RNF138

Summary

RNF138 (ring finger protein 138, HGNC:17765) is a protein-coding gene on chromosome 18q12.1, encoding E3 ubiquitin-protein ligase RNF138 (Q8WVD3). E3 ubiquitin-protein ligase involved in DNA damage response by promoting DNA resection and homologous recombination.

The protein encoded by this gene contains a RING finger, a motif present in a variety of functionally distinct proteins and known to be involved in protein-DNA and protein-protein interactions. Alternatively spliced transcript variants encoding distinct isoforms have been observed.

Source: NCBI Gene 51444 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 114 total
• MANE Select transcript: NM_016271

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17765
Approved symbol	RNF138
Name	ring finger protein 138
Location	18q12.1
Locus type	gene with protein product
Status	Approved
Aliases	STRIN, NARF
Ensembl gene	ENSG00000134758
Ensembl biotype	protein_coding
OMIM	616319
Entrez	51444

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 13 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000257190, ENST00000261593, ENST00000577999, ENST00000578107, ENST00000578914, ENST00000580499, ENST00000580519, ENST00000583733, ENST00000585103, ENST00000858584, ENST00000858585, ENST00000858586, ENST00000858587, ENST00000858588, ENST00000911687, ENST00000967832

RefSeq mRNA: 3 — MANE Select: NM_016271 NM_001191324, NM_016271, NM_198128

CCDS: CCDS11903, CCDS11904

Canonical transcript exons

ENST00000261593 — 8 exons

Exon	Start	End
ENSE00000916047	32113745	32113860
ENSE00000916048	32123518	32123574
ENSE00000916049	32124734	32124845
ENSE00000916050	32126693	32126800
ENSE00001818146	32091874	32092235
ENSE00001825499	32129119	32131561
ENSE00003527166	32111754	32111919
ENSE00003622366	32092700	32092886

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 98.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 36.8911 / max 492.5848, expressed in 1814 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
169863	16.8898	1769
169866	8.7706	1710
169864	7.5969	1561
169867	2.9166	1091
169868	0.6102	306
169865	0.1071	44

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	98.06	gold quality
secondary oocyte	CL:0000655	97.57	gold quality
right testis	UBERON:0004534	97.38	gold quality
left testis	UBERON:0004533	97.36	gold quality
testis	UBERON:0000473	96.47	gold quality
oocyte	CL:0000023	96.34	gold quality
bone marrow	UBERON:0002371	95.98	gold quality
mucosa of sigmoid colon	UBERON:0004993	95.52	gold quality
colonic mucosa	UBERON:0000317	95.23	gold quality
bronchial epithelial cell	CL:0002328	95.22	gold quality
bone element	UBERON:0001474	95.00	gold quality
ventricular zone	UBERON:0003053	94.53	gold quality
jejunal mucosa	UBERON:0000399	94.39	gold quality
cortical plate	UBERON:0005343	94.27	gold quality
bone marrow cell	CL:0002092	94.20	gold quality
epithelium of nasopharynx	UBERON:0001951	94.20	gold quality
epithelium of bronchus	UBERON:0002031	94.07	gold quality
mononuclear cell	CL:0000842	94.01	gold quality
monocyte	CL:0000576	94.00	gold quality
bronchus	UBERON:0002185	93.89	gold quality
leukocyte	CL:0000738	93.77	gold quality
embryo	UBERON:0000922	93.64	gold quality
ganglionic eminence	UBERON:0004023	93.59	gold quality
adult organism	UBERON:0007023	93.46	gold quality
trabecular bone tissue	UBERON:0002483	93.34	gold quality
germinal epithelium of ovary	UBERON:0001304	92.92	gold quality
mucosa of paranasal sinus	UBERON:0005030	92.74	gold quality
palpebral conjunctiva	UBERON:0001812	92.70	gold quality
choroid plexus epithelium	UBERON:0003911	92.36	gold quality
parietal pleura	UBERON:0002400	92.29	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	31.17
E-ANND-3	yes	5.79

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

203 targeting RNF138, 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-8485	100.00	77.57	4731
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3613-3P	100.00	76.36	7965
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-3924	100.00	72.09	2394
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753

Literature-anchored findings (GeneRIF, showing 17)

• NARF functions as a novel ubiquitin-ligase to regulate ubiquitylation and degradation of T cell factor/lymphoid enhancer factor (PMID:16714285)
• The RNF138 gene is highly expressed in glioma tissue and glioma cell lines and plays an important role in glioma cell proliferation, apoptosis, and cell cycle. (PMID:22155992)
• Data show that ubiquitin E3 ligase RNF138 regulates Ku80 antigen ubiquitylation in response to DNA damage. (PMID:26502055)
• Data show that ubiquitin E2 enzymes UBE2D1/2/3 and E3 ligase RNF138 accumulate at DNA-damage sites and act at early resection stages by promoting CtIP protein ubiquitylation and accrual. (PMID:26502057)
• RNF138 is a newly identified regulatory component of the HR mediated DNA repair pathway that has implications toward understanding how ubiquitination modifies the functions of the RAD51 paralog protein complex (PMID:27161866)
• Rad51d mediated by E3 Ligase Rnf138 has a role in the homologous recombination repair pathway (PMID:27195665)
• This study identify RNF138 as the E3 ubiquitin ligase promoting EA2-associated aberrant degradation of human CaV2.1 protein. (PMID:28167673)
• The role of RNF138 in glioblastoma and identify rpS3 as a crucial substrate of ubiquitination by RNF138, which underlies the radioresistance of glioblastoma. (PMID:29371697)
• data suggest that RNF138 modulates the cisplatin resistance in the GC cells, thus serving as a potential drug target to challenge chemotherapy failure. In addition, RNF138 can also be used as a marker to monitor the development of cisplatin resistance in GC treatment. (PMID:30260263)
• Study suggested that RNF138 was important for the proliferation, migration and invasion of glioma cells. Its downregulation inhibited the process of EMT by suppressing Erk signaling pathway in glioma. (PMID:30272353)
• Silencing microRNA29b3p expression protects human trabecular meshwork cells against oxidative injury via upregulation of RNF138 to activate the ERK pathway. (PMID:33907817)
• African Swine Fever Virus pI215L Negatively Regulates cGAS-STING Signaling Pathway through Recruiting RNF138 to Inhibit K63-Linked Ubiquitination of TBK1. (PMID:34759016)
• RING finger 138 deregulation distorts NF-small ka, CyrillicB signaling and facilities colitis switch to aggressive malignancy. (PMID:35697692)
• The Ubiquitin Ligase RNF138 Cooperates with CtIP to Stimulate Resection of Complex DNA Double-Strand Breaks in Human G1-Phase Cells. (PMID:36010636)
• RNF138 inhibits late inflammatory gene transcription through degradation of SMARCC1 of the SWI/SNF complex. (PMID:36800290)
• The role of RNF138 in DNA end resection is regulated by ubiquitylation and CDK phosphorylation. (PMID:38309501)
• Ring finger protein 138 inhibits transcription factor C/EBPalpha protein turnover leading to differentiation arrest in acute myeloid leukemia. (PMID:38666590)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rnf138	ENSMUSG00000024317
rattus_norvegicus	AABR07031480.1	ENSRNOG00000015645

Paralogs (4): RNF125 (ENSG00000101695), RNF114 (ENSG00000124226), RNF166 (ENSG00000158717), RNF180 (ENSG00000164197)

Protein

Protein identifiers

E3 ubiquitin-protein ligase RNF138 — Q8WVD3 (reviewed: Q8WVD3)

Alternative names: Nemo-like kinase-associated RING finger protein, RING finger protein 138, RING-type E3 ubiquitin transferase RNF138

All UniProt accessions (6): A0A140VJT9, Q8WVD3, J3KRU4, J3KSI2, J3QKM8, J3QLQ3

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin-protein ligase involved in DNA damage response by promoting DNA resection and homologous recombination. Recruited to sites of double-strand breaks following DNA damage and specifically promotes double-strand break repair via homologous recombination. Two different, non-exclusive, mechanisms have been proposed. According to a report, regulates the choice of double-strand break repair by favoring homologous recombination over non-homologous end joining (NHEJ): acts by mediating ubiquitination of XRCC5/Ku80, leading to remove the Ku complex from DNA breaks, thereby promoting homologous recombination. According to another report, cooperates with UBE2Ds E2 ubiquitin ligases (UBE2D1, UBE2D2, UBE2D3 or UBE2D4) to promote homologous recombination by mediating ubiquitination of RBBP8/CtIP. Together with NLK, involved in the ubiquitination and degradation of TCF/LEF. Also exhibits auto-ubiquitination activity in combination with UBE2K. May act as a negative regulator in the Wnt/beta-catenin-mediated signaling pathway.

Subunit / interactions. Interacts with NLK. Interacts with XRCC5/Ku80. Interacts with RBBP8/CtIP.

Subcellular location. Chromosome.

Post-translational modifications. Auto-ubiquitinated.

Domain organisation. The zinc finger domains (C2H2-type and C2HC-type zinc fingers) bind DNA and mediate recruitment to double-strand break sites. They show strong preference for DNA with 5’- or 3’-single-stranded overhangs, while they do not bind blunt-ended double-stranded DNA or poly(ADP-ribose) (PAR) polymers.

Pathway. Protein modification; protein ubiquitination.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8WVD3-1	1	yes
Q8WVD3-2	2

RefSeq proteins (3): NP_001178253, NP_057355, NP_937761 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001841	Znf_RING	Domain
IPR008598	Di19_Zn-bd	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR034734	ZF_C2HC_RNF	Domain
IPR052498	E3_ubiq-protein_ligase_RNF138	Family

Pfam: PF05605, PF13923, PF18574

UniProt features (21 total): binding site 4, zinc finger region 4, mutagenesis site 3, modified residue 2, sequence conflict 2, initiator methionine 1, chain 1, splice variant 1, sequence variant 1, domain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WVD3-F1	78.86	0.43

Functional residue map

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

Ligand- & substrate-binding residues (4): 101; 105; 86; 89

Post-translational modifications (2): 2, 142

Mutagenesis-validated functional residues (3):

Position	Phenotype
18–21	catalytic inactive mutant that abolishes ability to promote dna resection and homologous recombination.
18	catalytic inactive mutant that abolishes ability to promote dna resection and homologous recombination; when associated
54	catalytic inactive mutant that abolishes ability to promote dna resection and homologous recombination; when associated

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation
R-HSA-1280218	Adaptive Immune System
R-HSA-168256	Immune System
R-HSA-983169	Class I MHC mediated antigen processing & presentation

MSigDB gene sets: 416 (showing top): GSE45365_NK_CELL_VS_BCELL_UP, TGGTGCT_MIR29A_MIR29B_MIR29C, AAGCAAT_MIR137, TAATAAT_MIR126, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_RESPONSE_TO_PEPTIDE, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GOLDRATH_IMMUNE_MEMORY, AAGCCAT_MIR135A_MIR135B, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, ATGTTAA_MIR302C, GNF2_ANK1

GO Biological Process (7): double-strand break repair via homologous recombination (GO:0000724), DNA double-strand break processing involved in repair via single-strand annealing (GO:0010792), Wnt signaling pathway (GO:0016055), protein ubiquitination (GO:0016567), cellular response to leukemia inhibitory factor (GO:1990830), DNA repair (GO:0006281), DNA damage response (GO:0006974)

GO Molecular Function (8): single-stranded DNA binding (GO:0003697), zinc ion binding (GO:0008270), protein kinase binding (GO:0019901), ubiquitin protein ligase activity (GO:0061630), DNA binding (GO:0003677), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (3): nucleus (GO:0005634), site of double-strand break (GO:0035861), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Class I MHC mediated antigen processing & presentation	1
Immune System	1
Adaptive Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
recombinational repair	1
double-strand break repair	1
DNA double-strand break processing	1
double-strand break repair via single-strand annealing	1
cell surface receptor signaling pathway	1
protein modification by small protein conjugation	1
cellular response to cytokine stimulus	1
response to leukemia inhibitory factor	1
DNA metabolic process	1
DNA damage response	1
cellular response to stress	1
DNA binding	1
transition metal ion binding	1
kinase binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
nucleic acid binding	1
binding	1
catalytic activity	1
cation binding	1
intracellular membrane-bounded organelle	1
site of DNA damage	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

3163 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RNF138	NLK	Q9UBE8	681
RNF138	RNF8	O76064	605
RNF138	RNF126	Q9BV68	601
RNF138	RBBP8	Q99708	465
RNF138	TTC36	A6NLP5	446
RNF138	RNF14	Q9UBS8	406
RNF138	A0A0A6YYA0	A0A0A6YYA0	405
RNF138	TRAPPC8	Q9Y2L5	404
RNF138	RNF168	Q8IYW5	398
RNF138	STK33	Q9BYT3	388
RNF138	TICAM2	Q86XR7	384
RNF138	XRCC5	P13010	378
RNF138	STAT5A	P42229	376
RNF138	PELI1	Q96FA3	374
RNF138	NEDD8	Q15843	362

IntAct

133 interactions, top by confidence:

A	B	Type	Score
UBE2K	RNF138	psi-mi:“MI:0915”(physical association)	0.940
RNF138	UBE2K	psi-mi:“MI:0915”(physical association)	0.940
COPS8	COPS2	psi-mi:“MI:0914”(association)	0.850
FRYL	YWHAZ	psi-mi:“MI:0914”(association)	0.710
FAM136A	RBFOX3	psi-mi:“MI:0914”(association)	0.640
NAP1L5	IQGAP1	psi-mi:“MI:0914”(association)	0.640
UBE2K	ZFTRAF1	psi-mi:“MI:0914”(association)	0.620
MPDZ	SMCHD1	psi-mi:“MI:0914”(association)	0.590
TSTD2	RNF138	psi-mi:“MI:0915”(physical association)	0.560
EFEMP2	RNF138	psi-mi:“MI:0915”(physical association)	0.560
RNF138	NTAQ1	psi-mi:“MI:0915”(physical association)	0.560
ADRB2	RNF138	psi-mi:“MI:0915”(physical association)	0.560
DMWD	RNF138	psi-mi:“MI:0915”(physical association)	0.560
RNF138		psi-mi:“MI:0915”(physical association)	0.560
RNF138	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
FXN	RNF138	psi-mi:“MI:0915”(physical association)	0.560
GRN	RNF138	psi-mi:“MI:0915”(physical association)	0.560
GRIN2C	RNF138	psi-mi:“MI:0915”(physical association)	0.560
RNF138	GSN	psi-mi:“MI:0915”(physical association)	0.560
RNF138	HRAS	psi-mi:“MI:0915”(physical association)	0.560
LMNA	RNF138	psi-mi:“MI:0915”(physical association)	0.560
NF2	RNF138	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (151): UBE2K (Affinity Capture-MS), RNF138 (Affinity Capture-Western), LEF1 (Biochemical Activity), UBE2K (Affinity Capture-Western), RNF138 (Two-hybrid), RNF138 (Affinity Capture-MS), RNF138 (Affinity Capture-MS), RNF138 (Affinity Capture-MS), RNF138 (Affinity Capture-MS), C6orf165 (Two-hybrid), TCF7L2 (Biochemical Activity), RNF138 (Affinity Capture-Western), RNF138 (Affinity Capture-MS), RNF138 (Affinity Capture-MS), RNF138 (Affinity Capture-Western)

ESM2 similar proteins: A0A1L8GLK3, A0A974CYQ5, A2AHJ4, A5WW08, A7XUJ6, B5DF45, B6CJY4, B6CJY5, D2HWM5, P54731, P70196, Q1L721, Q1LZE1, Q28DL4, Q32LN5, Q3KPU8, Q3MV19, Q3U9F6, Q3ZCC3, Q4VBT5, Q5E9J6, Q5F3B2, Q5FWP4, Q5NU14, Q5NVC7, Q5RF77, Q6AYH3, Q6DJN2, Q6GPB6, Q6J1I7, Q6P256, Q6PCD5, Q6RI45, Q7T321, Q80UY2, Q8CIK8, Q8JFF3, Q8WVD3, Q921C3, Q95KF1

Diamond homologs: O13033, P15918, P15919, P24271, P34088, Q1L721, Q867B5, Q8WVD3, Q90523, Q91187, Q91829, B0BLU1, E7FAP1, F6UA42, P15533, Q1LZE1, Q32LN5, Q3KPU8, Q3U9F6, Q4U5R4, Q5F3B2, Q6GPB6, Q6INS5, Q6J1I7, Q6J1I8, Q6J212, Q6J2U6, Q7T321, Q80UY2, Q8R0K2, Q95KF1, Q95RX5, Q96A37, Q96EQ8, Q99PD2, Q9BZY9, Q9CQE0, Q9D9R0, Q9ET26, Q9FF61

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	RNF138	ubiquitination
RNF138	“down-regulates quantity by destabilization”	TCF7L2	polyubiquitination
UBE2K	“up-regulates activity”	RNF138	binding
RNF138	“down-regulates quantity by destabilization”	LEF1	polyubiquitination
CDK2	“up-regulates activity”	RNF138	phosphorylation
CDK1	“up-regulates activity”	RNF138	phosphorylation
RNF138	“down-regulates quantity by destabilization”	RAD51D	ubiquitination
ATM	“up-regulates activity”	RNF138	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 101 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.

GO biological processes:

GO term	Partners	Fold	FDR
protein neddylation	5	41.3×	1e-04
regulation of cell cycle	8	7.0×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	78
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3207 predictions. Top by Δscore:

Variant	Effect	Δscore
17:82464285:AGAAG:A	acceptor_gain	1.0000
17:82464286:GAAGG:G	acceptor_gain	1.0000
17:82468758:TTCTA:T	acceptor_loss	1.0000
17:82468759:TCTAG:T	acceptor_loss	1.0000
17:82468760:CTA:C	acceptor_loss	1.0000
17:82468761:TA:T	acceptor_loss	1.0000
17:82468762:A:AG	acceptor_gain	1.0000
17:82468762:AGAA:A	acceptor_loss	1.0000
17:82468763:G:GA	acceptor_gain	1.0000
17:82468763:GA:G	acceptor_gain	1.0000
17:82468763:GAA:G	acceptor_gain	1.0000
17:82468763:GAAA:G	acceptor_gain	1.0000
17:82468763:GAAAT:G	acceptor_gain	1.0000
17:82468897:G:GG	donor_gain	1.0000
17:82468898:TGAGT:T	donor_loss	1.0000
17:82468899:GAG:G	donor_loss	1.0000
17:82472560:GCAG:G	acceptor_loss	1.0000
17:82472562:A:AC	acceptor_loss	1.0000
17:82472562:A:AG	acceptor_gain	1.0000
17:82472562:AG:A	acceptor_gain	1.0000
17:82472562:AGG:A	acceptor_gain	1.0000
17:82472562:AGGG:A	acceptor_gain	1.0000
17:82472563:G:GC	acceptor_gain	1.0000
17:82472563:GG:G	acceptor_gain	1.0000
17:82472563:GGG:G	acceptor_gain	1.0000
17:82472563:GGGG:G	acceptor_gain	1.0000
17:82472563:GGGGT:G	acceptor_gain	1.0000
17:82472649:GCACA:G	donor_gain	1.0000
17:82472654:G:GG	donor_gain	1.0000
17:82472659:G:GT	donor_gain	1.0000

AlphaMissense

1637 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:32092828:T:C	C18R	1.000
18:32092830:C:G	C18W	1.000
18:32092837:T:C	C21R	1.000
18:32092859:C:A	P28H	1.000
18:32111755:T:C	F38L	1.000
18:32111757:C:A	F38L	1.000
18:32111757:C:G	F38L	1.000
18:32111758:T:C	C39R	1.000
18:32111759:G:A	C39Y	1.000
18:32111767:T:A	C42S	1.000
18:32111767:T:C	C42R	1.000
18:32111768:G:C	C42S	1.000
18:32111803:T:C	C54R	1.000
18:32111899:T:C	C86R	1.000
18:32113781:T:C	C105R	1.000
18:32124759:T:C	C159R	1.000
18:32126696:T:C	C189R	1.000
18:32126698:T:G	C189W	1.000
18:32126705:T:C	C192R	1.000
18:32126763:T:C	L211P	1.000
18:32092828:T:A	C18S	0.999
18:32092829:G:A	C18Y	0.999
18:32092829:G:C	C18S	0.999
18:32092829:G:T	C18F	0.999
18:32092835:T:A	V20D	0.999
18:32092837:T:A	C21S	0.999
18:32092838:G:A	C21Y	0.999
18:32092838:G:C	C21S	0.999
18:32092838:G:T	C21F	0.999
18:32092839:T:G	C21W	0.999

dbSNP variants (sampled 300 via entrez): RS1000172075 (18:32097863 G>A,T), RS1000233669 (18:32109247 A>G), RS1000292205 (18:32092402 G>A), RS1000342298 (18:32103773 C>T), RS1000396724 (18:32103004 A>G), RS1000490141 (18:32109463 A>G), RS1000563506 (18:32127426 A>C), RS1000582588 (18:32091862 C>G,T), RS1000680624 (18:32101849 C>T), RS1000704553 (18:32092755 C>T), RS1000835761 (18:32107843 A>C,T), RS1000841869 (18:32107696 A>G), RS1000944329 (18:32114937 T>C), RS1001122903 (18:32106551 T>A), RS1001135796 (18:32103949 A>G)

Disease associations

OMIM: gene MIM:616319 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST003084_6	Glucocorticoid-induced osteonecrosis	6.000000e-06
GCST008497_3	Change in neurofilament light levels	2.000000e-06
GCST010057_6	Lung function	3.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004314	forced expiratory volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, decreases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Valproic Acid	decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
triphenyl phosphate	affects expression	1
lead acetate	affects cotreatment, decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
PCI 5002	increases expression, affects cotreatment	1
Bortezomib	increases expression	1
Sunitinib	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	increases expression	1
Calcitriol	decreases expression, affects cotreatment	1
Cisplatin	affects cotreatment, decreases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Gold	decreases expression	1
Mercury	increases expression	1
Phenobarbital	affects expression	1
Testosterone	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Zinc	affects cotreatment, increases expression	1
Cyclosporine	increases expression	1
Antirheumatic Agents	decreases expression	1
Cadmium Chloride	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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