ANKRD13C

Chr 1

ankyrin repeat domain 13C

Also known as: dJ677H15.3

NCBI Gene: 81573 ENSG00000118454 UniProt: Q8N6S4 OMIM: 615125

The protein acts as a molecular chaperone for G protein-coupled receptors, regulating their biogenesis and exit from the endoplasmic reticulum. Mutations cause autosomal recessive neurodevelopmental disorders with intellectual disability and seizures. This gene is highly constrained against loss-of-function variation (pLI 0.998, LOEUF 0.248), indicating that complete loss of protein function is likely incompatible with normal development.

OMIM ResearchSummary from RefSeq, UniProt

Enables protein carrier activity and signaling receptor binding activity. Involved in cellular response to prostaglandin D stimulus; protein targeting to membrane; and regulation of anoikis. Located in endoplasmic reticulum and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Jun 2026]

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

0.25

LOEUF· LoF intol.

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.25LOEUF

pLI 0.998

Z-score 4.69

OE 0.10 (0.04–0.25)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

2.37Z-score

OE missense 0.61 (0.54–0.69)

177 obs / 290.5 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.10 (0.04–0.25)

0≤0.351.4

Missense OE?0.61 (0.54–0.69)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 3 / 31.3Missense obs/exp: 177 / 290.5Syn Z: 0.63

Background carrier burden — how many people carry a rare variant somewhere in ANKRD13C?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 230

542 rare PASS variants

Rare truncating (LoF)

1 in 5,300

54 rare PASS variants

Rare synonymous (reference)

1 in 240

251 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ANKRD13C. 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 270	1 in 5,000
South Asian	~43k	1 in 200	≈ 1 in 10,000
Remaining (unassigned)	~30k	1 in 140	≈ 1 in 7,500
European (Finnish)	~27k	1 in 420	≈ 1 in 27,000
Admixed American	~22k	1 in 130	1 in 1,600
African / African American	~21k	1 in 130	≈ 1 in 4,500
East Asian	~20k	1 in 250	≈ 1 in 4,600
Ashkenazi Jewish	~13k	1 in 270	≈ 1 in 13,000
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): 11 of 13 coding exons well covered in gnomAD exomes; exon 2 poorly covered; exon 6 marginal. Genomes: all 13.? see exons ↓