ANKRD52

Chr 12

ankyrin repeat domain 52

ENSG00000139645 UniProt: Q8NB46 OMIM: 620862

ANKRD52 encodes a regulatory subunit of protein phosphatase 6 (PP6) that is involved in recognizing phosphoprotein substrates for dephosphorylation. Mutations cause autosomal dominant neurodevelopmental disorders including developmental delay, intellectual disability, and seizures. This gene is extremely intolerant to loss-of-function variants, reflecting its critical role in normal development.

OMIM ResearchSummary from UniProt

Putative regulatory subunit of protein phosphatase 6 (PP6) that may be involved in the recognition of phosphoprotein substrates

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

0.09

LOEUF· LoF intol.

LOF

Mechanism· predicted

Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.09LOEUF

pLI 1.000

Z-score 6.61

OE 0.02 (0.01–0.09)

Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?

4.49Z-score

OE missense 0.50 (0.46–0.55)

324 obs / 645.1 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.02 (0.01–0.09)

0≤0.351.4

Missense OE?0.50 (0.46–0.55)

0≤0.61.4

Synonymous OE?0.89

0≤1.21.6

LoF obs/exp: 1 / 52.8Missense obs/exp: 324 / 645.1Syn Z: 1.49

Background carrier burden — how many people carry a rare variant somewhere in ANKRD52?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

891 rare PASS variants

Rare truncating (LoF)

1 in 19,000

20 rare PASS variants

Rare synonymous (reference)

1 in 57

564 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ANKRD52. 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 18,000
South Asian	~43k	1 in 79	≈ 1 in 43,000
Remaining (unassigned)	~30k	1 in 89	none seen
European (Finnish)	~27k	1 in 240	≈ 1 in 26,000
Admixed American	~22k	1 in 110	≈ 1 in 4,500
African / African American	~21k	1 in 69	≈ 1 in 17,000
East Asian	~20k	1 in 71	≈ 1 in 19,000
Ashkenazi Jewish	~13k	1 in 190	none seen
Middle Eastern	~2,884	1 in 67	none seen

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): All 28 coding exons well covered in gnomAD exomes and genomes.? see exons ↓