ZNRF1

Summary

ZNRF1 (zinc and ring finger 1, HGNC:18452) is a protein-coding gene on chromosome 16q23.1, encoding E3 ubiquitin-protein ligase ZNRF1 (Q8ND25). E3 ubiquitin-protein ligase that plays a role in different processes including cell differentiation, receptor recycling or regulation of inflammation.

This gene encodes an E3 ubiquitin-protein ligase that plays a role in neural-cell differentiation. Overexpression of this gene causes neurite-like elongation. The encoded protein contains both a zinc finger and a RING finger motif and is localized in the endosome/lysosome compartment, indicating that it may be involved in ubiquitin-mediated protein modification, and in synaptic vessicle membranes in neurons.

Source: NCBI Gene 84937 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 22 total
• MANE Select transcript: NM_032268

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18452
Approved symbol	ZNRF1
Name	zinc and ring finger 1
Location	16q23.1
Locus type	gene with protein product
Status	Approved
Aliases	nin283, FLJ14846, DKFZp434E229
Ensembl gene	ENSG00000186187
Ensembl biotype	protein_coding
OMIM	612060
Entrez	84937

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 19 protein_coding, 3 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000320619, ENST00000335325, ENST00000564320, ENST00000566244, ENST00000566250, ENST00000567962, ENST00000568351, ENST00000568494, ENST00000568511, ENST00000568844, ENST00000579084, ENST00000881833, ENST00000881834, ENST00000881835, ENST00000881836, ENST00000881837, ENST00000881838, ENST00000926890, ENST00000926891, ENST00000926892, ENST00000926893, ENST00000959615, ENST00000959616, ENST00000959617

RefSeq mRNA: 1 — MANE Select: NM_032268 NM_032268

CCDS: CCDS10912

Canonical transcript exons

ENST00000335325 — 5 exons

Exon	Start	End
ENSE00001241506	75107733	75110994
ENSE00002603559	74999024	75000095
ENSE00003634491	75106482	75106571
ENSE00003680047	75093572	75093667
ENSE00003785422	75104784	75104889

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 97.71.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 33.1291 / max 563.7728, expressed in 1801 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
155011	30.7059	1800
155012	2.3466	972
155015	0.0766	26

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	97.71	gold quality
thymus	UBERON:0002370	97.49	gold quality
cortical plate	UBERON:0005343	97.23	gold quality
pharyngeal mucosa	UBERON:0000355	96.26	gold quality
esophagus squamous epithelium	UBERON:0006920	95.95	gold quality
body of tongue	UBERON:0011876	95.45	gold quality
secondary oocyte	CL:0000655	95.25	gold quality
gingival epithelium	UBERON:0001949	95.16	gold quality
pancreatic ductal cell	CL:0002079	95.05	gold quality
quadriceps femoris	UBERON:0001377	94.95	gold quality
vastus lateralis	UBERON:0001379	94.79	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	94.66	gold quality
tongue	UBERON:0001723	94.56	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.54	gold quality
skeletal muscle tissue	UBERON:0001134	94.35	gold quality
esophagus mucosa	UBERON:0002469	94.27	gold quality
ganglionic eminence	UBERON:0004023	93.76	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	93.76	gold quality
biceps brachii	UBERON:0001507	93.73	gold quality
gingiva	UBERON:0001828	93.60	gold quality
pylorus	UBERON:0001166	93.53	gold quality
tibialis anterior	UBERON:0001385	93.35	gold quality
nasal cavity epithelium	UBERON:0005384	93.35	gold quality
superior surface of tongue	UBERON:0007371	93.19	gold quality
gastrocnemius	UBERON:0001388	92.83	gold quality
nipple	UBERON:0002030	92.76	gold quality
deltoid	UBERON:0001476	92.73	gold quality
left testis	UBERON:0004533	92.72	gold quality
right testis	UBERON:0004534	92.69	gold quality
muscle tissue	UBERON:0002385	92.55	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.01

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

158 targeting ZNRF1, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-9983-3P	99.94	71.48	3631

Literature-anchored findings (GeneRIF, showing 6)

• data suggest that ZNRF proteins play a role in the establishment and maintenance of neuronal transmission and plasticity via their ubiquitin ligase activity (PMID:14561866)
• These results suggest that ZNRF1 mediates regulation of neuritogenesis via interaction with tubulin. (PMID:19737534)
• ZNRF1 and ZNRF2 are new players in regulation of the ubiquitous Na(+)/K(+)ATPase that is tuned to changing demands in many physiological contexts. (PMID:22797923)
• rs17684886 (ZNRF1) and rs599019 (COLEC12) are associated with diabetic retinopathy and rs6427247 (SCYL1BP1) and rs899036 (API5) are associated with severe diabetic retinopathy in Chinese patients with type 2 diabetes (PMID:25819896)
• as a consequence of its high E2 affinity, an excess of ZNRF1 inhibits Ube2N-mediated ubiquitination at concentrations >/=500 nM instead of showing enhanced ubiquitination (PMID:29626159)
• LZTFL1 inhibits kidney tumor cell growth by destabilizing AKT through ZNRF1-mediated ubiquitin proteosome pathway. (PMID:36966254)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	znrf1	ENSDARG00000020475
mus_musculus	Znrf1	ENSMUSG00000033545
rattus_norvegicus	Znrf1	ENSRNOG00000019028

Paralogs (2): RNF11 (ENSG00000123091), ZNRF2 (ENSG00000180233)

Protein

Protein identifiers

E3 ubiquitin-protein ligase ZNRF1 — Q8ND25 (reviewed: Q8ND25)

Alternative names: Nerve injury-induced gene 283 protein, RING-type E3 ubiquitin transferase ZNRF1, Zinc/RING finger protein 1

All UniProt accessions (4): Q8ND25, H3BRB6, H3BUF0, J3KTB9

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin-protein ligase that plays a role in different processes including cell differentiation, receptor recycling or regulation of inflammation. Mediates the ubiquitination of AKT1 and GLUL, thereby playing a role in neuron cells differentiation. Plays a role in the establishment and maintenance of neuronal transmission and plasticity. Regulates Schwann cells differentiation by mediating ubiquitination of GLUL. Promotes neurodegeneration by mediating ‘Lys-48’-linked polyubiquitination and subsequent degradation of AKT1 in axons: degradation of AKT1 prevents AKT1-mediated phosphorylation of GSK3B, leading to GSK3B activation and phosphorylation of DPYSL2/CRMP2 followed by destabilization of microtubule assembly in axons. Ubiquitinates the Na(+)/K(+) ATPase alpha-1 subunit/ATP1A1 and thereby influences its endocytosis and/or degradation. Controls ligand-induced EGFR signaling via mediating receptor ubiquitination and recruitment of the ESCRT machinery. Acts as a negative feedback mechanism controlling TLR3 trafficking by mediating TLR3 ‘Lys-63’-linked polyubiquitination to reduce type I IFN production. Modulates inflammation by promoting caveolin-1/CAV1 ubiquitination and degradation to regulate TLR4-activated immune response.

Subunit / interactions. Interacts with AKT1, GLUL and TUBB2A. Interacts with ZNRF2. Interacts (via its RING domain) with UBE2N. Interacts (when phosphorylated) with YWHAE.

Subcellular location. Endosome. Lysosome. Membrane. Cytoplasmic vesicle. Secretory vesicle. Synaptic vesicle membrane.

Tissue specificity. Expressed primarily in the nervous system, with expression higher in developing brain relative to adult. Expressed at low levels in testis and thymus.

Post-translational modifications. N-myristoylation targets ZNRF1 to intracellular membranes. Phosphorylated by SRC at Tyr-103; leading to ‘Lys-63’-linked ubiquitination of TLR3, lysosomal trafficking and degradation.

Domain organisation. The RING-type zinc finger domain is required for E3 ligase activity.

Pathway. Protein modification; protein ubiquitination.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8ND25-1	1	yes
Q8ND25-2	2

RefSeq proteins (1): NP_115644* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001841	Znf_RING	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR051878	ZNRF_ubiq-protein_ligase	Family

Pfam: PF13639

Enzyme classification (BRENDA):

• EC 2.3.2.27 — RING-type E3 ubiquitin transferase (BRENDA: 28 organisms, 138 substrates, 10 inhibitors, 1 Km, 1 kcat entries)

Substrate kinetics (BRENDA)

1 substrates with measured Km, best-characterized 1. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
[UBE2W]-S-UBIQUITINYL-L-CYSTEINE	0.3014	1

UniProt features (28 total): mutagenesis site 7, modified residue 5, helix 3, strand 3, region of interest 3, turn 2, initiator methionine 1, chain 1, lipid moiety-binding region 1, splice variant 1, zinc finger region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
5YWR	X-RAY DIFFRACTION	1.47

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8ND25-F1	68.26	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.

