MKRN2

Summary

MKRN2 (makorin ring finger protein 2, HGNC:7113) is a protein-coding gene on chromosome 3p25.2, encoding E3 ubiquitin-protein ligase makorin-2 (Q9H000). E3 ubiquitin ligase catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins.

This gene encodes a probable E3 ubiquitin ligase containing several zinc finger domains, that is a member of the makorin RING zinc-finger protein family. This gene overlaps the v-raf-1 murine leukemia viral oncogene homolog 1 (RAF1) gene in an antisense orientation and may have a co-regulatory function with RAF1. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 23609 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 94 total
• MANE Select transcript: NM_014160

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7113
Approved symbol	MKRN2
Name	makorin ring finger protein 2
Location	3p25.2
Locus type	gene with protein product
Status	Approved
Aliases	RNF62, HSPC070
Ensembl gene	ENSG00000075975
Ensembl biotype	protein_coding
OMIM	608426
Entrez	23609

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 16 protein_coding, 5 retained_intron, 4 nonsense_mediated_decay

ENST00000170447, ENST00000411987, ENST00000448482, ENST00000676541, ENST00000676544, ENST00000676701, ENST00000677008, ENST00000677142, ENST00000677237, ENST00000677798, ENST00000677816, ENST00000677941, ENST00000678151, ENST00000679143, ENST00000900944, ENST00000900945, ENST00000900946, ENST00000900947, ENST00000923250, ENST00000923251, ENST00000923252, ENST00000923253, ENST00000923254, ENST00000941697, ENST00000941698

RefSeq mRNA: 2 — MANE Select: NM_014160 NM_001271707, NM_014160

CCDS: CCDS33702, CCDS63545

Canonical transcript exons

ENST00000170447 — 8 exons

Exon	Start	End
ENSE00001017436	12581808	12581952
ENSE00001017437	12574792	12575006
ENSE00001017441	12576631	12576741
ENSE00001213920	12570071	12570252
ENSE00001213978	12572069	12572373
ENSE00001300768	12582116	12583713
ENSE00001504342	12568875	12569003
ENSE00001692043	12557087	12557176

Expression profiles

Bgee: expression breadth ubiquitous, 270 present calls, max score 95.58.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.3432 / max 137.5809, expressed in 1813 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
35385	19.5993	1812
35384	1.5678	1148
35383	0.0981	25
35382	0.0780	23

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	95.58	gold quality
left testis	UBERON:0004533	94.76	gold quality
sperm	CL:0000019	94.65	gold quality
right testis	UBERON:0004534	94.64	gold quality
oocyte	CL:0000023	93.56	gold quality
testis	UBERON:0000473	93.35	gold quality
cerebellar hemisphere	UBERON:0002245	93.19	gold quality
cerebellar cortex	UBERON:0002129	93.04	gold quality
male germ cell	CL:0000015	93.00	gold quality
right hemisphere of cerebellum	UBERON:0014890	92.99	gold quality
cerebellum	UBERON:0002037	92.22	gold quality
apex of heart	UBERON:0002098	91.49	gold quality
lower esophagus mucosa	UBERON:0035834	91.24	gold quality
stromal cell of endometrium	CL:0002255	91.11	gold quality
gastrocnemius	UBERON:0001388	90.91	gold quality
muscle of leg	UBERON:0001383	90.78	gold quality
heart left ventricle	UBERON:0002084	90.63	gold quality
right atrium auricular region	UBERON:0006631	90.49	gold quality
cardiac ventricle	UBERON:0002082	90.46	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.44	gold quality
left ovary	UBERON:0002119	90.40	gold quality
cardiac atrium	UBERON:0002081	90.25	gold quality
endothelial cell	CL:0000115	90.24	gold quality
right ovary	UBERON:0002118	90.12	gold quality
heart	UBERON:0000948	90.02	gold quality
ovary	UBERON:0000992	89.77	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.73	gold quality
body of pancreas	UBERON:0001150	89.64	gold quality
descending thoracic aorta	UBERON:0002345	89.63	gold quality
tibial nerve	UBERON:0001323	89.58	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.25
E-GEOD-100618	no	463.45

