RNF144A

Summary

RNF144A (ring finger protein 144A, HGNC:20457) is a protein-coding gene on chromosome 2p25.1, encoding E3 ubiquitin-protein ligase RNF144A (P50876). E3 ubiquitin-protein ligase which accepts ubiquitin from E2 ubiquitin-conjugating enzymes UBE2L3 and UBE2L6 in the form of a thioester and then directly transfers the ubiquitin to targeted substrates.

This gene encodes a member of a family of RING finger domain-containing E3 ubiquitin ligases that also includes parkin and parc. The expression of this gene is induced by DNA damage. The encoded protein interacts with the cytoplasmic DNA-dependent protein kinase, catalytic subunit (DNA-PKcs) and promotes its degradation through ubiquitination. The orthologous mouse protein has been shown to interact with a ubiquitin-conjugating enzyme involved in embryonic development.

Source: NCBI Gene 9781 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 66 total
• MANE Select transcript: NM_014746

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20457
Approved symbol	RNF144A
Name	ring finger protein 144A
Location	2p25.1
Locus type	gene with protein product
Status	Approved
Aliases	UBCE7IP4, KIAA0161, hUIP4
Ensembl gene	ENSG00000151692
Ensembl biotype	protein_coding
OMIM	619454
Entrez	9781

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 15 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000320892, ENST00000416587, ENST00000432850, ENST00000433456, ENST00000467276, ENST00000471060, ENST00000480970, ENST00000902586, ENST00000902587, ENST00000902588, ENST00000902589, ENST00000902590, ENST00000902591, ENST00000937859, ENST00000942526, ENST00000942527, ENST00000942528, ENST00000942529

RefSeq mRNA: 7 — MANE Select: NM_014746 NM_001349181, NM_001349182, NM_001349183, NM_001349184, NM_001349185, NM_001349186, NM_014746

CCDS: CCDS1657

Canonical transcript exons

ENST00000320892 — 9 exons

Exon	Start	End
ENSE00001185444	6940948	6941147
ENSE00001185448	6917412	6917622
ENSE00001185452	7039629	7044179
ENSE00001281261	6996916	6997061
ENSE00003486990	7014454	7014558
ENSE00003558570	7020473	7020680
ENSE00003567668	7024369	7024516
ENSE00003618036	7014712	7014772
ENSE00003661422	7030126	7030215

Expression profiles

Bgee: expression breadth ubiquitous, 253 present calls, max score 93.95.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.4596 / max 262.1944, expressed in 1487 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
18689	13.6765	1477
18693	1.3363	101
18690	1.0340	458
18692	0.2636	77
18691	0.1423	67
18697	0.0069	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar hemisphere	UBERON:0002245	93.95	gold quality
cerebellar cortex	UBERON:0002129	93.90	gold quality
cerebellum	UBERON:0002037	93.55	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.27	gold quality
ganglionic eminence	UBERON:0004023	92.61	gold quality
corpus callosum	UBERON:0002336	92.22	gold quality
adrenal tissue	UBERON:0018303	91.32	gold quality
body of pancreas	UBERON:0001150	91.22	gold quality
inferior vagus X ganglion	UBERON:0005363	90.52	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	90.44	gold quality
cortical plate	UBERON:0005343	90.36	gold quality
paraflocculus	UBERON:0005351	90.08	gold quality
spinal cord	UBERON:0002240	89.76	gold quality
medial globus pallidus	UBERON:0002477	89.70	gold quality
nucleus accumbens	UBERON:0001882	89.42	gold quality
middle frontal gyrus	UBERON:0002702	89.33	gold quality
globus pallidus	UBERON:0001875	89.29	gold quality
cerebellar vermis	UBERON:0004720	88.41	gold quality
inferior olivary complex	UBERON:0002127	88.18	gold quality
CA1 field of hippocampus	UBERON:0003881	88.11	gold quality
subthalamic nucleus	UBERON:0001906	87.97	gold quality
putamen	UBERON:0001874	87.85	gold quality
caudate nucleus	UBERON:0001873	87.75	gold quality
endocervix	UBERON:0000458	87.68	gold quality
postcentral gyrus	UBERON:0002581	87.67	gold quality
adrenal gland	UBERON:0002369	87.58	gold quality
left adrenal gland	UBERON:0001234	87.48	gold quality
embryo	UBERON:0000922	87.45	gold quality
tibia	UBERON:0000979	87.40	gold quality
primary visual cortex	UBERON:0002436	87.07	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.06
E-CURD-119	yes	10.82

