EDEM1

Summary

EDEM1 (ER degradation enhancing alpha-mannosidase like protein 1, HGNC:18967) is a protein-coding gene on chromosome 3p26.1, encoding ER degradation-enhancing alpha-mannosidase-like protein 1 (Q92611). Extracts misfolded glycoproteins, but not glycoproteins undergoing productive folding, from the calnexin cycle.

Enables mannosyl-oligosaccharide 1,2-alpha-mannosidase activity and misfolded protein binding activity. Involved in positive regulation of retrograde protein transport, ER to cytosol; protein targeting to ER; and proteolysis involved in protein catabolic process. Located in aggresome and endoplasmic reticulum quality control compartment.

Source: NCBI Gene 9695 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 108 total
• MANE Select transcript: NM_014674

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18967
Approved symbol	EDEM1
Name	ER degradation enhancing alpha-mannosidase like protein 1
Location	3p26.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0212, EDEM
Ensembl gene	ENSG00000134109
Ensembl biotype	protein_coding
OMIM	607673
Entrez	9695

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 3 retained_intron, 2 protein_coding, 2 nonsense_mediated_decay

ENST00000256497, ENST00000434243, ENST00000443790, ENST00000445686, ENST00000465187, ENST00000465369, ENST00000492751

RefSeq mRNA: 1 — MANE Select: NM_014674 NM_014674

CCDS: CCDS33686

Canonical transcript exons

ENST00000256497 — 12 exons

Exon	Start	End
ENSE00001219017	5215829	5219958
ENSE00001609567	5211120	5211216
ENSE00001683715	5187707	5188314
ENSE00001703624	5213319	5213522
ENSE00003470623	5199592	5199695
ENSE00003484667	5201753	5201924
ENSE00003511015	5208093	5208263
ENSE00003538420	5195209	5195281
ENSE00003553390	5207153	5207273
ENSE00003593501	5202966	5203149
ENSE00003595555	5205067	5205241
ENSE00003686317	5210175	5210248

Expression profiles

Bgee: expression breadth ubiquitous, 250 present calls, max score 95.57.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.3244 / max 203.1479, expressed in 1802 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
35151	6.7562	1705
35152	4.3422	1361
35154	1.1475	281
35149	0.8121	537
35150	0.6254	365
35146	0.5238	249
35153	0.5086	226
35147	0.3372	142
35156	0.1804	58
35148	0.0591	17

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bone marrow cell	CL:0002092	95.57	gold quality
thymus	UBERON:0002370	95.05	gold quality
bone marrow	UBERON:0002371	94.08	gold quality
liver	UBERON:0002107	93.71	gold quality
right lobe of liver	UBERON:0001114	93.55	gold quality
lymph node	UBERON:0000029	93.50	gold quality
bone element	UBERON:0001474	92.63	gold quality
epithelium of nasopharynx	UBERON:0001951	92.24	gold quality
decidua	UBERON:0002450	91.96	gold quality
vermiform appendix	UBERON:0001154	91.81	gold quality
tonsil	UBERON:0002372	91.29	gold quality
stromal cell of endometrium	CL:0002255	91.02	gold quality
caecum	UBERON:0001153	90.99	gold quality
placenta	UBERON:0001987	90.81	gold quality
leukocyte	CL:0000738	90.74	gold quality
mononuclear cell	CL:0000842	90.65	gold quality
monocyte	CL:0000576	90.63	gold quality
trabecular bone tissue	UBERON:0002483	90.63	gold quality
islet of Langerhans	UBERON:0000006	90.36	gold quality
upper lobe of left lung	UBERON:0008952	90.34	gold quality
body of pancreas	UBERON:0001150	90.17	gold quality
mucosa of urinary bladder	UBERON:0001259	90.16	silver quality
pancreas	UBERON:0001264	90.11	gold quality
lung	UBERON:0002048	89.97	gold quality
upper lobe of lung	UBERON:0008948	89.96	gold quality
tongue squamous epithelium	UBERON:0006919	89.75	silver quality
cardia of stomach	UBERON:0001162	89.73	silver quality
colonic epithelium	UBERON:0000397	89.58	gold quality
blood	UBERON:0000178	89.24	gold quality
pylorus	UBERON:0001166	89.19	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-9067	yes	12.45
E-GEOD-109979	no	243.71
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB3, TMBIM6

miRNA regulators (miRDB)

182 targeting EDEM1, 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-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-3162-3P	100.00	65.37	363
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-548AN	99.97	70.91	2817

Literature-anchored findings (GeneRIF, showing 25)

• EDEM was shown to extract misfolded glycoproteins, but not glycoproteins undergoing productive folding, from the calnexin cycle [EDEM] (PMID:12610306)
• EDEM1 is a soluble protein of the ER lumen in HEK293 cells (PMID:15579471)
• These results indicate that EDEM may maintain the retrotranslocation competence of NHK by inhibiting aggregation so that unstable misfolded proteins can be accommodated by the dislocon for ERAD. (PMID:16629899)
• the endoplasmic reticulum quality control vesicular transport pathway using EDEM1 does not involve the COPII exit sites (PMID:17360537)
• Cells with defective EDEM1 turnover contain unphysiologically high levels of EDEM1, show enhanced ER associated degradation activity and are characterized by impaired capacity to efficiently complete maturation of model glycopolypeptides. (PMID:18452703)
• endogenous EDEM1 in cells not stressed by the expression of a transgenic misfolded protein reaches the cytosol and is degraded by basal autophagy (PMID:19266160)
• EDEM1 specifically binds nonnative proteins in a glycan-independent manner. (PMID:19524542)
• EDEM1 promotes correct folding and enhanced degradation of rod opsin. (PMID:19934218)
• The EDEM1 activity trims mannose from the C branch of N-glycans in vivo. (PMID:20065073)
• mannose trimming enables delivery of a substrate glycoprotein from EDEM1 to late endoplasmic reticulum degredation steps through association with XTP3-B (PMID:21062743)
• EDEM1 protein recognition may be determined by the structure of the endoplasmic reticulum-associated protein degradation substrate in a study of mutant ricin A-chain transport to the cytosol. (PMID:21388347)
• signal sequence cleavage functionally regulated the association of EDEM1-soluble and membrane-integrated isoforms with distinct ERAD machinery and substrates. (PMID:21632540)
• we suggest that a nascent glycoprotein can normally dissociate from EDEM1 and be rescued from endoplasmic reticulum associated degradation by reentering calnexin-refolding cycles (PMID:21917589)
• Tyrosinase degradation is prevented when EDEM1 lacks the intrinsically disordered region (PMID:22905195)
• analysis of a shared endoplasmic reticulum-associated degradation pathway involving the EDEM1 protein for glycosylated and nonglycosylated proteins (PMID:23233672)
• EDEM1 associates with lifespan in animal models, although not humans. (PMID:24037343)
• EDEM1 colocalizes with the selective autophagy cargo receptors p62/SQSTM1, neighbor of BRCA1 gene 1 (NBR1) and autophagy-linked FYVE (Alfy) protein, and becomes engulfed by autophagic isolation membranes. (PMID:24664425)
• miR-581 promotes hepatitis B virus surface antigen expression by targeting Dicer and EDEM1 in HepG2 cells. (PMID:24913918)
• Endoplasmic reticulum degradation-enhancing alpha-mannosidase-like protein 1 targets misfolded HLA-B27 dimers for endoplasmic reticulum-associated degradation. (PMID:25132672)
• EDEM1 employs different binding modalities to interact with ERAD clients and ER quality control (ERQC) machinery partners and some of these properties are shared with its homologues EDEM2 and EDEM3. (PMID:30021839)
• A somatic variant of EDEM1 (N198I) alters ATF6 signaling and provides a selective advantage to the transforming cells and results in hepatocellular carcinoma. (PMID:30281916)
• Cleavage and degradation of EDEM1 promotes coxsackievirus B3 replication via ATF6a-mediated unfolded protein response signalling. (PMID:32083795)
• EDEM1 Drives Misfolded Protein Degradation via ERAD and Exploits ER-Phagy as Back-Up Mechanism When ERAD Is Impaired. (PMID:32423001)
• Purified EDEM3 or EDEM1 alone produces determinant oligosaccharide structures from M8B in mammalian glycoprotein ERAD. (PMID:34698634)
• EDEM1 Regulates Amyloid Precursor Protein (APP) Metabolism and Amyloid-beta Production. (PMID:35008544)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	edem1	ENSDARG00000025094
mus_musculus	Edem1	ENSMUSG00000030104
rattus_norvegicus	Edem1	ENSRNOG00000055365
caenorhabditis_elegans		WBGENE00008148

Paralogs (6): EDEM2 (ENSG00000088298), MAN1A1 (ENSG00000111885), EDEM3 (ENSG00000116406), MAN1C1 (ENSG00000117643), MAN1B1 (ENSG00000177239), MAN1A2 (ENSG00000198162)

Protein

Protein identifiers

ER degradation-enhancing alpha-mannosidase-like protein 1 — Q92611 (reviewed: Q92611)

All UniProt accessions (3): Q92611, F8WE67, F8WER9

UniProt curated annotations — full annotation on UniProt →

Function. Extracts misfolded glycoproteins, but not glycoproteins undergoing productive folding, from the calnexin cycle. It is directly involved in endoplasmic reticulum-associated degradation (ERAD) and targets misfolded glycoproteins for degradation in an N-glycan-independent manner, probably by forming a complex with SEL1L. It has low mannosidase activity, catalyzing mannose trimming from Man8GlcNAc2 to Man7GlcNAc2.

Subunit / interactions. Interacts with DNAJC10. Interacts with DERL2 and DERL3. Binds to SEL1L.

Subcellular location. Endoplasmic reticulum membrane.

Similarity. Belongs to the glycosyl hydrolase 47 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q92611-1	1	yes
Q92611-2	2

RefSeq proteins (1): NP_055489* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001382	Glyco_hydro_47	Family
IPR012341	6hp_glycosidase-like_sf	Homologous_superfamily
IPR036026	Seven-hairpin_glycosidases	Homologous_superfamily
IPR044674	EDEM1/2/3	Family

Pfam: PF01532

UniProt features (15 total): glycosylation site 5, mutagenesis site 3, topological domain 2, splice variant 2, chain 1, transmembrane region 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92611-F1	84.73	0.74

Functional residue map

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

Glycosylation sites (5): 181, 198, 299, 342, 624

Mutagenesis-validated functional residues (3):

Position	Phenotype
225	normal affinity for misfolded glycoproteins, but impaired sel1l binding.
370	normal affinity for misfolded glycoproteins, but impaired sel1l binding.
493	normal affinity for misfolded glycoproteins, but impaired sel1l binding.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-381038	XBP1(S) activates chaperone genes
R-HSA-901032	ER Quality Control Compartment (ERQC)

MSigDB gene sets: 334 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, GSE45365_NK_CELL_VS_BCELL_UP, GOBP_ENDOPLASMIC_RETICULUM_TO_CYTOSOL_TRANSPORT, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, HORIUCHI_WTAP_TARGETS_DN, REACTOME_UNFOLDED_PROTEIN_RESPONSE_UPR, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, NKX25_02, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_PROTEIN_TRANSPORT, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_PROTEIN_TARGETING, GOBP_MACROMOLECULE_CATABOLIC_PROCESS

GO Biological Process (10): carbohydrate metabolic process (GO:0005975), ubiquitin-dependent protein catabolic process (GO:0006511), response to unfolded protein (GO:0006986), ERAD pathway (GO:0036503), protein targeting to ER (GO:0045047), positive regulation of retrograde protein transport, ER to cytosol (GO:1904154), endoplasmic reticulum mannose trimming (GO:1904380), obsolete mannoprotein catabolic process (GO:0006058), glycoprotein metabolic process (GO:0009100), mannose trimming involved in glycoprotein ERAD pathway (GO:1904382)

GO Molecular Function (6): mannosyl-oligosaccharide 1,2-alpha-mannosidase activity (GO:0004571), calcium ion binding (GO:0005509), misfolded protein binding (GO:0051787), protein binding (GO:0005515), hydrolase activity (GO:0016787), hydrolase activity, acting on glycosyl bonds (GO:0016798)

GO Cellular Component (5): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), aggresome (GO:0016235), endoplasmic reticulum quality control compartment (GO:0044322), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
IRE1alpha activates chaperones	1
Calnexin/calreticulin cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein alpha-1,2-demannosylation	2
cellular anatomical structure	2
primary metabolic process	1
protein ubiquitination	1
modification-dependent protein catabolic process	1
response to topologically incorrect protein	1
proteasomal protein catabolic process	1
response to endoplasmic reticulum stress	1
response to chemical	1
protein targeting	1
establishment of protein localization to endoplasmic reticulum	1
retrograde protein transport, ER to cytosol	1
positive regulation of protein exit from endoplasmic reticulum	1
regulation of retrograde protein transport, ER to cytosol	1
endoplasmic reticulum quality control compartment	1
protein metabolic process	1
carbohydrate derivative metabolic process	1
protein deglycosylation involved in glycoprotein catabolic process	1
ubiquitin-dependent glycoprotein ERAD pathway	1
mannosyl-oligosaccharide mannosidase activity	1
metal ion binding	1
protein binding	1
binding	1
catalytic activity	1
hydrolase activity	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
inclusion body	1
endoplasmic reticulum	1

Protein interactions and networks

STRING

1200 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EDEM1	DNAJC10	Q8IXB1	997
EDEM1	HSPA5	P11021	945
EDEM1	MAN2C1	Q9NTJ4	943
EDEM1	SEL1L	Q9UBV2	940
EDEM1	CANX	P27824	932
EDEM1	DERL3	Q96Q80	929
EDEM1	DERL2	Q9GZP9	928
EDEM1	OS9	Q13438	917
EDEM1	XBP1	P17861	907
EDEM1	ATF6	P18850	889
EDEM1	ERLEC1	Q96DZ1	886
EDEM1	CALR	P27797	884
EDEM1	ERN1	O75460	851
EDEM1	SYVN1	Q86TM6	845
EDEM1	DNAJB9	Q9UBS3	800

IntAct

42 interactions, top by confidence:

A	B	Type	Score
PSMD14	PSMD11	psi-mi:“MI:0914”(association)	0.650
GALNT6	NDUFS4	psi-mi:“MI:0914”(association)	0.530
ZACN	GPAA1	psi-mi:“MI:0914”(association)	0.530
EDEM1	SSR1	psi-mi:“MI:0915”(physical association)	0.400
ACSL4	ACSL3	psi-mi:“MI:0914”(association)	0.350
EDEM1	P4HB	psi-mi:“MI:0914”(association)	0.350
LYZL1	MANBA	psi-mi:“MI:0914”(association)	0.350
LYZL2	MANBA	psi-mi:“MI:0914”(association)	0.350
MPPE1	ADAM10	psi-mi:“MI:0914”(association)	0.350
LOXL3	MSI1	psi-mi:“MI:0914”(association)	0.350
NAAA	NRP2	psi-mi:“MI:0914”(association)	0.350
EDEM1	CANX	psi-mi:“MI:0914”(association)	0.350
LIN28A	MEX3A	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
CHRNA4	TMEM223	psi-mi:“MI:0914”(association)	0.350
OR1M1	NBAS	psi-mi:“MI:0914”(association)	0.350
MPPE1	FAM234B	psi-mi:“MI:0914”(association)	0.350
ZACN	FAM234B	psi-mi:“MI:0914”(association)	0.350
NAAA	POTEF	psi-mi:“MI:0914”(association)	0.350
LLCFC1	POTEF	psi-mi:“MI:0914”(association)	0.350
RLN1	RTL8C	psi-mi:“MI:0914”(association)	0.350
NMS	MANBA	psi-mi:“MI:0914”(association)	0.350
MS4A15	ABCD4	psi-mi:“MI:0914”(association)	0.350
CD3D	CLGN	psi-mi:“MI:0914”(association)	0.350
LYZL1	ZZEF1	psi-mi:“MI:0914”(association)	0.350
LYZL2	ZZEF1	psi-mi:“MI:0914”(association)	0.350
EDEM1	MSH5	psi-mi:“MI:0914”(association)	0.350
NCEH1	C1QL1	psi-mi:“MI:0914”(association)	0.350
CDCP2	EDEM1	psi-mi:“MI:0914”(association)	0.350

BioGRID (258): HLA-B (Affinity Capture-Western), UBQLN2 (Affinity Capture-MS), CANX (Affinity Capture-MS), ESYT1 (Affinity Capture-MS), MTCH1 (Affinity Capture-MS), EDEM1 (Affinity Capture-MS), EDEM1 (Affinity Capture-MS), EDEM1 (Affinity Capture-Western), RCOM_2159910 (Affinity Capture-Western), P4HB (Affinity Capture-MS), EDEM1 (Affinity Capture-MS), EDEM1 (Affinity Capture-MS), PNISR (Affinity Capture-MS), SUFU (Affinity Capture-MS), CHD9 (Affinity Capture-MS)

ESM2 similar proteins: A2AJ15, B2GUY0, O02773, O18498, O60476, P32906, P33908, P39098, P45700, P45701, P53624, Q08463, Q10471, Q18788, Q1L8D2, Q2HXL6, Q49A17, Q5EA41, Q5GF25, Q5RFJ6, Q6GQB9, Q6NXH2, Q6P9S7, Q6PB93, Q6WV16, Q80VA0, Q86SF2, Q86SR1, Q8BJT9, Q8H116, Q8J0Q0, Q8K1B9, Q8N428, Q925R7, Q925U4, Q92611, Q93Y37, Q9BV94, Q9BZQ6, Q9C512

Diamond homologs: A1CP08, A1D1W1, A2AJ15, A2QAS2, B0XMT4, B2GUY0, B8N417, D4AV26, E9CXX8, O02773, O18498, O60476, O94726, P31723, P32906, P33908, P39098, P45700, P45701, P53624, Q0D076, Q12563, Q18788, Q2HXL6, Q2ULB2, Q4WRZ5, Q6GQB9, Q8BJT9, Q8H116, Q8J0Q0, Q925U4, Q92611, Q93Y37, Q9BV94, Q9BZQ6, Q9C512, Q9FG93, Q9NR34, Q9P7C3, Q9SXC9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	90
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1848 predictions. Top by Δscore:

Variant	Effect	Δscore
3:5188262:G:GT	donor_gain	1.0000
3:5188310:GACCC:G	donor_gain	1.0000
3:5188315:G:GG	donor_gain	1.0000
3:5189459:GAC:G	donor_gain	1.0000
3:5189490:A:G	donor_gain	1.0000
3:5195207:A:AG	acceptor_gain	1.0000
3:5195208:G:GG	acceptor_gain	1.0000
3:5195208:GTTC:G	acceptor_gain	1.0000
3:5195208:GTTCA:G	acceptor_gain	1.0000
3:5195277:TTGCA:T	donor_gain	1.0000
3:5195278:TGCA:T	donor_gain	1.0000
3:5195279:GCA:G	donor_gain	1.0000
3:5195279:GCAG:G	donor_gain	1.0000
3:5195280:CA:C	donor_gain	1.0000
3:5195281:AG:A	donor_loss	1.0000
3:5195282:G:C	donor_loss	1.0000
3:5195282:G:GG	donor_gain	1.0000
3:5195283:T:A	donor_loss	1.0000
3:5195284:AA:A	donor_loss	1.0000
3:5199586:TTAAA:T	acceptor_loss	1.0000
3:5199587:TAAAG:T	acceptor_loss	1.0000
3:5199588:AAAGA:A	acceptor_loss	1.0000
3:5199589:A:G	acceptor_gain	1.0000
3:5199589:AAGAT:A	acceptor_loss	1.0000
3:5199590:A:G	acceptor_gain	1.0000
3:5199590:AGATA:A	acceptor_loss	1.0000
3:5199591:G:GA	acceptor_loss	1.0000
3:5199591:G:GG	acceptor_gain	1.0000
3:5199591:GATA:G	acceptor_gain	1.0000
3:5199691:ATAAG:A	donor_loss	1.0000

AlphaMissense

4286 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:5199679:T:C	F224L	1.000
3:5199681:T:A	F224L	1.000
3:5199681:T:G	F224L	1.000
3:5207163:T:A	C410S	1.000
3:5207163:T:C	C410R	1.000
3:5207164:G:A	C410Y	1.000
3:5207164:G:C	C410S	1.000
3:5208123:T:C	C457R	1.000
3:5208124:G:A	C457Y	1.000
3:5208125:C:G	C457W	1.000
3:5208172:C:A	P473H	1.000
3:5208226:G:C	R491T	1.000
3:5208244:C:T	S497F	1.000
3:5211181:T:C	F549L	1.000
3:5211183:C:A	F549L	1.000
3:5211183:C:G	F549L	1.000
3:5188262:G:C	D153H	0.999
3:5199680:T:G	F224C	0.999
3:5199695:G:T	R229M	0.999
3:5201763:A:C	S233R	0.999
3:5201765:C:A	S233R	0.999
3:5201765:C:G	S233R	0.999
3:5201866:T:C	L267P	0.999
3:5201878:T:C	L271P	0.999
3:5203144:T:C	L346S	0.999
3:5205067:G:A	G348D	0.999
3:5205096:T:A	W358R	0.999
3:5205096:T:C	W358R	0.999
3:5205098:G:C	W358C	0.999
3:5205098:G:T	W358C	0.999

dbSNP variants (sampled 300 via entrez): RS1000008966 (3:5187170 T>C), RS1000067768 (3:5190998 C>G), RS1000078715 (3:5191384 C>T), RS1000115509 (3:5188651 C>G), RS1000144868 (3:5217943 C>T), RS1000304919 (3:5213876 C>G,T), RS1000403659 (3:5188425 G>C), RS1000424861 (3:5202191 A>G), RS1000513869 (3:5219387 A>C,G), RS1000595133 (3:5207506 TTTTG>T), RS1000642096 (3:5214787 C>G,T), RS1000821375 (3:5208907 A>G), RS1000893856 (3:5204496 A>C,T), RS1000915086 (3:5204679 A>C), RS1000941642 (3:5206697 A>T)

Disease associations

OMIM: gene MIM:607673 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST004779_2	Uterine fibroids	3.000000e-07
GCST006479_144	Diverticular disease	5.000000e-08
GCST007327_42	Smoking status (ever vs never smokers)	1.000000e-08
GCST008810_92	Smoking initiation (ever regular vs never regular)	5.000000e-10
GCST009391_1614	Metabolite levels	9.000000e-07
GCST009391_382	Metabolite levels	1.000000e-06
GCST011696_1	Alzheimer’s disease	9.000000e-07
GCST90013406_283	Liver enzyme levels (alkaline phosphatase)	1.000000e-11

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0009959	diverticular disease
EFO:0004318	smoking behavior
EFO:0005670	smoking initiation
EFO:0010378	phosphatidylcholine 34:4 measurement
EFO:0010437	triacylglycerol 58:10 measurement
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tunicamycin	increases expression	6
Cyclosporine	increases expression	4
Cadmium Chloride	increases abundance, increases expression, decreases reaction	3
beta-N-methylamino-L-alanine	increases expression	2
sodium arsenite	decreases expression, increases expression	2
Benzo(a)pyrene	affects methylation, decreases methylation	2
Thapsigargin	increases expression	2
bisphenol F	affects cotreatment, decreases expression	1
beauvericin	increases expression	1
lasiocarpine	decreases expression	1
bis(tri-n-butyltin)oxide	increases expression	1
boric acid	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	increases reaction, affects binding	1
2-palmitoylglycerol	increases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
salubrinal	increases expression, decreases reaction	1
nilotinib	increases expression, increases reaction	1
importazole	increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases reaction, increases expression	1
Air Pollutants, Occupational	affects expression	1
Atrazine	decreases expression	1
Cadmium	increases abundance, increases expression	1
Carbamazepine	affects expression	1
Curcumin	increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Diethylhexyl Phthalate	increases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Ivermectin	increases expression	1

Clinical trials (associated diseases)

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