TTC9C

Chr 11

tetratricopeptide repeat domain 9C

NCBI Gene: 283237 ENSG00000162222 UniProt: Q8N5M4

TTC9C encodes a protein containing tetratricopeptide repeat domains that functions in ciliary assembly and maintenance. Mutations cause nephronophthisis 13, an autosomal recessive ciliopathy presenting with chronic kidney disease that progresses to end-stage renal disease, typically in childhood or adolescence. The gene shows low constraint against loss-of-function variants, consistent with the recessive inheritance pattern of associated disease.

Research

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.29

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.29LOEUF

pLI 0.000

Z-score 0.93

OE 0.69 (0.39–1.29)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.80Z-score

OE missense 1.23 (1.06–1.43)

120 obs / 97.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.69 (0.39–1.29)

0≤0.351.4

Missense OE?1.23 (1.06–1.43)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 7 / 10.2Missense obs/exp: 120 / 97.8Syn Z: -0.18

Background carrier burden — how many people carry a rare variant somewhere in TTC9C?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 330

264 rare PASS variants

Rare truncating (LoF)

1 in 1,300

42 rare PASS variants

Rare synonymous (reference)

1 in 480

99 rare PASS variants

Rare missense and truncating variants are carried at similar rates in TTC9C; this gene does not show strong loss-of-function constraint by this measure. 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 480	1 in 1,800
South Asian	~43k	1 in 110	1 in 2,300
Remaining (unassigned)	~30k	1 in 330	1 in 890
European (Finnish)	~27k	1 in 2,400	none seen
Admixed American	~22k	1 in 210	1 in 1,000
African / African American	~21k	1 in 160	≈ 1 in 4,400
East Asian	~20k	1 in 230	1 in 3,300
Ashkenazi Jewish	~13k	1 in 2,200	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 240	≈ 1 in 960

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 3 coding exons well covered in gnomAD exomes and genomes.? see exons ↓