TRIM71

Chr 3AD

tripartite motif containing 71

Also known as: HYC4, HYDCC1, LIN-41, LIN41

This E3 ubiquitin-protein ligase cooperates with the microRNA machinery to maintain embryonic stem cell proliferation and promotes the G1-S cell cycle transition by repressing CDKN1A expression. Mutations cause autosomal dominant congenital hydrocephalus. The gene is highly constrained against loss-of-function variants, indicating that functional copies are essential for normal development.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.171 OMIM phenotype
Clinical SummaryTRIM71
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
23 unique Pathogenic / Likely Pathogenic· 138 VUS of 193 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.17LOEUF
pLI 1.000
Z-score 4.69
OE 0.04 (0.010.17)
Highly constrained

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

Missense Constraint
3.28Z-score
OE missense 0.59 (0.530.65)
295 obs / 501.7 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.04 (0.010.17)
00.351.4
Missense OE0.59 (0.530.65)
00.61.4
Synonymous OE1.30
01.21.6
LoF obs/exp: 1 / 27.6Missense obs/exp: 295 / 501.7Syn Z: -3.53
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
moderateTRIM71-related neurodevelopmental disorder with ventriculomegaly and hydrocephalusLOFAD
DN
0.5081th %ile
GOF
0.6053th %ile
LOF
0.66top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.17

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

193 submitted variants in ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic3
VUS138
Likely Benign24
Benign2
Conflicting4
20
Pathogenic
3
Likely Pathogenic
138
VUS
24
Likely Benign
2
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
2
16
0
20
Likely Pathogenic
1
2
0
0
3
VUS
3
131
4
0
138
Likely Benign
0
5
0
19
24
Benign
0
0
1
1
2
Conflicting
4
Total61402120191

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

View in ClinVar →

Protein Context — Lollipop Plot

TRIM71 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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