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA, MTA1

miRNA regulators (miRDB)

181 targeting RNF144A, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-9985	99.98	72.11	2939
HSA-LET-7F-2-3P	99.98	70.98	2588

Literature-anchored findings (GeneRIF, showing 9)

• Functional analysis of the mouse counterpart. (PMID:10431818)
• The regulation of DNA-PKcs by RNF144A is important for proper apoptotic response during DNA damage, suggesting a tumor suppressor function for RNF144A. (PMID:24979766)
• both proper membrane localization and self-association are important for RNF144A function. (PMID:26216882)
• These findings suggest that RNF144A is epigenetically silenced in breast cancer cells by promoter hypermethylation and MBD4. (PMID:29473320)
• role for RNF144A in the regulation of EGF/EGFR signaling and EGF-dependent cell proliferation. (PMID:30171075)
• RNF144A functions as a tumor suppressor in breast cancer through ubiquitin ligase activity-dependent regulation of stability and oncogenic functions of HSPA2. (PMID:31406303)
• Solution structure of the zinc finger domain of human RNF144A ubiquitin ligase. (PMID:32557973)
• RNF144a induces ERK-dependent cell death under oxidative stress via downregulation of vaccinia-related kinase 3. (PMID:33067254)
• RNF144A exerts tumor suppressor function in breast cancer through targeting YY1 for proteasomal degradation to downregulate GMFG expression. (PMID:35103856)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rnf144aa	ENSDARG00000020600
mus_musculus	Rnf144a	ENSMUSG00000020642
rattus_norvegicus	Rnf144a	ENSRNOG00000007370
caenorhabditis_elegans		WBGENE00015926
caenorhabditis_elegans		WBGENE00021721

Paralogs (9): ANKIB1 (ENSG00000001629), RNF14 (ENSG00000013561), RNF19A (ENSG00000034677), RNF19B (ENSG00000116514), RNF144B (ENSG00000137393), RNF217 (ENSG00000146373), ARIH1 (ENSG00000166233), ARIH2 (ENSG00000177479), PRKN (ENSG00000185345)

Protein

Protein identifiers

E3 ubiquitin-protein ligase RNF144A — P50876 (reviewed: P50876)

Alternative names: RING finger protein 144A, UbcM4-interacting protein 4, Ubiquitin-conjugating enzyme 7-interacting protein 4

All UniProt accessions (3): P50876, C9JLH4, H7C3G0

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin-protein ligase which accepts ubiquitin from E2 ubiquitin-conjugating enzymes UBE2L3 and UBE2L6 in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Mediates the ubiquitination and degradation of the DNA damage kinase PRKDC during DNA damage. Positively regulates DNA virus or exogenous cytosolic DNA-triggered innate immune response by mediating STING1 ubiquitination and increasing its ‘Lys-6’-linked ubiquitination and translocation from the endoplasmic reticulum to the Golgi leading to downstream signaling pathways. Plays a positive role in EGF-dependent cell proliferation by prolonging EGF/EGFR signaling during EGF stimulation through EGFR ubiquitination. Increases ERK activity independently of EGFR signaling by promoting polyubiquitination and subsequent degradation of VRK3 in the cytosol.

Subunit / interactions. Self-associates. Interacts with UBE2L3.

Subcellular location. Cell membrane. Cytoplasmic vesicle membrane. Endosome membrane. Endoplasmic reticulum membrane.

Post-translational modifications. Auto-ubiquitinated.

