TRIM71

Chr 3AD

tripartite motif containing 71

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

NCBI Gene: 131405 ENSG00000206557 UniProt: Q2Q1W2 OMIM: 618570

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is an E3 ubiquitin-protein ligase that binds with miRNAs and maintains the growth and upkeep of embryonic stem cells. This gene also is involved in the G1-S phase transition of the cell cycle. [provided by RefSeq, Dec 2015]

OMIM ResearchGenerating clinical summary…

LOFmechanismADLOEUF 0.171 OMIM phenotype

Clinical Summary— TRIM71

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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.

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ClinVar Variants

7 unique Pathogenic / Likely Pathogenic· 135 VUS of 175 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.17LOEUF

pLI 1.000

Z-score 4.69

OE 0.04 (0.01–0.17)

Highly constrained

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

Missense Constraint?

3.28Z-score

OE missense 0.59 (0.53–0.65)

295 obs / 501.7 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.04 (0.01–0.17)

0≤0.351.4

Missense OE?0.59 (0.53–0.65)

0≤0.61.4

Synonymous OE?1.30

0≤1.21.6

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

This gene — mechanism propensity

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 · 43% of P/LP variants are LoF · 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

175 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4

Likely Pathogenic3

VUS135

Likely Benign25

Benign2

Conflicting4

Pathogenic

Likely Pathogenic

135

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	2	2	0	0	4
Likely Pathogenic	1	2	0	0	3
VUS	3	131	1	0	135
Likely Benign	0	6	0	19	25
Benign	0	0	1	1	2
Conflicting	—				4
Total	6	141	2	20	173

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

View in ClinVar →

16 pathogenic / likely-pathogenic (of 19) ClinVar copy-number / structural variants overlap TRIM71 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →