DALRD3

Chr 3AR

DALR anticodon binding domain containing 3

Also known as: DEE86, EIEE86

NCBI Gene: 55152 ENSG00000178149 UniProt: Q5D0E6 OMIM: 618904

The DALRD3 protein facilitates tRNA methylation by helping to target specific arginine tRNAs for modification by methyltransferases METTL2A and METTL2B. Autosomal recessive mutations cause developmental and epileptic encephalopathy 86, affecting both neurodevelopment and seizure control. The gene is extremely intolerant to loss-of-function variants (pLI near 1), suggesting that even heterozygous loss significantly impacts cellular function.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The exact function of this gene is not known. It encodes a protein with a DALR anticodon binding domain similar to that of class Ia aminoacyl tRNA synthetases. This gene is located in a cluster of genes (with a complex sense-anti-sense genome architecture) on chromosome 3, and contains two micro RNA (miRNA) precursors (mir-425 and mir-191) in one of its introns. Preferential expression of this gene (the miRNAs and other genes in the cluster) in testis suggests a role of this gene in spermatogenesis (PMID:19906709). [provided by RefSeq, Feb 2013]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Developmental and epileptic encephalopathy 86MIM #618910

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Developmental and epileptic encephalopathy 86; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.14

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.14LOEUF

pLI 0.000

Z-score 1.03

OE 0.77 (0.53–1.14)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.27Z-score

OE missense 0.95 (0.86–1.06)

269 obs / 281.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.77 (0.53–1.14)

0≤0.351.4

Missense OE?0.95 (0.86–1.06)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 18 / 23.4Missense obs/exp: 269 / 281.9Syn Z: 0.05

Background carrier burden — how many people carry a rare variant somewhere in DALRD3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 88

917 rare PASS variants

Rare truncating (LoF)

1 in 490

210 rare PASS variants

Rare synonymous (reference)

1 in 210

343 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for DALRD3. 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 110	1 in 500
South Asian	~43k	1 in 95	1 in 550
Remaining (unassigned)	~30k	1 in 65	1 in 780
European (Finnish)	~27k	1 in 330	1 in 1,100
Admixed American	~22k	1 in 61	1 in 520
African / African American	~21k	1 in 93	1 in 400
East Asian	~20k	1 in 75	1 in 450
Ashkenazi Jewish	~13k	1 in 470	1 in 1,300
Middle Eastern	~2,884	1 in 64	≈ 1 in 690

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): 11 of 12 coding exons well covered in gnomAD exomes; exon 2 marginal. Genomes: all 12.? see exons ↓