Domain organisation. Members of the RBR family are atypical E3 ligases. They interact with the E2 conjugating enzyme UBE2L3 and function like HECT-type E3 enzymes: they bind E2s via the first RING domain, but require an obligate trans-thiolation step during the ubiquitin transfer, requiring a conserved cysteine residue in the second RING domain.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the RBR family. RNF144 subfamily.

RefSeq proteins (7): NP_001336110, NP_001336111, NP_001336112, NP_001336113, NP_001336114, NP_001336115, NP_055561* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001841	Znf_RING	Domain
IPR002867	IBR_dom	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR017907	Znf_RING_CS	Conserved_site
IPR031127	E3_UB_ligase_RBR	Family
IPR044066	TRIAD_supradom	Domain

Pfam: PF01485, PF22191

Enzyme classification (BRENDA):

• EC 2.3.2.31 — RBR-type E3 ubiquitin transferase (BRENDA: 4 organisms, 35 substrates, 4 inhibitors, 0 Km, 0 kcat entries)

UniProt features (41 total): binding site 20, mutagenesis site 5, helix 4, zinc finger region 3, strand 3, chain 1, transmembrane region 1, sequence variant 1, turn 1, region of interest 1, active site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
1WIM	SOLUTION NMR
6L99	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P50876-F1	81.26	0.44

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): 198

Ligand- & substrate-binding residues (20): 46; 111; 116; 135; 138; 143; 146; 151; 156; 185; 188; 203 …

Mutagenesis-validated functional residues (5):

Position	Phenotype
20	complete loss of ubiquitin ligase activity and auto-ubiquitination; when associated with a-23.
23	complete loss of ubiquitin ligase activity and auto-ubiquitination; when associated with a-20.
252	preserves membrane localization but is defective ubiquitin ligase activity.
252	preserves membrane localization but is defective in self-association and ubiquitin ligase activity; when associated with
256	preserves membrane localization but is defective in self-association and ubiquitin ligase activity; when associated with

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8866654	E3 ubiquitin ligases ubiquitinate target proteins

MSigDB gene sets: 284 (showing top): FLECHNER_PBL_KIDNEY_TRANSPLANT_REJECTED_VS_OK_UP, chr2p25, AAGCCAT_MIR135A_MIR135B, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, MODULE_66, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_REGULATION_OF_IMMUNE_RESPONSE, ONKEN_UVEAL_MELANOMA_UP, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_PROTEIN_POLYUBIQUITINATION, GOZGIT_ESR1_TARGETS_UP, SCHLOSSER_SERUM_RESPONSE_DN, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_BIOTIC_STIMULUS

GO Biological Process (5): pattern recognition receptor signaling pathway (GO:0002221), ubiquitin-dependent protein catabolic process (GO:0006511), protein ubiquitination (GO:0016567), protein K6-linked ubiquitination (GO:0085020), cytoplasmic pattern recognition receptor signaling pathway (GO:0002753)

GO Molecular Function (7): zinc ion binding (GO:0008270), ubiquitin conjugating enzyme binding (GO:0031624), ubiquitin protein ligase activity (GO:0061630), ubiquitin-protein transferase activity (GO:0004842), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (12): ubiquitin ligase complex (GO:0000151), cytoplasm (GO:0005737), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), endosome membrane (GO:0010008), endosome (GO:0005768), endoplasmic reticulum (GO:0005783), membrane (GO:0016020), cytoplasmic vesicle membrane (GO:0030659), organelle membrane (GO:0031090), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Protein ubiquitination	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	3
endomembrane system	3
cellular anatomical structure	2
intracellular membrane-bounded organelle	2
membrane	2
cytoplasmic vesicle	2
innate immune response-activating signaling pathway	1
protein ubiquitination	1
modification-dependent protein catabolic process	1
protein modification by small protein conjugation	1
protein polyubiquitination	1
positive regulation of cytokine production	1
pattern recognition receptor signaling pathway	1
intracellular receptor signaling pathway	1
transition metal ion binding	1
ubiquitin-like protein conjugating enzyme binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
ubiquitin-like protein transferase activity	1
binding	1
catalytic activity	1
cation binding	1
intracellular protein-containing complex	1
transferase complex	1
intracellular anatomical structure	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cell periphery	1
endosome	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
vesicle membrane	1
membrane-bounded organelle	1
intracellular vesicle	1

Protein interactions and networks

STRING

747 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RNF144A	EIPR1	Q53HC9	582
RNF144A	RING1	Q06587	574
RNF144A	FAM227B	Q96M60	560
RNF144A	PRKDC	P78527	548
RNF144A	CMPK2	Q5EBM0	520
RNF144A	RNF223	E7ERA6	477
RNF144A	VXN	Q8TAG6	443
RNF144A	TRAPPC12	Q8WVT3	443
RNF144A	RNFT2	Q96EX2	431
RNF144A	RNFT1	Q5M7Z0	430
RNF144A	DCDC2C	A8MYV0	430
RNF144A	MRPL37	Q9BZE1	428
RNF144A	RNF183	Q96D59	402
RNF144A	RNF130	Q86XS8	397
RNF144A	TMEM129	A0AVI4	395

IntAct

44 interactions, top by confidence:

A	B	Type	Score
RNF144A	UBE2L3	psi-mi:“MI:0915”(physical association)	0.670
RNF144A	CKAP4	psi-mi:“MI:0915”(physical association)	0.590
SGTA	RNF144A	psi-mi:“MI:0915”(physical association)	0.560
RNF144A	SGTB	psi-mi:“MI:0915”(physical association)	0.560
SLC7A1	RNF144A	psi-mi:“MI:0915”(physical association)	0.560
RNF144A	SEC22A	psi-mi:“MI:0915”(physical association)	0.560
RNF144A	DGAT2L6	psi-mi:“MI:0915”(physical association)	0.560
RNF144A	PAQR6	psi-mi:“MI:0915”(physical association)	0.560
RNF144A	MFSD5	psi-mi:“MI:0915”(physical association)	0.560
YIF1A	RNF144A	psi-mi:“MI:0915”(physical association)	0.560
RNF144A	RFT1	psi-mi:“MI:0915”(physical association)	0.560
	RNF144A	psi-mi:“MI:0915”(physical association)	0.560
RNF144A	CYSLTR2	psi-mi:“MI:0915”(physical association)	0.370
UBE2L6	RNF144A	psi-mi:“MI:0915”(physical association)	0.370
HIP2	RNF144A	psi-mi:“MI:0915”(physical association)	0.370
RNF144A	UBE2H	psi-mi:“MI:0915”(physical association)	0.370
RNF144A	UBE2V1	psi-mi:“MI:0915”(physical association)	0.370
UBE2V2	RNF144A	psi-mi:“MI:0915”(physical association)	0.370
RNF144A	COL1A1	psi-mi:“MI:0914”(association)	0.350
SGTA	RNF144A	psi-mi:“MI:0915”(physical association)	0.000
SGTB	RNF144A	psi-mi:“MI:0915”(physical association)	0.000
SLC7A1	RNF144A	psi-mi:“MI:0915”(physical association)	0.000
SEC22A	RNF144A	psi-mi:“MI:0915”(physical association)	0.000
DGAT2L6	RNF144A	psi-mi:“MI:0915”(physical association)	0.000
PAQR6	RNF144A	psi-mi:“MI:0915”(physical association)	0.000
MFSD5	RNF144A	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (126): PRKDC (Affinity Capture-Western), PRKDC (Reconstituted Complex), RNF144A (Biochemical Activity), UBE2L3 (Reconstituted Complex), PRKDC (Biochemical Activity), CKAP4 (Affinity Capture-MS), RNF144A (Biochemical Activity), RNF144A (Affinity Capture-Western), CKAP4 (Affinity Capture-MS), RNF144A (Affinity Capture-RNA), UBC (Biochemical Activity), RNF144A (Affinity Capture-Western), UBE2L3 (Reconstituted Complex), RNF144A (Reconstituted Complex), RNF144A (Biochemical Activity)

ESM2 similar proteins: A2VEA3, B1H1E4, D3Z7P3, F1LSG8, O89050, O94925, P13264, P50876, P97834, Q07G17, Q08211, Q12800, Q13042, Q28141, Q28D01, Q2NL67, Q32NS4, Q3MHJ2, Q4R9A8, Q4VC33, Q5F398, Q5NVP9, Q5R532, Q5R874, Q5RB35, Q5RBB8, Q5RBN9, Q5RKJ1, Q6AYU1, Q6GR10, Q6NRT5, Q6NW85, Q6PFJ9, Q7L5Y9, Q7SXR3, Q7Z6J6, Q86TJ2, Q8C6G8, Q8CI71, Q8R349

Diamond homologs: A2VEA3, A5PK27, B1H1E4, O01965, O76924, O95376, P0C8K8, P36113, P50876, Q22431, Q32NS4, Q54CX4, Q5UQ35, Q6NW85, Q6PFJ9, Q6T486, Q7Z419, Q84RQ8, Q84RR0, Q84RR2, Q8BKD6, Q8L829, Q8W468, Q925F3, Q94981, Q949V6, Q9C5A4, Q9LVW9, Q9LVX0, Q9P3U4, Q9SKC2, Q9SKC3, Q9SKC4, Q9Y4X5, Q9Z1K5, Q9Z1K6, A4IIY1, Q5RFV4, Q6DH94, Q04638

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	RNF144A	ubiquitination
RNF144A	“down-regulates quantity by destabilization”	PRKDC	polyubiquitination
RNF144A	“down-regulates quantity by destabilization”	PARP1	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 18 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
Antigen processing: Ubiquitination & Proteasome degradation	5	13.3×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
protein polyubiquitination	5	41.2×	8e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	41
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2685 predictions. Top by Δscore:

Variant	Effect	Δscore
2:6978840:G:GG	donor_gain	1.0000
2:6997001:G:GT	donor_gain	1.0000
2:6997001:G:T	donor_gain	1.0000
2:7024367:A:AG	acceptor_gain	1.0000
2:7024368:G:GA	acceptor_gain	1.0000
2:7024368:GT:G	acceptor_gain	1.0000
2:7024368:GTGCT:G	acceptor_gain	1.0000
2:7024513:GGAC:G	donor_gain	1.0000
2:7024514:GAC:G	donor_gain	1.0000
2:7024514:GACG:G	donor_gain	1.0000
2:7024517:G:GG	donor_gain	1.0000
2:7024521:G:GG	donor_gain	1.0000
2:7039763:G:GT	donor_gain	1.0000
2:7039797:G:GT	donor_gain	1.0000
2:7039797:G:T	donor_gain	1.0000
2:6917618:CCCAG:C	donor_loss	0.9900
2:6917619:CCAGG:C	donor_loss	0.9900
2:6917620:CAG:C	donor_loss	0.9900
2:6917621:AG:A	donor_loss	0.9900
2:6917622:GG:G	donor_loss	0.9900
2:6917623:GTAGA:G	donor_loss	0.9900
2:6917624:T:G	donor_loss	0.9900
2:6974572:AT:A	acceptor_gain	0.9900
2:6974573:T:TA	acceptor_gain	0.9900
2:6974574:G:A	acceptor_gain	0.9900
2:6978838:GA:G	donor_gain	0.9900
2:6996915:GACT:G	acceptor_gain	0.9900
2:7012167:A:T	donor_gain	0.9900
2:7024363:CCACA:C	acceptor_loss	0.9900
2:7024364:CACAG:C	acceptor_loss	0.9900

AlphaMissense

1923 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:6996984:T:C	C20R	1.000
2:6996985:G:A	C20Y	1.000
2:6996986:C:G	C20W	1.000
2:6996993:T:C	C23R	1.000
2:7014511:T:C	C65R	1.000
2:7024412:T:A	C185S	1.000
2:7024412:T:C	C185R	1.000
2:7024413:G:C	C185S	1.000
2:7024421:T:A	C188S	1.000
2:7024421:T:C	C188R	1.000
2:7024422:G:C	C188S	1.000
2:7024451:T:C	C198R	1.000
2:7024452:G:A	C198Y	1.000
2:7024461:T:C	M201T	1.000
2:7024466:T:A	C203S	1.000
2:7024466:T:C	C203R	1.000
2:7024467:G:A	C203Y	1.000
2:7024467:G:C	C203S	1.000
2:7024467:G:T	C203F	1.000
2:7024468:C:G	C203W	1.000
2:7024475:T:A	C206S	1.000
2:7024475:T:C	C206R	1.000
2:7024476:G:A	C206Y	1.000
2:7024476:G:C	C206S	1.000
2:7024477:C:G	C206W	1.000
2:7024487:T:C	F210L	1.000
2:7024488:T:C	F210S	1.000
2:7024488:T:G	F210C	1.000
2:7024489:C:A	F210L	1.000
2:7024489:C:G	F210L	1.000

dbSNP variants (sampled 300 via entrez): RS1000024619 (2:7022337 C>T), RS1000026833 (2:7059003 G>A,T), RS1000040602 (2:6980989 A>G), RS1000047879 (2:6967149 T>C), RS1000067977 (2:6998646 A>AGCT), RS1000073570 (2:6961881 T>A,C), RS1000092034 (2:6942015 C>A), RS1000093873 (2:7040408 T>C), RS1000094587 (2:6937688 C>T), RS1000123073 (2:6942192 G>C), RS1000125523 (2:7048969 A>C), RS1000137456 (2:7017139 C>A), RS1000164372 (2:6983730 G>A), RS1000168944 (2:7020791 A>G), RS1000177789 (2:7052254 T>C)

Disease associations

OMIM: gene MIM:619454 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST000618_32	Response to antipsychotic treatment	2.000000e-07
GCST003089_1	Manic episodes in bipolar disorder	6.000000e-06
GCST004862_213	Itch intensity from mosquito bite adjusted by bite size	4.000000e-07
GCST006409_42	Allergic rhinitis	1.000000e-14
GCST006530_1	Esophageal adenocarcinoma x smoking interaction	2.000000e-07
GCST007354_23	Intracranial aneurysm	4.000000e-14
GCST007521_2	Asthma-chronic obstructive pulmonary disease overlap syndrome	3.000000e-06
GCST007994_16	Asthma (age of onset)	2.000000e-06
GCST007995_13	Asthma (childhood onset)	2.000000e-13
GCST012484_17	Cerebral amyloid angiopathy x APOEe4 status interaction in Alzheimer’s disease	5.000000e-06
GCST90014325_8	Asthma	8.000000e-18

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0007706	manic or hypomanic episode
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0008378	mosquito bite reaction size measurement
EFO:0006527	smoking status measurement
EFO:0009759	Chronic Obstructive Asthma
EFO:0007659	APOE carrier status

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation, increases expression	4
sodium arsenite	affects methylation, decreases expression	2
Arsenic Trioxide	increases expression, affects binding, decreases reaction	2
Calcitriol	decreases expression, increases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Valproic Acid	increases expression	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
uranyl acetate	affects expression	1
bisphenol A	increases methylation	1
trichostatin A	increases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
periodate-oxidized adenosine	affects expression	1
aflatoxin B2	increases methylation	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
K 7174	decreases expression	1
abrine	decreases expression	1
bisphenol S	decreases methylation	1
jinfukang	increases expression	1
Resveratrol	decreases expression	1
Allergens	increases expression	1
Arsenic	decreases methylation	1
Azathioprine	decreases expression	1
Benzene	decreases expression	1
Cisplatin	decreases expression	1
Demecolcine	decreases expression	1
Doxorubicin	decreases expression	1
Lipopolysaccharides	increases expression, affects response to substance	1

Clinical trials (associated diseases)

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