MORC3

protein-coding

MORC family CW-type zinc finger 3, the group of Zinc fingers CW-type

Gene summary

This gene encodes a protein that localizes to the nuclear matrix and forms nuclear bodies via an ATP-dependent mechanism. The protein is predicted to have coiled-coil and zinc finger domains and has RNA binding activity. Alternative splicing produces multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Feb 2016]

Previous symbols:

ZCWCC3

MANE transcript

NM_015358.3

Inheritance

—

ClinVar variants

U:105B:8

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.11

Max pathogenic AF

—

Genomic locus

chr21:36,320,189-36,386,148

External References & Databases

Ensembl (ENSG00000159256)

Transcript & Mutation Effects

hg38 • Region Span ~66.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MORC3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 96

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015358.3. 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				1 clinvar	1 clinvar	2
missense			95 clinvar	6 clinvar		101
nonsense			1 clinvar			1
start loss			1 clinvar			1
frameshift						0
splice donor/acceptor (+/-2bp)			8 clinvar			8
Total	0	0	105	7	1	113

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 16 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015358.3	RefSeq	NP_056173.1	17	MANE Select
ENST00000400485.6	Ensembl	ENSP00000383333.1	17	MANE Select
NM_001320445.2	RefSeq	NP_001307374.1	15	Standard
NM_001320446.2	RefSeq	NP_001307375.1	15	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Interactome of polycomb repressive complex 2 (PRC2)

Biological Process

protein phosphorylation
cell aging
post-embryonic development
viral process
peptidyl-serine phosphorylation

Molecular Function

RNA binding
zinc ion binding

Cellular Component

nucleoplasm
nuclear matrix
PML body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000400485
Coding exons: 17
Length: 65960
Individuals with no LoFs: 124780
Homozygous LoFs: 0
Heterozygous LoFs: 14
Defined: 124794
p: 0.0000561

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.89	320	502	0.637	0.0000262	6272
Missense (PolyPhen)		48	183.72	0.26127		2338
Synonymous	0.0374	177	178	0.996	0.0000100	1655
Loss of Function	5.68	5	47.1	0.106	0.00000241	594

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00013	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.000056	0.000056	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000063	0.000062	rare
South Asian	0	0.0	absent
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Nuclear factor which forms MORC3-NBs (nuclear bodies) via an ATP-dependent mechanism (PubMed:20501696). Sumoylated MORC3-NBs can also associate with PML-NBs (PubMed:20501696). Recruits TP53 and SP100 to PML-NBs, thus regulating TP53 activity (PubMed:17332504). Binds RNA in vitro (PubMed:11927593). May be required for influenza A transcription during viral infection (PubMed:26202233). {ECO:0000269|PubMed:11927593, ECO:0000269|PubMed:17332504, ECO:0000269|PubMed:20501696, ECO:0000269|PubMed:26202233}.;

Recessive Scores

pRec: 0.110

Intolerance Scores

LoFtool: 0.202
RVIS EVS: -0.71
RVIS percentile EVS: 14.57

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.420

Gene Damage Prediction

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