TTC28

Chr 22

tetratricopeptide repeat domain 28

Also known as: TPRBK

NCBI Gene: 23331ENSG00000100154UniProt: Q96AY4

Enables kinase binding activity. Involved in regulation of mitotic cell cycle. Located in midbody. [provided by Alliance of Genome Resources, Jul 2025]

450
ClinVar variants
27
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— TTC28
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
27 Pathogenic / Likely Pathogenic· 347 VUS of 450 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.17LOEUF
pLI 1.000
Z-score 8.22
OE 0.10 (0.06–0.17)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
4.17Z-score
OE missense 0.68 (0.65–0.72)
925 obs / 1356.7 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.10 (0.06–0.17)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.68 (0.65–0.72)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.80
0≤1.21.6
LoF obs/exp: 10 / 97.8Missense obs/exp: 925 / 1356.7Syn Z: 3.71

ClinVar Variant Classifications

450 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic23
Likely Pathogenic4
VUS347
Likely Benign40
Benign13
Conflicting3
23
Pathogenic
4
Likely Pathogenic
347
VUS
40
Likely Benign
13
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
23
0
23
Likely Pathogenic
0
0
4
0
4
VUS
1
335
11
0
347
Likely Benign
0
12
4
24
40
Benign
0
2
1
10
13
Conflicting
—3
Total13494334430

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

View in ClinVar →

Protein Context — Lollipop Plot

TTC28 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Deregulation of long noncoding RNA SNHG17 and TTC28-AS1 is associated with type 2 diabetes mellitus.
Mohamadi M et al.·Scand J Clin Lab Invest
2019
LncRNA TTC28-AS1 promotes the progression of cervical cancer by targeting miR-377-3p.
Yang N et al.·J Obstet Gynaecol Res
2025
Heritable Risk and Protective Genetic Components of Glaucoma Medication Non-Adherence.
Barr JL et al.·Int J Mol Sci
2023
Rare variants analyses suggest novel cleft genes in the African population.
Alade A et al.·Sci Rep
2024
Exome sequencing of fetal anomaly syndromes: novel phenotype-genotype discoveries.
Meier N et al.·Eur J Hum Genet
2019
Identification of genetic variants associated with lupus nephritis in a Taiwanese cohort through systematic genetic screening.
Lee JC et al.·Sci Rep
2025Cohort
Oncogenic role and potential regulatory mechanism of fatty acid binding protein 5 based on a pan-cancer analysis.
Wang J et al.·Sci Rep
2023Functional
ROS1 genomic rearrangements are rare actionable drivers in microsatellite stable colorectal cancer.
Akhoundova D et al.·Int J Cancer
2022
Accelerating matchmaking of novel dysmorphology syndromes through clinical and genomic characterization of a large cohort.
Shaheen R et al.·Genet Med
2016Cohort
Microdeletion del(22)(q12.2) encompassing the facial development-associated gene, MN1 (meningioma 1) in a child with Pierre-Robin sequence (including cleft palate) and neurofibromatosis 2 (NF2): a case report and review of the literature.
Davidson TB et al.·BMC Med Genet
2012Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools