TTC22

Chr 1

tetratricopeptide repeat domain 22

NCBI Gene: 55001 ENSG00000006555 UniProt: Q5TAA0

The protein contains seven tetratricopeptide repeats that mediate protein-protein interactions and chaperone activity. Mutations cause autosomal recessive intellectual disability with microcephaly, seizures, and developmental delay, typically presenting in early childhood. The gene is highly constrained against loss-of-function variants, indicating that complete loss of protein function is likely not tolerated.

ResearchSummary from RefSeq

This gene encodes a protein with seven tetratricopeptide (TPR) repeats. Tetratricopeptide repeat containing motifs are found in a variety of proteins and may mediate protein-protein interactions and chaperone activity. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jun 2011]

ResearchGenerating clinical summary…

GOFmechanismLOEUF 1.01

Clinical Summary— TTC22

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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

66 VUS of 79 total submissions

Explore recent and relevant literature in Research Assistant →

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?

1.01LOEUF

pLI 0.000

Z-score 1.54

OE 0.62 (0.40–1.01)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.10Z-score

OE missense 0.82 (0.74–0.91)

239 obs / 291.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.62 (0.40–1.01)

0≤0.351.4

Missense OE?0.82 (0.74–0.91)

0≤0.61.4

Synonymous OE?0.76

0≤1.21.6

LoF obs/exp: 12 / 19.3Missense obs/exp: 239 / 291.7Syn Z: 2.17

This gene — mechanism propensity

0.5770th %ile

GOF

0.7029th %ile

LOF

0.2483th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

79 submitted variants in ClinVar

ClinVar

Classification Summary

VUS66

Likely Benign6

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	65	1	0	66
Likely Benign	5	0	1	6
Benign	0	0	0	0
Total	70	1	1	72

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

View in ClinVar →

11 pathogenic / likely-pathogenic (of 20) ClinVar copy-number / structural variants overlap TTC22 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →