MARCHF8

Summary

MARCHF8 (membrane associated ring-CH-type finger 8, HGNC:23356) is a protein-coding gene on chromosome 10q11.21-q11.22, encoding E3 ubiquitin-protein ligase MARCHF8 (Q5T0T0). E3 ubiquitin-protein ligase that plays several important roles in innate immunity and adaptive immunity.

MARCH8 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. MARCH8 induces the internalization of several membrane glycoproteins (Goto et al., 2003 [PubMed 12582153]; Bartee et al., 2004 [PubMed 14722266]).

Source: NCBI Gene 220972 — RefSeq curated summary.

At a glance

• GWAS associations: 46
• Clinical variants (ClinVar): 4 total
• MANE Select transcript: NM_001282866

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23356
Approved symbol	MARCHF8
Name	membrane associated ring-CH-type finger 8
Location	10q11.21-q11.22
Locus type	gene with protein product
Status	Approved
Aliases	c-MIR, CMIR, MARCH-VIII, RNF178
Ensembl gene	ENSG00000165406
Ensembl biotype	protein_coding
OMIM	613335
Entrez	220972

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 20 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000319836, ENST00000395769, ENST00000451376, ENST00000453424, ENST00000453980, ENST00000476962, ENST00000602712, ENST00000855428, ENST00000855429, ENST00000855430, ENST00000855431, ENST00000855432, ENST00000855433, ENST00000855434, ENST00000855435, ENST00000855437, ENST00000855438, ENST00000912270, ENST00000912271, ENST00000912272, ENST00000912273, ENST00000960530, ENST00000960531

RefSeq mRNA: 5 — MANE Select: NM_001282866 NM_001002266, NM_001282866, NM_001401645, NM_001401646, NM_145021

CCDS: CCDS60519, CCDS7213

Canonical transcript exons

ENST00000395771 — 0 exons

Expression profiles

Bgee: expression breadth ubiquitous, 135 present calls, max score 96.28.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.9986 / max 1716.9630, expressed in 1785 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
109241	9.1481	1688
109240	3.2597	592
109242	2.3822	1314
109239	0.1503	28
109232	0.0532	4
109233	0.0051	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
thymus	UBERON:0002370	96.28	silver quality
bone marrow cell	CL:0002092	95.31	gold quality
blood	UBERON:0000178	94.45	gold quality
bone marrow	UBERON:0002371	94.11	gold quality
islet of Langerhans	UBERON:0000006	92.36	gold quality
corpus callosum	UBERON:0002336	92.35	gold quality
right testis	UBERON:0004534	92.22	gold quality
left testis	UBERON:0004533	92.09	gold quality
testis	UBERON:0000473	91.84	gold quality
monocyte	CL:0000576	90.97	gold quality
leukocyte	CL:0000738	90.95	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.85	gold quality
pancreas	UBERON:0001264	88.35	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.01	gold quality
right adrenal gland cortex	UBERON:0035827	87.99	gold quality
rectum	UBERON:0001052	87.76	gold quality
ventricular zone	UBERON:0003053	87.66	gold quality
granulocyte	CL:0000094	87.60	gold quality
spinal cord	UBERON:0002240	87.51	gold quality
cerebellum	UBERON:0002037	87.50	gold quality
cerebellar hemisphere	UBERON:0002245	87.49	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	87.49	gold quality
cerebellar cortex	UBERON:0002129	87.47	gold quality
right adrenal gland	UBERON:0001233	87.38	gold quality
colonic epithelium	UBERON:0000397	87.21	gold quality
left adrenal gland	UBERON:0001234	87.19	gold quality
adrenal gland	UBERON:0002369	87.16	gold quality
tonsil	UBERON:0002372	87.15	gold quality
right hemisphere of cerebellum	UBERON:0014890	87.15	gold quality
left adrenal gland cortex	UBERON:0035825	87.11	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-9221	yes	20.56
E-ANND-3	yes	5.73
E-MTAB-9467	no	1.88

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

158 targeting MARCHF8, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
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-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-8062	99.88	68.43	995
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-20B-5P	99.88	74.01	2621

Literature-anchored findings (GeneRIF, showing 30)

• c-MIR induced specific down-regulation of B7-2 surface expression through ubiquitination, rapid endocytosis, and lysosomal degradation (PMID:12582153)
• Of the classifier’s 11 informative genes, expression of MIR and WDR40 showed statistically significant increases for both Grade 1B and Grade >or=3A rejection. (PMID:18096478)
• Membrane-Associated RING-CH proteins MARCH VIII and MARCH IV associate with Bap31 and target CD81 and CD44 to lysosomes (PMID:21151997)
• MARCH8 protein localizes in lysosomes in HeLa cells (PMID:21752829)
• MARCH8 expression led to direct ubiquitination of CD98 and routing of CD98 to late endosomes/lysosomes (PMID:21757542)
• MARCH8-mediated polyubiquitination and degradation of IL1RAP is an important mechanism for negative regulation of IL-1beta-induced signaling pathways. (PMID:22904187)
• endogenous MARCH-8 regulates the steady-state cell surface expression of TRAIL-R1. (PMID:23300075)
• MARCH 8 mediates the ubiquitination and lysosomal degradation of the transferrin receptor. (PMID:23606747)
• MARCH8 is highly expressed in terminally differentiated myeloid cells, and that it is a potent antiviral protein that targets viral envelope glycoproteins and reduces their incorporation into virions. (PMID:26523972)
• Kaposi’s sarcoma-associated herpesvirus RTA not only downregulated HLA-DRalpha at the protein level through direct binding and degradation through the proteasome pathway but also indirectly downregulated the protein level of HLA-DRalpha by enhancing the expression of MARCH8, a member of the membrane-associated RING-CH (MARCH) proteins. (PMID:27356905)
• Salmonella typhimurium SteD caused MARCH8-dependent ubiquitination and depletion of surface-localized mature MHC class II antigens. (PMID:27832589)
• YopJ mediates Ser- and Lys-acetylation and affects auto-ubiquitination of ubiquitin ligase MARCH8 in human cells. (PMID:28103160)
• Two additional regulators of BST2 constitutive ubiquitylation and sorting to the lysosomes: the E3 ubiquitin ligases NEDD4 and MARCH8, are reported. (PMID:28320822)
• Knockdown of MARCH8 inactivated the PI3K and ss-catenin stat3 signaling pathways by changing protein expression levels or the phosphorylation of related proteins and inhibited migration and invasion of MKN-45 and AGS cells. (PMID:30138931)
• MARCH8, a RING-finger E3 ligase, catalyzes K63-linked NS2 polyubiquitination in vitro and in HCV-infected cells. MARCH8 is required for infection with HCV, dengue, and Zika viruses and specifically mediates HCV envelopment. (PMID:30759391)
• MHC II ubiquitination by E3 ubiquitin-protein ligase MARCH8 (MARCH8) and CD83 antigen (CD83) plays a critical role in T cell thymic selection [Review]. (PMID:31063934)
• MicroRNA-199a-5p regulates glioma progression via targeting MARCH8. (PMID:31539136)
• MARCH8 inhibits viral infection by two different mechanisms. (PMID:32778221)
• MARCH8 Inhibits Ebola Virus Glycoprotein, Human Immunodeficiency Virus Type 1 Envelope Glycoprotein, and Avian Influenza Virus H5N1 Hemagglutinin Maturation. (PMID:32934085)
• Membrane-Associated RING-CH 8 Functions as a Novel PD-L1 E3 Ligase to Mediate PD-L1 Degradation Induced by EGFR Inhibitors. (PMID:34183449)
• MARCH8 inhibits influenza A virus infection by targeting viral M2 protein for ubiquitination-dependent degradation in lysosomes. (PMID:34285233)
• MARCH8 Restricts Influenza A Virus Infectivity but Does Not Downregulate Viral Glycoprotein Expression at the Surface of Infected Cells. (PMID:34517760)
• Membrane-associated RING-CH protein (MARCH8) is a novel glycolysis repressor targeted by miR-32 in colorectal cancer. (PMID:36064706)
• HPV upregulates MARCHF8 ubiquitin ligase and inhibits apoptosis by degrading the death receptors in head and neck cancer. (PMID:36867660)
• Ubiquitin ligase MARCH8 promotes the malignant progression of hepatocellular carcinoma through PTEN ubiquitination and degradation. (PMID:37098835)
• E3 Ubiquitin Ligase MARCH8 Promotes Pancreatic Cancer Growth and Metastasis by Activating STAT3 via Degradation of PTPN4. (PMID:37747937)
• EGR1 functions as a new host restriction factor for SARS-CoV-2 to inhibit virus replication through the E3 ubiquitin ligase MARCH8. (PMID:37772822)
• The membrane-associated ubiquitin ligase MARCHF8 stabilizes the human papillomavirus oncoprotein E7 by degrading CUL1 and UBE2L3 in head and neck cancer. (PMID:38226814)
• Human MARCH1, 2, and 8 block Ebola virus envelope glycoprotein cleavage via targeting furin P domain. (PMID:38299743)
• MARCH8 inhibits pseudorabies virus replication by trapping the viral cell-to-cell fusion complex in the trans-Golgi network. (PMID:38944094)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	marchf8	ENSDARG00000062489
mus_musculus	Marchf8	ENSMUSG00000025702
rattus_norvegicus	Marchf8	ENSRNOG00000012297
drosophila_melanogaster	CG4080	FBGN0035983

Paralogs (6): MARCHF2 (ENSG00000099785), MARCHF9 (ENSG00000139266), MARCHF4 (ENSG00000144583), MARCHF1 (ENSG00000145416), MARCHF3 (ENSG00000173926), MARCHF11 (ENSG00000183654)

Protein

Protein identifiers

E3 ubiquitin-protein ligase MARCHF8 — Q5T0T0 (reviewed: Q5T0T0)

Alternative names: Cellular modulator of immune recognition, Membrane-associated RING finger protein 8, Membrane-associated RING-CH protein VIII, RING finger protein 178, RING-type E3 ubiquitin transferase MARCHF8

All UniProt accessions (2): A0A0A0MSM7, Q5T0T0

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin-protein ligase that plays several important roles in innate immunity and adaptive immunity. Mediates ubiquitination of CD86 and MHC class II proteins, such as HLA-DR alpha and beta, and promotes their subsequent endocytosis and sorting to lysosomes via multivesicular bodies. Possesses a very broad antiviral activity by specifically inactivating different viral fusion proteins. Targets and ubiquitinates cytoplasmic lysine residues of viral envelope glycoproteins with single transmembrane domains leading to their lysosomal degradation. Therefore, shows broad-spectrum inhibition against many viruses including retroviruses, rhabdoviruses, arenaviruses, sarbecoviruses or influenzaviruses. Strongly blocks human immunodeficiency virus type 1 envelope glycoprotein incorporation into virions by down-regulating its cell surface expression. Also blocks ebola virus glycoprotein/GP incorporation via surface down-regulation. Mediates ‘Lys-63’-linked polyubiquitination of influenza M2 to target it to lysosome for degradation. Mediates the regulation of constitutive ubiquitination and trafficking of the viral restriction factor BST2 within the endocytic pathway. Plays a role in maintenance of immune tolerance to self by promoting the turnover and proteasomal degradation of PD-L1/CD274 via ubiquitination. Catalyzes the ‘Lys-63’-linked polyubiquitylation of cGAS thereby inhibiting its DNA binding ability and impairing its antiviral innate immunity. Negatively regulates IL7-mediated T-cell homeostasis by mediating ‘Lys-27’-linked polyubiquitination of IL7R, leading to its lysosomal degradation. (Microbial infection) Mediates ‘Lys-63’-linked polyubiquitination of hepatitis C virus/HCV protein NS2 which allows its binding to HGS, an ESCRT-0 complex component, and this interaction is essential for HCV envelopment.

Subunit / interactions. Interacts with CD86.

Subcellular location. Golgi apparatus membrane. Endoplasmic reticulum membrane. Cytoplasmic vesicle membrane. Lysosome membrane. Early endosome membrane.

Tissue specificity. Broadly expressed. Present in immature dendritic cells (at protein level).

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

Pathway. Protein modification; protein ubiquitination.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5T0T0-1	1	yes
Q5T0T0-2	2

RefSeq proteins (5): NP_001002266, NP_001269795, NP_001388574, NP_001388575, NP_659458 (=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 (30 total): binding site 8, mutagenesis site 5, strand 5, transmembrane region 2, sequence variant 2, compositionally biased region 2, chain 1, modified residue 1, splice variant 1, helix 1, zinc finger region 1, region of interest 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2D8S	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5T0T0-F1	71.21	0.44

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): 99; 107; 110; 123; 126; 80; 83; 97

Post-translational modifications (1): 253

Mutagenesis-validated functional residues (5):

Position	Phenotype
80	strong loss of catalytic activity; when associated with s-83, s-123 and s-126.
83	strong loss of catalytic activity; when associated with s-80, s-123 and s-126.
114	almost complete loss of ebolavirus restriction and il7r degradation.
123	strong loss of catalytic activity; when associated with s-80, s-83 and s-126.
126	strong loss of catalytic activity; when associated with s-80, s-83 and s-123.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 203 (showing top): RNGTGGGC_UNKNOWN, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_OF_PEPTIDE_OR_POLYSACCHARIDE_ANTIGEN_VIA_MHC_CLASS_II, GOCC_VACUOLAR_MEMBRANE, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_OF_PEPTIDE_ANTIGEN, GNF2_ANK1, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION, GNF2_SPTA1, GOBP_ADAPTIVE_IMMUNE_RESPONSE, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_PROTEIN_POLYUBIQUITINATION, GNF2_PCAF, CAIRO_HEPATOBLASTOMA_UP, GOBP_PROTEASOMAL_PROTEIN_CATABOLIC_PROCESS

GO Biological Process (7): protein polyubiquitination (GO:0000209), adaptive immune response (GO:0002250), antigen processing and presentation of peptide antigen via MHC class II (GO:0002495), immune response (GO:0006955), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), immune system process (GO:0002376), protein ubiquitination (GO:0016567)

GO Molecular Function (7): ubiquitin-protein transferase activity (GO:0004842), zinc ion binding (GO:0008270), MHC protein binding (GO:0042287), 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), lysosome (GO:0005764), lysosomal membrane (GO:0005765), endosome (GO:0005768), endoplasmic reticulum membrane (GO:0005789), host cell plasma membrane (GO:0020002), early endosome membrane (GO:0031901), late endosome membrane (GO:0031902), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), membrane (GO:0016020), cytoplasmic vesicle membrane (GO:0030659), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
endomembrane system	3
cytoplasm	3
cellular anatomical structure	2
cytoplasmic vesicle	2
endosome membrane	2
intracellular membrane-bounded organelle	2
protein ubiquitination	1
immune response	1
antigen processing and presentation of peptide or polysaccharide antigen via MHC class II	1
antigen processing and presentation of peptide antigen	1
immune system process	1
response to stimulus	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
biological_process	1
protein modification by small protein conjugation	1
ubiquitin-like protein transferase activity	1
transition metal ion binding	1
signaling receptor binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
binding	1
catalytic activity	1
cation binding	1
Golgi apparatus	1
bounding membrane of organelle	1
intracellular anatomical structure	1
lytic vacuole	1
lysosome	1
lytic vacuole membrane	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
host cell membrane	1
early endosome	1
late endosome	1
vesicle membrane	1
intracellular vesicle	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

22 interactions, top by confidence:

A	B	Type	Score
VAMP2	MARCHF8	psi-mi:“MI:0915”(physical association)	0.560
CYB5B	MARCHF8	psi-mi:“MI:0915”(physical association)	0.560
MARCHF8	TMEM14C	psi-mi:“MI:0915”(physical association)	0.560
ARR3	MARCHF8	psi-mi:“MI:0915”(physical association)	0.560
GOSR2	MARCHF8	psi-mi:“MI:0915”(physical association)	0.560
MARCHF8	FA2H	psi-mi:“MI:0915”(physical association)	0.560
K4.2	GLI4	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
CCDC47	ESYT2	psi-mi:“MI:0914”(association)	0.350
TMEM14C	MARCHF8	psi-mi:“MI:0915”(physical association)	0.000
GOSR2	MARCHF8	psi-mi:“MI:0915”(physical association)	0.000
FA2H	MARCHF8	psi-mi:“MI:0915”(physical association)	0.000
CYB5B	MARCHF8	psi-mi:“MI:0915”(physical association)	0.000
ARR3	MARCHF8	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (152): MARCH8 (Biochemical Activity), MARCH8 (Affinity Capture-MS), MARCH8 (PCA), MARCH8 (Affinity Capture-Western), HCVgp1 (Affinity Capture-Western), HCVgp1 (Biochemical Activity), UBE2H (Reconstituted Complex), MARCH8 (Two-hybrid), MARCH8 (Two-hybrid), MARCH8 (Two-hybrid), MARCH8 (Two-hybrid), MARCH8 (Two-hybrid), VAMP2 (Two-hybrid), MARCH8 (Affinity Capture-Western), CCDC47 (Affinity Capture-MS)

ESM2 similar proteins: A0A571BF63, A0JMQ9, A0JN69, A1L1R5, E7EZI4, O41933, P0C7U3, P33279, P40145, P97490, Q0IH10, Q0VD59, Q11122, Q1L8G6, Q1LVZ2, Q28EX7, Q28GL3, Q28IK8, Q32L65, Q3UF64, Q4R8E0, Q5I0I2, Q5M7Z0, Q5PQ35, Q5RAG4, Q5T0T0, Q5XH39, Q5XIE5, Q68FA7, Q6NRX0, Q6NTV1, Q6NZ21, Q6NZQ8, Q6ZPS6, Q6ZUJ8, Q803Q4, Q86UD3, Q8BGN6, Q8BPQ7, Q8BRX9

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

7 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	MARCHF8	ubiquitination
MARCHF8	“down-regulates quantity by destabilization”	HLA-DRB4	polyubiquitination
MARCHF8	“down-regulates quantity by destabilization”	HLA-DRB3	polyubiquitination
MARCHF8	“down-regulates quantity by destabilization”	HLA-DRA	polyubiquitination
MARCHF8	“down-regulates quantity by destabilization”	SLC3A2	polyubiquitination
MARCHF8	“down-regulates quantity”	TNFRSF10A	ubiquitination
MARCHF8	“down-regulates quantity by destabilization”	CDH1	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

2131 predictions. Top by Δscore:

Variant	Effect	Δscore
10:45458191:T:A	donor_gain	1.0000
10:45459115:CTCA:C	donor_loss	1.0000
10:45459116:TCACC:T	donor_loss	1.0000
10:45459117:CA:C	donor_loss	1.0000
10:45459118:A:AC	donor_gain	1.0000
10:45459119:C:CC	donor_gain	1.0000
10:45459263:TCCCA:T	acceptor_gain	1.0000
10:45459264:CCCA:C	acceptor_gain	1.0000
10:45459264:CCCAC:C	acceptor_gain	1.0000
10:45459265:CCA:C	acceptor_gain	1.0000
10:45459265:CCAC:C	acceptor_gain	1.0000
10:45459266:CA:C	acceptor_gain	1.0000
10:45459266:CAC:C	acceptor_gain	1.0000
10:45459267:ACTA:A	acceptor_loss	1.0000
10:45459268:C:CC	acceptor_gain	1.0000
10:45459268:C:T	acceptor_loss	1.0000
10:45459269:T:G	acceptor_loss	1.0000
10:45461227:GTA:G	donor_loss	1.0000
10:45461228:TACTT:T	donor_loss	1.0000
10:45461229:A:AC	donor_gain	1.0000
10:45461229:A:C	donor_loss	1.0000
10:45461230:C:CG	donor_gain	1.0000
10:45461230:CT:C	donor_gain	1.0000
10:45461230:CTTTT:C	donor_gain	1.0000
10:45461276:G:A	donor_gain	1.0000
10:45461410:TC:T	acceptor_gain	1.0000
10:45461411:CC:C	acceptor_gain	1.0000
10:45461411:CCTA:C	acceptor_loss	1.0000
10:45461412:C:CC	acceptor_gain	1.0000
10:45461412:CT:C	acceptor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000021639 (10:45563885 T>A), RS1000033858 (10:45569496 G>A), RS1000039093 (10:45576894 C>T), RS1000107217 (10:45473765 C>G), RS1000126166 (10:45492952 A>G), RS1000138732 (10:45565384 T>C), RS1000144250 (10:45589099 C>T), RS1000171430 (10:45540726 A>G), RS1000176506 (10:45475255 C>A,T), RS1000185135 (10:45521138 T>C), RS1000215993 (10:45520885 T>C), RS1000218733 (10:45563024 T>C), RS1000263736 (10:45471902 C>A), RS1000325736 (10:45557408 C>A,T), RS1000329499 (10:45532223 C>T)

