MACROD1

protein-coding

mono-ADP ribosylhydrolase 1, the group of Macro domain containing

Gene summary

Enables ADP-ribosylglutamate hydrolase activity and deacetylase activity. Involved in DNA damage response; peptidyl-glutamate ADP-deribosylation; and purine nucleoside metabolic process. Located in nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_014067.4

Inheritance

—

ClinVar variants

U:65B:3

Top phenotype

Peripheral neuropathy

gnomAD constraint

pLI —, LoF o/e 0.19

Max pathogenic AF

—

Genomic locus

chr11:63,998,558-64,166,113

External References & Databases

Ensembl (ENSG00000133315)

Transcript & Mutation Effects

hg38 • Region Span ~167.6 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 MACROD1 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 160

Peripheral neuropathyTotal: 111

FLRT1-related disorderTotal: 16

not providedTotal: 14

Hereditary spastic paraplegiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014067.4. 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			1 clinvar	2 clinvar		3
missense			57 clinvar	1 clinvar		58
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	0	0	65	3	0	68

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 43 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014067.4	RefSeq	NP_054786.2	10	MANE Select
ENST00000255681.7	Ensembl	ENSP00000255681.6	10	MANE Select
NM_001411019.1	RefSeq	NP_001397948.1	10	Standard
ENST00000675777.1	Ensembl	ENSP00000502549.1	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

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

Molecular Function

protein binding
hydrolase activity, acting on glycosyl bonds
deacetylase activity

Cellular Component

nucleus
nucleoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000255681
Coding exons: 10
Length: 167549
Individuals with no LoFs: 125727
Homozygous LoFs: 0
Heterozygous LoFs: 19
Defined: 125746
p: 0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.794	131	159	0.823	0.00000876	2017
Missense (PolyPhen)		59	76.201	0.77427		928
Synonymous	-1.60	87	69.9	1.24	0.00000409	660
Loss of Function	2.95	3	15.5	0.193	7.01e-7	198

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	0.00071	0.00071	rare
Finnish	0.00010	0.000046	rare
European (Non-Finnish)	0.000048	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. Plays a role in estrogen signaling. Binds to androgen receptor (AR) and amplifies the transactivation function of AR in response to androgen. May play an important role in carcinogenesis and/or progression of hormone-dependent cancers by feed-forward mechanism that activates ESR1 transactivation. Could be an ESR1 coactivator, providing a positive feedback regulatory loop for ESR1 signal transduction. Could be involved in invasive growth by down-regulating CDH1 in endometrial cancer cells. Enhances ESR1-mediated transcription activity. {ECO:0000269|PubMed:17893710, ECO:0000269|PubMed:17914104, ECO:0000269|PubMed:19022849, ECO:0000269|PubMed:19403568, ECO:0000269|PubMed:21257746, ECO:0000269|PubMed:23474712}.;
Disease: DISEASE: Note=A chromosomal aberration involving MACROD1 is found in acute leukemia. Translocation t(11;21)(q13;q22) that forms a RUNX1-MACROD1 fusion protein. {ECO:0000269|PubMed:17532767}.;

Recessive Scores

pRec: 0.143

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.349

Gene Damage Prediction

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