RNF34

Summary

RNF34 (ring finger protein 34, HGNC:17297) is a protein-coding gene on chromosome 12q24.31, encoding E3 ubiquitin-protein ligase RNF34 (Q969K3). E3 ubiquitin-protein ligase that regulates several biological processes through the ubiquitin-mediated proteasomal degradation of various target proteins.

The protein encoded by this gene contains a RINF finger, a motif known to be involved in protein-protein and protein-DNA interactions. This protein interacts with DNAJA3/hTid-1, which is a DnaJ protein reported to function as a modulator of apoptosis. Overexpression of this gene in Hela cells was shown to confer the resistance to TNF-alpha induced apoptosis, suggesting an anti-apoptotic function of this protein. This protein can be cleaved by caspase-3 during the induction of apoptosis. This protein also targets p53 and phospho-p53 for degradation. Alternatively splicing results in multiple transcript variants encoding distinct isoforms.

Source: NCBI Gene 80196 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 6 total
• MANE Select transcript: NM_025126

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17297
Approved symbol	RNF34
Name	ring finger protein 34
Location	12q24.31
Locus type	gene with protein product
Status	Approved
Aliases	RIFF, FLJ21786, RIF
Ensembl gene	ENSG00000170633
Ensembl biotype	protein_coding
OMIM	608299
Entrez	80196

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 13 protein_coding, 3 retained_intron

ENST00000361234, ENST00000392464, ENST00000392465, ENST00000553407, ENST00000554484, ENST00000554606, ENST00000554868, ENST00000555076, ENST00000556562, ENST00000557402, ENST00000613529, ENST00000867130, ENST00000867131, ENST00000867133, ENST00000917689, ENST00000964569

RefSeq mRNA: 4 — MANE Select: NM_025126 NM_001256858, NM_001394208, NM_025126, NM_194271

CCDS: CCDS31915, CCDS73538, CCDS9221

Canonical transcript exons

ENST00000361234 — 6 exons

Exon	Start	End
ENSE00001123957	121420242	121420334
ENSE00001123964	121417504	121417911
ENSE00002459568	121400118	121400218
ENSE00002472007	121423386	121424348
ENSE00003605258	121416159	121416377
ENSE00003687697	121420577	121420778

Expression profiles

Bgee: expression breadth ubiquitous, 279 present calls, max score 99.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.5082 / max 243.7578, expressed in 1814 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
128428	22.4441	1813
128427	1.0642	679

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.94	gold quality
oocyte	CL:0000023	99.84	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	96.16	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	96.14	gold quality
biceps brachii	UBERON:0001507	95.95	gold quality
triceps brachii	UBERON:0001509	93.99	gold quality
gluteal muscle	UBERON:0002000	93.91	gold quality
cortical plate	UBERON:0005343	93.68	gold quality
ganglionic eminence	UBERON:0004023	93.35	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.33	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.21	gold quality
middle temporal gyrus	UBERON:0002771	93.08	gold quality
Brodmann (1909) area 23	UBERON:0013554	93.05	gold quality
granulocyte	CL:0000094	93.01	gold quality
adult organism	UBERON:0007023	92.48	gold quality
primary visual cortex	UBERON:0002436	92.35	gold quality
cerebellar hemisphere	UBERON:0002245	91.92	gold quality
cerebellar cortex	UBERON:0002129	91.90	gold quality
vastus lateralis	UBERON:0001379	91.89	gold quality
cerebellum	UBERON:0002037	91.71	gold quality
mucosa of transverse colon	UBERON:0004991	91.70	gold quality
skeletal muscle tissue	UBERON:0001134	91.69	gold quality
muscle of leg	UBERON:0001383	91.61	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.60	gold quality
muscle organ	UBERON:0001630	91.56	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	91.54	gold quality
gastrocnemius	UBERON:0001388	91.38	gold quality
lymph node	UBERON:0000029	91.27	gold quality
Brodmann (1909) area 9	UBERON:0013540	91.24	gold quality
blood	UBERON:0000178	91.16	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.78

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HNF4A

miRNA regulators (miRDB)

48 targeting RNF34, 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-4262	100.00	73.26	3931
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-1284	99.67	73.56	1353
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-6751-5P	99.56	64.99	1145
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-409-3P	99.50	66.33	1192
HSA-MIR-6833-5P	99.50	68.93	1161
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-5009-3P	99.45	69.43	1341

Literature-anchored findings (GeneRIF, showing 7)

• a novel gene, hRFI, preferentially expressed in esophageal cancer (hRFI) (PMID:12118383)
• hRFI may act as an oncogenic molecule affecting the apoptotic pathway (PMID:15595643)
• CARPs together with MDM2 enhance p53 degradation, thereby inhibiting p53-mediated cell death. (PMID:18382127)
• The previously unknown small molecule inhibitor-dependent interaction of Cbeta1 with the cell cycle and apoptosis regulatory protein-1 was verified. (PMID:20564261)
• Data indicate AE induces caspase-8-mediated activation of mitochondrial death pathways by decreasing the stability of CARP mRNAs in a p53-independent manner. (PMID:21308745)
• Data indicate that E3 ligase RNF34 is associated with nucleotide-binding oligomerization domain-containing protein 1 (NOD1). (PMID:25012219)
• Study identified RNF34 as an important regulator of immunity and mitophagy by inducing the autophagic degradation of MAVS aggregates. RNF34 promoted the K63 to K27/K29 ubiquitination transition of MAVS and degraded activated MAVS oligomers. The loss of RNF34 led to defects in mitophagy. The RNF34-mediated mitochondrial quality control mechanism links the innate immune response, mitochondrial homeostasis, and infection. (PMID:31304625)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rnf34a	ENSDARG00000038300
danio_rerio	rnf34b	ENSDARG00000054036
mus_musculus	Rnf34	ENSMUSG00000029474
rattus_norvegicus	Rnf34	ENSRNOG00000001331
drosophila_melanogaster	CG17019	FBGN0033783

Paralogs (1): RFFL (ENSG00000092871)

Protein

Protein identifiers

E3 ubiquitin-protein ligase RNF34 — Q969K3 (reviewed: Q969K3)

Alternative names: Caspase regulator CARP1, Caspases-8 and -10-associated RING finger protein 1, FYVE-RING finger protein Momo, Human RING finger homologous to inhibitor of apoptosis protein, RING finger protein 34, RING finger protein RIFF, RING-type E3 ubiquitin transferase RNF34

All UniProt accessions (7): Q969K3, A0A087WTM5, G3V4D1, G3V504, G3V566, G3V5F1, H7BYJ1

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin-protein ligase that regulates several biological processes through the ubiquitin-mediated proteasomal degradation of various target proteins. Ubiquitinates the caspases CASP8 and CASP10, promoting their proteasomal degradation, to negatively regulate cell death downstream of death domain receptors in the extrinsic pathway of apoptosis. May mediate ‘Lys-48’-linked polyubiquitination of RIPK1 and its subsequent proteasomal degradation thereby indirectly regulating the tumor necrosis factor-mediated signaling pathway (Ref.13). Negatively regulates p53/TP53 through its direct ubiquitination and targeting to proteasomal degradation. Indirectly, may also negatively regulate p53/TP53 through ubiquitination and degradation of SFN. Mediates PPARGC1A proteasomal degradation probably through ubiquitination thereby indirectly regulating the metabolism of brown fat cells. Possibly involved in innate immunity, through ‘Lys-48’-linked polyubiquitination of NOD1 and its subsequent proteasomal degradation.

Subunit / interactions. Interacts with CASP8 and CASP10. Interacts (via RING-type zinc finger) with PPARGC1A. Interacts with NOD1. Interacts with p53/TP53; involved in p53/TP53 ubiquitination. Interacts (via RING-type zinc finger) with MDM2; the interaction stabilizes MDM2.

Subcellular location. Cell membrane. Endomembrane system. Nucleus. Nucleus speckle. Cytoplasm. Cytosol.

Tissue specificity. Ubiquitous. Detected in heart, brain, liver, skeletal muscle, kidney, pancreas, spleen, thymus, prostate, testis, ovary, colon and leukocytes.

Post-translational modifications. Autoubiquitinated (in vitro). Proteolytically cleaved by caspases upon induction of apoptosis by TNF.

Domain organisation. The RING-type zinc finger is required for the ubiquitination of target proteins. The FYVE-type zinc finger domain is required for localization and may confer affinity for cellular compartments enriched in phosphatidylinositol 5-phosphate and phosphatidylinositol 3-phosphate phospholipids.

Pathway. Protein modification; protein ubiquitination.

Isoforms (2)

UniProt ID	Names	Canonical?
Q969K3-1	1	yes
Q969K3-2	2

RefSeq proteins (4): NP_001243787, NP_001381137, NP_079402, NP_919247 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001841	Znf_RING	Domain
IPR011011	Znf_FYVE_PHD	Homologous_superfamily
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR036361	SAP_dom_sf	Homologous_superfamily
IPR049320	CARP1_2_FYVE	Domain
IPR049323	CARP1_FYVE	Domain
IPR051728	RING-FYVE_E3_ubiquitin-ligase	Family
IPR055111	RNF34_RFFL_HeH	Domain
IPR057299	RNF34_RFFL_SAP	Domain

Pfam: PF13920, PF21272, PF22968, PF23632

UniProt features (19 total): modified residue 3, sequence conflict 3, compositionally biased region 3, domain 2, mutagenesis site 2, zinc finger region 2, chain 1, splice variant 1, region of interest 1, site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q969K3-F1	72.36	0.45

Functional residue map

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

Catalytic / active sites (1): 232–233 (cleavage; by caspase-3)

Post-translational modifications (3): 169, 254, 256

Mutagenesis-validated functional residues (2):

Position	Phenotype
328	loss of e3 ubiquitin protein ligase activity.
342	loss of e3 ubiquitin protein ligase activity.

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-6804757	Regulation of TP53 Degradation
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation
R-HSA-1280218	Adaptive Immune System
R-HSA-168256	Immune System
R-HSA-212436	Generic Transcription Pathway
R-HSA-3700989	Transcriptional Regulation by TP53
R-HSA-5633007	Regulation of TP53 Activity
R-HSA-6806003	Regulation of TP53 Expression and Degradation
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-983169	Class I MHC mediated antigen processing & presentation

MSigDB gene sets: 226 (showing top): AP1_01, GOBP_RESPONSE_TO_COLD, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GOBP_NUCLEOTIDE_BINDING_DOMAIN_LEUCINE_RICH_REPEAT_CONTAINING_RECEPTOR_SIGNALING_PATHWAY, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_NEGATIVE_REGULATION_OF_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, GOBP_REGULATION_OF_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_VIA_DEATH_DOMAIN_RECEPTORS, GOBP_REGULATION_OF_IMMUNE_RESPONSE, AP1_Q4_01

GO Biological Process (11): ubiquitin-dependent protein catabolic process (GO:0006511), apoptotic process (GO:0006915), protein ubiquitination (GO:0016567), nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway (GO:0035872), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), cellular response to cold (GO:0070417), protein K48-linked ubiquitination (GO:0070936), regulation of signal transduction by p53 class mediator (GO:1901796), negative regulation of signal transduction by p53 class mediator (GO:1901797), negative regulation of extrinsic apoptotic signaling pathway via death domain receptors (GO:1902042), regulation of oxygen metabolic process (GO:2000374)

GO Molecular Function (8): p53 binding (GO:0002039), zinc ion binding (GO:0008270), ubiquitin protein ligase binding (GO:0031625), ubiquitin protein ligase activity (GO:0061630), phosphatidylinositol phosphate binding (GO:1901981), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (9): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), endomembrane system (GO:0012505), nuclear body (GO:0016604), nuclear speck (GO:0016607), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Regulation of TP53 Expression and Degradation	1
Class I MHC mediated antigen processing & presentation	1
Immune System	1
RNA Polymerase II Transcription	1
Generic Transcription Pathway	1
Transcriptional Regulation by TP53	1
Regulation of TP53 Activity	1
Gene expression (Transcription)	1
Adaptive Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
signal transduction by p53 class mediator	2
protein ubiquitination	1
modification-dependent protein catabolic process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
protein modification by small protein conjugation	1
cytoplasmic pattern recognition receptor signaling pathway	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
response to cold	1
cellular response to stress	1
protein polyubiquitination	1
regulation of intracellular signal transduction	1
regulation of signal transduction by p53 class mediator	1
negative regulation of intracellular signal transduction	1
extrinsic apoptotic signaling pathway via death domain receptors	1
regulation of extrinsic apoptotic signaling pathway via death domain receptors	1
negative regulation of extrinsic apoptotic signaling pathway	1
regulation of metabolic process	1
oxygen metabolic process	1
protein binding	1
transition metal ion binding	1
ubiquitin-like protein ligase binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
phospholipid binding	1
binding	1
catalytic activity	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1
vacuole	1
plasma membrane	1
nucleoplasm	1

Protein interactions and networks

STRING

1078 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RNF34	DEDD	O75618	681
RNF34	DNAJA3	Q96EY1	580
RNF34	KLHL42	Q9P2K6	501
RNF34	ASB6	Q9NWX5	486
RNF34	TRIM37	O94972	466
RNF34	GON4L	Q3T8J9	448
RNF34	CEP250	Q9BV73	445
RNF34	AIG1	Q9NVV5	442
RNF34	RASL11A	Q6T310	437
RNF34	MLLT6	P55198	437
RNF34	TESPA1	A2RU30	434
RNF34	D6RGC4	D6RGC4	419
RNF34	WDR13	Q9H1Z4	414
RNF34	ACTR5	Q9H9F9	410
RNF34	DIP2A	Q14689	410

IntAct

65 interactions, top by confidence:

A	B	Type	Score
UNC119	UNC119B	psi-mi:“MI:0914”(association)	0.640
APPBP2	RNF34	psi-mi:“MI:0915”(physical association)	0.560
RNF34	APPBP2	psi-mi:“MI:0915”(physical association)	0.560
CRYAA	RNF34	psi-mi:“MI:0915”(physical association)	0.560
RNF34	DMWD	psi-mi:“MI:0915”(physical association)	0.560
DR1	RNF34	psi-mi:“MI:0915”(physical association)	0.560
RNF34		psi-mi:“MI:0915”(physical association)	0.560
RNF34	GLE1	psi-mi:“MI:0915”(physical association)	0.560
RNF34	KLK6	psi-mi:“MI:0915”(physical association)	0.560
RNF34	GTF3C3	psi-mi:“MI:0915”(physical association)	0.560
RNF34	GIPC1	psi-mi:“MI:0915”(physical association)	0.560
RNF34	PANK2	psi-mi:“MI:0915”(physical association)	0.560
RNF34	SPRED1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (104): RNF34 (Two-hybrid), UBE2D2 (Reconstituted Complex), CASP8 (Affinity Capture-Western), CASP9 (Affinity Capture-Western), CASP10 (Affinity Capture-Western), RNF34 (Affinity Capture-MS), RNF34 (Affinity Capture-MS), RNF34 (Affinity Capture-MS), UNC119B (Affinity Capture-MS), EFCAB7 (Affinity Capture-MS), RNF34 (Affinity Capture-MS), KLHL15 (Affinity Capture-MS), RNF34 (Affinity Capture-MS), HSPA8 (Affinity Capture-MS), TSR3 (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8GLK3, A0A974CYQ5, A2AHJ4, A5WW08, D2HNY3, D2HWM5, E7F6T8, F1ND48, O15040, O70260, O95071, P59328, Q3TLR7, Q4V837, Q58DC2, Q58WW2, Q5E9J6, Q5F479, Q5FWP4, Q5NVC7, Q5R9B8, Q5RF77, Q5RGA4, Q5RHI5, Q5ZLG9, Q62671, Q66JG1, Q6DDH2, Q6P1W0, Q6P256, Q6PCD5, Q6PJI9, Q6RI45, Q80TP3, Q80U93, Q810L3, Q8C0M0, Q8CBW4, Q8CIK8, Q8CIN9

Diamond homologs: A2AWP0, A5D8Q0, A9JTP3, A9ULZ2, D3ZDI6, O14064, O62640, O88738, P41437, Q05AK5, Q13075, Q24307, Q28H51, Q5BKL8, Q5E9J6, Q5NVC7, Q60989, Q68LP1, Q6AYH3, Q6GNY1, Q6R7D0, Q6R7I2, Q6TEM9, Q804S5, Q80SY4, Q86YT6, Q8JGN5, Q8JHV9, Q8R516, Q8WY64, Q969K3, Q96AX9, Q96CA5, Q96P09, Q99KR6, Q9JIB3, Q9JIB6, Q9LY87, Q9NR09, Q9QUK4

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	RNF34	ubiquitination
RNF34	“down-regulates quantity by destabilization”	PPARGC1A	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	2
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1791 predictions. Top by Δscore:

Variant	Effect	Δscore
12:121416313:C:G	donor_gain	1.0000
12:121416318:G:GT	donor_gain	1.0000
12:121417503:GCAT:G	acceptor_gain	1.0000
12:121417763:GCA:G	donor_gain	1.0000
12:121420572:TTCA:T	acceptor_loss	1.0000
12:121420574:CAG:C	acceptor_loss	1.0000
12:121420575:A:AG	acceptor_gain	1.0000
12:121420575:A:AT	acceptor_loss	1.0000
12:121420576:G:GC	acceptor_gain	1.0000
12:121420576:GA:G	acceptor_gain	1.0000
12:121420576:GAAC:G	acceptor_gain	1.0000
12:121420670:G:GT	donor_gain	1.0000
12:121420739:AACCG:A	donor_gain	1.0000
12:121420774:GTCCT:G	donor_gain	1.0000
12:121420775:TCCT:T	donor_gain	1.0000
12:121420778:TG:T	donor_loss	1.0000
12:121420779:G:GG	donor_gain	1.0000
12:121420780:T:A	donor_loss	1.0000
12:121423381:TTCA:T	acceptor_loss	1.0000
12:121423384:A:AG	acceptor_gain	1.0000
12:121423384:AGAT:A	acceptor_gain	1.0000
12:121423384:AGATG:A	acceptor_gain	1.0000
12:121423385:G:GT	acceptor_gain	1.0000
12:121423385:GAT:G	acceptor_gain	1.0000
12:121423385:GATG:G	acceptor_gain	1.0000
12:121423385:GATGG:G	acceptor_gain	1.0000
12:121430466:CAGT:C	acceptor_gain	1.0000
12:121430468:GT:G	acceptor_gain	1.0000
12:121430470:C:CC	acceptor_gain	1.0000
12:121402804:G:GT	donor_gain	0.9900

AlphaMissense

2445 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:121416336:T:C	C62R	1.000
12:121417573:T:C	C99R	1.000
12:121417646:T:C	L123P	1.000
12:121420665:T:C	L272P	1.000
12:121420669:G:C	K273N	1.000
12:121420669:G:T	K273N	1.000
12:121420677:T:A	L276Q	1.000
12:121420677:T:C	L276P	1.000
12:121420725:T:A	L292Q	1.000
12:121420725:T:C	L292P	1.000
12:121420746:T:C	L299S	1.000
12:121423430:T:A	C325S	1.000
12:121423430:T:C	C325R	1.000
12:121423431:G:A	C325Y	1.000
12:121423431:G:C	C325S	1.000
12:121423432:T:G	C325W	1.000
12:121423439:T:A	C328S	1.000
12:121423439:T:C	C328R	1.000
12:121423440:G:A	C328Y	1.000
12:121423440:G:C	C328S	1.000
12:121423441:C:G	C328W	1.000
12:121423464:T:A	V336D	1.000
12:121423467:T:C	L337P	1.000
12:121423470:T:C	L338P	1.000
12:121423475:T:A	C340S	1.000
12:121423475:T:C	C340R	1.000
12:121423476:G:A	C340Y	1.000
12:121423476:G:C	C340S	1.000
12:121423477:T:G	C340W	1.000
12:121423479:G:A	G341E	1.000

dbSNP variants (sampled 300 via entrez): RS1000505227 (12:121410175 A>G), RS1000790500 (12:121398145 G>A), RS1000932822 (12:121423222 G>A), RS1001137130 (12:121403823 T>C), RS1001171898 (12:121407086 C>G), RS1001368745 (12:121400782 A>G), RS1001605737 (12:121420171 A>G), RS1001656623 (12:121420419 T>C), RS1001727513 (12:121413494 C>T), RS1001798438 (12:121400952 G>A), RS1002075002 (12:121413200 T>C), RS1002403021 (12:121402399 A>G), RS1002779736 (12:121402088 A>G), RS1003283320 (12:121418617 G>A), RS1003348099 (12:121411616 A>G)

Disease associations

OMIM: gene MIM:608299 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Fluorouracil	affects cotreatment, decreases reaction, increases expression, increases activity, decreases response to substance	4
Valproic Acid	affects expression, decreases expression	2
FR900359	increases phosphorylation	1
beta-lapachone	decreases expression	1
sodium arsenite	decreases expression	1
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
BAY 11-7085	affects cotreatment, decreases reaction, increases expression	1
abrine	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
Irinotecan	decreases reaction, increases activity, decreases response to substance	1
Resveratrol	affects cotreatment, increases expression	1
Arsenic Trioxide	increases expression	1
Leflunomide	decreases expression	1
Acetaminophen	increases expression	1
Arsenic	affects methylation	1
Catechin	decreases expression, affects cotreatment	1
Cisplatin	decreases reaction, increases activity, decreases response to substance	1
Demecolcine	increases expression	1
Nickel	increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Quercetin	decreases phosphorylation	1
Smoke	decreases expression	1
Vincristine	increases expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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