MARCHF1

Summary

MARCHF1 (membrane associated ring-CH-type finger 1, HGNC:26077) is a protein-coding gene on chromosome 4q32.2-q32.3, encoding E3 ubiquitin-protein ligase MARCHF1 (Q8TCQ1). E3 ubiquitin-protein ligase that mediates ubiquitination of TFRC, CD86, FAS and MHC class II proteins, such as HLA-DR alpha and beta, and promotes their subsequent endocytosis and sorting to lysosomes via multivesicular bodies.

MARCH1 is a member of the MARCH family of membrane-bound E3 ubiquitin ligases (EC 6.3.2.19). MARCH proteins add ubiquitin (see MIM 191339) to target lysines in substrate proteins, thereby signaling their vesicular transport between membrane compartments. MARCH1 downregulates the surface expression of major histocompatibility complex (MHC) class II molecules (see MIM 142880) and other glycoproteins by directing them to the late endosomal/lysosomal compartment (Bartee et al., 2004 [PubMed 14722266]; Thibodeau et al., 2008 [PubMed 18389477]; De Gassart et al., 2008 [PubMed 18305173]).

Source: NCBI Gene 55016 — RefSeq curated summary.

At a glance

• GWAS associations: 25
• Clinical variants (ClinVar): 55 total
• MANE Select transcript: NM_001394959

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26077
Approved symbol	MARCHF1
Name	membrane associated ring-CH-type finger 1
Location	4q32.2-q32.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20668, MARCH-I, RNF171
Ensembl gene	ENSG00000145416
Ensembl biotype	protein_coding
OMIM	613331
Entrez	55016

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 5 protein_coding, 5 protein_coding_CDS_not_defined, 4 retained_intron, 1 nonsense_mediated_decay

ENST00000274056, ENST00000339875, ENST00000503008, ENST00000503104, ENST00000505391, ENST00000505517, ENST00000507270, ENST00000508725, ENST00000510075, ENST00000510696, ENST00000510786, ENST00000511245, ENST00000512214, ENST00000514618, ENST00000515471

RefSeq mRNA: 3 — MANE Select: NM_001394959 NM_001166373, NM_001394959, NM_017923

CCDS: CCDS3806, CCDS54814, CCDS93664

Canonical transcript exons

ENST00000514618 — 10 exons

Exon	Start	End
ENSE00001276826	163613314	163613393
ENSE00002026167	163612271	163613038
ENSE00002057094	163988501	163988709
ENSE00002060780	164111588	164111662
ENSE00002069195	163524718	163529046
ENSE00002081441	164383870	164384019
ENSE00003496414	163854021	163854169
ENSE00003585212	163700813	163700863
ENSE00003675604	163545596	163545743
ENSE00003788704	163585749	163585929

Expression profiles

Bgee: expression breadth ubiquitous, 246 present calls, max score 96.75.

FANTOM5 (CAGE): breadth broad, TPM avg 13.0859 / max 430.4623, expressed in 633 samples.

FANTOM5 promoters (16 alternative TSS)

Promoter ID	TPM avg	Samples expressed
54683	8.3810	399
54698	1.7946	248
54697	1.4736	261
54678	0.2922	121
54696	0.2142	88
54679	0.1568	76
54680	0.1334	63
54681	0.1297	64
54682	0.1064	60
54693	0.0974	53

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	96.75	gold quality
mononuclear cell	CL:0000842	96.61	gold quality
leukocyte	CL:0000738	96.20	gold quality
endothelial cell	CL:0000115	93.07	gold quality
sural nerve	UBERON:0015488	89.17	gold quality
corpus callosum	UBERON:0002336	88.88	gold quality
lymph node	UBERON:0000029	88.46	gold quality
superficial temporal artery	UBERON:0001614	87.84	gold quality
epithelium of nasopharynx	UBERON:0001951	87.07	gold quality
nasopharynx	UBERON:0001728	87.06	gold quality
ganglionic eminence	UBERON:0004023	86.89	gold quality
vermiform appendix	UBERON:0001154	86.83	gold quality
blood	UBERON:0000178	86.45	gold quality
buccal mucosa cell	CL:0002336	86.21	silver quality
cortical plate	UBERON:0005343	86.13	gold quality
calcaneal tendon	UBERON:0003701	86.08	gold quality
granulocyte	CL:0000094	85.32	gold quality
spleen	UBERON:0002106	84.92	gold quality
lower lobe of lung	UBERON:0008949	84.81	gold quality
prefrontal cortex	UBERON:0000451	83.61	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	83.47	gold quality
caecum	UBERON:0001153	82.81	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.23	gold quality
parietal pleura	UBERON:0002400	82.00	gold quality
spinal cord	UBERON:0002240	81.86	gold quality
secondary oocyte	CL:0000655	81.39	gold quality
tonsil	UBERON:0002372	81.12	gold quality
Brodmann (1909) area 23	UBERON:0013554	80.97	gold quality
pleura	UBERON:0000977	80.93	gold quality
visceral pleura	UBERON:0002401	80.66	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	98.56
E-HCAD-35	yes	90.89
E-MTAB-10287	yes	22.99
E-CURD-112	yes	14.41
E-MTAB-8410	yes	13.20
E-MTAB-9801	yes	8.65
E-MTAB-6678	yes	7.90
E-MTAB-8060	no	47.61
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

180 targeting MARCHF1, 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-5692A	100.00	74.40	6850
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-656-3P	100.00	72.15	2788
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-548C-3P	99.99	74.01	7587
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4775	99.98	75.00	6394
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-5696	99.98	72.36	4487
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502

Literature-anchored findings (GeneRIF, showing 19)

• MARCH I is a major regulator of HLA-DR traffic, and its loss contributes to the acquisition of the potent immunostimulatory properties of mature human DCs. (PMID:18305173)
• The immunosuppressive effect of IL-10 on antigen presentation is mediated through induced expression of MARCH1. (PMID:18389477)
• expression of MARCH1 or MARCH8 causes a drastic change CD98 trafficking after endocytosis (PMID:21757542)
• MARCH1 is capable of autoubiquitination, thus regulating its own expression. (PMID:22508929)
• findings highlight the complex regulation of MARCH1 trafficking in the endocytic pathway as well as the intricate interactions between its cytoplasmic tails. (PMID:23264739)
• MARCH1 ubiquitinates INSR to decrease cell surface INSR levels, but unlike other INSR ubiquitin ligases, MARCH1 acts in the basal state rather than after insulin stimulation. (PMID:27577745)
• MARCH1 functions as a tumor promoter by upregulating the NF-kappaB and the Wnt/b-catenin pathways, indicating that MARCH1 may be a therapeutic target for patients with ovarian cancer. (PMID:27633480)
• found downstream sequence elements, present in the first coding exon of March-I in antigen-presenting cells (APCs), that confer regulation of March-I expression in activated APCs (PMID:29378848)
• March-I undergoes lysine-independent ubiquitination by an as yet unidentified E3 ubiquitin ligase that, together with Ube2D1, regulates March-I expression (PMID:29414787)
• Results show that MARCH1 deficiency results in sex-specific changes in body weight, adiposity, and increases glucose clearance. Genetic association study for MARCH1 in type 2 diabetes risk in publicly-available datasets found evidence suggestive of association. These data show a link between immune function and diabetes implicating MARCH1 as a regulator of lipid metabolism and glucose tolerance in sex-specific manner. (PMID:30356278)
• Membrane-associated RING-CH (MARCH) 1 and 2 are MARCH family members that inhibit HIV-1 infection (PMID:30630952)
• MARCH1 has an important role in the development and progression of hepatocellular carcinoma. (PMID:30793486)
• ciRs-6 upregulates March1 to suppress bladder cancer growth by sponging miR-653. (PMID:31819015)
• 5-FU inhibits migration and invasion of CRC cells through PI3K/AKT pathway regulated by MARCH1. (PMID:33085122)
• The Immune-Specific E3 Ubiquitin Ligase MARCH1 Is Upregulated during Human Cytomegalovirus Infection to Regulate Iron Levels. (PMID:35045264)
• MARCH1 silencing suppresses growth of oral squamous cell carcinoma through regulation of PHLPP2. (PMID:35122633)
• Human MARCH1, 2, and 8 block Ebola virus envelope glycoprotein cleavage via targeting furin P domain. (PMID:38299743)
• MARCH-I: A negative regulator of dendritic cell maturation. (PMID:38331309)
• MARCH1 negatively regulates TBK1-mTOR signaling pathway by ubiquitinating TBK1. (PMID:39061024)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	marchf1	ENSDARG00000037487
mus_musculus	Marchf1	ENSMUSG00000036469
rattus_norvegicus	Marchf1	ENSRNOG00000026310

Paralogs (6): MARCHF2 (ENSG00000099785), MARCHF9 (ENSG00000139266), MARCHF4 (ENSG00000144583), MARCHF8 (ENSG00000165406), MARCHF3 (ENSG00000173926), MARCHF11 (ENSG00000183654)

Protein

Protein identifiers

E3 ubiquitin-protein ligase MARCHF1 — Q8TCQ1 (reviewed: Q8TCQ1)

