TRIM32

Chr 9AR

tripartite motif containing 32

Also known as: BBS11, HT2A, LGMD2H, LGMDR8, TATIP

NCBI Gene: 22954 ENSG00000119401 UniProt: Q13049 OMIM: 602290

TRIM32 encodes a tripartite motif protein that localizes to cytoplasmic bodies and the nucleus, where it interacts with transcriptional machinery. Mutations cause autosomal recessive limb-girdle muscular dystrophy type 8 and Bardet-Biedl syndrome 11 through a predicted gain-of-function mechanism. The low pLI score (0.0017) indicates tolerance to loss-of-function variants, consistent with the gain-of-function pathogenic mechanism.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The protein localizes to cytoplasmic bodies. The protein has also been localized to the nucleus, where it interacts with the activation domain of the HIV-1 Tat protein. The Tat protein activates transcription of HIV-1 genes. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.852 OMIM phenotypes

Clinical Summary— TRIM32

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Gene-Disease Validity (ClinGen)

Bardet-Biedl syndrome 11 · ARLimited

Limited evidence — not for standalone diagnostic reporting

2 total gene-disease associations curated

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

84 unique Pathogenic / Likely Pathogenic· 398 VUS of 783 total submissions

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Clinical Trials

2 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — TRIM32

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.85LOEUF

pLI 0.002

Z-score 1.98

OE 0.45 (0.26–0.85)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.83Z-score

OE missense 0.88 (0.81–0.96)

335 obs / 380.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.45 (0.26–0.85)

0≤0.351.4

Missense OE?0.88 (0.81–0.96)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 7 / 15.4Missense obs/exp: 335 / 380.4Syn Z: 0.62

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

limitedTRIM32-related Bardet-Biedl syndromeOTHERAR

definitiveTRIM32-related limb-girdle muscular dystrophyLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.7230th %ile

GOF

0.72top 25%

LOF

0.2580th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

783 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic51

Likely Pathogenic33

VUS398

Likely Benign240

Benign8

Conflicting51

Pathogenic

Likely Pathogenic

398

VUS

240

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	38	1	12	0	51
Likely Pathogenic	31	2	0	0	33
VUS	3	361	31	3	398
Likely Benign	1	2	4	233	240
Benign	0	0	7	1	8
Conflicting	—				51
Total	73	366	54	237	781

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

View in ClinVar →

30 pathogenic / likely-pathogenic (of 84) ClinVar copy-number / structural variants overlap TRIM32 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →