TRIM37

Chr 17

tripartite motif containing 37

Also known as: MUL, POB1, TEF3

NCBI Gene: 4591 ENSG00000108395 UniProt: O94972

The protein functions as an E3 ubiquitin-protein ligase that prevents centriole reduplication, mediates histone H2A monoubiquitination for transcriptional repression, and positively regulates peroxisome import by stabilizing PEX5. Mutations cause mulibrey nanism, an autosomal recessive disorder affecting multiple tissues of mesodermal origin including muscle, liver, brain, and eye. This gene is not highly constrained against loss-of-function variants.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the tripartite motif (TRIM) family, whose members are involved in diverse cellular functions such as developmental patterning and oncogenesis. The TRIM motif includes zinc-binding domains, a RING finger region, a B-box motif and a coiled-coil domain. The RING finger and B-box domains chelate zinc and might be involved in protein-protein and/or protein-nucleic acid interactions. Mutations in this gene are associated with mulibrey (muscle-liver-brain-eye) nanism, an autosomal recessive disorder that involves several tissues of mesodermal origin. TRIM37 localizes in peroxisomal membranes, and has been implicated in human peroxisomal biogenesis disorders. [provided by RefSeq, Jul 2020]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtMulibrey nanism

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · mulibrey nanism · AR · ClinGen 2020

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.64

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — TRIM37

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.64LOEUF

pLI 0.000

Z-score 3.85

OE 0.47 (0.35–0.64)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.82Z-score

OE missense 0.90 (0.83–0.97)

476 obs / 529.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.47 (0.35–0.64)

0≤0.351.4

Missense OE?0.90 (0.83–0.97)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 29 / 61.6Missense obs/exp: 476 / 529.1Syn Z: -0.06

Background carrier burden — how many people carry a rare variant somewhere in TRIM37?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 73

1,151 rare PASS variants

Rare truncating (LoF)

1 in 630

188 rare PASS variants

Rare synonymous (reference)

1 in 110

421 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TRIM37. 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 82	1 in 890
South Asian	~43k	1 in 38	1 in 1,600
Remaining (unassigned)	~30k	1 in 65	1 in 370
European (Finnish)	~27k	1 in 340	1 in 1,400
Admixed American	~22k	1 in 64	1 in 1,000
African / African American	~21k	1 in 43	1 in 1,800
East Asian	~20k	1 in 77	1 in 570
Ashkenazi Jewish	~13k	1 in 430	1 in 900
Middle Eastern	~2,884	1 in 69	≈ 1 in 720

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.