MKRN3

protein-coding

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

Gene summary

The protein encoded by this gene contains a RING (C3HC4) zinc finger motif and several C3H zinc finger motifs. This gene is intronless and imprinted, with expression only from the paternal allele. Disruption of the imprinting at this locus may contribute to Prader-Willi syndrome. An antisense RNA of unknown function has been found overlapping this gene. [provided by RefSeq, Jul 2008]

Previous symbols:

ZNF127
D15S9

MANE transcript

NM_005664.4

Inheritance

ClinVar variants

P:14U:67B:42

Top phenotype

Central precocious puberty

gnomAD constraint

pLI —, LoF o/e 0.25

Max pathogenic AF

—

Genomic locus

chr15:23,565,674-23,630,075

External References & Databases

Ensembl (ENSG00000179455)

Transcript & Mutation Effects

hg38 • Region Span ~64.4 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

precocious puberty, central, 2STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0014137

Submitter: Ambry Genetics

precocious puberty, central, 2STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0014137

Submitter: PanelApp Australia

precocious puberty, central, 2STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0014137

Submitter: Labcorp Genetics (formerly Invitae)

precocious puberty, central, 2STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0014137

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Central precocious pubertyAD

Manifestation: Endocrine

Intervention: General

Rationale: 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

Comments: In Precocious puberty, treatment with gonadotropin-releasing hormone receptor analogs/LHRH agonists can be beneficial

Refs: 23738509

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MKRN3 variants in ClinVar

7 Conditions Cataloged

Inborn genetic diseasesTotal: 66

not providedTotal: 45

not specifiedTotal: 12

Precocious puberty, central, 2Total: 11

MKRN3-related disorderTotal: 9

Prader-Willi syndromeTotal: 3

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005664.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				28 clinvar		28
missense	2 clinvar	1 clinvar	65 clinvar	14 clinvar		82
nonsense	1 clinvar	1 clinvar	1 clinvar			3
start loss						0
frameshift	3 clinvar	6 clinvar	1 clinvar			10
splice donor/acceptor (+/-2bp)						0
Total	6	8	67	42	0	123

Highest pathogenic variant AF is 0.000040902785

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 17 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005664.4	RefSeq	NP_005655.1	1	MANE Select
ENST00000314520.6	Ensembl	ENSP00000313881.3	1	MANE Select
ENST00000564592.2	Ensembl	ENSP00000455368.1	3	Standard
ENST00000564592.3	Ensembl	ENSP00000455368.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Prader-Willi and Angelman Syndrome

Biological Process

protein ubiquitination

Molecular Function

protein binding
transferase activity
identical protein binding
metal ion binding

Cellular Component

ribonucleoprotein complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000314520
Coding exons: 1
Length: 62611
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.423	329	308	1.07	0.0000182	3309
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: E3 ubiquitin ligase catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins. {ECO:0000250, ECO:0000269|PubMed:19066619}.;

Recessive Scores

pRec: 0.110

Intolerance Scores

LoFtool: 0.589
RVIS EVS: -1.13
RVIS percentile EVS: 6.48

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.592

Gene Damage Prediction

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