MKRN1

Summary

MKRN1 (makorin ring finger protein 1, HGNC:7112) is a protein-coding gene on chromosome 7q34, encoding E3 ubiquitin-protein ligase makorin-1 (Q9UHC7). E3 ubiquitin ligase catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins. It is a selective cancer dependency (DepMap: 10.3% of cell lines).

This gene encodes a protein that belongs to a novel class of zinc finger proteins. The encoded protein functions as a transcriptional co-regulator, and as an E3 ubiquitin ligase that promotes the ubiquitination and proteasomal degradation of target proteins. The protein encoded by this gene is thought to regulate RNA polymerase II-catalyzed transcription. Substrates for this protein’s E3 ubiquitin ligase activity include the capsid protein of the West Nile virus and the catalytic subunit of the telomerase ribonucleoprotein. This protein controls cell cycle arrest and apoptosis by regulating p21, a cell cycle regulator, and the tumor suppressor protein p53. Pseudogenes of this gene are present on chromosomes 1, 3, 9, 12 and 20, and on the X chromosome. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 23608 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 90 total
• Cancer dependency (DepMap): dependent in 10.3% of screened cell lines
• MANE Select transcript: NM_013446

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7112
Approved symbol	MKRN1
Name	makorin ring finger protein 1
Location	7q34
Locus type	gene with protein product
Status	Approved
Aliases	RNF61
Ensembl gene	ENSG00000133606
Ensembl biotype	protein_coding
OMIM	607754
Entrez	23608

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 15 protein_coding, 4 nonsense_mediated_decay, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000255977, ENST00000443720, ENST00000463142, ENST00000467513, ENST00000468447, ENST00000471104, ENST00000473444, ENST00000474576, ENST00000475010, ENST00000475180, ENST00000480552, ENST00000481705, ENST00000494939, ENST00000495305, ENST00000496169, ENST00000498535, ENST00000855466, ENST00000855467, ENST00000855468, ENST00000855469, ENST00000855470, ENST00000855471

RefSeq mRNA: 3 — MANE Select: NM_013446 NM_001145125, NM_001291663, NM_013446

CCDS: CCDS47725, CCDS5860

Canonical transcript exons

ENST00000255977 — 8 exons

Exon	Start	End
ENSE00001035029	140453033	140454729
ENSE00001267990	140479160	140479505
ENSE00003513796	140471883	140472011
ENSE00003599128	140455790	140455900
ENSE00003609051	140455095	140455233
ENSE00003651626	140459707	140459936
ENSE00003693959	140456652	140456866
ENSE00003787700	140459007	140459233

Expression profiles

Bgee: expression breadth ubiquitous, 300 present calls, max score 99.41.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 58.8430 / max 9180.9631, expressed in 1819 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
86556	41.5765	1801
86555	16.6874	1799
86554	0.4281	132
86553	0.1172	45
86550	0.0338	20

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	99.41	gold quality
male germ cell	CL:0000015	99.06	gold quality
endothelial cell	CL:0000115	98.90	gold quality
monocyte	CL:0000576	98.54	gold quality
mononuclear cell	CL:0000842	98.51	gold quality
blood	UBERON:0000178	98.46	gold quality
bone marrow	UBERON:0002371	98.46	gold quality
leukocyte	CL:0000738	98.40	gold quality
trabecular bone tissue	UBERON:0002483	98.39	gold quality
cortical plate	UBERON:0005343	98.29	gold quality
bone element	UBERON:0001474	98.15	gold quality
ganglionic eminence	UBERON:0004023	97.77	gold quality
left testis	UBERON:0004533	97.69	gold quality
right testis	UBERON:0004534	97.55	gold quality
bone marrow cell	CL:0002092	97.49	gold quality
rectum	UBERON:0001052	97.42	gold quality
epithelium of nasopharynx	UBERON:0001951	97.39	gold quality
mucosa of transverse colon	UBERON:0004991	97.35	gold quality
testis	UBERON:0000473	97.25	gold quality
amniotic fluid	UBERON:0000173	97.06	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	97.03	gold quality
transverse colon	UBERON:0001157	96.68	gold quality
granulocyte	CL:0000094	96.61	gold quality
ventricular zone	UBERON:0003053	96.59	gold quality
calcaneal tendon	UBERON:0003701	96.44	gold quality
nipple	UBERON:0002030	96.42	gold quality
Brodmann (1909) area 23	UBERON:0013554	96.36	gold quality
tendon	UBERON:0000043	96.32	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.24	gold quality
ileal mucosa	UBERON:0000331	96.18	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-9221	yes	21.73
E-HCAD-9	yes	7.25
E-MTAB-9467	yes	4.03
E-MTAB-6075	no	568.86
E-MTAB-10042	no	124.38
E-HCAD-10	no	2.89
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

145 targeting MKRN1, 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-3120-5P	100.00	65.56	965
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 10.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 15)

• MKRN1 may represent a nuclear protein with multiple nuclear functions, including regulating RNA polymerase II-catalyzed transcription. (PMID:16785614)
• Data indicate that MKRN1 is a novel modulator of p53 and p21, preferentially leading cells to p53-dependent apoptosis by suppressing p21. (PMID:19536131)
• Makorin 1 is a novel SEREX antigen of esophageal squamous cell carcinoma (PMID:19604354)
• MKRN1 could induce WNV capsid protein ubiquitination and degradation in a proteasome-dependent manner (PMID:19846531)
• Results verified MKRN1 as an ubiquitin E3 ligase of p14ARF, it potentially regulates cellular aging and tumorigenesis in gastric cancer. (PMID:23104211)
• EGFR/PI3K/AKT-mediated ubiquitination and degradation of PTEN are dependent on the MKRN1 E3 ligase. (PMID:26183061)
• In combination testing, MKRN1 + HPV showed the highest sensitivity and specificity levels. The MKRN1 biomarker may be a useful adjunct in primary cervical cytology screening. (PMID:26817873)
• HAdV-C5 histone-like core protein pVII binds to and promotes self-ubiquitination of a cellular E3 ubiquitin ligase named MKRN1. This mutual interaction between the pVII and MKRN1 proteins may prime MKRN1 for proteasomal degradation, because the MKRN1 protein is efficiently degraded during the late phase of HAdV-C5 infection. (PMID:29142133)
• MKRN1 functions as a novel E3 ligase of APC that positively regulates Wnt/beta-catenin-mediated biological processes. (PMID:29713058)
• directly binds to the cytoplasmic poly(A)-binding protein; mediates the recognition of poly(A) tails to prevent the production of erroneous proteins from prematurely polyadenylated transcripts (PMID:31640799)
• Gastrointestinal stromal tumors with BRAF gene fusions. A report of two cases showing low or absent KIT expression resulting in diagnostic pitfalls. (PMID:34398495)
• MKRN1/2 serve as tumor suppressors in renal clear cell carcinoma by regulating the expression of p53. (PMID:36938725)
• MKRN1 promotes colorectal cancer metastasis by activating the TGF-beta signalling pathway through SNIP1 protein degradation. (PMID:37620897)
• MKRN1 regulates the expression profiles and transcription factor activity in HeLa cells inhibition suppresses cervical cancer cell progression. (PMID:38480859)
• CircVPS8 promotes the malignant phenotype and inhibits ferroptosis of glioma stem cells by acting as a scaffold for MKRN1, SOX15 and HNF4A. (PMID:39098847)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	mkrn1	ENSDARG00000041665
mus_musculus	Mkrn1	ENSMUSG00000029922
rattus_norvegicus	Mkrn1	ENSRNOG00000009280
drosophila_melanogaster	Mkrn1	FBGN0029152
drosophila_melanogaster	CG5334	FBGN0030577
drosophila_melanogaster	CG5347	FBGN0030578
drosophila_melanogaster	CG12477	FBGN0036809
caenorhabditis_elegans		WBGENE00002278

Paralogs (3): MKRN2 (ENSG00000075975), MKRN3 (ENSG00000179455), (ENSG00000300293)

Protein

Protein identifiers

E3 ubiquitin-protein ligase makorin-1 — Q9UHC7 (reviewed: Q9UHC7)

Alternative names: RING finger protein 61, RING-type E3 ubiquitin transferase makorin-1

All UniProt accessions (11): C9IY57, C9IZP5, C9J031, C9JYI0, C9JYX8, Q9UHC7, F8WAS8, F8WBJ4, F8WEY8, H7C4H5, H7C588

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin ligase catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins. These substrates include FILIP1, p53/TP53, CDKN1A and TERT. Keeps cells alive by suppressing p53/TP53 under normal conditions, but stimulates apoptosis by repressing CDKN1A under stress conditions. Acts as a negative regulator of telomerase. Has negative and positive effects on RNA polymerase II-dependent transcription.

Subunit / interactions. Interacts with p53/TP53 and CDKN1A. Interacts with TERT, modulating telomere length homeostasis.

Tissue specificity. Ubiquitous.

Post-translational modifications. Auto-ubiquitinated; which leads to proteasomal degradation.

Induction. Frequently induced in esophageal squamous cell carcinoma (SCC) tissues.

Pathway. Protein modification; protein ubiquitination.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9UHC7-1	1	yes
Q9UHC7-2	2
Q9UHC7-3	3
Q9UHC7-4	4

RefSeq proteins (3): NP_001138597, NP_001278592, NP_038474* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000571	Znf_CCCH	Domain
IPR001841	Znf_RING	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR017907	Znf_RING_CS	Conserved_site
IPR018957	Znf_C3HC4_RING-type	Domain
IPR031644	MKRN1_C	Domain
IPR036855	Znf_CCCH_sf	Homologous_superfamily
IPR041367	Znf-CCCH_4	Domain
IPR045072	MKRN-like	Family

Pfam: PF00097, PF00642, PF14608, PF15815, PF18044

UniProt features (21 total): zinc finger region 5, splice variant 4, sequence conflict 4, sequence variant 2, region of interest 2, compositionally biased region 2, chain 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UHC7-F1	67.48	0.21

Functional residue map

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

Mutagenesis-validated functional residues (1):

Position	Phenotype
307	loss of e3 ligase activity, but no effect on transcription regulation.

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-198323	AKT phosphorylates targets in the cytosol
R-HSA-8948751	Regulation of PTEN stability and activity
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-1280218	Adaptive Immune System
R-HSA-162582	Signal Transduction
R-HSA-168256	Immune System
R-HSA-6807070	PTEN Regulation
R-HSA-9006925	Intracellular signaling by second messengers
R-HSA-983169	Class I MHC mediated antigen processing & presentation

MSigDB gene sets: 266 (showing top): REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, IVANOVA_HEMATOPOIESIS_MATURE_CELL, AGGCACT_MIR5153P, MORF_RAF1, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4, BLALOCK_ALZHEIMERS_DISEASE_UP, GTGTTGA_MIR505, MCBRYAN_PUBERTAL_BREAST_3_4WK_UP, GGCAGTG_MIR3243P, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_PROTEIN_POLYUBIQUITINATION, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN

GO Biological Process (2): protein polyubiquitination (GO:0000209), protein ubiquitination (GO:0016567)

GO Molecular Function (6): RNA binding (GO:0003723), 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 (1): cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
PIP3 activates AKT signaling	2
PTEN Regulation	1
Class I MHC mediated antigen processing & presentation	1
Intracellular signaling by second messengers	1
Immune System	1
Signal Transduction	1
Adaptive Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein ubiquitination	1
protein modification by small protein conjugation	1
nucleic acid binding	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
cytoplasm	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1183 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MKRN1	TERT	O14746	822
MKRN1	RNF130	Q86XS8	668
MKRN1	FAM131B	Q86XD5	657
MKRN1	CLCN6	P51797	639
MKRN1	BRAF	P15056	555
MKRN1	KIAA1549	Q9HCM3	543
MKRN1	PABPC1	P11940	538
MKRN1	C1QBP	Q07021	509
MKRN1	ZRANB2	O95218	501
MKRN1	EMC2	Q15006	497
MKRN1	NPM1	P06748	485
MKRN1	DNAJB1	P25685	470
MKRN1	ZNF598	Q86UK7	462
MKRN1	UBOX5	O94941	445
MKRN1	GNAI1	P04898	428

IntAct

109 interactions, top by confidence:

A	B	Type	Score
MKRN1	TP53	psi-mi:“MI:0915”(physical association)	0.600
TP53	MKRN1	psi-mi:“MI:0915”(physical association)	0.600
TP53	MKRN1	psi-mi:“MI:0407”(direct interaction)	0.600
NAA10	MKRN1	psi-mi:“MI:0915”(physical association)	0.560
RAD23A	MKRN1	psi-mi:“MI:0915”(physical association)	0.560
BYSL	MKRN1	psi-mi:“MI:0915”(physical association)	0.560
UBE2D1	MKRN1	psi-mi:“MI:0915”(physical association)	0.560
MKRN1	UBE2D4	psi-mi:“MI:0915”(physical association)	0.560
RAD23B	MKRN1	psi-mi:“MI:0915”(physical association)	0.560
DAXX	MKRN1	psi-mi:“MI:0915”(physical association)	0.560
MTURN	MKRN1	psi-mi:“MI:0915”(physical association)	0.560
FAM161A	MKRN1	psi-mi:“MI:0915”(physical association)	0.560
UBASH3A	MKRN1	psi-mi:“MI:0915”(physical association)	0.560
OTUB2	MKRN1	psi-mi:“MI:0915”(physical association)	0.560
SDCBP	MKRN1	psi-mi:“MI:0915”(physical association)	0.560
YOD1	MKRN1	psi-mi:“MI:0915”(physical association)	0.560
SNRNP70	GTPBP1	psi-mi:“MI:0914”(association)	0.530
PAIP2B	CASC3	psi-mi:“MI:0914”(association)	0.530
IGF2BP3	PTCD1	psi-mi:“MI:0914”(association)	0.530
GSPT2	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
MKRN1	CDKN1A	psi-mi:“MI:0915”(physical association)	0.520
CDKN1A	MKRN1	psi-mi:“MI:0915”(physical association)	0.520

BioGRID (282): MKRN1 (Affinity Capture-MS), MKRN1 (Affinity Capture-MS), MKRN1 (Affinity Capture-MS), MKRN1 (Affinity Capture-MS), MKRN1 (Affinity Capture-Western), MKRN1 (Affinity Capture-Western), Igf2bp1 (Affinity Capture-MS), Hnrnpf (Affinity Capture-MS), Hnrnpa3 (Affinity Capture-MS), Caprin1 (Affinity Capture-MS), Hnrnpa1 (Affinity Capture-MS), Hnrnpu (Affinity Capture-MS), Ybx1 (Affinity Capture-MS), Syncrip (Affinity Capture-MS), L1td1 (Affinity Capture-MS)

ESM2 similar proteins: A0JMY5, A2A791, A5WW08, A6QLA0, B1AY10, B5DF11, O15164, O76080, O88878, O88974, O96028, P35922, P40798, P51115, P93831, Q02395, Q06787, Q12986, Q13434, Q15047, Q3MHN7, Q3UWM4, Q5BJ56, Q5E9J6, Q5FWP4, Q5NVC7, Q5R7T9, Q5RF77, Q5VN06, Q64127, Q6INA9, Q6P256, Q6PFK1, Q6ZMT4, Q6ZNB6, Q7TN31, Q810L3, Q8BVE8, Q8K203, Q8N302

Diamond homologs: A0A7H0DMZ7, B0F0H3, E0X9N4, P0C775, P17366, P87607, Q13064, Q13434, Q49PZ0, Q4SRI6, Q4VBT5, Q5NU13, Q5NU14, Q5ZA07, Q60764, Q6GLD9, Q6GLT5, Q6IDS6, Q76R05, Q805K3, Q85318, Q8JFF3, Q8QN38, Q8V571, Q9DD48, Q9DFG8, Q9ERV1, Q9H000, Q9N373, Q9QXP6, Q9TT91, Q9UHC7, B6VQ60, P0CS64, P0CS65, Q6NVV0, Q9M022, Q803C1

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	MKRN1	ubiquitination
MKRN1	“down-regulates quantity by destabilization”	TERT	polyubiquitination
MKRN1	“down-regulates quantity by destabilization”	CDKN1A	polyubiquitination
MKRN1	“down-regulates quantity by destabilization”	TP53	polyubiquitination
MKRN1	“down-regulates quantity by destabilization”	CDKN2A	polyubiquitination
MKRN1	“up-regulates activity”	PABPC1	ubiquitination
MKRN1	“up-regulates activity”	RPS10	ubiquitination
MKRN1	“down-regulates quantity by destabilization”	PTEN	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 70 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
Ovarian tumor domain proteases	6	46.4×	1e-06
mRNA Polyadenylation	5	12.2×	4e-03
Processing of Capped Intron-Containing Pre-mRNA	5	11.4×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	71
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1380 predictions. Top by Δscore:

Variant	Effect	Δscore
7:140454725:TGGGC:T	acceptor_gain	1.0000
7:140454728:GC:G	acceptor_gain	1.0000
7:140454729:CC:C	acceptor_gain	1.0000
7:140454730:C:CC	acceptor_gain	1.0000
7:140454730:CTGT:C	acceptor_loss	1.0000
7:140454731:T:C	acceptor_loss	1.0000
7:140455234:C:CC	acceptor_gain	1.0000
7:140456650:A:AC	donor_gain	1.0000
7:140456651:C:CA	donor_gain	1.0000
7:140456679:G:C	donor_gain	1.0000
7:140456683:TCCTC:T	donor_gain	1.0000
7:140456684:CCTCC:C	donor_gain	1.0000
7:140456704:TGAG:T	donor_gain	1.0000
7:140456862:CACGA:C	acceptor_gain	1.0000
7:140456863:ACGA:A	acceptor_gain	1.0000
7:140456864:CGA:C	acceptor_gain	1.0000
7:140456864:CGAC:C	acceptor_gain	1.0000
7:140456865:GA:G	acceptor_gain	1.0000
7:140456865:GAC:G	acceptor_loss	1.0000
7:140456866:AC:A	acceptor_loss	1.0000
7:140456867:C:CA	acceptor_loss	1.0000
7:140456867:C:CC	acceptor_gain	1.0000
7:140456868:T:A	acceptor_loss	1.0000
7:140456876:G:C	acceptor_gain	1.0000
7:140456876:G:GC	acceptor_gain	1.0000
7:140459003:TTAC:T	donor_loss	1.0000
7:140459004:TACTT:T	donor_loss	1.0000
7:140459005:A:AC	donor_gain	1.0000
7:140459005:ACTTT:A	donor_loss	1.0000
7:140459006:C:A	donor_loss	1.0000

AlphaMissense

3164 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:140455161:A:C	H390Q	1.000
7:140455161:A:T	H390Q	1.000
7:140455163:G:C	H390D	1.000
7:140455163:G:T	H390N	1.000
7:140455169:A:C	Y388D	1.000
7:140455169:A:G	Y388H	1.000
7:140455169:A:T	Y388N	1.000
7:140455171:A:G	F387S	1.000
7:140455173:A:C	C386W	1.000
7:140455174:C:A	C386F	1.000
7:140455174:C:G	C386S	1.000
7:140455174:C:T	C386Y	1.000
7:140455175:A:C	C386G	1.000
7:140455175:A:G	C386R	1.000
7:140455175:A:T	C386S	1.000
7:140455185:A:C	F382L	1.000
7:140455185:A:T	F382L	1.000
7:140455186:A:C	F382C	1.000
7:140455186:A:G	F382S	1.000
7:140455187:A:C	F382V	1.000
7:140455187:A:G	F382L	1.000
7:140455187:A:T	F382I	1.000
7:140455191:G:C	C380W	1.000
7:140455192:C:A	C380F	1.000
7:140455192:C:G	C380S	1.000
7:140455192:C:T	C380Y	1.000
7:140455193:A:C	C380G	1.000
7:140455193:A:G	C380R	1.000
7:140455193:A:T	C380S	1.000
7:140455204:C:T	G376E	1.000

dbSNP variants (sampled 300 via entrez): RS1000004675 (7:140453545 A>C), RS1000019984 (7:140469758 CAA>C), RS1000190839 (7:140474371 T>C,G), RS1000252789 (7:140462760 C>G,T), RS1000372779 (7:140464564 G>C), RS1000380284 (7:140479361 C>A,G), RS1000521394 (7:140457872 C>T), RS1000744081 (7:140463630 A>G), RS1000757767 (7:140467895 G>C,T), RS1000775671 (7:140461007 A>G), RS1000812028 (7:140462574 T>C), RS1000968984 (7:140470829 A>C), RS1001029639 (7:140471092 T>A,G), RS1001042545 (7:140470609 A>C), RS1001054657 (7:140455350 T>A,C)

Disease associations

OMIM: gene MIM:607754 | 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
GCST007325_171	General risk tolerance (MTAG)	1.000000e-08
GCST007326_30	Number of sexual partners	9.000000e-11
GCST90000047_149	Age at first sexual intercourse	2.000000e-13
GCST90000050_59	Age at first birth	3.000000e-08
GCST90002387_388	Immature fraction of reticulocytes	1.000000e-13
GCST90006999_2	Gut microbiota relative abundance (unassigned genus belonging to family Lachnospiraceae)	8.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0008579	risk-taking behaviour
EFO:0009749	age at first sexual intercourse measurement
EFO:0009101	age at first birth measurement
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	3
trichostatin A	affects cotreatment, decreases expression	2
cobaltous chloride	increases expression	2
Tretinoin	increases expression	2
Cyclosporine	increases expression	2
triphenyl phosphate	affects expression	1
bisphenol A	increases expression, affects cotreatment	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
chloropicrin	increases expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
ICG 001	decreases expression	1
dorsomorphin	affects cotreatment, 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	increases expression	1
Sunitinib	increases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Dexamethasone	affects cotreatment, increases expression	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	increases expression	1
Estradiol	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Lead	affects methylation	1
Methyl Methanesulfonate	increases expression	1
Tobacco Smoke Pollution	increases expression	1

Cellosaurus cell lines

6 cell lines: 3 embryonic stem cell, 2 transformed cell line, 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A4E0	SEES3-1V human MKRN1, clone1	Embryonic stem cell	Male
CVCL_A4E1	SEES3-1V human MKRN1, clone2	Embryonic stem cell	Male
CVCL_A4E2	SEES3-1V human MKRN1, clone3	Embryonic stem cell	Male
CVCL_B3B2	Abcam HEK293T MKRN1 KO	Transformed cell line	Female
CVCL_D9KE	Ubigene HEK293 MKRN1 KO	Transformed cell line	Female
CVCL_W920	THJ-16T	Cancer cell line	Female

Clinical trials (associated diseases)

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