ETV5

Chr 3

ETS variant transcription factor 5

Also known as: ERM

NCBI Gene: 2119 ENSG00000244405 UniProt: P41161 OMIM: 601600

Enables DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Involved in cellular response to oxidative stress; negative regulation of transcription by RNA polymerase II; and positive regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.09

Clinical Summary— ETV5

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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

1 unique Pathogenic / Likely Pathogenic· 49 VUS of 86 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.09LOEUF

pLI 1.000

Z-score 5.28

OE 0.00 (0.00–0.09)

Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?

1.99Z-score

OE missense 0.68 (0.60–0.76)

203 obs / 300.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.09)

0≤0.351.4

Missense OE?0.68 (0.60–0.76)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 0 / 32.5Missense obs/exp: 203 / 300.1Syn Z: 0.53

This gene — mechanism propensity

0.3693th %ile

GOF

0.2198th %ile

LOF

0.84top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.09

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

86 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS49

Likely Benign4

Benign13

Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	0	0	1
Likely Pathogenic	0	0	0	0
VUS	49	0	0	49
Likely Benign	1	0	3	4
Benign	1	9	3	13
Total	52	9	6	67

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

View in ClinVar →

40 pathogenic / likely-pathogenic (of 42) ClinVar copy-number / structural variants overlap ETV5 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →