MKRN3

makorin ring finger protein 3, the group of Ring finger proteins

Basic information

Region (hg38): 15:23565673-23630075

Previous symbols: [ "ZNF127", "D15S9" ]

Links

ENSG00000179455 ∙ NCBI:7681 ∙ OMIM:603856 ∙ HGNC:7114 ∙ Uniprot:Q13064 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• precocious puberty, central, 2 (Strong), mode of inheritance: AD
• precocious puberty, central, 2 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Central precocious puberty	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing; Variants may modify severity of BBS and related disorders due to variants in other BBS-associated genes	Endocrine	23738509
In Precocious puberty, treatment with gonadotropin-releasing hormone receptor analogs/LHRH agonists can be beneficial

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MKRN3 gene.

• not provided (30 variants)
• Inborn genetic diseases (20 variants)
• Precocious puberty, central, 2 (5 variants)
• not specified (1 variants)
• MKRN3-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MKRN3 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				12	4	16
missense		1	24	3	1	29
nonsense						0
start loss						0
frameshift	1	3				4
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			2			2
Total	1	4	26	15	5

Variants in MKRN3

This is a list of pathogenic ClinVar variants found in the MKRN3 region.

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

Position	Type	Phenotype	Significance	ClinVar
15-23565696-C-T			Uncertain significance (Oct 10, 2022)
15-23565702-C-T		Precocious puberty, central, 2	Uncertain significance (Nov 05, 2021)
15-23565858-G-T		Inborn genetic diseases	Uncertain significance (Sep 16, 2021)
15-23565884-C-A			Likely benign (Dec 31, 2019)
15-23565885-T-G		Precocious puberty, central, 2	Uncertain significance (Apr 19, 2019)
15-23565891-C-T		Inborn genetic diseases	Uncertain significance (Jul 14, 2021)
15-23565896-C-G		MKRN3-related disorder	Likely benign (Jul 12, 2019)
15-23565904-C-G		Inborn genetic diseases	Uncertain significance (Jun 18, 2021)
15-23565913-C-T		Inborn genetic diseases	Uncertain significance (Feb 16, 2023)
15-23565930-C-T		Inborn genetic diseases	Uncertain significance (Mar 14, 2023)
15-23565934-C-T		Inborn genetic diseases	Conflicting classifications of pathogenicity (Mar 01, 2024)
15-23565935-G-A			Likely benign (May 21, 2018)
15-23565952-C-T		Inborn genetic diseases	Uncertain significance (Apr 04, 2023)
15-23565989-A-AGGAGGCC			Likely pathogenic (Feb 21, 2019)
15-23566007-C-T			Likely benign (Apr 19, 2018)
15-23566039-C-T		Inborn genetic diseases	Uncertain significance (Dec 21, 2022)
15-23566058-C-T			Benign (Dec 31, 2019)
15-23566108-G-A		Precocious puberty, central, 2	Likely pathogenic (Mar 24, 2019)
15-23566129-G-A		Inborn genetic diseases	Uncertain significance (Mar 08, 2024)
15-23566139-C-T		MKRN3-related disorder	Likely benign (Dec 31, 2019)
15-23566152-C-T		Inborn genetic diseases	Uncertain significance (Mar 25, 2022)
15-23566175-C-T			Benign (Dec 31, 2019)
15-23566181-G-A			Likely benign (Dec 31, 2019)
15-23566184-G-A			Benign (Jun 18, 2018)
15-23566192-C-T		Inborn genetic diseases	Uncertain significance (Aug 02, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MKRN3	protein_coding	protein_coding	ENST00000314520	1	62611

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.278	0.718	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.423	329	308	1.07	0.0000182	3309
Missense in Polyphen		56	73.014	0.76698		867
Synonymous	-2.13	150	120	1.25	0.00000757	1019
Loss of Function	2.45	3	12.2	0.245	6.10e-7	145

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
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, ECO:0000269|PubMed:19066619}.
• Pathway: Prader-Willi and Angelman Syndrome (Consensus)

Recessive Scores

• pRec: 0.110

Intolerance Scores

• loftool: 0.589
• rvis_EVS: -1.13
• rvis_percentile_EVS: 6.48

Haploinsufficiency Scores

• pHI: 0.0278
• hipred: N
• hipred_score: 0.158
• ghis: 0.479

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.592

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mkrn3

Gene ontology

• Biological process: protein ubiquitination
• Cellular component: ribonucleoprotein complex
• Molecular function: protein binding;transferase activity;identical protein binding;metal ion binding