ANKRD30B

Chr 18

ankyrin repeat domain 30B

ENSG00000180777 UniProt: Q9BXX2 OMIM: 616565

ANKRD30B encodes an ankyrin repeat domain-containing protein involved in cellular signaling pathways. Mutations cause autosomal recessive intellectual disability with microcephaly and seizures. The gene shows low constraint against loss-of-function variants, consistent with the recessive inheritance pattern observed in affected individuals.

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.91

LOEUF

Multiple*

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

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.91LOEUF

pLI 0.000

Z-score 2.14

OE 0.70 (0.55–0.91)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.72Z-score

OE missense 1.08 (1.01–1.16)

630 obs / 581.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.70 (0.55–0.91)

0≤0.351.4

Missense OE?1.08 (1.01–1.16)

0≤0.61.4

Synonymous OE?1.13

0≤1.21.6

LoF obs/exp: 42 / 59.9Missense obs/exp: 630 / 581.2Syn Z: -1.46

Background carrier burden — how many people carry a rare variant somewhere in ANKRD30B?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 25

1,712 rare PASS variants

Rare truncating (LoF)

1 in 210

320 rare PASS variants

Rare synonymous (reference)

1 in 67

594 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ANKRD30B. 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 39	1 in 260
South Asian	~43k	1 in 19	1 in 200
Remaining (unassigned)	~30k	1 in 20	1 in 200
European (Finnish)	~27k	1 in 62	1 in 860
Admixed American	~22k	1 in 26	1 in 200
African / African American	~21k	1 in 22	1 in 180
East Asian	~20k	1 in 31	1 in 180
Ashkenazi Jewish	~13k	1 in 80	1 in 500
Middle Eastern	~2,884	1 in 35	1 in 240

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 21 of 43 coding exons well covered in gnomAD exomes; exons 23, 29, 30, 31 poorly covered; exons 4, 6, 8, 9, 10 and 12 more marginal. Genomes: 37 of 43 (exons 23, 24, 29, 30, 31, 32 below).? see exons ↓