TMF1

Chr 3

TATA element modulatory factor 1

Also known as: ARA160, TMF

TMF1 encodes a transcriptional coactivator that regulates androgen receptor signaling and mediates retrograde transport processes between cellular compartments including the Golgi apparatus and endoplasmic reticulum. The gene is highly constrained against loss-of-function variants (LOEUF 0.502), but no human disease associations have been established for TMF1 mutations to date.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
3
Pubs (1 yr)
11
P/LP submissions
0%
P/LP missense
0.50
LOEUF
DN
Mechanism· predicted
Clinical SummaryTMF1
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.34) despite low pLI — interpret in context.
📋
ClinVar Variants
11 unique Pathogenic / Likely Pathogenic· 132 VUS of 177 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.50LOEUF
pLI 0.000
Z-score 4.54
OE 0.34 (0.240.50)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.42Z-score
OE missense 0.95 (0.881.02)
517 obs / 544.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.34 (0.240.50)
00.351.4
Missense OE0.95 (0.881.02)
00.61.4
Synonymous OE1.11
01.21.6
LoF obs/exp: 19 / 55.5Missense obs/exp: 517 / 544.4Syn Z: -1.22
DN
0.73top 25%
GOF
0.5464th %ile
LOF
0.3164th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

177 submitted variants in ClinVar

Classification Summary

Pathogenic10
Likely Pathogenic1
VUS132
Likely Benign10
Conflicting1
10
Pathogenic
1
Likely Pathogenic
132
VUS
10
Likely Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
10
0
10
Likely Pathogenic
0
0
1
0
1
VUS
0
130
2
0
132
Likely Benign
0
9
0
1
10
Benign
0
0
0
0
0
Conflicting
1
Total0139131154

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

View in ClinVar →

Protein Context — Lollipop Plot

TMF1 · protein map & ClinVar variants

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

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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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC