TBC1D22A

Chr 22

TBC1 domain family member 22A

Also known as: C22orf4, HSC79E021

NCBI Gene: 25771ENSG00000054611UniProt: Q8WUA7

Enables 14-3-3 protein binding activity and protein homodimerization activity. Predicted to be active in Golgi apparatus. [provided by Alliance of Genome Resources, Jul 2025]

0
ClinVar variants
0
Pathogenic / LP
0.42
pLI score
0
Active trials
Clinical Summary— TBC1D22A
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.22) despite low pLI — interpret in context.
Some data sources returned errors (2)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

clinvarCount: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.44LOEUF
pLI 0.419
Z-score 3.76
OE 0.22 (0.12–0.44)
Moderately constrained

More LoF-intolerant than ~75% 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.
1.20Z-score
OE missense 0.81 (0.74–0.90)
268 obs / 329.2 exp
Tolerant

Mild missense constraint

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.0.22 (0.12–0.44)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.81 (0.74–0.90)
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.1.11
0≤1.21.6
LoF obs/exp: 6 / 27.1Missense obs/exp: 268 / 329.2Syn Z: -1.00

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

TBC1D22A · 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
High Expression of TBC1 Domain Family Member 22A is Related to Poor Prognosis in Ovarian Serous Cystadenocarcinoma.
Lv X et al.·Int J Med Sci
2024
Four-Generation Pedigree of Monozygotic Female Twins Reveals Genetic Factors in Twinning Process by Whole-Genome Sequencing.
Liu S et al.·Twin Res Hum Genet
2018
Genotype-Phenotype Associations in Phelan-McDermid Syndrome: Insights into Novel Genes Beyond SHANK3.
Nevado J et al.·Int J Mol Sci
2025
Identification and validation of genes associated with prognosis of cisplatin-resistant ovarian cancer.
Liu D et al.·BMC Cancer
2024
Genetic and metabolic profiling of individuals with Phelan-McDermid syndrome presenting with seizures.
Jain L et al.·Clin Genet
2022
Genetic and Lifestyle-Related Factors Influencing Serum Hyper-Propionylcarnitine Concentrations and Their Association with Metabolic Syndrome and Cardiovascular Disease Risk.
Lee YH et al.·Int J Mol Sci
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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External Resources

Links to major genomics databases and tools