Alternative names: Membrane-associated RING finger protein 1, Membrane-associated RING-CH protein I, RING finger protein 171, RING-type E3 ubiquitin transferase MARCHF1

All UniProt accessions (4): B7Z739, Q8TCQ1, D6REN1, D6RGC4

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin-protein ligase that mediates ubiquitination of TFRC, CD86, FAS and MHC class II proteins, such as HLA-DR alpha and beta, and promotes their subsequent endocytosis and sorting to lysosomes via multivesicular bodies. By constitutively ubiquitinating MHC class II proteins in immature dendritic cells, down-regulates their cell surface localization thus sequestering them in the intracellular endosomal system. Also regulates insulin sensitivity by controlling surface expression of the insulin receptor subunit beta/INSR by direct ubiquitination and degradation. (Microbial infection) Plays a role in iron metabolism by regulating the levels of the transferrin receptor TFRC during human cytomegalovirus infection, subsequently contributing to a proviral effect.

Subunit / interactions. Interacts with CD83; this interaction antagonizes MARCHF1-mediated MHC II and CD86 down-regulation.

Subcellular location. Golgi apparatus. trans-Golgi network membrane. Lysosome membrane. Cytoplasmic vesicle membrane. Late endosome membrane. Early endosome membrane. Cell membrane.

Tissue specificity. Expressed in antigen presenting cells, APCs, located in lymph nodes and spleen. Also expressed in lung. Expression is high in follicular B-cells, moderate in dendritic cells and low in splenic T-cells.

Post-translational modifications. Ubiquitinated via ubiquitin-conjugating enzyme E2 D1/UBE2D1 independently of lysines, leading to proteolytic degradation. Has a short half-life. Instability/short half-life permits rapid changes that allow efficient induction of antigen presentation once antigen presenting cells, APCs, receive maturation signals. Small changes in protein levels significantly alter the cell surface display of MHC class II proteins.

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

Induction. By IL10/interleukin-10. By human cytomegalovirus infection. Transcription is repressed by insulin through FOXO1.

Pathway. Protein modification; protein ubiquitination.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8TCQ1-1	1	yes
Q8TCQ1-2	2

RefSeq proteins (3): NP_001159845, NP_001381888, NP_060393 (=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 (19 total): binding site 8, region of interest 3, transmembrane region 2, splice variant 2, compositionally biased region 2, chain 1, zinc finger region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TCQ1-F1	70.17	0.39

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

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 201 (showing top): GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_OF_PEPTIDE_OR_POLYSACCHARIDE_ANTIGEN_VIA_MHC_CLASS_II, chr4q32, GOCC_VACUOLAR_MEMBRANE, TGACCTY_ERR1_Q2, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_OF_PEPTIDE_ANTIGEN, CAGCTG_AP4_Q5, PAX2_01, PAX8_B, CEBP_Q2, GOCC_TRANS_GOLGI_NETWORK, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION, BRN2_01, MODULE_301, TCF11_01, TGANTCA_AP1_C

GO Biological Process (5): protein polyubiquitination (GO:0000209), antigen processing and presentation of peptide antigen via MHC class II (GO:0002495), immune response (GO:0006955), immune system process (GO:0002376), protein ubiquitination (GO:0016567)

GO Molecular Function (6): zinc ion binding (GO:0008270), MHC protein binding (GO:0042287), ubiquitin protein ligase activity (GO:0061630), ubiquitin-protein transferase activity (GO:0004842), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (15): cytoplasm (GO:0005737), lysosome (GO:0005764), lysosomal membrane (GO:0005765), endosome (GO:0005768), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), early endosome membrane (GO:0031901), late endosome membrane (GO:0031902), trans-Golgi network membrane (GO:0032588), Golgi membrane (GO:0000139), 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
intracellular membrane-bounded organelle	2
organelle membrane	2
endosome membrane	2
protein ubiquitination	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
biological_process	1
protein modification by small protein conjugation	1
transition metal ion binding	1
signaling receptor binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
ubiquitin-like protein transferase activity	1
catalytic activity	1
cation binding	1
intracellular anatomical structure	1
lytic vacuole	1
lysosome	1
lytic vacuole membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1
early endosome	1
late endosome	1
trans-Golgi network	1
Golgi apparatus	1
bounding membrane of organelle	1
vesicle membrane	1
intracellular vesicle	1

Protein interactions and networks

STRING

1076 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MARCHF1	HLA-DPA1	P01905	730
MARCHF1	CD86	P42081	705
MARCHF1	UBE2H	P37286	669
MARCHF1	HLA-DQA2	P01906	635
MARCHF1	CD83	Q01151	633
MARCHF1	STAP2	Q9UGK3	632
MARCHF1	CDC34	P49427	631
MARCHF1	TFRC	P02786	630
MARCHF1	UBE2D1	P51668	609
MARCHF1	HLA-DRA	P01903	602
MARCHF1	UBA1	P22314	591
MARCHF1	IL10	P22301	561
MARCHF1	CD276	Q5ZPR3	552
MARCHF1	CD4	P01730	542
MARCHF1	Q5Y7H0	Q5Y7H0	521

IntAct

3 interactions, top by confidence:

A	B	Type	Score
P		psi-mi:“MI:0914”(association)	0.350
MARCHF1	STXBP3	psi-mi:“MI:0914”(association)	0.350

BioGRID (176): MARCH1 (Affinity Capture-Western), INSR (Biochemical Activity), MARCH1 (Affinity Capture-RNA), MARCH1 (Proximity Label-MS), MARCH1 (Proximity Label-MS), MARCH1 (Proximity Label-MS), MARCH1 (Proximity Label-MS), MARCH1 (Proximity Label-MS), MARCH1 (Proximity Label-MS), MARCH1 (Proximity Label-MS), MARCH1 (Proximity Label-MS), MARCH1 (Affinity Capture-Western), MAVS (Affinity Capture-Western), TMEM173 (Affinity Capture-Western), SNX27 (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

6 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	MARCHF1	ubiquitination
MARCHF1	“down-regulates quantity by destabilization”	HLA-DRB4	polyubiquitination
MARCHF1	“down-regulates quantity by destabilization”	HLA-DRB3	polyubiquitination
MARCHF1	“down-regulates quantity by destabilization”	HLA-DRA	polyubiquitination
MARCHF1	“down-regulates quantity by destabilization”	CD86	ubiquitination
MARCHF1	“down-regulates quantity by destabilization”	INSR	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	48
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2181 predictions. Top by Δscore:

Variant	Effect	Δscore
4:163529046:CCTT:C	acceptor_gain	1.0000
4:163545590:TCTTA:T	donor_loss	1.0000
4:163545591:CTTAC:C	donor_loss	1.0000
4:163545592:TTAC:T	donor_loss	1.0000
4:163545593:TA:T	donor_loss	1.0000
4:163545594:A:AT	donor_loss	1.0000
4:163545744:C:CC	acceptor_gain	1.0000
4:163545751:C:CT	acceptor_gain	1.0000
4:163585751:T:A	donor_gain	1.0000
4:163585928:TT:T	acceptor_gain	1.0000
4:163585930:C:CC	acceptor_gain	1.0000
4:163613309:CTTA:C	donor_loss	1.0000
4:163613310:TTAC:T	donor_loss	1.0000
4:163613311:TACC:T	donor_loss	1.0000
4:163613312:A:AC	donor_gain	1.0000
4:163613313:C:CC	donor_gain	1.0000
4:163613313:C:CG	donor_loss	1.0000
4:163700808:CCTA:C	donor_gain	1.0000
4:163700811:A:AC	donor_gain	1.0000
4:163700812:C:CC	donor_gain	1.0000
4:163700860:CATT:C	acceptor_gain	1.0000
4:163700861:ATTC:A	acceptor_loss	1.0000
4:163700862:TT:T	acceptor_gain	1.0000
4:163700863:TC:T	acceptor_loss	1.0000
4:163700864:C:CC	acceptor_gain	1.0000
4:163700864:CTG:C	acceptor_loss	1.0000
4:163700865:T:A	acceptor_loss	1.0000
4:163529049:T:C	acceptor_gain	0.9900
4:163545589:CTCTT:C	donor_loss	0.9900
4:163545594:A:AC	donor_gain	0.9900

AlphaMissense

3582 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:163528905:A:T	V238E	1.000
4:163528917:C:G	R234P	1.000
4:163528919:G:C	N233K	1.000
4:163528919:G:T	N233K	1.000
4:163528932:A:G	L229P	1.000
4:163528976:G:C	F214L	1.000
4:163528976:G:T	F214L	1.000
4:163528977:A:G	F214S	1.000
4:163528978:A:G	F214L	1.000
4:163528980:A:T	V213D	1.000
4:163528986:C:T	G211D	1.000
4:163528987:C:G	G211R	1.000
4:163528989:C:T	G210E	1.000
4:163528990:C:G	G210R	1.000
4:163528990:C:T	G210R	1.000
4:163528998:C:T	G207D	1.000
4:163528999:C:G	G207R	1.000
4:163529004:G:T	A205D	1.000
4:163529005:C:G	A205P	1.000
4:163529010:A:T	V203E	1.000
4:163529016:A:G	L201P	1.000
4:163529018:T:A	K200N	1.000
4:163529018:T:G	K200N	1.000
4:163529026:A:G	W198R	1.000
4:163529026:A:T	W198R	1.000
4:163529027:A:C	F197L	1.000
4:163529027:A:T	F197L	1.000
4:163529028:A:C	F197C	1.000
4:163529028:A:G	F197S	1.000
4:163529029:A:G	F197L	1.000

