DBR1

Chr 3AR

debranching RNA lariats 1

Also known as: XGIP

NCBI Gene: 51163 ENSG00000138231 UniProt: Q9UK59 OMIM: 607024

The protein encoded by this gene is an RNA lariat debranching enzyme that hydrolyzes 2'-5' prime branched phosphodiester bonds. The encoded protein specifically targets the bonds at the branch point of excised lariat intron RNA, converting them to linear molecules that are then degraded. This protein may also be involved in retroviral replication. [provided by RefSeq, Nov 2011]

OMIM Research

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{Encephalitis, acute, infection (viral)-induced, susceptibility to, 11}MIM #619441

Xerosis and growth failure with immune and pulmonary dysfunction syndromeMIM #620510

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Xerosis and growth failure with immune and pulmonary dysfunction syndrome; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.02

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.02LOEUF

pLI 0.000

Z-score 1.50

OE 0.67 (0.45–1.02)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.79Z-score

OE missense 0.87 (0.78–0.96)

251 obs / 288.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.67 (0.45–1.02)

0≤0.351.4

Missense OE?0.87 (0.78–0.96)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 16 / 23.9Missense obs/exp: 251 / 288.8Syn Z: 0.31

Background carrier burden — how many people carry a rare variant somewhere in DBR1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 68

662 rare PASS variants

Rare truncating (LoF)

1 in 2,000

92 rare PASS variants

Rare synonymous (reference)

1 in 160

253 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for DBR1. 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 120	1 in 1,900
South Asian	~43k	1 in 93	1 in 3,300
Remaining (unassigned)	~30k	1 in 94	1 in 3,000
European (Finnish)	~27k	1 in 1,200	≈ 1 in 8,800
Admixed American	~22k	1 in 99	1 in 1,800
African / African American	~21k	1 in 95	1 in 1,300
East Asian	~20k	1 in 110	1 in 1,600
Ashkenazi Jewish	~13k	1 in 360	none seen
Middle Eastern	~2,884	1 in 97	1 in 470

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 8 coding exons well covered in gnomAD exomes; exon 4 marginal. Genomes: all 8.? see exons ↓