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

73 targeting MKRN2, 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-3163	100.00	77.23	8605
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
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
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488
HSA-MIR-548Y	99.94	71.28	3514

Literature-anchored findings (GeneRIF, showing 9)

• MKRN2 and RAF1 are co-expressed in tissues and cell lines (PMID:11597136)
• Over-expression of MKRN2 in K562 cells increased cell proliferation. Our results indicated possible roles of MKRN2 in normal and malignant hematopoiesis. (PMID:24675897)
• These results delineate a novel role of MKRN2 in negatively regulating NF-kappaB-mediated inflammatory responses, cooperatively with PDLIM2. (PMID:28378844)
• Results suggested that MKRN2 inhibited NSCLC progression by reducing the metastatic potential of cancer cells. Our findings provide critical insight into the association of MKRN2 expression with favorable clinicopathological characteristics in NSCLC patients. (PMID:30103781)
• Integrated analysis of exosomal lncRNA and mRNA expression profiles reveals the involvement of lnc-MKRN2-42:1 in the pathogenesis of Parkinson’s disease. (PMID:31814304)
• Ubiquitination of IGF2BP3 by E3 ligase MKRN2 regulates the proliferation and migration of human neuroblastoma SHSY5Y cells. (PMID:32560817)
• MKRN1/2 serve as tumor suppressors in renal clear cell carcinoma by regulating the expression of p53. (PMID:36938725)
• [Overexpression of MKRN2 Inhibits the Growth of Ovarian Cancer Cells]. (PMID:37528788)
• Identifying cellular RNA-binding proteins during infection uncovers a role for MKRN2 in influenza mRNA trafficking. (PMID:38753876)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	mkrn2	ENSDARG00000007630
mus_musculus	Mkrn2	ENSMUSG00000000439
rattus_norvegicus	Mkrn2	ENSRNOG00000009176
drosophila_melanogaster	Mkrn1	FBGN0029152
drosophila_melanogaster	CG5334	FBGN0030577
drosophila_melanogaster	CG5347	FBGN0030578
drosophila_melanogaster	CG12477	FBGN0036809
caenorhabditis_elegans		WBGENE00002278

Paralogs (3): MKRN1 (ENSG00000133606), MKRN3 (ENSG00000179455), (ENSG00000300293)

Protein

Protein identifiers

E3 ubiquitin-protein ligase makorin-2 — Q9H000 (reviewed: Q9H000)

Alternative names: RING finger protein 62, RING-type E3 ubiquitin transferase makorin-2

All UniProt accessions (7): Q9H000, A0A7I2V388, A0A7I2V422, A0A7I2V4L9, A0A7I2V5D2, A0A7I2YQI0, C9J494

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin ligase catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins. Promotes the polyubiquitination and proteasome-dependent degradation of RELA/p65, thereby suppressing RELA-mediated NF-kappaB transactivation and negatively regulating inflammatory responses. Plays a role in the regulation of spermiation and in male fertility.

Subunit / interactions. Interacts with PDLIM2 (via LIM zinc-binding domain). Interacts with RELA.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Expressed in sperm, with significantly reduced expression in sperm of patients with oligoasthenoteratozoospermia (at protein level). Widely expressed with expression in testis, ovary, small intestine, colon, peripheral blood leukocytes, fetal liver, bone marrow, thymus, lymph node and spleen.

Pathway. Protein modification; protein ubiquitination.

Miscellaneous. Partially overlaps and is antisense to the RAF1 proto-oncogene.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H000-1	1	yes
Q9H000-2	2

RefSeq proteins (2): NP_001258636, NP_054879* (*=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
IPR036855	Znf_CCCH_sf	Homologous_superfamily
IPR045072	MKRN-like	Family

Pfam: PF00642, PF14608

UniProt features (15 total): zinc finger region 5, sequence conflict 2, region of interest 2, compositionally biased region 2, chain 1, modified residue 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H000-F1	71.78	0.31

Functional residue map

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

Post-translational modifications (1): 139

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 158 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GOBP_REGULATION_OF_INFLAMMATORY_RESPONSE_TO_ANTIGENIC_STIMULUS, GOBP_INFLAMMATORY_RESPONSE, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_MALE_GAMETE_GENERATION, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_PHOSPHATIDYLINOSITOL_3_KINASE_PROTEIN_KINASE_B_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_NEGATIVE_REGULATION_OF_DEFENSE_RESPONSE, GOBP_REGULATION_OF_NON_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_NON_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_NEGATIVE_REGULATION_OF_INFLAMMATORY_RESPONSE, GOBP_INFLAMMATORY_RESPONSE_TO_ANTIGENIC_STIMULUS, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION

GO Biological Process (10): protein polyubiquitination (GO:0000209), negative regulation of inflammatory response to antigenic stimulus (GO:0002862), DNA-templated transcription (GO:0006351), ubiquitin-dependent protein catabolic process (GO:0006511), spermatogenesis (GO:0007283), protein ubiquitination (GO:0016567), cell differentiation (GO:0030154), phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0043491), positive regulation of transcription by RNA polymerase II (GO:0045944), negative regulation of non-canonical NF-kappaB signal transduction (GO:1901223)

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 (2): nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein ubiquitination	2
inflammatory response to antigenic stimulus	1
regulation of inflammatory response to antigenic stimulus	1
negative regulation of inflammatory response	1
negative regulation of immune response	1
gene expression	1
RNA biosynthetic process	1
modification-dependent protein catabolic process	1
developmental process involved in reproduction	1
male gamete generation	1
protein modification by small protein conjugation	1
cellular developmental process	1
intracellular signaling cassette	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
non-canonical NF-kappaB signal transduction	1
regulation of non-canonical NF-kappaB signal transduction	1
negative regulation of intracellular signal transduction	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
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1668 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MKRN2	M0R1W7	M0R1W7	472
MKRN2	TSEN2	Q8NCE0	454
MKRN2	ZNF598	Q86UK7	452
MKRN2	CEP131	Q9UPN4	424
MKRN2	CAMSAP3	Q9P1Y5	422
MKRN2	PDLIM2	Q96JY6	400
MKRN2	RAF1	P04049	394
MKRN2	DUOXA2	Q1HG44	392
MKRN2	VEZF1	Q14119	358
MKRN2	OTUD4	Q01804	351
MKRN2	PPARD	Q03181	350
MKRN2	ZBTB37	Q5TC79	349
MKRN2	RPS10	P46783	340
MKRN2	SETD5	Q9C0A6	337
MKRN2	ZNF428	Q96B54	323
MKRN2	YIPF2	Q9BWQ6	323

IntAct

131 interactions, top by confidence:

A	B	Type	Score
EZH2	EPOP	psi-mi:“MI:0914”(association)	0.730
UBE2D1	MKRN2	psi-mi:“MI:0915”(physical association)	0.720
MKRN2	UBE2D4	psi-mi:“MI:0915”(physical association)	0.720
MKRN2	UBE2D1	psi-mi:“MI:0915”(physical association)	0.720
UBE2D4	MKRN2	psi-mi:“MI:0915”(physical association)	0.720
HTT	MKRN2	psi-mi:“MI:0915”(physical association)	0.670
rep	MKRN2	psi-mi:“MI:0915”(physical association)	0.670
MKRN2	HTT	psi-mi:“MI:0915”(physical association)	0.670
CARNMT1	NUP42	psi-mi:“MI:0914”(association)	0.640
	MKRN2	psi-mi:“MI:0915”(physical association)	0.560
MKRN2	AIRIM	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (477): MKRN2 (Two-hybrid), MKRN2 (Two-hybrid), UBE2D4 (Two-hybrid), C1orf109 (Two-hybrid), MKRN2 (Affinity Capture-MS), MKRN2 (Affinity Capture-MS), MKRN2 (Affinity Capture-MS), MKRN2 (Affinity Capture-MS), MKRN2 (Affinity Capture-MS), MKRN2 (Affinity Capture-MS), MKRN2 (Affinity Capture-MS), MKRN2 (Affinity Capture-MS), MKRN2 (Biochemical Activity), MKRN2 (Affinity Capture-MS), MKRN2 (Affinity Capture-MS)

ESM2 similar proteins: A2RV29, A4QP16, B0JZ85, F4I7L1, O23463, O48772, O64571, P43243, P43244, Q0VD35, Q10KL8, Q28EG9, Q32NW2, Q3KQ71, Q569K4, Q5R4W8, Q5ZDJ6, Q66IH2, Q6AXX3, Q6NPP4, Q6PBT9, Q7XHR2, Q8BXJ8, Q8GSA7, Q8K310, Q8LMR2, Q8S9H7, Q90Y35, Q94AD9, Q9C682, Q9D8C3, Q9ERV1, Q9FFH1, Q9FH37, Q9FYG2, Q9H000, Q9H6B1, Q9H898, Q9LES2, Q9LES3

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

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	MKRN2	ubiquitination
MKRN2	“down-regulates quantity by destabilization”	RELA	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 91 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
Transport of Mature mRNA derived from an Intron-Containing Transcript	7	20.9×	1e-05
mRNA 3’-end processing	5	19.3×	9e-04

GO biological processes:

GO term	Partners	Fold	FDR
mRNA export from nucleus	5	19.2×	1e-03
negative regulation of translation	5	12.7×	5e-03
RNA splicing	9	10.3×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	78
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1796 predictions. Top by Δscore:

Variant	Effect	Δscore
3:12557174:CAG:C	donor_loss	1.0000
3:12557177:G:GA	donor_loss	1.0000
3:12557178:T:A	donor_loss	1.0000
3:12568975:GGC:G	donor_gain	1.0000
3:12569028:GCT:G	donor_gain	1.0000
3:12569029:C:G	donor_gain	1.0000
3:12569064:A:G	donor_gain	1.0000
3:12569069:G:GT	donor_gain	1.0000
3:12570065:GTTTA:G	acceptor_loss	1.0000
3:12570066:TTTA:T	acceptor_loss	1.0000
3:12570067:TTA:T	acceptor_loss	1.0000
3:12570068:TA:T	acceptor_loss	1.0000
3:12570069:A:AG	acceptor_gain	1.0000
3:12570070:G:GG	acceptor_gain	1.0000
3:12570070:GAT:G	acceptor_gain	1.0000
3:12570250:GAA:G	donor_gain	1.0000
3:12570253:G:GG	donor_gain	1.0000
3:12572065:TCA:T	acceptor_loss	1.0000
3:12572067:A:AG	acceptor_gain	1.0000
3:12572068:G:GT	acceptor_gain	1.0000
3:12572068:GAT:G	acceptor_gain	1.0000
3:12572068:GATC:G	acceptor_gain	1.0000
3:12572068:GATCT:G	acceptor_gain	1.0000
3:12572262:G:GT	donor_gain	1.0000
3:12572262:G:T	donor_gain	1.0000
3:12572370:AAAGG:A	donor_loss	1.0000
3:12572372:AGGT:A	donor_loss	1.0000
3:12572373:GGTAA:G	donor_loss	1.0000
3:12572374:GTA:G	donor_loss	1.0000
3:12572375:T:G	donor_loss	1.0000

AlphaMissense

2782 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:12568957:T:A	C37S	1.000
3:12568957:T:C	C37R	1.000
3:12568958:G:A	C37Y	1.000
3:12568958:G:C	C37S	1.000
3:12568959:C:G	C37W	1.000
3:12568981:T:A	C45S	1.000
3:12568981:T:C	C45R	1.000
3:12568982:G:C	C45S	1.000
3:12568983:T:G	C45W	1.000
3:12568999:T:A	C51S	1.000
3:12568999:T:C	C51R	1.000
3:12569000:G:C	C51S	1.000
3:12574861:T:A	C238S	1.000
3:12574861:T:C	C238R	1.000
3:12574862:G:A	C238Y	1.000
3:12574862:G:C	C238S	1.000
3:12574862:G:T	C238F	1.000
3:12574863:C:G	C238W	1.000
3:12574870:T:A	C241S	1.000
3:12574870:T:C	C241R	1.000
3:12574871:G:A	C241Y	1.000
3:12574871:G:C	C241S	1.000
3:12574871:G:T	C241F	1.000
3:12574872:C:G	C241W	1.000
3:12574915:T:C	F256L	1.000
3:12574916:T:C	F256S	1.000
3:12574917:T:A	F256L	1.000
3:12574917:T:G	F256L	1.000
3:12574918:G:A	G257R	1.000
3:12574918:G:C	G257R	1.000

dbSNP variants (sampled 300 via entrez): RS1000129221 (3:12556747 A>G,T), RS1000143842 (3:12557990 C>G), RS1000175331 (3:12573860 T>C), RS1000280775 (3:12567883 C>T), RS1000368371 (3:12561181 A>G), RS1000511172 (3:12572646 C>T), RS1000559159 (3:12563154 T>A), RS1000649833 (3:12566803 A>C,T), RS1000684996 (3:12579435 A>G), RS1000771687 (3:12559886 A>G,T), RS1000848564 (3:12583704 A>C,G), RS1000849756 (3:12567644 A>G), RS1001020256 (3:12566589 G>C), RS1001251906 (3:12555462 T>C), RS1001367241 (3:12583772 T>A)

Disease associations

OMIM: gene MIM:608426 | disease phenotypes: MIM:611553, MIM:611554

GenCC curated gene-disease

Mondo (4): RASopathy (MONDO:0021060), Noonan syndrome 5 (MONDO:0012690), LEOPARD syndrome 2 (MONDO:0012691), Noonan syndrome and Noonan-related syndrome (MONDO:0020297)

Orphanet (4): RASopathy (Orphanet:536391), Noonan syndrome with multiple lentigines (Orphanet:500), Noonan syndrome (Orphanet:648), Noonan syndrome and Noonan-related syndrome (Orphanet:98733)

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST005956_72	Waist-to-hip ratio adjusted for BMI	1.000000e-07
GCST005957_11	Waist-to-hip ratio adjusted for BMI (age <50)	9.000000e-06
GCST005958_19	Waist-to-hip ratio adjusted for BMI (age >50)	2.000000e-06
GCST005962_29	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	9.000000e-09
GCST90002394_227	Monocyte percentage of white cells	5.000000e-12
GCST90020025_1930	Waist-to-hip ratio adjusted for BMI	4.000000e-10
GCST90020026_187	Hip index	3.000000e-15
GCST90020026_188	Hip index	2.000000e-10
GCST90020026_189	Hip index	4.000000e-11
GCST90020027_156	Waist-hip index	1.000000e-11
GCST90020027_160	Waist-hip index	9.000000e-11

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0007989	monocyte percentage of leukocytes
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
C537117	LEOPARD syndrome, 2 (supp.)
C548083	Noonan Syndrome 5 (supp.)
C537846	Noonan like syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	2
Aflatoxin B1	decreases methylation	2
sodium arsenite	increases expression	1
cobaltous chloride	increases expression	1
tobacco tar	decreases expression	1
manganese chloride	decreases expression, increases abundance	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
K 7174	increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1
Manganese	decreases expression, increases abundance	1
Methapyrilene	increases methylation	1
Methotrexate	increases expression	1
Phenobarbital	affects expression	1
Ribonucleotides	affects binding	1
Smoke	decreases expression	1
Tretinoin	decreases expression	1
Urethane	increases expression	1
Valproic Acid	affects expression	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04888936	Not specified	RECRUITING	Clinical, Genetic, and Epidemiologic Study of Children and Adults With RASopathies
NCT05761314	Not specified	RECRUITING	Solid Tumors in RASopathies
NCT06331117	Not specified	UNKNOWN	Effect of RAS/MAPK Pathway Hyperactivation on Growth’ and Bone’ Profile of the RASopathies
NCT06355622	Not specified	UNKNOWN	Prevalence and Characterization of Pain in RASopathies
NCT06489067	Not specified	RECRUITING	Study of the Thyroid Function and Echostructural Morphology in Patients Affected With Rasopathies (ECORAS2023)
NCT06776380	Not specified	RECRUITING	Pubertal Development in Patients with RASopathies
NCT07005297	Not specified	NOT_YET_RECRUITING	Clinical Genetics Branch Eligibility Screening Survey
NCT07344480	Not specified	RECRUITING	Retrospective Natural History Study of RASopathy-associated Cardiomyopathy (RAS-CM)
NCT07464821	Not specified	RECRUITING	National Multicentre Study on Lipid Profile in Noonan Syndrome and Related Disorders: Trends by Age, Gender and Genotype