MACROD2

protein-coding

mono-ADP ribosylhydrolase 2, the group of Macro domain containing

Gene summary

The protein encoded by this gene is a deacetylase involved in removing ADP-ribose from mono-ADP-ribosylated proteins. The encoded protein has been shown to translocate from the nucleus to the cytoplasm upon DNA damage. [provided by RefSeq, May 2017]

Previous symbols:

C20orf133

MANE transcript

NM_001351661.2

Inheritance

ClinVar variants

U:59B:12

Top phenotype

FLRT3-related disorder

gnomAD constraint

pLI —, LoF o/e 0.22

Max pathogenic AF

—

Genomic locus

chr20:13,995,369-16,053,197

External References & Databases

Ensembl (ENSG00000172264)

Transcript & Mutation Effects

hg38 • Region Span ~2,057.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

syndromic diseaseLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0002254

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MACROD2 variants in ClinVar

10 Conditions Cataloged

not specifiedTotal: 118

not providedTotal: 57

FLRT3-related disorderTotal: 8

MACROD2-related disorderTotal: 6

Hypogonadotropic hypogonadism 21 with or without anosmiaTotal: 5

HYPOGONADOTROPIC HYPOGONADISM 21 WITH ANOSMIA, SUSCEPTIBILITY TOTotal: 3

High myopiaTotal: 1

Disorder of sexual differentiationTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001351661.2. 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	3 clinvar		4
missense			50 clinvar	6 clinvar	3 clinvar	59
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	0	0	59	9	3	71

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 19 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001351661.2	RefSeq	NP_001338590.1	18	MANE Select
ENST00000684519.1	Ensembl	ENSP00000507484.1	18	MANE Select
NM_001033087.2	RefSeq	NP_001028259.1	10	Standard
NM_001351663.2	RefSeq	NP_001338592.1	18	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

cellular response to DNA damage stimulus
brain development
response to bacterium
purine nucleoside metabolic process
protein de-ADP-ribosylation

Molecular Function

hydrolase activity, acting on glycosyl bonds
deacetylase activity

Cellular Component

nucleus
nucleolus
centrosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000217246
Coding exons: 17
Length: 2057828
Individuals with no LoFs: 125727
Homozygous LoFs: 0
Heterozygous LoFs: 11
Defined: 125738
p: 0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.708	196	226	0.867	0.0000114	2819
Missense (PolyPhen)		61	88.529	0.68904		1114
Synonymous	0.794	72	81.1	0.888	0.00000458	726
Loss of Function	3.78	6	27.3	0.220	0.00000123	360

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00027	0.00027	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000044	0.000044	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Removes ADP-ribose from glutamate residues in proteins bearing a single ADP-ribose moiety. Inactive towards proteins bearing poly-ADP-ribose. Deacetylates O-acetyl-ADP ribose, a signaling molecule generated by the deacetylation of acetylated lysine residues in histones and other proteins. {ECO:0000269|PubMed:21257746, ECO:0000269|PubMed:23474712}.;

Intolerance Scores

LoFtool: 0.705
RVIS EVS: 0.46
RVIS percentile EVS: 78.59

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.336

Gene Damage Prediction

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