ERI1

Chr 8AR

exoribonuclease 1

Also known as: 3'HEXO, HEXO, HXAL, SEMDGC, SEMDGS, THEX1

NCBI Gene: 90459 ENSG00000104626 UniProt: Q8IV48 OMIM: 608739

The protein is a 3'-5' exonuclease that degrades histone mRNAs after DNA replication and processes 5.8S ribosomal RNA, playing a key role in chondrogenesis. Biallelic mutations cause Hoxha-Aliu syndrome and spondyloepimetaphyseal dysplasia (Guo-Campeau type), both skeletal dysplasias with autosomal recessive inheritance. The gene shows tolerance to loss-of-function variants (pLI near 0), consistent with the recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Enables 3'-5' exonuclease activity. Involved in maturation of 5.8S rRNA. Located in cytoplasm and nucleolus. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Hoxha-Aliu syndromeMIM #620662

Spondyloepimetaphyseal dysplasia, Guo-Campeau typeMIM #620663

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Hoxha-Aliu syndrome; Spondyloepimetaphyseal dysplasia, Guo-Campeau type; no ClinGen or GenCC tier

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

1.07

LOEUF

LOF

Mechanism· G2P

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.07LOEUF

pLI 0.000

Z-score 1.35

OE 0.63 (0.39–1.07)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-1.38Z-score

OE missense 1.30 (1.16–1.46)

217 obs / 167.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.63 (0.39–1.07)

0≤0.351.4

Missense OE?1.30 (1.16–1.46)

0≤0.61.4

Synonymous OE?1.53

0≤1.21.6

LoF obs/exp: 10 / 15.8Missense obs/exp: 217 / 167.0Syn Z: -3.23

Background carrier burden — how many people carry a rare variant somewhere in ERI1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 97

620 rare PASS variants

Rare truncating (LoF)

1 in 460

105 rare PASS variants

Rare synonymous (reference)

1 in 220

222 rare PASS variants

Rare missense and truncating variants are carried at similar rates in ERI1; this gene does not show strong loss-of-function constraint by this measure. 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 140	1 in 420
South Asian	~43k	1 in 110	1 in 2,100
Remaining (unassigned)	~30k	1 in 79	1 in 690
European (Finnish)	~27k	1 in 320	1 in 1,100
Admixed American	~22k	1 in 230	1 in 1,600
African / African American	~21k	1 in 100	1 in 530
East Asian	~20k	1 in 170	1 in 1,200
Ashkenazi Jewish	~13k	1 in 410	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 110	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.

Exome coverage (gnomAD): 3 of 7 coding exons well covered in gnomAD exomes; exons 1, 4, 5, 6 marginal. Genomes: 6 of 7 (exon 2 below).? see exons ↓