TTC5

Chr 14AR

tetratricopeptide repeat domain 5

Also known as: NEDCAFD, Strap

TTC5 encodes a cofactor protein that regulates multiple cellular processes including actin dynamics, autophagy, DNA damage response, and mitochondrial ATP production through interactions with various protein complexes. Mutations in TTC5 cause autosomal recessive intellectual disability with microcephaly, seizures, and spasticity, typically presenting in early childhood. The gene shows very low constraint against loss-of-function variants (pLI near 0), consistent with recessive inheritance where heterozygous carriers are unaffected.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismARLOEUF 0.791 OMIM phenotype
Clinical SummaryTTC5
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
28 unique Pathogenic / Likely Pathogenic· 56 VUS of 108 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.79LOEUF
pLI 0.000
Z-score 2.37
OE 0.50 (0.320.79)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.53Z-score
OE missense 0.90 (0.811.01)
216 obs / 239.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.50 (0.320.79)
00.351.4
Missense OE0.90 (0.811.01)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 13 / 26.0Missense obs/exp: 216 / 239.1Syn Z: -0.06

ClinVar Variant Classifications

108 submitted variants in ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic4
VUS56
Likely Benign9
Benign2
Conflicting1
24
Pathogenic
4
Likely Pathogenic
56
VUS
9
Likely Benign
2
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
2
19
0
24
Likely Pathogenic
3
1
0
0
4
VUS
3
47
6
0
56
Likely Benign
0
3
1
5
9
Benign
0
1
1
0
2
Conflicting
1
Total95427596

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TTC5 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