DALRD3

Chr 3

DALR anticodon binding domain containing 3

Also known as: DEE86, EIEE86

NCBI Gene: 55152 ENSG00000178149 UniProt: Q5D0E6

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.

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]

ResearchGenerating clinical summary…

LOEUF 1.14

Clinical Summary— DALRD3

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 82 VUS of 116 total submissions

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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

ClinVar Variant Classifications

116 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic1

VUS82

Likely Benign11

Benign4

Conflicting1

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	1	0	0	0	1
VUS	3	77	2	0	82
Likely Benign	0	3	1	7	11
Benign	0	2	2	0	4
Conflicting	—				1
Total	4	82	5	7	99

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

View in ClinVar →

13 pathogenic / likely-pathogenic (of 16) ClinVar copy-number / structural variants overlap DALRD3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →