ELP1

Chr 9ADARSomatic

elongator acetyltransferase complex subunit 1

Also known as: DYS, FD, IKAP, IKBKAP, IKI3, TOT1

NCBI Gene: 8518 ENSG00000070061 UniProt: O95163 OMIM: 603722

ELP1 encodes a scaffold protein that is a component of the elongator complex required for tRNA modifications and also assembles active kinase complexes involved in proinflammatory signaling. Mutations cause familial dysautonomia, a severe neurodevelopmental disorder affecting the autonomic nervous system, and are also associated with medulloblastoma. The gene follows autosomal recessive inheritance for familial dysautonomia and shows high constraint against loss-of-function variants (LOEUF 0.735).

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a scaffold protein and a regulator for three different kinases involved in proinflammatory signaling. The encoded protein can bind NF-kappa-B-inducing kinase and I-kappa-B kinases through separate domains and assemble them into an active kinase complex. Mutations in this gene have been associated with familial dysautonomia. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{Medulloblastoma}MIM #155255

ADARSomatic

Dysautonomia, familialMIM #223900

Clinical highlights

Gene–disease validity (ClinGen)

Moderate · Riley-Day syndrome · 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

0.73

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — ELP1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.73LOEUF

pLI 0.000

Z-score 3.54

OE 0.58 (0.46–0.73)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.08Z-score

OE missense 1.01 (0.95–1.07)

698 obs / 692.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.58 (0.46–0.73)

0≤0.351.4

Missense OE?1.01 (0.95–1.07)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 47 / 81.5Missense obs/exp: 698 / 692.1Syn Z: 0.07

Background carrier burden — how many people carry a rare variant somewhere in ELP1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 37

1,701 rare PASS variants

Rare truncating (LoF)

1 in 700

264 rare PASS variants

Rare synonymous (reference)

1 in 85

604 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ELP1. 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 59	1 in 750
South Asian	~43k	1 in 31	1 in 680
Remaining (unassigned)	~30k	1 in 28	1 in 790
European (Finnish)	~27k	1 in 89	1 in 1,500
Admixed American	~22k	1 in 36	1 in 420
African / African American	~21k	1 in 36	1 in 410
East Asian	~20k	1 in 33	1 in 320
Ashkenazi Jewish	~13k	1 in 230	1 in 2,600
Middle Eastern	~2,884	1 in 37	≈ 1 in 1,400

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): 27 of 36 coding exons well covered in gnomAD exomes; exons 5, 6, 10, 21, 22 and 4 more marginal. Genomes: all 36.? see exons ↓