ANKRD18B

Chr 9

ankyrin repeat domain 18B

Also known as: bA255A11.3, bA255A11.5

NCBI Gene: 441459 ENSG00000230453 UniProt: A2A2Z9 OMIM: 618930

The protein is an ankyrin repeat-containing protein that functions in cellular signaling and protein-protein interactions. Mutations cause autosomal recessive intellectual disability with developmental delay, seizures, and distinctive facial features. This gene is not highly constrained against loss-of-function variants, which is 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

0.82

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.82LOEUF

pLI 0.000

Z-score 2.42

OE 0.58 (0.41–0.82)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.47Z-score

OE missense 0.94 (0.86–1.02)

400 obs / 427.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.58 (0.41–0.82)

0≤0.351.4

Missense OE?0.94 (0.86–1.02)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 22 / 38.1Missense obs/exp: 400 / 427.3Syn Z: 0.74

Background carrier burden — how many people carry a rare variant somewhere in ANKRD18B?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 40

1,215 rare PASS variants

Rare truncating (LoF)

1 in 360

180 rare PASS variants

Rare synonymous (reference)

1 in 100

392 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ANKRD18B. 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 56	1 in 420
South Asian	~43k	1 in 35	1 in 240
Remaining (unassigned)	~30k	1 in 38	1 in 230
European (Finnish)	~27k	1 in 130	1 in 710
Admixed American	~22k	1 in 46	1 in 260
African / African American	~21k	1 in 47	1 in 200
East Asian	~20k	1 in 45	1 in 420
Ashkenazi Jewish	~13k	1 in 130	1 in 1,100
Middle Eastern	~2,884	1 in 40	≈ 1 in 600

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): 13 of 19 coding exons well covered in gnomAD exomes; exons 7, 8, 18 poorly covered; exons 6, 13, 19 marginal. Genomes: 18 of 19 (exon 8 below).? see exons ↓