dbSNP variants (sampled 300 via entrez): RS1000010873 (4:164361804 T>C), RS1000011408 (4:164316677 G>A), RS1000011628 (4:163956607 G>A), RS1000014017 (4:164275599 T>A), RS1000019147 (4:163724277 C>T), RS1000023707 (4:163764944 C>A), RS1000025572 (4:164120732 C>T), RS1000025848 (4:163721432 A>T), RS1000030401 (4:163560583 G>A), RS1000032994 (4:163804444 T>C), RS1000034175 (4:163769047 A>G), RS1000034730 (4:163729229 G>A,T), RS1000035366 (4:163653311 G>C), RS1000039235 (4:164316000 T>C), RS1000039520 (4:164114514 G>A)

Disease associations

OMIM: gene MIM:613331 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

25 associations (top):

Study	Trait	p-value
GCST001033_1	Type 2 diabetes	9.000000e-06
GCST002376_3	Urinary uromodulin levels	4.000000e-07
GCST003264_215	Post bronchodilator FEV1/FVC ratio	4.000000e-06
GCST004746_29	Small cell lung carcinoma	9.000000e-06
GCST006496_2	Glomerular filtration rate change in heart transplantation	1.000000e-06
GCST009179_5	Pars triangularis volume	7.000000e-06
GCST009597_162	Multiple sclerosis	6.000000e-09
GCST009879_2	Coronary artery disease	2.000000e-29
GCST010476_3	Myocardial infarction	2.000000e-25
GCST010477_1	Hypertension	1.000000e-07
GCST010478_2	Chronic kidney disease	2.000000e-08
GCST010836_4	Ischemic stroke	6.000000e-09
GCST011140_6	Glucagon levels in response to oral glucose tolerance test (decremental area under the curve for 0-30 minutes)	2.000000e-08
GCST012489_29	Heel bone mineral density x serum urate levels interaction	2.000000e-08
GCST90013406_113	Liver enzyme levels (alkaline phosphatase)	3.000000e-41
GCST90020024_647	A body shape index	2.000000e-09
GCST90020024_648	A body shape index	2.000000e-10
GCST90020025_1285	Waist-to-hip ratio adjusted for BMI	1.000000e-08
GCST90020025_1286	Waist-to-hip ratio adjusted for BMI	6.000000e-11
GCST90020025_1287	Waist-to-hip ratio adjusted for BMI	1.000000e-10
GCST90020027_1556	Waist-hip index	2.000000e-08
GCST90020027_1557	Waist-hip index	7.000000e-11
GCST90020027_1558	Waist-hip index	1.000000e-10
GCST90020029_590	Waist circumference adjusted for body mass index	3.000000e-08
GCST90020029_591	Waist circumference adjusted for body mass index	2.000000e-08

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0005663	urinary uromodulin measurement
EFO:0004713	FEV/FVC ratio
EFO:0006829	GFR change measurement
EFO:0007043	response to transplant
EFO:0008463	glucagon measurement
EFO:0004531	urate measurement
EFO:0009270	heel bone mineral density
EFO:0004533	alkaline phosphatase measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs4431170	MARCHF1		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation	3
Aflatoxin B1	increases methylation, decreases expression, decreases methylation	3
Nickel	increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
methylmercuric chloride	decreases expression	1
methyleugenol	decreases expression	1
arsenite	affects binding, decreases reaction	1
cobaltous chloride	increases expression	1
benzo(e)pyrene	decreases methylation	1
potassium chromate(VI)	decreases expression	1
aflatoxin B2	decreases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Poly(amidoamine)	increases expression	1
licochalcone B	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Acetaminophen	decreases expression	1
Arsenic	affects methylation	1
Calcitriol	increases expression	1
Carbamazepine	affects expression	1
Choline	affects expression	1
Cisplatin	affects cotreatment, increases expression	1
Chlordecone	affects response to substance	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression	1
Methapyrilene	decreases methylation	1
Thimerosal	increases expression	1
Tobacco Smoke Pollution	increases methylation	1
Tretinoin	decreases expression	1

Clinical trials (associated diseases)

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