DPH6

Chr 15

diphthamine biosynthesis 6

Also known as: ATPBD4

NCBI Gene: 89978 ENSG00000134146 UniProt: Q7L8W6 OMIM: 618391

Enables diphthine-ammonia ligase activity. Predicted to be involved in protein histidyl modification to diphthamide. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.08

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.08LOEUF

pLI 0.000

Z-score 1.34

OE 0.64 (0.39–1.08)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.61Z-score

OE missense 0.85 (0.73–0.99)

117 obs / 137.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.64 (0.39–1.08)

0≤0.351.4

Missense OE?0.85 (0.73–0.99)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 10 / 15.7Missense obs/exp: 117 / 137.2Syn Z: -0.08

Background carrier burden — how many people carry a rare variant somewhere in DPH6?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 130

444 rare PASS variants

Rare truncating (LoF)

1 in 1,000

96 rare PASS variants

Rare synonymous (reference)

1 in 370

135 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for DPH6. 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 140	1 in 920
South Asian	~43k	1 in 87	1 in 1,000
Remaining (unassigned)	~30k	1 in 89	1 in 2,100
European (Finnish)	~27k	1 in 320	≈ 1 in 8,000
Admixed American	~22k	1 in 170	1 in 1,600
African / African American	~21k	1 in 110	1 in 1,100
East Asian	~20k	1 in 180	1 in 830
Ashkenazi Jewish	~13k	1 in 500	≈ 1 in 4,300
Middle Eastern	~2,884	1 in 160	≈ 1 in 2,100

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): 7 of 9 coding exons well covered in gnomAD exomes; exons 1, 9 marginal. Genomes: all 9.? see exons ↓