ANKRD13D

Chr 11

ankyrin repeat domain 13D

NCBI Gene: 338692 ENSG00000172932 UniProt: Q6ZTN6 OMIM: 615126

The protein specifically binds to Lys-63-linked ubiquitin chains and regulates internalization of ligand-activated EGFR at the cell membrane. Mutations cause autosomal recessive neurodevelopmental disorder with intellectual disability, seizures, and dysmorphic features. The gene shows significant constraint against loss-of-function variants (LOEUF 0.428), suggesting intolerance to complete protein loss.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a member of the ankyrin repeat domain (ANKRD) 13 family, which currently consists of four proteins containing ubiquitin-interacting motifs. These proteins are integral membrane proteins that bind specifically to Lys-63-linked ubiquitin chains on membrane-bound proteins, targeting those proteins for rapid internalization. [provided by RefSeq, Dec 2016]

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

0.43

LOEUF

GOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.43LOEUF

pLI 0.349

Z-score 3.97

OE 0.23 (0.13–0.43)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.64Z-score

OE missense 0.77 (0.69–0.84)

296 obs / 386.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.23 (0.13–0.43)

0≤0.351.4

Missense OE?0.77 (0.69–0.84)

0≤0.61.4

Synonymous OE?0.89

0≤1.21.6

LoF obs/exp: 7 / 30.8Missense obs/exp: 296 / 386.8Syn Z: 1.13

Background carrier burden — how many people carry a rare variant somewhere in ANKRD13D?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 94

784 rare PASS variants

Rare truncating (LoF)

1 in 3,000

84 rare PASS variants

Rare synonymous (reference)

1 in 68

348 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ANKRD13D. 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 130	1 in 2,800
South Asian	~43k	1 in 73	1 in 1,300
Remaining (unassigned)	~30k	1 in 80	1 in 4,900
European (Finnish)	~27k	1 in 340	1 in 3,200
Admixed American	~22k	1 in 100	1 in 2,000
African / African American	~21k	1 in 100	≈ 1 in 5,400
East Asian	~20k	1 in 150	1 in 2,300
Ashkenazi Jewish	~13k	1 in 320	none seen
Middle Eastern	~2,884	1 in 73	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 15 coding exons well covered in gnomAD exomes and genomes.? see exons ↓