BNIP3

Chr 10

BCL2 interacting protein 3

Also known as: HABON, NIP3

NCBI Gene: 664 ENSG00000176171 UniProt: Q12983 OMIM: 603293

This gene encodes a mitochondrial pro-apoptotic protein that induces cell death by overcoming BCL2 suppression and participates in mitochondrial quality control by facilitating degradation of damaged mitochondrial proteins. The gene shows very low constraint against loss-of-function variants (pLI near 0, LOEUF 1.46), suggesting loss of function is well-tolerated in the general population. No established Mendelian diseases have been definitively linked to BNIP3 mutations in the pediatric population.

OMIM ResearchSummary from RefSeq, UniProt

This gene is encodes a mitochondrial protein that contains a BH3 domain and acts as a pro-apoptotic factor. The encoded protein interacts with anti-apoptotic proteins, including the E1B 19 kDa protein and Bcl2. This gene is silenced in tumors by DNA methylation. [provided by RefSeq, Dec 2014]

OMIM ResearchGenerating clinical summary…

Active trials

434

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.46

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.46LOEUF

pLI 0.000

Z-score 0.53

OE 0.82 (0.48–1.46)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.83Z-score

OE missense 0.78 (0.66–0.93)

90 obs / 114.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.82 (0.48–1.46)

0≤0.351.4

Missense OE?0.78 (0.66–0.93)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 8 / 9.8Missense obs/exp: 90 / 114.9Syn Z: 0.30

Background carrier burden — how many people carry a rare variant somewhere in BNIP3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 400

223 rare PASS variants

Rare truncating (LoF)

1 in 3,600

37 rare PASS variants

Rare synonymous (reference)

1 in 570

87 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for BNIP3. 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 560	1 in 5,400
South Asian	~43k	1 in 320	none seen
Remaining (unassigned)	~30k	1 in 410	1 in 4,100
European (Finnish)	~27k	1 in 2,100	≈ 1 in 13,000
Admixed American	~22k	1 in 280	1 in 2,500
African / African American	~21k	1 in 360	1 in 2,500
East Asian	~20k	1 in 140	1 in 2,200
Ashkenazi Jewish	~13k	1 in 690	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 390	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): 5 of 6 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 6.? see exons ↓