ERF

Chr 19AD

ETS2 repressor factor

Also known as: CHYTS, CRS4, PE-2, PE2

NCBI Gene: 2077 ENSG00000105722 UniProt: P50548 OMIM: 611888

ERF encodes a transcriptional repressor that binds to the ETS2 promoter and regulates genes involved in cellular proliferation and trophoblast differentiation. Mutations cause Chitayat syndrome and craniosynostosis 4, both inherited in an autosomal dominant pattern. The gene is highly constrained against loss-of-function variants (pLI 0.99), indicating that haploinsufficiency is likely not tolerated in the general population.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

ETS2 is a transcription factor and protooncogene involved in development, apoptosis, and the regulation of telomerase. The protein encoded by this gene binds to the ETS2 promoter and is a strong repressor of ETS2 transcription. Several transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Aug 2015]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Chitayat syndromeMIM #617180

Craniosynostosis 4MIM #600775

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · craniosynostosis 4 · AD · ClinGen 2021

Interpreting a novel variant

Curated mechanisms (Gene2Phenotype) include both loss of function and gain of function. Which applies is variant-dependent — do not assume a null variant is, or isn’t, the pathogenic class without checking the specific variant.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

769

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.26

LOEUF· LoF intol.

Multiple*

Mechanism· G2P

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.26LOEUF

pLI 0.990

Z-score 3.73

OE 0.06 (0.02–0.26)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

2.25Z-score

OE missense 0.66 (0.60–0.74)

238 obs / 358.1 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.06 (0.02–0.26)

0≤0.351.4

Missense OE?0.66 (0.60–0.74)

0≤0.61.4

Synonymous OE?1.18

0≤1.21.6

LoF obs/exp: 1 / 18.2Missense obs/exp: 238 / 358.1Syn Z: -1.84

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 95

674 rare PASS variants

Rare truncating (LoF)

1 in 6,100

38 rare PASS variants

Rare synonymous (reference)

1 in 100

411 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ERF. 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 170	1 in 8,100
South Asian	~43k	1 in 99	≈ 1 in 9,600
Remaining (unassigned)	~30k	1 in 120	1 in 3,300
European (Finnish)	~27k	1 in 260	1 in 5,000
Admixed American	~22k	1 in 120	1 in 3,200
African / African American	~21k	1 in 100	1 in 3,500
East Asian	~20k	1 in 160	1 in 3,900
Ashkenazi Jewish	~13k	1 in 520	1 in 2,000
Middle Eastern	~2,884	1 in 96	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.