MARCHF2

Summary

MARCHF2 (membrane associated ring-CH-type finger 2, HGNC:28038) is a protein-coding gene on chromosome 19p13.2, encoding E3 ubiquitin-protein ligase MARCHF2 (Q9P0N8). E3 ubiquitin-protein ligase that may mediate ubiquitination of TFRC and CD86, and promote their subsequent endocytosis and sorting to lysosomes via multivesicular bodies.

MARCH2 is a member of the MARCH family of membrane-bound E3 ubiquitin ligases (EC 6.3.2.19). MARCH enzymes add ubiquitin (see MIM 191339) to target lysines in substrate proteins, thereby signaling their vesicular transport between membrane compartments. MARCH2 reduces surface accumulation of several glycoproteins and appears to regulate early endosome-to-trans-Golgi network (TGN) trafficking (Bartee et al., 2004 [PubMed 14722266]; Nakamura et al., 2005 [PubMed 15689499]).

Source: NCBI Gene 51257 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 58 total
• MANE Select transcript: NM_001005415

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28038
Approved symbol	MARCHF2
Name	membrane associated ring-CH-type finger 2
Location	19p13.2
Locus type	gene with protein product
Status	Approved
Aliases	HSPC240, MARCH-II, RNF172
Ensembl gene	ENSG00000099785
Ensembl biotype	protein_coding
OMIM	613332
Entrez	51257

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 29 protein_coding, 1 retained_intron

ENST00000215555, ENST00000381035, ENST00000594796, ENST00000595142, ENST00000595213, ENST00000601283, ENST00000601724, ENST00000602117, ENST00000860152, ENST00000860153, ENST00000860154, ENST00000860155, ENST00000860156, ENST00000860157, ENST00000860158, ENST00000860159, ENST00000860160, ENST00000860161, ENST00000860162, ENST00000860163, ENST00000860164, ENST00000860165, ENST00000940436, ENST00000961605, ENST00000961606, ENST00000961607, ENST00000961608, ENST00000961609, ENST00000961610, ENST00000961611

RefSeq mRNA: 7 — MANE Select: NM_001005415 NM_001005415, NM_001005416, NM_001369776, NM_001369777, NM_001369778, NM_001369779, NM_016496

CCDS: CCDS12202, CCDS32894

Canonical transcript exons

ENST00000215555 — 5 exons

Exon	Start	End
ENSE00000655621	8430658	8430867
ENSE00001248925	8421789	8422016
ENSE00002998340	8438388	8439017
ENSE00003155730	8413305	8413420
ENSE00003643696	8426609	8426804

Expression profiles

Bgee: expression breadth ubiquitous, 250 present calls, max score 97.83.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.6477 / max 543.2523, expressed in 1801 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
173666	22.0662	1801
173668	0.2901	47
173669	0.2118	23
173667	0.0796	25

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	97.83	gold quality
monocyte	CL:0000576	97.62	gold quality
mononuclear cell	CL:0000842	97.53	gold quality
leukocyte	CL:0000738	97.31	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.60	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.22	gold quality
lower esophagus	UBERON:0013473	96.20	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.02	gold quality
right frontal lobe	UBERON:0002810	95.74	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.73	gold quality
right atrium auricular region	UBERON:0006631	95.71	gold quality
right coronary artery	UBERON:0001625	95.31	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.16	gold quality
granulocyte	CL:0000094	95.08	gold quality
heart left ventricle	UBERON:0002084	95.00	gold quality
gastrocnemius	UBERON:0001388	94.80	gold quality
blood	UBERON:0000178	94.75	gold quality
cardiac atrium	UBERON:0002081	94.58	gold quality
cingulate cortex	UBERON:0003027	94.44	gold quality
muscle of leg	UBERON:0001383	94.43	gold quality
cardiac ventricle	UBERON:0002082	94.42	gold quality
anterior cingulate cortex	UBERON:0009835	94.35	gold quality
left coronary artery	UBERON:0001626	94.27	gold quality
Brodmann (1909) area 9	UBERON:0013540	94.14	gold quality
right lobe of thyroid gland	UBERON:0001119	94.06	gold quality
ascending aorta	UBERON:0001496	93.93	gold quality
popliteal artery	UBERON:0002250	93.91	gold quality
thoracic aorta	UBERON:0001515	93.90	gold quality
tibial artery	UBERON:0007610	93.90	gold quality
aorta	UBERON:0000947	93.74	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-9221	yes	18.87
E-HCAD-1	yes	6.62
E-MTAB-6379	no	55.79
E-MTAB-9467	no	0.78
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

26 targeting MARCHF2, 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-548AW	99.99	72.57	3559
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-6861-3P	99.60	68.46	444
HSA-MIR-891B	99.59	69.81	1083
HSA-MIR-3616-5P	99.55	67.02	989
HSA-MIR-573	99.55	67.44	955
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-12117	99.50	67.57	868
HSA-MIR-142-5P	99.48	70.92	2416
HSA-MIR-5590-3P	99.48	70.91	2429
HSA-MIR-653-5P	99.46	67.35	1300
HSA-MIR-6839-3P	99.39	68.86	1301
HSA-MIR-3678-3P	99.31	67.10	1432
HSA-MIR-664A-3P	99.22	71.08	2696
HSA-MIR-4795-5P	99.11	66.90	876
HSA-MIR-3194-3P	98.83	66.22	1167
HSA-MIR-6728-3P	98.63	67.63	1534
HSA-MIR-1267	98.24	69.05	837
HSA-MIR-6732-3P	98.17	67.52	802
HSA-MIR-3190-3P	97.61	66.95	1406
HSA-MIR-4800-5P	97.22	65.91	324
HSA-MIR-4448	97.04	66.22	752

Literature-anchored findings (GeneRIF, showing 12)

• Depletion of MARCH-II by small interfering RNA perturbed the trans-Golgi network (TGN) localization of syntaxin 6 and TGN38/46 (PMID:15689499)
• MARCH2 is co-localized with DLG1 at sites of cell-cell contact. (PMID:17980554)
• The MARCH2 E3 ligase activity regulates cell surface beta(2)AR expression and, consequently, its signaling. (PMID:23166351)
• Data indicate that E3 ubiquitin ligase MARCH2 co-immunoprecipitated and co-localized with CAL and syntaxin 6 (STX6), and show the ubiquitination of CFTR by MARCH2. (PMID:23818989)
• MARCH2 has a role in regulating autophagy by promoting CFTR ubiquitination and degradation and PIK3CA-AKT-MTOR signaling (PMID:27308891)
• In this study, the authors found the expression of MARCH2 to be upregulated upon HIV-1 infection. MARCH2 inhibits the production and infection of HIV-1 through ligase activity-dependent envelope protein degradation and/or intracellular retention. (PMID:29573664)
• Membrane-associated RING-CH (MARCH) 1 and 2 are MARCH family members that inhibit HIV-1 infection (PMID:30630952)
• MARCH2 reduced secretion of alpha1-antitrypsin and haptoglobin, and coexpression of the ubiquitination-resistant ERGIC3 variant largely restored their secretion, suggesting that MARCH2-mediated ERGIC3 ubiquitination is the major cause of the decrease in trafficking of ERGIC3-binding secretory proteins. (PMID:31142615)
• Human MARCH1, 2, and 8 block Ebola virus envelope glycoprotein cleavage via targeting furin P domain. (PMID:38299743)
• MARCH2, a Novel Oncogene-regulated SNAIL E3 Ligase, Suppresses Triple-negative Breast Cancer Metastases. (PMID:38457262)
• MARCH family E3 ubiquitin ligases selectively target and degrade cadherin family proteins. (PMID:38722959)
• KLF15-activated MARCH2 boosts cell proliferation and epithelial-mesenchymal transition and presents diagnostic significance for hepatocellular carcinoma. (PMID:38848952)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	marchf2	ENSDARG00000061738
mus_musculus	Marchf2	ENSMUSG00000079557
rattus_norvegicus	Marchf2	ENSRNOG00000007769

Paralogs (6): MARCHF9 (ENSG00000139266), MARCHF4 (ENSG00000144583), MARCHF1 (ENSG00000145416), MARCHF8 (ENSG00000165406), MARCHF3 (ENSG00000173926), MARCHF11 (ENSG00000183654)

Protein

Protein identifiers

E3 ubiquitin-protein ligase MARCHF2 — Q9P0N8 (reviewed: Q9P0N8)

Alternative names: Membrane-associated RING finger protein 2, Membrane-associated RING-CH protein II, RING finger protein 172, RING-type E3 ubiquitin transferase MARCHF2

All UniProt accessions (5): Q9P0N8, M0QXU4, M0R0S4, M0R138, M0R1P2

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin-protein ligase that may mediate ubiquitination of TFRC and CD86, and promote their subsequent endocytosis and sorting to lysosomes via multivesicular bodies. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfer the ubiquitin to targeted substrates. Together with GOPC/CAL mediates the ubiquitination and lysosomal degradation of CFTR. Ubiquitinates and therefore mediates the degradation of DLG1. Regulates the intracellular trafficking and secretion of alpha1-antitrypsin/SERPINA1 and HP/haptoglobin via ubiquitination and degradation of the cargo receptor ERGIC3. Negatively regulates the antiviral and antibacterial immune response by repression of the NF-kB and type 1 IFN signaling pathways, via MARCHF2-mediated K48-linked polyubiquitination of IKBKG/NEMO, resulting in its proteasomal degradation. May be involved in endosomal trafficking through interaction with STX6. (Microbial infection) Positively regulates the degradation of Vesicular stomatitis virus (VSV) G protein via the lysosomal degradation pathway. Represses HIV-1 viral production and may inhibit the translocation of HIV-1 env to the cell surface, resulting in decreased viral cell-cell transmission.

Subunit / interactions. Interacts with STX6; the interaction promotes MARCHF2-mediated ubiquitination and degradation of CFTR. Interacts with MARCHF3. Interacts with GOPC/CAL; the interaction leads to CFTR ubiquitination and degradation. Interacts with CFTR; the interaction leads to CFTR ubiquitination and degradation. Interacts (via PDZ domain) with DLG1 (via PDZ domains); the interaction leads to DLG1 ubiquitination and degradation. Interacts with ERGIC3. Interacts with ADRB2. Interacts with IKBKG/NEMO; during the late stages of macrophage viral and bacterial infection; the interaction leads to ubiquitination and degradation of IKBKG/NEMO.

Subcellular location. Endoplasmic reticulum membrane. Lysosome membrane. Endosome membrane. Golgi apparatus membrane. Cytoplasm. Cell membrane.

Tissue specificity. Broadly expressed.

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

Induction. (Microbial infection) Induced by HIV-1 infection.

Pathway. Protein modification; protein ubiquitination.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9P0N8-1	1	yes
Q9P0N8-2	2

RefSeq proteins (7): NP_001005415, NP_001005416, NP_001356705, NP_001356706, NP_001356707, NP_001356708, NP_057580 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001841	Znf_RING	Domain
IPR011016	Znf_RING-CH	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily

Pfam: PF12906

UniProt features (24 total): binding site 8, mutagenesis site 7, transmembrane region 2, sequence variant 2, region of interest 2, chain 1, splice variant 1, zinc finger region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9P0N8-F1	72.53	0.25

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 (8): 90; 93; 106; 109; 64; 67; 80; 82

Mutagenesis-validated functional residues (7):

Position	Phenotype
64	abolishes ubiquitination of ergic3 and cftr, and degradation of cftr; when associated with s-67. reduces ubiquitination
67	abolishes ubiquitination of ergic3 and cftr, and degradation of cftr; when associated with s-64. reduces ubiquitination
90	abolishes ubiquitination of ikbkg/nemo; when associated with s-64 and s-67.
97	reduces ubiquitination of dlg1. no effect on interaction with dlg1. abolishes ubiquitination of and interaction with dlg
106	reduces ubiquitination of dlg1; when associated with s-64, s-67 and s-109.
109	reduces ubiquitination of dlg1; when associated with s-64, s-67 and s-106.
243–246	abolishes ubiquitination of and interaction with dlg1; when associated with a-97.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 163 (showing top): GOCC_VACUOLAR_MEMBRANE, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, KESHELAVA_MULTIPLE_DRUG_RESISTANCE, MARTINEZ_RB1_TARGETS_DN, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CATABOLIC_PROCESS, GOBP_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_DEFENSE_RESPONSE_TO_VIRUS, GOBP_DEFENSE_RESPONSE_TO_BACTERIUM, RICKMAN_TUMOR_DIFFERENTIATED_MODERATELY_VS_POORLY_UP

GO Biological Process (6): endocytosis (GO:0006897), protein ubiquitination (GO:0016567), suppression of viral release by host (GO:0044790), antibacterial innate immune response (GO:0140367), antiviral innate immune response (GO:0140374), positive regulation of lysosomal protein catabolic process (GO:1905167)

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 (14): Golgi membrane (GO:0000139), cytoplasm (GO:0005737), lysosomal membrane (GO:0005765), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), plasma membrane (GO:0005886), endosome membrane (GO:0010008), cytoplasmic vesicle (GO:0031410), lysosome (GO:0005764), endosome (GO:0005768), Golgi apparatus (GO:0005794), endomembrane system (GO:0012505), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cytoplasm	4
endomembrane system	3
defense response to virus	2
innate immune response	2
bounding membrane of organelle	2
intracellular membrane-bounded organelle	2
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	1
protein modification by small protein conjugation	1
defense response to bacterium	1
positive regulation of protein catabolic process in the vacuole	1
lysosomal protein catabolic process	1
regulation of lysosomal protein catabolic process	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
Golgi apparatus	1
intracellular anatomical structure	1
lysosome	1
lytic vacuole membrane	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1
endosome	1
cytoplasmic vesicle membrane	1
intracellular vesicle	1
lytic vacuole	1
cytoplasmic vesicle	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

809 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MARCHF2	STX6	O43752	932
MARCHF2	MARCHF5	Q9NX47	853
MARCHF2	TGOLN2	O43493	815
MARCHF2	TFRC	P02786	641
MARCHF2	VAMP3	Q15836	573
MARCHF2	ITIH2	P19823	558
MARCHF2	MARCHF7	Q9H992	544
MARCHF2	UBE2H	P37286	543
MARCHF2	MAL2	Q969L2	529
MARCHF2	SERINC3	Q13530	524
MARCHF2	H2BC12	O60814	522
MARCHF2	CDC34	P49427	516
MARCHF2	BCAP31	P51572	493
MARCHF2	UBA1	P22314	490
MARCHF2	MARCHF1	Q8TCQ1	486

IntAct

89 interactions, top by confidence:

A	B	Type	Score
MARCHF2	LDLRAD1	psi-mi:“MI:0915”(physical association)	0.780
LDLRAD1	MARCHF2	psi-mi:“MI:0915”(physical association)	0.780
MARCHF2	FATE1	psi-mi:“MI:0915”(physical association)	0.720
FATE1	MARCHF2	psi-mi:“MI:0915”(physical association)	0.720
MARCHF2	ERGIC3	psi-mi:“MI:0915”(physical association)	0.710
MARCHF2	ERGIC3	psi-mi:“MI:2364”(proximity)	0.710
MARCHF2	ERGIC3	psi-mi:“MI:0403”(colocalization)	0.710
ERGIC3	MARCHF2	psi-mi:“MI:0915”(physical association)	0.710
MARCHF2	SYNE4	psi-mi:“MI:0915”(physical association)	0.560
MARCHF2	KASH5	psi-mi:“MI:0915”(physical association)	0.560
KASH5	MARCHF2	psi-mi:“MI:0915”(physical association)	0.560
MARCHF2	MUC1	psi-mi:“MI:0915”(physical association)	0.560
MARCHF2	SCN3B	psi-mi:“MI:0915”(physical association)	0.560
CCL4	MARCHF2	psi-mi:“MI:0915”(physical association)	0.560
CREB3L1	MARCHF2	psi-mi:“MI:0915”(physical association)	0.560
PLPPR2	MARCHF2	psi-mi:“MI:0915”(physical association)	0.560
GPX8	MARCHF2	psi-mi:“MI:0915”(physical association)	0.560
TMEM86B	MARCHF2	psi-mi:“MI:0915”(physical association)	0.560
GJA8	MARCHF2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (100): FATE1 (Two-hybrid), CCDC155 (Two-hybrid), SYNE4 (Two-hybrid), LDLRAD1 (Two-hybrid), CFTR (Affinity Capture-Western), MARCH2 (Affinity Capture-Western), CFTR (Reconstituted Complex), MARCH2 (Affinity Capture-Western), ERGIC3 (Affinity Capture-Western), MARCH2 (Co-localization), MARCH2 (Proximity Label-MS), MARCH2 (Two-hybrid), CD79A (Two-hybrid), LPPR2 (Two-hybrid), TSPAN12 (Two-hybrid)

ESM2 similar proteins: A0A087WTH1, A0A125YWU9, A0PK84, A6PVL3, C9JQL5, F1QHM7, F1QX91, O15503, O41933, O70418, O88728, P0DI73, P13164, P26376, Q01628, Q01629, Q08755, Q0II74, Q21642, Q32L65, Q3UNB8, Q3YBM2, Q5FVR1, Q5FWL7, Q5I0I2, Q5R8D6, Q5RF75, Q5Y5T3, Q6DHI1, Q76IC6, Q7M734, Q7TQJ1, Q8BGI3, Q8CES1, Q8CFA6, Q8IYP9, Q8N6L7, Q8WVZ1, Q91WU6, Q921C1

Diamond homologs: A0JN69, A6NNE9, A6P320, F4JKK0, O60103, O60337, P40318, P90489, P90495, Q0IH10, Q0P496, Q0VD59, Q1LVZ2, Q28EX7, Q32L65, Q3TZ87, Q5I0I2, Q5PQ35, Q5R9W1, Q5T0T0, Q5XIE5, Q5XIV2, Q68FA7, Q6NZQ8, Q6ZQ89, Q80TE3, Q86UD3, Q86YJ5, Q8BRX9, Q8CBH7, Q8TCQ1, Q99M02, Q9DBD2, Q9P0N8, Q9P2E8, Q0X0A5, Q28IK8, Q3KNM2, Q3ZC24, Q5R9W2

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	MARCHF2	ubiquitination
MARCHF2	“down-regulates quantity by destabilization”	CFTR	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	47
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1482 predictions. Top by Δscore:

Variant	Effect	Δscore
19:8426607:A:AG	acceptor_gain	1.0000
19:8426607:AGT:A	acceptor_gain	1.0000
19:8426608:G:GG	acceptor_gain	1.0000
19:8426608:GT:G	acceptor_gain	1.0000
19:8426608:GTG:G	acceptor_gain	1.0000
19:8426608:GTGAT:G	acceptor_gain	1.0000
19:8430654:GCA:G	acceptor_loss	1.0000
19:8430655:CA:C	acceptor_loss	1.0000
19:8430656:A:AG	acceptor_gain	1.0000
19:8430656:AGT:A	acceptor_gain	1.0000
19:8430657:G:GA	acceptor_gain	1.0000
19:8430657:GT:G	acceptor_gain	1.0000
19:8430657:GTG:G	acceptor_gain	1.0000
19:8430864:GCTG:G	donor_gain	1.0000
19:8430865:CTGG:C	donor_loss	1.0000
19:8430866:TGG:T	donor_loss	1.0000
19:8430868:G:GG	donor_gain	1.0000
19:8430868:GT:G	donor_loss	1.0000
19:8430869:T:A	donor_loss	1.0000
19:8413419:AGG:A	donor_loss	0.9900
19:8413421:G:GC	donor_loss	0.9900
19:8421773:ACT:A	acceptor_gain	0.9900
19:8421775:T:A	acceptor_gain	0.9900
19:8421810:AGGC:A	donor_gain	0.9900
19:8426605:CCA:C	acceptor_loss	0.9900
19:8426607:A:AC	acceptor_loss	0.9900
19:8426608:G:GT	acceptor_loss	0.9900
19:8426608:GTGA:G	acceptor_gain	0.9900
19:8426609:T:TA	acceptor_gain	0.9900
19:8426802:G:GT	donor_gain	0.9900

AlphaMissense

1569 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:8426629:T:C	I66T	1.000
19:8426676:T:A	C82S	1.000
19:8426677:G:C	C82S	1.000
19:8426709:T:C	C93R	1.000
19:8426711:T:G	C93W	1.000
19:8426721:T:A	W97R	1.000
19:8426721:T:C	W97R	1.000
19:8426723:G:C	W97C	1.000
19:8426723:G:T	W97C	1.000
19:8426725:T:C	L98P	1.000
19:8426748:T:A	C106S	1.000
19:8426748:T:C	C106R	1.000
19:8426749:G:A	C106Y	1.000
19:8426749:G:C	C106S	1.000
19:8426750:C:G	C106W	1.000
19:8426757:T:A	C109S	1.000
19:8426757:T:C	C109R	1.000
19:8426758:G:C	C109S	1.000
19:8426770:T:C	F113S	1.000
19:8430658:T:A	W125R	1.000
19:8430658:T:C	W125R	1.000
19:8430707:A:C	D141A	1.000
19:8430707:A:T	D141V	1.000
19:8430818:T:C	L178P	1.000
19:8430827:T:C	L181P	1.000
19:8430859:T:A	W192R	1.000
19:8430859:T:C	W192R	1.000
19:8438424:T:A	W207R	1.000
19:8438424:T:C	W207R	1.000
19:8438426:G:C	W207C	1.000

dbSNP variants (sampled 300 via entrez): RS1000235901 (19:8419605 A>G), RS1000251345 (19:8419767 G>A,C), RS1000372333 (19:8424491 C>A,T), RS1000529588 (19:8427393 C>G,T), RS1000554807 (19:8416198 C>T), RS1000596483 (19:8430090 G>A,T), RS1000658222 (19:8423109 G>A), RS1000827975 (19:8424683 A>G,T), RS1000850048 (19:8435018 T>A,C), RS1000896806 (19:8436149 T>G), RS1001071008 (19:8414826 G>A,T), RS1001131325 (19:8428696 G>A,T), RS1001183560 (19:8413341 C>A,G,T), RS1001269741 (19:8428482 T>A,C), RS1001583146 (19:8424417 C>T)

Disease associations

OMIM: gene MIM:613332 | 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
GCST006979_746	Heel bone mineral density	1.000000e-11
GCST90002390_519	Mean corpuscular hemoglobin	4.000000e-10
GCST90002392_58	Mean corpuscular volume	2.000000e-13

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density
EFO:0004527	mean corpuscular hemoglobin

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, affects expression, increases expression	5
Benzo(a)pyrene	affects methylation, increases expression	4
(+)-JQ1 compound	decreases expression, increases expression	2
Acetaminophen	decreases expression, increases expression	2
tert-Butylhydroperoxide	decreases expression, increases methylation	2
bisphenol F	increases expression, affects cotreatment	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
di-n-butylphosphoric acid	affects expression	1
perfluoro-n-nonanoic acid	decreases expression	1
entinostat	increases expression	1
abrine	decreases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	increases expression	1
Air Pollutants	increases abundance, decreases expression	1
Cadmium	increases abundance, increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	affects expression	1
Ethyl Methanesulfonate	increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Pantothenic Acid	increases expression	1
Selenium	increases expression	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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