TTC5

Chr 14AR

tetratricopeptide repeat domain 5

Also known as: NEDCAFD, Strap

NCBI Gene: 91875 ENSG00000136319 UniProt: Q8N0Z6 OMIM: 619014

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.

OMIM ResearchSummary from RefSeq, UniProt

Enables ribosome binding activity. Involved in positive regulation of mRNA catabolic process. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.791 OMIM phenotype

Clinical Summary— TTC5

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

9 unique Pathogenic / Likely Pathogenic· 49 VUS of 80 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.79LOEUF

pLI 0.000

Z-score 2.37

OE 0.50 (0.32–0.79)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.53Z-score

OE missense 0.90 (0.81–1.01)

216 obs / 239.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.50 (0.32–0.79)

0≤0.351.4

Missense OE?0.90 (0.81–1.01)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 13 / 26.0Missense obs/exp: 216 / 239.1Syn Z: -0.06

ClinVar Variant Classifications

80 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5

Likely Pathogenic4

VUS49

Likely Benign9

Benign1

Conflicting1

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	3	2	0	0	5
Likely Pathogenic	3	1	0	0	4
VUS	3	46	0	0	49
Likely Benign	0	3	1	5	9
Benign	0	1	0	0	1
Conflicting	—				1
Total	9	53	1	5	69

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

View in ClinVar →

19 pathogenic / likely-pathogenic (of 28) ClinVar copy-number / structural variants overlap TTC5 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →