts, nor in acini (at protein level).

Post-translational modifications. Autoubiquitinated.

Disease relevance. Developmental and epileptic encephalopathy 73 (DEE73) [MIM:618379] 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. DEE73 is an autosomal dominant form with onset at birth. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The RING-type zinc finger domain is required for E3 ligase activity and for promoting ER stress-induced JNK activation and apoptosis.

Pathway. Protein modification; protein ubiquitination.

Isoforms (2)

UniProt ID	Names	Canonical?
O43567-1	1	yes
O43567-2	2

RefSeq proteins (10): NP_001365214, NP_001365215, NP_001365216, NP_001365217, NP_001365218, NP_001365219, NP_001365220, NP_009213, NP_899237, NP_899239 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001841	Znf_RING	Domain
IPR003137	PA_domain	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR044744	ZNRF4/RNF13/RNF167_PA	Domain
IPR046450	PA_dom_sf	Homologous_superfamily
IPR051653	E3_ligase_sorting_rcpt	Family

Pfam: PF02225, PF13639

UniProt features (36 total): mutagenesis site 10, sequence variant 5, strand 4, splice variant 2, topological domain 2, helix 2, turn 2, compositionally biased region 2, signal peptide 1, chain 1, glycosylation site 1, transmembrane region 1, domain 1, zinc finger region 1, region of interest 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
5ZC4	X-RAY DIFFRACTION	1.91
5ZBU	X-RAY DIFFRACTION	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43567-F1	74.65	0.34

Functional residue map

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

Glycosylation sites (1): 88

Mutagenesis-validated functional residues (10):

Position	Phenotype
1–183	no effect on er stress-induced jnk activation and apoptosis.
43	no effect on glycosylation.
52–162	no effect on er stress-induced jnk activation and apoptosis. no effect on interaction with ern1.
88	loss of glycosylation.
165–381	abolishes er stress-induced jnk activation and apoptosis.
184–207	abolishes er stress-induced jnk activation and apoptosis. disrupts localization to endoplasmic reticulum.
243	abolishes er stress-induced jnk activation and apoptosis. abolishes interaction with ern1. does not affect localization
258	complete loss of e3 ligase activity; when associated with a-260.
260	complete loss of e3 ligase activity; when associated with a-258.
270	drastically reduces e3 ligase activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 318 (showing top): GCM_MAP4K4, GOCC_VACUOLAR_MEMBRANE, GCANCTGNY_MYOD_Q6, ATACCTC_MIR202, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, CAGCTG_AP4_Q5, ATGTTAA_MIR302C, GOBP_JNK_CASCADE, GOBP_PROTEIN_AUTOUBIQUITINATION, TCF11_01, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_DN, ACATTCC_MIR1_MIR206, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION

GO Biological Process (5): ubiquitin-dependent protein catabolic process (GO:0006511), positive regulation of JNK cascade (GO:0046330), organelle localization (GO:0051640), protein autoubiquitination (GO:0051865), protein ubiquitination (GO:0016567)

GO Molecular Function (7): ubiquitin-protein transferase activity (GO:0004842), zinc ion binding (GO:0008270), JUN kinase binding (GO:0008432), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (13): nuclear inner membrane (GO:0005637), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), lysosomal membrane (GO:0005765), endosome (GO:0005768), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), late endosome membrane (GO:0031902), nucleus (GO:0005634), lysosome (GO:0005764), endosome membrane (GO:0010008), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
protein ubiquitination	2
endomembrane system	2
cytoplasm	2
intracellular membrane-bounded organelle	2
modification-dependent protein catabolic process	1
JNK cascade	1
positive regulation of MAPK cascade	1
regulation of JNK cascade	1
localization	1
protein modification by small protein conjugation	1
ubiquitin-like protein transferase activity	1
transition metal ion binding	1
protein kinase binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
binding	1
catalytic activity	1
cation binding	1
organelle inner membrane	1
nuclear membrane	1
nuclear lumen	1
intracellular anatomical structure	1
lysosome	1
lytic vacuole membrane	1
cytoplasmic vesicle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
late endosome	1
endosome membrane	1
lytic vacuole	1
endosome	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1

Protein interactions and networks

STRING

678 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RNF13	TMEM183A	Q8IXX5	588
RNF13	HSF2BP	O75031	480
RNF13	AP3S1	Q92572	480
RNF13	VRK2	Q86Y07	461
RNF13	SNAPIN	O95295	435
RNF13	SQSTM1	Q13501	421
RNF13	LRCOL1	A6NCL2	412
RNF13	EIF3F	O00303	405
RNF13	RNF183	Q96D59	403
RNF13	IFT56	A0AVF1	401
RNF13	CGRRF1	Q99675	381
RNF13	TTC7B	Q86TV6	375
RNF13	PARP16	Q8N5Y8	366
RNF13	NUS1	Q96E22	364
RNF13	PCMT1	P22061	359

IntAct

41 interactions, top by confidence:

A	B	Type	Score
UBE2N	RNF13	psi-mi:“MI:0915”(physical association)	0.590
MANSC1	KLRG2	psi-mi:“MI:0914”(association)	0.530
SPINT2	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
CLEC11A	VWA8	psi-mi:“MI:0914”(association)	0.530
LGALS1	PODXL	psi-mi:“MI:0914”(association)	0.530
RNF13	UBE2D1	psi-mi:“MI:0915”(physical association)	0.370
RNF13	UBE2D2	psi-mi:“MI:0915”(physical association)	0.370
RNF13	UBE2D3	psi-mi:“MI:0915”(physical association)	0.370
RNF13	UBE2D4	psi-mi:“MI:0915”(physical association)	0.370
UBE2E1	RNF13	psi-mi:“MI:0915”(physical association)	0.370
UBE2E3	RNF13	psi-mi:“MI:0915”(physical association)	0.370
STAT5A	R3HDM2	psi-mi:“MI:0914”(association)	0.350
NES	RPL10	psi-mi:“MI:0914”(association)	0.350
LGALS8	SLC22A23	psi-mi:“MI:0914”(association)	0.350
STX12	NBAS	psi-mi:“MI:0914”(association)	0.350
VTI1B	NBAS	psi-mi:“MI:0914”(association)	0.350
CLEC11A	VWA8	psi-mi:“MI:0914”(association)	0.350
LGALS9	PODXL	psi-mi:“MI:0914”(association)	0.350
VIPR1	GPR89A	psi-mi:“MI:0914”(association)	0.350
RNF13	AP3D1	psi-mi:“MI:0914”(association)	0.350
Npc1	ESYT2	psi-mi:“MI:0914”(association)	0.350
CHEK1	RNF13	psi-mi:“MI:0914”(association)	0.350
HPSE2	RNF13	psi-mi:“MI:0914”(association)	0.350
KLRC3	RNF13	psi-mi:“MI:0914”(association)	0.350
VIPR1	SLC33A1	psi-mi:“MI:0914”(association)	0.350

BioGRID (131): RNF13 (Affinity Capture-RNA), RNF13 (Affinity Capture-MS), RNF13 (Affinity Capture-MS), RNF13 (Affinity Capture-MS), RNF13 (Affinity Capture-MS), AP3S2 (Affinity Capture-MS), AP3D1 (Affinity Capture-MS), HDGFRP3 (Affinity Capture-MS), AP3S1 (Affinity Capture-MS), TYK2 (Affinity Capture-MS), NR2F2 (Affinity Capture-MS), NR2F1 (Affinity Capture-MS), CD63 (Affinity Capture-MS), TSPAN3 (Affinity Capture-MS), CLCN7 (Affinity Capture-MS)

ESM2 similar proteins: A2VDZ5, A7SAZ1, B3LV44, B4NJP3, C5IAW9, O08722, O08747, O08775, O14522, O43567, O54965, O60502, O75460, O95185, P06213, P15127, P15208, P28827, P28828, P35918, P35968, P59823, P59824, P60029, Q09499, Q0VD51, Q26261, Q5GIT4, Q5MD89, Q5RCV8, Q5ZLK8, Q66HG0, Q6AY64, Q6DIW0, Q6NZZ3, Q6UX71, Q761X5, Q7T2Z5, Q7YQL9, Q7Z4R8

Diamond homologs: A5WWA0, E9QAU8, G3X9R7, O22197, O22755, O43567, O54965, O64763, P0C034, P0CH30, P0DPR2, Q06003, Q07G42, Q08D68, Q0II22, Q0VD51, Q10R93, Q14B02, Q29RU0, Q2TA44, Q3U2C5, Q4KLR8, Q4R6Y5, Q5NCP0, Q5RCV8, Q5RF74, Q5SPX3, Q5SSZ7, Q5XF85, Q641J8, Q66HG0, Q68DV7, Q69U49, Q6AY01, Q6DIP3, Q6IRP0, Q6NML0, Q6NQG7, Q6NRX0, Q6Y290

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RNF13	“up-regulates activity”	SNAPIN	polyubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 49 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Synthesis of active ubiquitin: roles of E1 and E2 enzymes	5	57.6×	4e-06
E3 ubiquitin ligases ubiquitinate target proteins	5	30.2×	3e-05
Antigen processing: Ubiquitination & Proteasome degradation	8	9.3×	5e-05

GO biological processes:

GO term	Partners	Fold	FDR
protein K48-linked ubiquitination	6	24.7×	5e-05
protein polyubiquitination	5	14.1×	2e-03
ubiquitin-dependent protein catabolic process	6	10.9×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	3
Uncertain significance	145
Likely benign	105
Benign	21

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
1810266	NM_183381.3(RNF13):c.901G>T (p.Glu301Ter)	Pathogenic
625147	NM_183381.3(RNF13):c.932T>C (p.Leu311Ser)	Pathogenic
625148	NM_183381.3(RNF13):c.935T>C (p.Leu312Pro)	Pathogenic
1204067	NM_183381.3(RNF13):c.932del (p.Leu311fs)	Likely pathogenic
1308257	NM_183381.3(RNF13):c.932T>A (p.Leu311Ter)	Likely pathogenic
1810407	NM_183381.3(RNF13):c.919G>T (p.Glu307Ter)	Likely pathogenic

SpliceAI

2216 predictions. Top by Δscore:

Variant	Effect	Δscore
3:149846136:TAGCA:T	donor_gain	1.0000
3:149846137:AGCA:A	donor_gain	1.0000
3:149846137:AGCAG:A	donor_loss	1.0000
3:149846138:GCA:G	donor_gain	1.0000
3:149846138:GCAG:G	donor_gain	1.0000
3:149846139:CA:C	donor_gain	1.0000
3:149846141:G:GG	donor_gain	1.0000
3:149846142:T:A	donor_loss	1.0000
3:149846143:A:AG	donor_loss	1.0000
3:149846144:AGTA:A	donor_loss	1.0000
3:149852514:A:AG	acceptor_gain	1.0000
3:149852515:G:GA	acceptor_gain	1.0000
3:149852515:GT:G	acceptor_gain	1.0000
3:149852515:GTAT:G	acceptor_gain	1.0000
3:149852515:GTATA:G	acceptor_gain	1.0000
3:149872023:TTTCA:T	acceptor_loss	1.0000
3:149872024:TTCA:T	acceptor_loss	1.0000
3:149872025:TCA:T	acceptor_loss	1.0000
3:149872026:CAGG:C	acceptor_loss	1.0000
3:149872027:AG:A	acceptor_gain	1.0000
3:149872028:GG:G	acceptor_gain	1.0000
3:149872150:TAAAG:T	donor_loss	1.0000
3:149872151:AAAGG:A	donor_loss	1.0000
3:149872152:AAGGT:A	donor_loss	1.0000
3:149872153:AGGTA:A	donor_loss	1.0000
3:149872154:GGTAT:G	donor_loss	1.0000
3:149872155:G:GC	donor_loss	1.0000
3:149872156:T:A	donor_loss	1.0000
3:149895463:T:TA	acceptor_gain	1.0000
3:149895468:TGCA:T	acceptor_loss	1.0000

AlphaMissense

2522 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:149852564:T:C	F55L	1.000
3:149852565:T:G	F55C	1.000
3:149852566:T:A	F55L	1.000
3:149852566:T:G	F55L	1.000
3:149852567:G:C	G56R	1.000
3:149852567:G:T	G56C	1.000
3:149852568:G:A	G56D	1.000
3:149852568:G:T	G56V	1.000
3:149872062:T:A	C77S	1.000
3:149872062:T:C	C77R	1.000
3:149872063:G:A	C77Y	1.000
3:149872063:G:C	C77S	1.000
3:149872129:G:C	R99T	1.000
3:149872137:T:A	C102S	1.000
3:149872137:T:C	C102R	1.000
3:149872138:G:A	C102Y	1.000
3:149872138:G:C	C102S	1.000
3:149872138:G:T	C102F	1.000
3:149872139:T:G	C102W	1.000
3:149872143:T:C	F104L	1.000
3:149872144:T:G	F104C	1.000
3:149872145:T:A	F104L	1.000
3:149872145:T:G	F104L	1.000
3:149872154:G:C	K107N	1.000
3:149872154:G:T	K107N	1.000
3:149895474:T:A	V108D	1.000
3:149895482:G:C	A111P	1.000
3:149895483:C:A	A111E	1.000
3:149895486:A:C	Q112P	1.000
3:149895503:G:C	A118P	1.000

dbSNP variants (sampled 300 via entrez): RS1000004986 (3:149959154 A>G), RS1000010526 (3:149951807 C>A,T), RS1000014251 (3:149955393 G>A,C,T), RS1000030495 (3:149933274 TTTTA>T), RS1000031553 (3:149819238 C>T), RS1000101952 (3:149932629 G>A,C), RS1000102398 (3:149863828 C>G), RS1000105077 (3:149910410 G>A), RS1000166775 (3:149934598 C>A,T), RS1000172288 (3:149896088 T>A), RS1000198439 (3:149847442 A>G), RS1000211992 (3:149940086 TTTTCTC>T), RS1000226628 (3:149850359 A>G), RS1000231080 (3:149952115 C>T), RS1000265445 (3:149893407 T>G)

Disease associations

OMIM: gene MIM:609247 | disease phenotypes: MIM:618379

GenCC curated gene-disease

Disease	Classification	Inheritance
developmental and epileptic encephalopathy, 73	Strong	Autosomal dominant

Mondo (1): developmental and epileptic encephalopathy, 73 (MONDO:0034106)

Orphanet (1): RNF13-related severe early-onset epileptic encephalopathy (Orphanet:544503)

HPO phenotypes

53 total (30 of 53 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000023	Inguinal hernia
HP:0000252	Microcephaly
HP:0000331	Short chin
HP:0000341	Narrow forehead
HP:0000407	Sensorineural hearing impairment
HP:0000446	Narrow nasal bridge
HP:0000496	Abnormality of eye movement
HP:0000518	Cataract
HP:0000668	Hypodontia
HP:0000711	Restlessness
HP:0000737	Irritability
HP:0001182	Tapered finger
HP:0001250	Seizure
HP:0001257	Spasticity
HP:0001272	Cerebellar atrophy
HP:0001276	Hypertonia
HP:0001290	Generalized hypotonia
HP:0001371	Flexion contracture
HP:0001382	Joint hypermobility
HP:0001385	Hip dysplasia
HP:0001508	Failure to thrive
HP:0001999	Abnormal facial shape
HP:0002069	Bilateral tonic-clonic seizure
HP:0002079	Hypoplasia of the corpus callosum
HP:0002098	Respiratory distress
HP:0002164	Nail dysplasia
HP:0002187	Profound intellectual disability
HP:0002188	Delayed CNS myelination
HP:0002650	Scoliosis

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003471_1	Myocardial infarction	1.000000e-11
GCST010142_40	Fish- and plant-related diet	1.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008111	diet measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	5
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
bisphenol A	increases expression, affects cotreatment	1
lead acetate	affects cotreatment, decreases expression	1
sodium arsenite	affects cotreatment, decreases expression	1
cobaltous chloride	increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
methacrylaldehyde	increases expression, increases abundance, affects cotreatment	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluoro-n-nonanoic acid	affects methylation	1
nickel acetate	affects expression	1
K 7174	increases expression	1
torcetrapib	increases expression	1
abrine	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1
Acrolein	affects cotreatment, increases expression, increases abundance	1
Air Pollutants	increases expression, affects cotreatment, increases abundance	1
Arsenic	affects expression	1
Clozapine	increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Gold	decreases expression	1

Clinical trials (associated diseases)

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