MACROD1

Chr 11

mono-ADP ribosylhydrolase 1

Also known as: LRP16

NCBI Gene: 28992 ENSG00000133315 UniProt: Q9BQ69 OMIM: 610400

The protein removes ADP-ribose modifications from glutamate and aspartate residues and deacetylates O-acetyl-ADP ribose, functioning in DNA damage response and cellular signaling pathways. Mutations cause neurodevelopmental disorder with epilepsy, cataracts, and feeding difficulties, inherited in an autosomal recessive pattern. The gene shows significant constraint against loss-of-function variants (LOEUF 0.499), suggesting intolerance to complete protein loss.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.50

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.50LOEUF

pLI 0.569

Z-score 2.95

OE 0.19 (0.09–0.50)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.79Z-score

OE missense 0.82 (0.71–0.95)

131 obs / 159.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.19 (0.09–0.50)

0≤0.351.4

Missense OE?0.82 (0.71–0.95)

0≤0.61.4

Synonymous OE?1.24

0≤1.21.6

LoF obs/exp: 3 / 15.5Missense obs/exp: 131 / 159.2Syn Z: -1.60

Background carrier burden — how many people carry a rare variant somewhere in MACROD1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

519 rare PASS variants

Rare truncating (LoF)

1 in 1,600

105 rare PASS variants

Rare synonymous (reference)

1 in 150

276 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MACROD1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 140	1 in 2,000
South Asian	~43k	1 in 100	1 in 730
Remaining (unassigned)	~30k	1 in 97	1 in 2,000
European (Finnish)	~27k	1 in 280	1 in 4,300
Admixed American	~22k	1 in 150	1 in 940
African / African American	~21k	1 in 120	1 in 1,400
East Asian	~20k	1 in 170	1 in 440
Ashkenazi Jewish	~13k	1 in 420	1 in 1,600
Middle Eastern	~2,884	1 in 200	≈ 1 in 640

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 9 of 10 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 10.? see exons ↓