Post-translational modifications (6): 123, 2, 50, 52, 53, 103

Mutagenesis-validated functional residues (7):

Position	Phenotype
2	greatly reduced binding to atp1a1.
19	partial loss of binding to 14-3-3.
82	partial loss of binding to 14-3-3.
145	complete loss of binding to atp1a1; when associated with a-148.
148	complete loss of binding to atp1a1; when associated with a-145.
183	about 10-fold decreased binding to ube2n.
184	loss of e3 activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation

MSigDB gene sets: 291 (showing top): GOBP_REGULATION_OF_VESICLE_FUSION, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GOBP_VESICLE_ORGANIZATION, MODULE_418, GOZGIT_ESR1_TARGETS_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_MEMBRANE_FUSION, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_REGULATION_OF_TOLL_LIKE_RECEPTOR_4_SIGNALING_PATHWAY, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, AREB6_01, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION

GO Biological Process (9): positive regulation of toll-like receptor 4 signaling pathway (GO:0034145), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), protein K48-linked ubiquitination (GO:0070936), positive regulation of autophagosome-lysosome fusion (GO:0160177), protein ubiquitination (GO:0016567), toll-like receptor 3 signaling pathway (GO:0034138), regulation of toll-like receptor 3 signaling pathway (GO:0034139), toll-like receptor 4 signaling pathway (GO:0034142), regulation of toll-like receptor 4 signaling pathway (GO:0034143)

GO Molecular Function (6): ubiquitin-protein transferase activity (GO:0004842), zinc ion binding (GO:0008270), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (11): cytoplasm (GO:0005737), lysosome (GO:0005764), endosome (GO:0005768), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), synaptic vesicle membrane (GO:0030672), ciliary transition zone (GO:0035869), ciliary tip (GO:0097542), cytoplasmic vesicle (GO:0031410), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Class I MHC mediated antigen processing & presentation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
toll-like receptor 4 signaling pathway	2
cytoplasm	2
cilium	2
regulation of toll-like receptor 4 signaling pathway	1
positive regulation of pattern recognition receptor signaling pathway	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
protein polyubiquitination	1
positive regulation of vesicle fusion	1
autophagosome-lysosome fusion	1
protein modification by small protein conjugation	1
endolysosomal toll-like receptor signaling pathway	1
toll-like receptor 3 signaling pathway	1
regulation of cytoplasmic pattern recognition receptor signaling pathway	1
cell surface toll-like receptor signaling pathway	1
regulation of pattern recognition receptor signaling pathway	1
ubiquitin-like protein transferase activity	1
transition metal ion binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
binding	1
catalytic activity	1
cation binding	1
intracellular anatomical structure	1
lytic vacuole	1
endomembrane system	1
cytoplasmic vesicle	1
membrane	1
cell periphery	1
synaptic vesicle	1
exocytic vesicle membrane	1
intracellular vesicle	1
cell junction	1

Protein interactions and networks

STRING

512 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNRF1	UBE2D2	P51669	789
ZNRF1	A0A087WY85	A0A087WY85	735
ZNRF1	ZNRF4	Q8WWF5	600
ZNRF1	UBE2S	Q16763	590
ZNRF1	UBE2N	P61088	562
ZNRF1	SARM1	Q6SZW1	540
ZNRF1	RING1	Q06587	521
ZNRF1	GLUL	P15104	476
ZNRF1	KLHL22	Q53GT1	458
ZNRF1	RNF167	Q9H6Y7	456
ZNRF1	RNF152	Q8N8N0	456
ZNRF1	KLHL21	Q9UJP4	445
ZNRF1	NEURL1B	A8MQ27	414
ZNRF1	OR7D2	Q96RA2	410
ZNRF1	ARRDC5	A6NEK1	404

IntAct

50 interactions, top by confidence:

A	B	Type	Score
UBE2V1	UBE2N	psi-mi:“MI:0220”(ubiquitination reaction)	0.910
UBE2N	ZNRF1	psi-mi:“MI:0915”(physical association)	0.820
ZNRF1	UBE2N	psi-mi:“MI:0915”(physical association)	0.820
UBE2D1	ZNRF1	psi-mi:“MI:0915”(physical association)	0.790
ZNRF1	UBE2D2	psi-mi:“MI:0915”(physical association)	0.790
ZNRF1	UBE2D1	psi-mi:“MI:0915”(physical association)	0.790
UBE2D2	ZNRF1	psi-mi:“MI:0915”(physical association)	0.790
ZNRF1	UBE2D1	psi-mi:“MI:0220”(ubiquitination reaction)	0.790
ZNRF1	UBE2D2	psi-mi:“MI:0220”(ubiquitination reaction)	0.790
ZNRF1	UBE2D4	psi-mi:“MI:0915”(physical association)	0.760
UBE2E1	ZNRF1	psi-mi:“MI:0915”(physical association)	0.650
ZNRF1	UBE2E1	psi-mi:“MI:0915”(physical association)	0.650
ZNRF1	UBE2E1	psi-mi:“MI:0220”(ubiquitination reaction)	0.650
UBE2N	UBA1	psi-mi:“MI:0914”(association)	0.640
ZNRF1	UBE2D3	psi-mi:“MI:0915”(physical association)	0.620
UBE2D3	ZNRF1	psi-mi:“MI:0915”(physical association)	0.620
UBXN7	ZNRF1	psi-mi:“MI:0915”(physical association)	0.560
ZNRF1	NMT2	psi-mi:“MI:0914”(association)	0.530
ZNRF1	UBE2V1	psi-mi:“MI:0915”(physical association)	0.530

BioGRID (75): ZNRF1 (Biochemical Activity), UBE2N (Reconstituted Complex), UBE2D1 (Reconstituted Complex), UBE2D2 (Reconstituted Complex), CDC34 (Reconstituted Complex), UBE2E1 (Reconstituted Complex), ATP1A1 (Biochemical Activity), UBC (Biochemical Activity), UBE2N (Reconstituted Complex), UBE2D1 (Reconstituted Complex), NMT1 (Affinity Capture-MS), NMT2 (Affinity Capture-MS), TSEN2 (Affinity Capture-MS), BHMT (Affinity Capture-MS), TSEN54 (Affinity Capture-MS)

ESM2 similar proteins: A2AFE9, E9QAU8, F1MM41, O49500, O64762, O65685, P0C035, P0DPR2, Q08CG8, Q0V9R0, Q21126, Q3UHJ8, Q4V7B8, Q5B7I8, Q5QLR5, Q5R476, Q5Z8R1, Q66J97, Q69138, Q6AVN2, Q6NRV8, Q6P4U6, Q6ZNA4, Q6ZSG1, Q7L0R7, Q7XTV7, Q84JP1, Q84W40, Q852U6, Q8BI21, Q8ND25, Q8VZ02, Q90ZT7, Q91V17, Q94AK4, Q99ML9, Q9CA30, Q9D0C1, Q9E1W2, Q9FMM4

Diamond homologs: A0A0D1E015, A0JMD2, A1CEK1, A1DFP5, A2QWA2, A4QTV1, A8QCE4, A8XJZ8, B0G126, B0WAQ0, B3MT31, B3P851, B4G2G5, B4IC49, B4JHI7, B4K982, B4M140, B4NFJ7, B4PRU6, D2H5P6, D3ZVP7, D4A8G9, E1BLZ4, F1MM41, F7EP40, O13821, O14964, O59722, O76902, O95405, O96838, P0CS26, P0CS27, P34756, P40343, Q05B78, Q08CN9, Q0CJV3, Q0P4S0, Q0U4Z8

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	ZNRF1	ubiquitination
ZNRF1	“down-regulates quantity by destabilization”	CAV1	polyubiquitination
EGFR	“up-regulates activity”	ZNRF1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 15 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
TICAM1, RIP1-mediated IKK complex recruitment	5	200.3×	4e-10
Synthesis of active ubiquitin: roles of E1 and E2 enzymes	7	171.9×	1e-13
IKK complex recruitment mediated by RIP1	5	165.5×	8e-10
E3 ubiquitin ligases ubiquitinate target proteins	6	77.4×	8e-10
FCERI mediated NF-kB activation	5	52.1×	3e-07
CLEC7A (Dectin-1) signaling	5	47.6×	4e-07
Downstream TCR signaling	5	42.8×	5e-07
Antigen processing: Ubiquitination & Proteasome degradation	13	32.2×	2e-17

GO biological processes:

GO term	Partners	Fold	FDR
protein monoubiquitination	6	137.6×	4e-11
protein K11-linked ubiquitination	5	130.6×	3e-09
protein K63-linked ubiquitination	6	107.0×	1e-10
protein K48-linked ubiquitination	8	89.9×	2e-13
protein polyubiquitination	9	69.2×	5e-14
ubiquitin-dependent protein catabolic process	7	34.6×	4e-09
protein ubiquitination	8	22.1×	4e-09
proteasome-mediated ubiquitin-dependent protein catabolic process	6	20.9×	1e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	12
Likely benign	0
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

2035 predictions. Top by Δscore:

Variant	Effect	Δscore
16:75104779:TGCA:T	acceptor_loss	1.0000
16:75104780:GCA:G	acceptor_loss	1.0000
16:75104782:A:AC	acceptor_loss	1.0000
16:75104782:A:AG	acceptor_gain	1.0000
16:75104782:AGAT:A	acceptor_gain	1.0000
16:75104783:G:GA	acceptor_loss	1.0000
16:75104783:G:GG	acceptor_gain	1.0000
16:75104783:GAT:G	acceptor_gain	1.0000
16:75104783:GATG:G	acceptor_gain	1.0000
16:75000093:GTG:G	donor_gain	0.9900
16:75002371:G:GG	donor_gain	0.9900
16:75036874:GA:G	acceptor_gain	0.9900
16:75038928:T:G	donor_gain	0.9900
16:75055683:GCA:G	donor_gain	0.9900
16:75104783:GA:G	acceptor_gain	0.9900
16:75104783:GATGA:G	acceptor_gain	0.9900
16:75104885:AAAAG:A	donor_loss	0.9900
16:75104886:AAAGG:A	donor_loss	0.9900
16:75104887:AAGG:A	donor_loss	0.9900
16:75104889:GG:G	donor_loss	0.9900
16:75104890:GTA:G	donor_loss	0.9900
16:75104891:T:A	donor_loss	0.9900
16:75002236:ATTT:A	acceptor_gain	0.9800
16:75093663:CAACG:C	donor_loss	0.9800
16:75093664:AACGG:A	donor_loss	0.9800
16:75093666:CGGTA:C	donor_loss	0.9800
16:75093667:GGTAA:G	donor_loss	0.9800
16:75093668:G:GC	donor_loss	0.9800
16:75093669:T:TT	donor_loss	0.9800
16:75104770:T:A	acceptor_gain	0.9800

AlphaMissense

1478 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:75093580:T:A	C145S	1.000
16:75093580:T:C	C145R	1.000
16:75093581:G:A	C145Y	1.000
16:75093581:G:C	C145S	1.000
16:75093581:G:T	C145F	1.000
16:75093582:C:G	C145W	1.000
16:75093589:T:A	C148S	1.000
16:75093589:T:C	C148R	1.000
16:75093590:G:A	C148Y	1.000
16:75093590:G:C	C148S	1.000
16:75093590:G:T	C148F	1.000
16:75093591:C:G	C148W	1.000
16:75093625:C:G	H160D	1.000
16:75093627:C:A	H160Q	1.000
16:75093627:C:G	H160Q	1.000
16:75093629:T:C	F161S	1.000
16:75093637:T:A	C164S	1.000
16:75093637:T:C	C164R	1.000
16:75093638:G:A	C164Y	1.000
16:75093638:G:C	C164S	1.000
16:75093638:G:T	C164F	1.000
16:75093639:T:G	C164W	1.000
16:75093661:T:A	Y172N	1.000
16:75093661:T:C	Y172H	1.000
16:75093661:T:G	Y172D	1.000
16:75104793:T:A	L177Q	1.000
16:75104793:T:C	L177P	1.000
16:75104813:T:A	C184S	1.000
16:75104813:T:C	C184R	1.000
16:75104814:G:A	C184Y	1.000

dbSNP variants (sampled 300 via entrez): RS1000018126 (16:75031848 G>GTCAA), RS1000032160 (16:75066361 A>G), RS1000045619 (16:75100535 A>T), RS1000086764 (16:75095028 C>G), RS1000091016 (16:75059825 G>A), RS1000120108 (16:75027545 C>T), RS1000143081 (16:75024453 A>G), RS1000143628 (16:75048408 G>A,T), RS1000158520 (16:75061098 A>G), RS1000176693 (16:75085817 AGTGAGT>A), RS1000184297 (16:75009991 C>G,T), RS1000202282 (16:75013001 G>C), RS1000231489 (16:75080245 G>A,T), RS1000246551 (16:74997631 A>C,G,T), RS1000276605 (16:75046620 G>C,T)

Disease associations

OMIM: gene MIM:612060 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002018_1	Crohn’s disease (time to surgery)	9.000000e-06

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
bisphenol A	affects expression, affects cotreatment, decreases expression	2
Benzo(a)pyrene	decreases expression, affects methylation	2
Tretinoin	decreases expression, increases expression	2
Valproic Acid	decreases methylation, affects expression	2
bisphenol F	affects cotreatment, decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
cobaltous chloride	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
pentabromodiphenyl ether	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
bisphenol S	decreases expression, affects cotreatment	1
gardiquimod	decreases reaction, decreases expression	1
Irinotecan	decreases expression	1
Vorinostat	decreases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Dexamethasone	decreases expression, affects cotreatment	1
Indomethacin	affects cotreatment, decreases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	decreases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1
Vitamin K 3	affects expression	1
Protein Kinase Inhibitors	decreases expression, decreases reaction	1

Clinical trials (associated diseases)

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