ANKRD39

Chr 2

ankyrin repeat domain 39

NCBI Gene: 51239 ENSG00000213337 UniProt: Q53RE8

ANKRD39 encodes an ankyrin repeat domain-containing protein that functions in protein-protein interactions and cellular signaling pathways. Mutations cause autosomal recessive developmental and epileptic encephalopathy with severe intellectual disability and seizures beginning in infancy. The gene shows low constraint against loss-of-function variants, consistent with its recessive inheritance pattern.

Research

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.21

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.21LOEUF

pLI 0.001

Z-score 1.13

OE 0.61 (0.33–1.21)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.18Z-score

OE missense 0.95 (0.82–1.11)

112 obs / 117.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.61 (0.33–1.21)

0≤0.351.4

Missense OE?0.95 (0.82–1.11)

0≤0.61.4

Synonymous OE?0.86

0≤1.21.6

LoF obs/exp: 6 / 9.8Missense obs/exp: 112 / 117.5Syn Z: 0.81

Background carrier burden — how many people carry a rare variant somewhere in ANKRD39?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 240

267 rare PASS variants

Rare truncating (LoF)

1 in 4,500

49 rare PASS variants

Rare synonymous (reference)

1 in 340

110 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ANKRD39. 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 310	1 in 9,200
South Asian	~43k	1 in 150	1 in 1,700
Remaining (unassigned)	~30k	1 in 250	≈ 1 in 7,500
European (Finnish)	~27k	1 in 310	≈ 1 in 20,000
Admixed American	~22k	1 in 140	1 in 1,900
African / African American	~21k	1 in 100	1 in 1,000
East Asian	~20k	1 in 200	1 in 1,400
Ashkenazi Jewish	~13k	1 in 930	none seen
Middle Eastern	~2,884	1 in 190	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 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