TTC38

Chr 22

tetratricopeptide repeat domain 38

Also known as: LL22NC03-5H6.5

NCBI Gene: 55020 ENSG00000075234 UniProt: Q5R3I4

TTC38 encodes a protein localized to extracellular exosomes, though its specific molecular function remains unclear. Mutations in this gene are associated with congenital microcephaly, and the gene shows tolerance to loss-of-function variants based on population genetics data. The inheritance pattern and additional clinical features require further characterization.

ResearchSummary from RefSeq

Located in extracellular exosome. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Active trials

—

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.10

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.10LOEUF

pLI 0.000

Z-score 1.12

OE 0.78 (0.56–1.10)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.41Z-score

OE missense 0.93 (0.84–1.03)

275 obs / 294.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.78 (0.56–1.10)

0≤0.351.4

Missense OE?0.93 (0.84–1.03)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 23 / 29.6Missense obs/exp: 275 / 294.6Syn Z: 0.66

Background carrier burden — how many people carry a rare variant somewhere in TTC38?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 66

680 rare PASS variants

Rare truncating (LoF)

1 in 400

153 rare PASS variants

Rare synonymous (reference)

1 in 91

287 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TTC38. 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 90	1 in 760
South Asian	~43k	1 in 56	1 in 300
Remaining (unassigned)	~30k	1 in 51	1 in 210
European (Finnish)	~27k	1 in 240	1 in 560
Admixed American	~22k	1 in 64	1 in 640
African / African American	~21k	1 in 62	1 in 460
East Asian	~20k	1 in 79	1 in 710
Ashkenazi Jewish	~13k	1 in 170	≈ 1 in 4,300
Middle Eastern	~2,884	1 in 72	1 in 390

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