ELP2

Chr 18AR

elongator acetyltransferase complex subunit 2

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

NCBI Gene: 55250ENSG00000134759UniProt: Q6IA86

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]

Primary Disease Associations & Inheritance

Intellectual developmental disorder, autosomal recessive 58MIM #617270
AR
275
ClinVar variants
62
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ELP2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
62 Pathogenic / Likely Pathogenic· 162 VUS of 275 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.88LOEUF
pLI 0.000
Z-score 2.30
OE 0.68 (0.53–0.88)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.58Z-score
OE missense 0.92 (0.85–1.00)
419 obs / 453.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.68 (0.53–0.88)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.92 (0.85–1.00)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.00
0≤1.21.6
LoF obs/exp: 40 / 59.1Missense obs/exp: 419 / 453.5Syn Z: 0.02

ClinVar Variant Classifications

275 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic49
Likely Pathogenic13
VUS162
Likely Benign38
Benign7
Conflicting6
49
Pathogenic
13
Likely Pathogenic
162
VUS
38
Likely Benign
7
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
2
46
0
49
Likely Pathogenic
6
3
4
0
13
VUS
2
144
15
1
162
Likely Benign
0
13
3
22
38
Benign
0
3
1
3
7
Conflicting
—6
Total91656926275

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

View in ClinVar →

Protein Context — Lollipop Plot

ELP2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

ELP2-related intellectual developmental disorder

limited
ARUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Intellectual developmental disorder, autosomal recessive 58

MIM #617270

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — ELP2
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
HACE1, GLRX5, and ELP2 gene variant cause spastic paraplegies.
Sager G et al.·Acta Neurol Belg
2022
Epilepsy or neurodevelopmental disorders are associated with homozygous and pathogenic ELP2 variation in three siblings.
Khalilov D et al.·Neurocase
2022
ELP2 compound heterozygous variants associated with cortico-cerebellar atrophy, nodular heterotopia and epilepsy: Phenotype expansion and review of the literature.
Russo A et al.·Eur J Med Genet
2021Review
Elp2 mutations perturb the epitranscriptome and lead to a complex neurodevelopmental phenotype.
Kojic M et al.·Nat Commun
2021
Clinical and molecular findings in a Turkish family with an ultra-rare condition, ELP2-related neurodevelopmental disorder.
Dogan M et al.·Mol Biol Rep
2021
The Elp2 subunit is essential for elongator complex assembly and functional regulation.
Dong C et al.·Structure
2015Functional
Elongator and the role of its subcomplexes in human diseases.
Gaik M et al.·EMBO Mol Med
2023Review
Aberrant RNA Splicing Is a Primary Link between Genetic Variation and Pancreatic Cancer Risk.
Tian J et al.·Cancer Res
2022
ELP2 is a novel gene implicated in neurodevelopmental disabilities.
Cohen JS et al.·Am J Med Genet A
2015Case report
A novel ELP1 mutation impairs the function of the Elongator complex and causes a severe neurodevelopmental phenotype.
Kojic M et al.·J Hum Genet
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools