MGRN1

Summary

MGRN1 (mahogunin ring finger 1, HGNC:20254) is a protein-coding gene on chromosome 16p13.3, encoding E3 ubiquitin-protein ligase MGRN1 (O60291). E3 ubiquitin-protein ligase.

Enables ubiquitin-protein transferase activity. Involved in endosome to lysosome transport; negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway; and protein monoubiquitination. Located in several cellular components, including early endosome; endoplasmic reticulum; and nucleus.

Source: NCBI Gene 23295 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 159 total
• MANE Select transcript: NM_015246

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20254
Approved symbol	MGRN1
Name	mahogunin ring finger 1
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0544, RNF156
Ensembl gene	ENSG00000102858
Ensembl biotype	protein_coding
OMIM	607559
Entrez	23295

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 18 protein_coding, 5 protein_coding_CDS_not_defined, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000262370, ENST00000399577, ENST00000415496, ENST00000536343, ENST00000585676, ENST00000586183, ENST00000587145, ENST00000587747, ENST00000588015, ENST00000588111, ENST00000588994, ENST00000590457, ENST00000590790, ENST00000591673, ENST00000591895, ENST00000592256, ENST00000593224, ENST00000615397, ENST00000902781, ENST00000902782, ENST00000902783, ENST00000902784, ENST00000902785, ENST00000938432, ENST00000938433, ENST00000938434, ENST00000938435

RefSeq mRNA: 4 — MANE Select: NM_015246 NM_001142289, NM_001142290, NM_001142291, NM_015246

CCDS: CCDS42115, CCDS45401, CCDS45402, CCDS59256

Canonical transcript exons

ENST00000262370 — 17 exons

Exon	Start	End
ENSE00000667047	4651963	4652051
ENSE00000865790	4652678	4652824
ENSE00001289905	4688796	4690972
ENSE00002785940	4624826	4625048
ENSE00003469259	4671391	4671459
ENSE00003525229	4650365	4650483
ENSE00003528845	4683224	4683269
ENSE00003577484	4681550	4681776
ENSE00003592118	4680032	4680097
ENSE00003634043	4682823	4682946
ENSE00003636956	4665102	4665151
ENSE00003642308	4668265	4668312
ENSE00003647174	4673498	4673657
ENSE00003648476	4677463	4677572
ENSE00003680393	4683843	4683932
ENSE00003692617	4664709	4664775
ENSE00003784640	4657246	4657363

Expression profiles

Bgee: expression breadth ubiquitous, 248 present calls, max score 95.24.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 45.4541 / max 7652.6556, expressed in 1821 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
152477	32.9112	1817
152483	5.6439	927
152484	1.8942	523
152482	1.4969	268
152476	1.1213	802
152475	0.7358	442
152480	0.6157	166
152481	0.4274	98
152486	0.2474	125
207717	0.1878	61

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	95.24	gold quality
cerebellar hemisphere	UBERON:0002245	94.60	gold quality
cerebellar cortex	UBERON:0002129	94.53	gold quality
right frontal lobe	UBERON:0002810	93.73	gold quality
cerebellum	UBERON:0002037	93.53	gold quality
stromal cell of endometrium	CL:0002255	93.23	gold quality
granulocyte	CL:0000094	93.05	gold quality
sural nerve	UBERON:0015488	93.05	gold quality
cortical plate	UBERON:0005343	92.99	gold quality
gastrocnemius	UBERON:0001388	92.77	gold quality
left uterine tube	UBERON:0001303	92.65	gold quality
body of stomach	UBERON:0001161	92.44	gold quality
body of uterus	UBERON:0009853	92.13	gold quality
muscle of leg	UBERON:0001383	91.96	gold quality
pancreatic ductal cell	CL:0002079	91.87	silver quality
popliteal artery	UBERON:0002250	91.82	gold quality
tibial artery	UBERON:0007610	91.80	gold quality
middle frontal gyrus	UBERON:0002702	91.76	gold quality
lower esophagus muscularis layer	UBERON:0035833	91.69	gold quality
lower esophagus	UBERON:0013473	91.67	gold quality
monocyte	CL:0000576	91.66	gold quality
right uterine tube	UBERON:0001302	91.64	gold quality
blood	UBERON:0000178	91.58	gold quality
right lobe of liver	UBERON:0001114	91.54	gold quality
left adrenal gland	UBERON:0001234	91.49	gold quality
left adrenal gland cortex	UBERON:0035825	91.49	gold quality
mononuclear cell	CL:0000842	91.48	gold quality
leukocyte	CL:0000738	91.47	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	91.37	gold quality
adenohypophysis	UBERON:0002196	91.12	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.71

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

63 targeting MGRN1, 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-6867-5P	100.00	82.21	3464
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-3175	99.65	66.30	2031

Literature-anchored findings (GeneRIF, showing 13)

• a role for Mahogunin in a proteasome-independent ubiquitylation pathway: TSG101 is a specific Mahogunin substrate (PMID:17229889)
• Study shows that both (Ctm)PrP and cyPrP can interact with and disrupt the function of Mahogunin (Mgrn), a cytosolic ubiquitin ligase whose loss causes spongiform neurodegeneration. (PMID:19524515)
• It therefore seems probable that the role of MGRN1 in the adrenal relates to the trafficking and/or degradation of the melanocortin 2 receptor. (PMID:21862608)
• data suggest that MGRN1 selectively targets misfolded proteins for degradation and may exhibit viable therapeutic potential for the treatment of spongiform neurodegeneration (PMID:23756845)
• Mahogunin-mediated alpha-tubulin ubiquitination via noncanonical K6 linkage regulates microtubule stability and mitotic spindle orientation. (PMID:24556679)
• Catalytic inactivation of MGRN1 results in elevated levels of GP78 and a consequential increase in the initiation of mitophagy. (PMID:26743086)
• Hypomethylation of CpG sites in RPTOR, MGRN1 and RAPSN in blood is associated with breast cancer. (PMID:27577081)
• Regulation of Mfn1 by MGRN1 and the proteasome modulates mitochondrial fusion. (PMID:27713096)
• With aging, the neuroprotective e3 ligase MGRN1 relocates from the cytosol to the nucleus of neurons, where it associates with chromatin and potentiates the cellular response to proteotoxic stress. This nuclear shift is due to a proteasome impairment dependent increase of a monoubiquitinated form of MGRN1. (PMID:28475871)
• epletion of MGRN1 activity may hamper physiologically important processes like mitochondrial movement in neuronal processes and intracellular transport of ligands through the endosomal pathway thereby contributing to the pathogenesis of neurodegeneration in certain types of prion diseases (PMID:28902452)
• In a heterologous expression system, MC1R-dependent Arrestins B ubiquitination was enhanced by overexpression of MGRN1 and was impaired by siRNA-mediated MGRN1 knockdown thus pointing to MGRN1 as the responsible E3-ligase. (PMID:28947386)
• Mahogunin Ring Finger 1 regulates pigmentation by controlling the pH of melanosomes in melanocytes and melanoma cells. (PMID:34921635)
• MGRN1 depletion promotes intercellular adhesion in melanoma by upregulation of E-cadherin and inhibition of CDC42. (PMID:38008393)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	mgrn1b	ENSDARG00000004796
danio_rerio	mgrn1a	ENSDARG00000100072
mus_musculus	Mgrn1	ENSMUSG00000022517
rattus_norvegicus	Mgrn1	ENSRNOG00000003234
drosophila_melanogaster	Mrgn1	FBGN0030514
caenorhabditis_elegans		WBGENE00007529

Paralogs (1): RNF157 (ENSG00000141576)

Protein

Protein identifiers

E3 ubiquitin-protein ligase MGRN1 — O60291 (reviewed: O60291)

Alternative names: Mahogunin RING finger protein 1, RING finger protein 156, RING-type E3 ubiquitin transferase MGRN1

All UniProt accessions (6): O60291, B4DR12, K7EIM7, K7EJN3, K7EPJ5, K7ERA1

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin-protein ligase. Mediates monoubiquitination at multiple sites of TSG101 in the presence of UBE2D1, but not of UBE2G1, nor UBE2H. Plays a role in the regulation of endosome-to-lysosome trafficking. Impairs MC1R- and MC4R-signaling by competing with GNAS-binding to MCRs and inhibiting agonist-induced cAMP production. Does not inhibit ADRB2-signaling. Does not promote MC1R ubiquitination. Acts also as a negative regulator of hedgehog signaling.

Subunit / interactions. Interacts with MC1R and MC4R, but not with TBXA2R. Interacts with TSG101. Interacts with mislocalized cytosolically exposed PRNP; this interaction alters MGRN1 subcellular location and causes lysosomal enlargement.

Subcellular location. Early endosome Cytoplasm. Cytosol. Nucleus Cytoplasm. Cell membrane Cytoplasm. Cell membrane.

Post-translational modifications. Autoubiquitinated in vitro.

Domain organisation. The RING finger is required for ubiquitin ligase activity.

Pathway. Protein modification; protein ubiquitination.

Isoforms (4)

UniProt ID	Names	Canonical?
O60291-1	1, (+)S	yes
O60291-2	2, (+)L
O60291-3	3, (-)L
O60291-4	4, (-)S

RefSeq proteins (4): NP_001135761, NP_001135762, NP_001135763, NP_056061* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001841	Znf_RING	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR045194	MGRN1/RNF157-like	Family
IPR058981	MGRN1/RNF157-like_N	Domain

Pfam: PF13920, PF26192

UniProt features (18 total): modified residue 3, compositionally biased region 3, splice variant 2, sequence conflict 2, region of interest 2, initiator methionine 1, chain 1, lipid moiety-binding region 1, mutagenesis site 1, zinc finger region 1, short sequence motif 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
9QRU	ELECTRON MICROSCOPY	3.03
9QS6	ELECTRON MICROSCOPY	3.3
9QSH	ELECTRON MICROSCOPY	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60291-F1	66.59	0.32

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 (4): 471, 524, 2, 411

Mutagenesis-validated functional residues (1):

Position	Phenotype
406–409	loss of tsg101-binding and drastic reduction of tsg101-ubiquitination.

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: 203 (showing top): GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_PHENOL_CONTAINING_COMPOUND_BIOSYNTHETIC_PROCESS, GOBP_LYSOSOMAL_TRANSPORT, GOBP_BEHAVIOR, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GOBP_ENDOSOME_TO_LYSOSOME_TRANSPORT, MORF_HDAC1, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_VACUOLAR_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_BEHAVIOR, GOBP_VESICLE_MEDIATED_TRANSPORT, BROWNE_HCMV_INFECTION_48HR_DN

GO Biological Process (12): protein polyubiquitination (GO:0000209), protein monoubiquitination (GO:0006513), smoothened signaling pathway (GO:0007224), heart development (GO:0007507), endosome to lysosome transport (GO:0008333), protein ubiquitination (GO:0016567), negative regulation of G protein-coupled receptor signaling pathway (GO:0045744), negative regulation of smoothened signaling pathway (GO:0045879), negative regulation of melanin biosynthetic process (GO:0048022), protein-containing complex assembly (GO:0065003), negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0106072), positive regulation of eating behavior (GO:1904000)

GO Molecular Function (7): ubiquitin-protein transferase activity (GO:0004842), zinc ion binding (GO:0008270), ubiquitin protein ligase activity (GO:0061630), protein sequestering activity (GO:0140311), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (10): ubiquitin ligase complex (GO:0000151), nucleus (GO:0005634), cytoplasm (GO:0005737), early endosome (GO:0005769), endoplasmic reticulum (GO:0005783), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), extracellular exosome (GO:0070062), endosome (GO:0005768)

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
cellular anatomical structure	3
protein ubiquitination	2
negative regulation of signal transduction	2
intracellular membrane-bounded organelle	2
cytoplasm	2
endomembrane system	2
cell surface receptor signaling pathway	1
animal organ development	1
circulatory system development	1
lysosomal transport	1
intercellular transport	1
vesicle-mediated transport	1
protein modification by small protein conjugation	1
G protein-coupled receptor signaling pathway	1
regulation of G protein-coupled receptor signaling pathway	1
smoothened signaling pathway	1
regulation of smoothened signaling pathway	1
melanin biosynthetic process	1
regulation of melanin biosynthetic process	1
negative regulation of secondary metabolite biosynthetic process	1
cellular component assembly	1
protein-containing complex organization	1
adenylate cyclase-activating G protein-coupled receptor signaling pathway	1
negative regulation of G protein-coupled receptor signaling pathway	1
regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway	1
eating behavior	1
regulation of eating behavior	1
positive regulation of feeding behavior	1
ubiquitin-like protein transferase activity	1
transition metal ion binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
protein binding	1
molecular sequestering activity	1
binding	1
catalytic activity	1
cation binding	1
intracellular protein-containing complex	1
transferase complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1076 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MGRN1	ATRN	O75882	962
MGRN1	MEGF8	Q7Z7M0	849
MGRN1	CDC34	P49427	718
MGRN1	MC1R	Q01726	695
MGRN1	ATXN3L	Q9H3M9	572
MGRN1	ASIP	P42127	571
MGRN1	ATXN3	P54252	554
MGRN1	ARIH2	O95376	528
MGRN1	MOSMO	Q8NHV5	512
MGRN1	AMFR	P26442	510
MGRN1	ASB7	Q9H672	508
MGRN1	HTT	P42858	494
MGRN1	ASB13	Q8WXK3	489
MGRN1	POLR3K	Q9Y2Y1	488
MGRN1	KLHL20	Q9Y2M5	470

IntAct

86 interactions, top by confidence:

A	B	Type	Score
MGRN1	TSG101	psi-mi:“MI:0915”(physical association)	0.750
TSG101	MGRN1	psi-mi:“MI:0407”(direct interaction)	0.750
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
LGALS1	PODXL	psi-mi:“MI:0914”(association)	0.530
PSG8	PEX7	psi-mi:“MI:0914”(association)	0.530
MGRN1	ATRN	psi-mi:“MI:0914”(association)	0.530
SMPD1	CLGN	psi-mi:“MI:0914”(association)	0.530
PSG3	MGRN1	psi-mi:“MI:0914”(association)	0.530
CENPH	PSMD11	psi-mi:“MI:0914”(association)	0.530
EDN3	MGRN1	psi-mi:“MI:0914”(association)	0.530
PSG8	MGRN1	psi-mi:“MI:0914”(association)	0.530
UBE2G2	MGRN1	psi-mi:“MI:0915”(physical association)	0.370
UBE2D1	MGRN1	psi-mi:“MI:0915”(physical association)	0.370
MGRN1	UBE2D2	psi-mi:“MI:0915”(physical association)	0.370
UBE2D3	MGRN1	psi-mi:“MI:0915”(physical association)	0.370
MGRN1	UBE2E1	psi-mi:“MI:0915”(physical association)	0.370
MGRN1	UBE2I	psi-mi:“MI:0915”(physical association)	0.370
MGRN1	UBE2T	psi-mi:“MI:0915”(physical association)	0.370
MGRN1	UBE2D4	psi-mi:“MI:0915”(physical association)	0.370
MGRN1	UBE2W	psi-mi:“MI:0915”(physical association)	0.370
MGRN1	UBE2Q2	psi-mi:“MI:0915”(physical association)	0.370
MGRN1		psi-mi:“MI:0915”(physical association)	0.370

BioGRID (156): APBB1 (Affinity Capture-Western), MGRN1 (Affinity Capture-Western), MGRN1 (Two-hybrid), MGRN1 (Affinity Capture-MS), MGRN1 (Affinity Capture-MS), MGRN1 (Affinity Capture-MS), MGRN1 (Affinity Capture-MS), MGRN1 (Affinity Capture-Western), AMFR (Affinity Capture-Western), MGRN1 (Affinity Capture-MS), MGRN1 (Affinity Capture-MS), ANKRD46 (Affinity Capture-MS), ATRN (Affinity Capture-MS), C9orf40 (Affinity Capture-MS), MGRN1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0N7L4N2, A5WV69, B9G4M9, C5DQ18, D0NMF4, E2AX35, F4JP36, O13980, O43085, O60291, O96838, P0CO33, P0CV11, P34335, P34535, P34553, P39718, P53117, P53224, P53938, P58239, P60571, P62512, P85831, P87139, Q09446, Q10109, Q19192, Q20687, Q4WIN1, Q5B8K7, Q5R9E4, Q624D2, Q6C3U1, Q6CAP3, Q6TLE4, Q700C2, Q74ZY6, Q756T2, Q75C24

Diamond homologs: A8MQ27, O60291, O76050, Q0MW30, Q0WS06, Q3TEL6, Q4FE47, Q557E7, Q5M870, Q5XIQ4, Q6INH1, Q6R7D2, Q7ZUL9, Q84ME1, Q8CJC5, Q8VCM5, Q923S6, Q94HV7, Q96EH8, Q96PX1, Q9BR09, Q9D074, Q9D0S4, M0R5D6, Q8LA32, Q9LFH6, Q9S752, Q8BUH7, Q9BY78, Q9LDD1, Q9LYW5, Q9SJU0, Q8L7N4, A1E2V0, O10296, O62640, P41435, P41437, Q24306, Q8W5R5

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	MGRN1	ubiquitination
MGRN1	“up-regulates activity”	TSG101	monoubiquitination
UBE2D1	“up-regulates activity”	MGRN1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 83 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
Synthesis of active ubiquitin: roles of E1 and E2 enzymes	7	46.0×	4e-08
E3 ubiquitin ligases ubiquitinate target proteins	5	17.3×	7e-04
Downstream TCR signaling	5	11.5×	4e-03
Antigen processing: Ubiquitination & Proteasome degradation	10	6.6×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
protein K48-linked ubiquitination	8	20.4×	3e-06
protein modification process	5	18.5×	9e-04
ERAD pathway	5	13.7×	2e-03
protein polyubiquitination	7	12.2×	4e-04
ubiquitin-dependent protein catabolic process	8	9.0×	5e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	112
Likely benign	12
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

3349 predictions. Top by Δscore:

Variant	Effect	Δscore
16:4625044:GTCCG:G	donor_gain	1.0000
16:4625049:G:GG	donor_gain	1.0000
16:4625049:GTG:G	donor_loss	1.0000
16:4625050:T:G	donor_loss	1.0000
16:4650359:A:AG	acceptor_gain	1.0000
16:4650360:A:G	acceptor_gain	1.0000
16:4650362:CA:C	acceptor_loss	1.0000
16:4650363:A:AG	acceptor_gain	1.0000
16:4650363:AG:A	acceptor_gain	1.0000
16:4650364:G:GA	acceptor_gain	1.0000
16:4650364:GG:G	acceptor_gain	1.0000
16:4650364:GGA:G	acceptor_gain	1.0000
16:4650364:GGAA:G	acceptor_gain	1.0000
16:4650364:GGAAA:G	acceptor_gain	1.0000
16:4650479:TCCAG:T	donor_loss	1.0000
16:4650481:CAGGT:C	donor_loss	1.0000
16:4650482:AGGT:A	donor_loss	1.0000
16:4650483:GG:G	donor_loss	1.0000
16:4650484:GTG:G	donor_loss	1.0000
16:4650485:T:G	donor_loss	1.0000
16:4651959:CTAG:C	acceptor_loss	1.0000
16:4651960:TA:T	acceptor_loss	1.0000
16:4651961:A:AC	acceptor_loss	1.0000
16:4651961:A:AG	acceptor_gain	1.0000
16:4651962:G:GG	acceptor_gain	1.0000
16:4651962:GT:G	acceptor_gain	1.0000
16:4651962:GTT:G	acceptor_gain	1.0000
16:4651962:GTTT:G	acceptor_gain	1.0000
16:4651962:GTTTC:G	acceptor_gain	1.0000
16:4652053:T:A	donor_loss	1.0000

AlphaMissense

3762 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:4650373:T:C	F33L	1.000
16:4650374:T:C	F33S	1.000
16:4650375:T:A	F33L	1.000
16:4650375:T:G	F33L	1.000
16:4650385:T:C	F37L	1.000
16:4650387:T:A	F37L	1.000
16:4650387:T:G	F37L	1.000
16:4650406:T:C	F44L	1.000
16:4650408:C:A	F44L	1.000
16:4650408:C:G	F44L	1.000
16:4650434:T:A	L53H	1.000
16:4650436:T:C	F54L	1.000
16:4650437:T:C	F54S	1.000
16:4650438:T:A	F54L	1.000
16:4650438:T:G	F54L	1.000
16:4650440:G:A	G55E	1.000
16:4650455:T:C	L60P	1.000
16:4652030:A:T	K92I	1.000
16:4671406:T:G	Y248D	1.000
16:4671410:T:C	L249P	1.000
16:4671413:T:C	L250P	1.000
16:4671424:T:G	Y254D	1.000
16:4671427:G:C	G255R	1.000
16:4671428:G:A	G255D	1.000
16:4673534:T:A	C278S	1.000
16:4673534:T:C	C278R	1.000
16:4673535:G:A	C278Y	1.000
16:4673535:G:C	C278S	1.000
16:4673536:T:G	C278W	1.000
16:4673541:T:A	V280E	1.000

dbSNP variants (sampled 300 via entrez): RS1000005991 (16:4686956 A>AG), RS1000030996 (16:4647947 C>G,T), RS1000125700 (16:4660245 G>A,C), RS1000149491 (16:4686510 C>G,T), RS1000155459 (16:4653635 C>A,T), RS1000180470 (16:4626811 C>T), RS1000219895 (16:4680853 C>A,G,T), RS1000355199 (16:4680940 G>A), RS1000361087 (16:4645887 GCA>G), RS1000371369 (16:4655590 C>G,T), RS1000377771 (16:4689357 A>G), RS1000502882 (16:4662702 G>C), RS1000513613 (16:4683724 C>G,T), RS1000554852 (16:4639799 C>A), RS1000577593 (16:4676530 C>T)

Disease associations

OMIM: gene MIM:607559 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST005722_2	Milk allergy (maternal genetic effects)	4.000000e-06
GCST010173_87	Triglyceride levels	3.000000e-10
GCST010242_56	HDL cholesterol levels	4.000000e-09
GCST90000025_81	Appendicular lean mass	2.000000e-12
GCST90002384_356	Hemoglobin	1.000000e-09
GCST90020024_741	A body shape index	3.000000e-08

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0005939	parental genotype effect measurement
EFO:0007019	milk allergy measurement
EFO:0004530	triglyceride measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004980	appendicular lean mass
EFO:0004509	hemoglobin measurement
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
nobiletin	decreases expression, decreases reaction	1
sodium arsenate	decreases expression, decreases reaction	1
butyraldehyde	decreases expression	1
aflatoxin B2	decreases methylation	1
ICG 001	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	affects methylation	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Cadmium	decreases expression, increases abundance	1
Caffeine	decreases phosphorylation	1
Cisplatin	decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	increases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Ozone	affects expression, increases abundance	1
Smoke	decreases expression	1
Valproic Acid	decreases expression, increases methylation	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	decreases expression, increases abundance	1
Particulate Matter	increases expression	1
Magnetite Nanoparticles	increases expression, decreases methylation	1

Clinical trials (associated diseases)

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