TTC23

Chr 15

tetratricopeptide repeat domain 23

Also known as: HCC-8

NCBI Gene: 64927 ENSG00000103852 UniProt: Q5W5X9

TTC23 encodes a protein that participates in ciliary Hedgehog signaling pathways and is located in the cilium. Mutations cause autosomal recessive nephronophthisis, a ciliopathy characterized by chronic kidney disease that typically progresses to end-stage renal disease in childhood or adolescence. The gene shows low constraint against loss-of-function variants, consistent with its recessive inheritance pattern.

ResearchSummary from RefSeq, UniProt

Predicted to be involved in positive regulation of smoothened signaling pathway. Predicted to be located in cilium. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.75

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?

1.75LOEUF

pLI 0.000

Z-score -1.41

OE 1.31 (0.99–1.75)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.06Z-score

OE missense 0.99 (0.89–1.10)

239 obs / 241.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.31 (0.99–1.75)

0≤0.351.4

Missense OE?0.99 (0.89–1.10)

0≤0.61.4

Synonymous OE?1.07

0≤1.21.6

LoF obs/exp: 31 / 23.6Missense obs/exp: 239 / 241.6Syn Z: -0.57

Background carrier burden — how many people carry a rare variant somewhere in TTC23?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 77

702 rare PASS variants

Rare truncating (LoF)

1 in 450

159 rare PASS variants

Rare synonymous (reference)

1 in 210

204 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TTC23. 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 96	1 in 520
South Asian	~43k	1 in 71	1 in 180
Remaining (unassigned)	~30k	1 in 67	1 in 520
European (Finnish)	~27k	1 in 220	1 in 1,800
Admixed American	~22k	1 in 76	1 in 200
African / African American	~21k	1 in 78	1 in 300
East Asian	~20k	1 in 100	1 in 280
Ashkenazi Jewish	~13k	1 in 730	1 in 930
Middle Eastern	~2,884	1 in 81	1 in 290

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): All 10 coding exons well covered in gnomAD exomes and genomes.? see exons ↓