NRG4

Chr 15

neuregulin 4

Also known as: HRG4

NCBI Gene: 145957 ENSG00000169752 UniProt: Q8WWG1 OMIM: 610894

The neuregulins, including NRG4, activate type-1 growth factor receptors (see EGFR; MIM 131550) to initiating cell-to-cell signaling through tyrosine phosphorylation (Harari et al., 1999 [PubMed 10348342]).[supplied by OMIM, Mar 2008]

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.33

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.33LOEUF

pLI 0.028

Z-score 1.07

OE 0.52 (0.23–1.33)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.41Z-score

OE missense 0.86 (0.69–1.07)

54 obs / 63.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.52 (0.23–1.33)

0≤0.351.4

Missense OE?0.86 (0.69–1.07)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 3 / 5.8Missense obs/exp: 54 / 63.1Syn Z: 0.28

Background carrier burden — how many people carry a rare variant somewhere in NRG4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 750

151 rare PASS variants

Rare truncating (LoF)

1 in 2,600

40 rare PASS variants

Rare synonymous (reference)

1 in 2,600

43 rare PASS variants

Rare missense and truncating variants are carried at similar rates in NRG4; this gene does not show strong loss-of-function constraint by this measure. 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 650	1 in 5,400
South Asian	~43k	1 in 710	1 in 6,100
Remaining (unassigned)	~30k	1 in 600	1 in 2,700
European (Finnish)	~27k	1 in 2,000	≈ 1 in 27,000
Admixed American	~22k	1 in 620	1 in 1,200
African / African American	~21k	1 in 430	1 in 2,200
East Asian	~20k	1 in 630	≈ 1 in 6,600
Ashkenazi Jewish	~13k	1 in 1,300	none seen
Middle Eastern	~2,884	1 in 360	none seen

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): 1 of 5 coding exons well covered in gnomAD exomes; exons 2, 3, 5, 6 marginal. Genomes: all 5.? see exons ↓