TRIM71

Chr 3

tripartite motif containing 71

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

NCBI Gene: 131405 ENSG00000206557 UniProt: Q2Q1W2

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.

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]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtHydrocephalus, congenital, 4

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.17

LOEUF· LoF intol.

LOF

Mechanism· G2P

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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

Background carrier burden — how many people carry a rare variant somewhere in TRIM71?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 58

1,075 rare PASS variants

Rare truncating (LoF)

1 in 20,000

21 rare PASS variants

Rare synonymous (reference)

1 in 74

681 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TRIM71. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 67	1 in 50,000
South Asian	~43k	1 in 72	1 in 4,900
Remaining (unassigned)	~30k	1 in 55	≈ 1 in 15,000
European (Finnish)	~27k	1 in 170	≈ 1 in 8,800
Admixed American	~22k	1 in 64	none seen
African / African American	~21k	1 in 75	≈ 1 in 21,000
East Asian	~20k	1 in 65	none seen
Ashkenazi Jewish	~13k	1 in 200	≈ 1 in 4,800
Middle Eastern	~2,884	1 in 61	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