SKIC3

Chr 5AR

SKI3 subunit of superkiller complex

Also known as: KIAA0372, Ski3, THES, TTC37

NCBI Gene: 9652ENSG00000198677UniProt: Q6PGP7

This gene encodes a protein with twenty tetratricopeptide (TPR) repeats. Tetratricopeptide repeat containing motifs are found in a variety of proteins and may mediate protein-protein interactions and chaperone activity. Mutations in this gene are associated with trichohepatoenteric syndrome. [provided by RefSeq, Jul 2010]

Primary Disease Associations & Inheritance

Trichohepatoenteric syndrome 1MIM #222470
AR
357
ClinVar variants
48
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SKIC3
🧬
Gene-Disease Validity (ClinGen)
trichohepatoenteric syndrome 1 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
48 Pathogenic / Likely Pathogenic· 132 VUS of 357 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.78LOEUF
pLI 0.000
Z-score 3.36
OE 0.63 (0.52–0.78)
Tolerant

Typical tolerance to LoF variation

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.
0.48Z-score
OE missense 0.95 (0.90–1.01)
746 obs / 783.9 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.0.63 (0.52–0.78)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.95 (0.90–1.01)
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.1.00
0≤1.21.6
LoF obs/exp: 62 / 97.9Missense obs/exp: 746 / 783.9Syn Z: 0.02

ClinVar Variant Classifications

357 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic37
Likely Pathogenic11
VUS132
Likely Benign174
Benign3
37
Pathogenic
11
Likely Pathogenic
132
VUS
174
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
18
0
19
0
37
Likely Pathogenic
9
1
1
0
11
VUS
1
126
5
0
132
Likely Benign
0
4
86
84
174
Benign
0
0
3
0
3
Total2813111484357

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

View in ClinVar →

Protein Context — Lollipop Plot

SKIC3 · protein map & ClinVar variants

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

Gene2Phenotype Curations

SKIC3-related trichohepatoenteric syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Trichohepatoenteric syndrome 1

MIM #222470

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — SKIC3
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Novel SKIC3 variants in tricho-hepato-enteric syndrome with hemochromatosis.
Ochiai K et al.·Hum Genome Var
2025🔓 Open Access
A Case Report on Tricho-Hepato-Enteric Syndrome: The SKIC3 Gene in Focus.
Zidan T et al.·Cureus
2024🔓 Open AccessCase report
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