Disease associations

OMIM: gene MIM:613335 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

46 associations (top):

Study	Trait	p-value
GCST000503_10	Mean corpuscular volume	1.000000e-10
GCST000585_14	Mean corpuscular volume	3.000000e-11
GCST000587_14	Mean corpuscular hemoglobin	4.000000e-12
GCST001765_22	Red blood cell traits	2.000000e-16
GCST002221_67	Cholesterol, total	8.000000e-09
GCST002223_44	HDL cholesterol	2.000000e-10
GCST002606_16	Prostate cancer	5.000000e-09
GCST002606_35	Prostate cancer	1.000000e-08
GCST002896_7	Cholesterol, total	3.000000e-08
GCST004004_20	Mean corpuscular volume	3.000000e-08
GCST004004_43	Mean corpuscular volume	3.000000e-11
GCST004006_11	Mean corpuscular hemoglobin	6.000000e-09
GCST004006_23	Mean corpuscular hemoglobin	8.000000e-16
GCST004232_71	HDL cholesterol levels	7.000000e-09
GCST004235_55	Total cholesterol levels	1.000000e-07
GCST005993_46	Mean corpuscular hemoglobin	5.000000e-35
GCST005996_31	Red blood cell count	3.000000e-11
GCST007209_4	Gallstone disease	2.000000e-27
GCST008070_14	HDL cholesterol levels	7.000000e-06
GCST008075_183	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	1.000000e-09
GCST008075_75	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	2.000000e-08
GCST008084_204	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	4.000000e-11
GCST008084_88	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	3.000000e-09
GCST008085_102	HDL cholesterol levels in current drinkers	6.000000e-07
GCST008085_175	HDL cholesterol levels in current drinkers	1.000000e-07
GCST90002385_477	High light scatter reticulocyte count	5.000000e-09
GCST90002385_478	High light scatter reticulocyte count	4.000000e-53
GCST90002386_398	High light scatter reticulocyte percentage of red cells	1.000000e-57
GCST90002386_399	High light scatter reticulocyte percentage of red cells	3.000000e-14
GCST90002387_355	Immature fraction of reticulocytes	2.000000e-51

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0004509	hemoglobin measurement
EFO:0004527	mean corpuscular hemoglobin
EFO:0004574	total cholesterol measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004305	erythrocyte count
EFO:0004329	alcohol drinking
EFO:0007986	reticulocyte count
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0010701	mean reticulocyte volume
EFO:0007990	neutrophil percentage of leukocytes
EFO:0009188	Red cell distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation, increases methylation	2
Aflatoxin B1	increases methylation, decreases methylation	2
Cadmium Chloride	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	increases expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Air Pollutants	decreases expression	1
Arsenic	affects methylation	1
Cadmium	decreases expression, increases abundance	1
Cisplatin	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Estradiol	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Methyl Methanesulfonate	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1

Clinical trials (associated diseases)

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