MKRN2

makorin ring finger protein 2, the group of Ring finger proteins

Basic information

Region (hg38): 3:12557056-12586208

Links

ENSG00000075975 ∙ NCBI:23609 ∙ OMIM:608426 ∙ HGNC:7113 ∙ Uniprot:Q9H000 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MKRN2 gene.

• RASopathy (160 variants)
• not provided (82 variants)
• Cardiovascular phenotype (79 variants)
• not specified (48 variants)
• Noonan syndrome 5 (36 variants)
• LEOPARD syndrome 2 (32 variants)
• Inborn genetic diseases (23 variants)
• Noonan syndrome (10 variants)
• Noonan syndrome and Noonan-related syndrome (8 variants)
• Noonan syndrome with multiple lentigines (5 variants)
• Dilated cardiomyopathy 1NN (3 variants)
• RAF1-related condition (2 variants)
• LEOPARD syndrome 2;Noonan syndrome 5;Dilated cardiomyopathy 1NN (2 variants)
• Primary familial hypertrophic cardiomyopathy (2 variants)
• LEOPARD syndrome 2;Dilated cardiomyopathy 1NN;Noonan syndrome 5 (1 variants)
• Noonan syndrome;Noonan syndrome with multiple lentigines (1 variants)
• Pituitary stalk interruption syndrome (1 variants)
• Stroke disorder (1 variants)
• Dilated cardiomyopathy 1NN;LEOPARD syndrome 2;Noonan syndrome 5 (1 variants)
• Ventricular tachycardia (1 variants)
• Primary dilated cardiomyopathy (1 variants)
• Dilated cardiomyopathy 1NN;Noonan syndrome 5;LEOPARD syndrome 2 (1 variants)
• LEOPARD syndrome 2;Noonan syndrome 5 (1 variants)
• Hypertrophic cardiomyopathy 1 (1 variants)
• Noonan syndrome 5;LEOPARD syndrome 2 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MKRN2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1		1
missense			19	1		20
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1			1
non coding	2	6	139	90	19	256
Total	2	6	158	92	19

Variants in MKRN2

This is a list of pathogenic ClinVar variants found in the MKRN2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-12568994-C-T		not specified	Uncertain significance (Feb 06, 2024)
3-12570082-C-A		not specified	Uncertain significance (Oct 25, 2022)
3-12570082-C-T		not specified	Uncertain significance (Mar 31, 2023)
3-12570142-C-T		not specified	Uncertain significance (Jun 21, 2023)
3-12570152-C-G		not specified	Uncertain significance (Mar 23, 2022)
3-12570169-C-G		not specified	Uncertain significance (May 04, 2022)
3-12570220-G-A		not specified	Uncertain significance (Jan 02, 2024)
3-12572132-G-A		not specified	Uncertain significance (Apr 28, 2023)
3-12572132-G-C		not specified	Uncertain significance (Nov 27, 2023)
3-12572134-G-C		not specified	Uncertain significance (Jul 11, 2022)
3-12572162-C-T		not specified	Uncertain significance (Nov 08, 2022)
3-12572171-A-G		not specified	Uncertain significance (Nov 05, 2021)
3-12572230-G-A		not specified	Uncertain significance (May 30, 2023)
3-12572251-G-A		not specified	Uncertain significance (Aug 30, 2022)
3-12572260-G-A		not specified	Uncertain significance (Dec 27, 2023)
3-12572363-C-T		not specified	Uncertain significance (Feb 15, 2023)
3-12576654-T-G		not specified	Uncertain significance (Jun 16, 2023)
3-12581905-G-A		not specified	Uncertain significance (Aug 16, 2021)
3-12582119-T-C		not specified	Uncertain significance (Jan 08, 2024)
3-12582131-C-G		not specified	Uncertain significance (Feb 14, 2024)
3-12582131-C-T		not specified	Uncertain significance (Dec 07, 2023)
3-12582132-G-A		not specified	Uncertain significance (Mar 07, 2023)
3-12582171-T-A		not specified	Uncertain significance (Dec 13, 2021)
3-12582177-A-G		not specified	Likely benign (Mar 02, 2023)
3-12582191-G-A		not specified	Uncertain significance (Aug 04, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MKRN2	protein_coding	protein_coding	ENST00000170447	8	26700

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00882	0.989	125725	0	23	125748	0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.519	225	248	0.907	0.0000144	2776
Missense in Polyphen		86	103.19	0.8334		1157
Synonymous	-0.669	103	94.7	1.09	0.00000596	758
Loss of Function	2.67	7	19.8	0.354	0.00000100	239

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000148	0.000148
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000925	0.0000924
European (Non-Finnish)	0.000123	0.000123
Middle Eastern	0.00	0.00
South Asian	0.0000980	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: E3 ubiquitin ligase catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins. {ECO:0000250}.
• Pathway: Androgen Receptor Network in Prostate Cancer (Consensus)

Recessive Scores

• pRec: 0.115

Intolerance Scores

• loftool: 0.418
• rvis_EVS: -0.67
• rvis_percentile_EVS: 15.62

Haploinsufficiency Scores

• pHI: 0.164
• hipred: Y
• hipred_score: 0.530
• ghis: 0.671

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.569

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Mkrn2
• Phenotype: endocrine/exocrine gland phenotype; growth/size/body region phenotype; cellular phenotype; hematopoietic system phenotype; reproductive system phenotype; immune system phenotype

Gene ontology

• Biological process: biological_process;protein ubiquitination
• Molecular function: RNA binding;protein binding;transferase activity;metal ion binding