NIBAN2

Chr 9

niban apoptosis regulator 2

Also known as: C9orf88, FAM129B, MEG-3, MINERVA, OC58, bA356B19.6

NCBI Gene: 64855 ENSG00000136830 UniProt: Q96TA1 OMIM: 614045

NIBAN2 encodes a transcription coactivator that suppresses apoptosis and is involved in regulating nucleotide metabolism and gonadotropin secretion. Mutations cause autosomal recessive neurodevelopmental disorder with early infantile epileptic encephalopathy, developmental delay, and intellectual disability. The gene is highly constrained against loss-of-function variants, indicating that biallelic mutations are likely required for disease manifestation.

OMIM ResearchSummary from RefSeq, UniProt

Enables transcription coactivator activity. Involved in several processes, including gonadotropin secretion; negative regulation of DNA biosynthetic process; and regulation of DNA-templated transcription. Located in several cellular components, including adherens junction; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.45

LOEUF

GOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.45LOEUF

pLI 0.017

Z-score 4.44

OE 0.28 (0.17–0.45)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.42Z-score

OE missense 0.95 (0.87–1.02)

445 obs / 470.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.28 (0.17–0.45)

0≤0.351.4

Missense OE?0.95 (0.87–1.02)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 12 / 43.6Missense obs/exp: 445 / 470.6Syn Z: 0.69

Background carrier burden — how many people carry a rare variant somewhere in NIBAN2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 43

963 rare PASS variants

Rare truncating (LoF)

1 in 1,500

99 rare PASS variants

Rare synonymous (reference)

1 in 94

472 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for NIBAN2. 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 45	1 in 1,300
South Asian	~43k	1 in 46	1 in 5,300
Remaining (unassigned)	~30k	1 in 36	1 in 680
European (Finnish)	~27k	1 in 120	1 in 3,900
Admixed American	~22k	1 in 43	1 in 1,800
African / African American	~21k	1 in 39	1 in 1,900
East Asian	~20k	1 in 52	1 in 1,400
Ashkenazi Jewish	~13k	1 in 170	≈ 1 in 3,900
Middle Eastern	~2,884	1 in 53	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): 13 of 14 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 14.? see exons ↓