ELP2

Chr 18AR

elongator acetyltransferase complex subunit 2

Also known as: MRT58, SHINC-2, STATIP1, StIP

NCBI Gene: 55250 ENSG00000134759 UniProt: Q6IA86 OMIM: 616054

ELP2 encodes a core subunit of the elongator complex, which catalyzes essential tRNA modifications including carboxymethyluridine formation at the wobble base position and functions as a histone acetyltransferase that associates with RNA polymerase II for transcriptional elongation. Biallelic mutations cause autosomal recessive intellectual developmental disorder. This represents a relatively recently described cause of intellectual disability involving defects in tRNA modification pathways.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a core subunit of the elongator complex, a histone acetyltransferase complex that associates with RNA polymerase II. In addition to histone acetylation, the encoded protein effects transcriptional elongation and may help remodel chromatin. [provided by RefSeq, May 2016]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Intellectual developmental disorder, autosomal recessive 58MIM #617270

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · complex neurodevelopmental disorder with motor features · AR · ClinGen 2025

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

0.88

LOEUF

LOF

Mechanism· G2P

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.88LOEUF

pLI 0.000

Z-score 2.30

OE 0.68 (0.53–0.88)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.58Z-score

OE missense 0.92 (0.85–1.00)

419 obs / 453.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.68 (0.53–0.88)

0≤0.351.4

Missense OE?0.92 (0.85–1.00)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 40 / 59.1Missense obs/exp: 419 / 453.5Syn Z: 0.02

Background carrier burden — how many people carry a rare variant somewhere in ELP2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 58

1,059 rare PASS variants

Rare truncating (LoF)

1 in 660

221 rare PASS variants

Rare synonymous (reference)

1 in 130

392 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ELP2. 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 80	1 in 660
South Asian	~43k	1 in 56	1 in 650
Remaining (unassigned)	~30k	1 in 43	1 in 680
European (Finnish)	~27k	1 in 300	≈ 1 in 8,900
Admixed American	~22k	1 in 57	1 in 400
African / African American	~21k	1 in 57	1 in 700
East Asian	~20k	1 in 68	1 in 800
Ashkenazi Jewish	~13k	1 in 130	≈ 1 in 3,200
Middle Eastern	~2,884	1 in 48	1 in 480

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): 20 of 22 coding exons well covered in gnomAD exomes; exons 8, 19 marginal. Genomes: all 22.? see exons ↓